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Menéndez R, Méndez R, Latorre A, González-Jiménez P, Peces-Barba G, Molina-Molina M, España PP, García E, Consuegra-Vanegas A, García-Clemente MM, Panadero C, Figueira-Gonçalves JM, De la Rosa-Carrillo D, Sibila O, Martínez-Pitarch MD, Toledo-Pons N, López-Ramírez C, Almonte-Batista W, Macías-Paredes A, Villamon M, Domínguez-Álvarez M, Pérez-Rodas EN, Lázaro J, Quirós S, Cordovilla R, Cano-Pumarega I, Torres A. Clustering patients with COVID-19 according to respiratory support requirements, and its impact on short- and long-term outcome (RECOVID study). Pulmonology 2025; 31:2442175. [PMID: 39750717 DOI: 10.1080/25310429.2024.2442175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 11/19/2024] [Indexed: 01/04/2025] Open
Abstract
INTRODUCTION The Spanish Society of Pulmonology and Thoracic Surgery created a registry for hospitalised patients with COVID-19 and the different types of respiratory support used (RECOVID). Objectives. To describe the profile of hospitalised patients with COVID-19, comorbidities, respiratory support treatments and setting. In addition, we aimed to identify varying profiles of patients according to outcomes and the complexity of respiratory support needed. METHODS Multicentre, observational study in 49 Spanish hospitals. A protocol collected demographic data, comorbidities, respiratory support, treatment setting and 1-year follow-up. Patients were described using either frequency and percentages or median and interquartile range, as appropriate. A cluster analysis made it possible to identify different types of profile among the patients. RESULTS In total, 2148 of 2454 hospitalised patients (87.5%) received care in the conventional ward, whilst 126 in IRCU and 180 in ICU. In IRCU, 30% required high-flow nasal oxygen whilst 25%, non-invasive mechanical ventilation and 17%, mechanical ventilation. Four clusters of patients were identified. Two clusters were more likely to require IRCU/ICU admission, although primarily Cluster 2: Cluster (C) 1 consisted of patients without comorbidities and C2, those with comorbidities. Both presented higher inflammatory levels and lower lymphocyte count and SpO2/FiO2; however, C2 showed worse values. Two different clusters identified patients requiring less complex respiratory support. C3 presented higher comorbidities and elevated lymphocyte count, SpO2/FiO2 and low C-reactive protein (CRP). C4 included those without comorbidities except for arterial hypertension, lymphopenia and an intermediate CRP. In-hospital mortality and subsequent 1-year mortality were greater for C2 (28.6% and 7.1%) and C1 (11.1%, 8.3%) than for C4 (3.3%, 1.8%) and C3 (0%, 0%). CONCLUSIONS The cluster analysis identified four clinical phenotypes requiring distinct types of respiratory support, with great differences present per characteristics and outcomes.
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Affiliation(s)
- Rosario Menéndez
- Pneumology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain
- Respiratory Infections, Research Institute La Fe (IISLAFE), Valencia, Spain
| | - Raúl Méndez
- Pneumology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain
- Respiratory Infections, Research Institute La Fe (IISLAFE), Valencia, Spain
| | - Ana Latorre
- Respiratory Infections, Research Institute La Fe (IISLAFE), Valencia, Spain
| | - Paula González-Jiménez
- Pneumology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain
- Respiratory Infections, Research Institute La Fe (IISLAFE), Valencia, Spain
| | | | - María Molina-Molina
- ILD Unit, Pneumology Service, Hospital Universitario de Bellvitge-IDIBELL, Hospitalet de Llobregat, Hospitalet de Llobregat, Spain
| | | | - Estela García
- Pneumology Service, Hospital de Cabueñes, Gijón, Spain
| | | | | | | | | | | | - Oriol Sibila
- Pneumology Service, Hospital Clínic, Barcelona, Spain
| | | | - Nuria Toledo-Pons
- Pneumology Service, Hospital Son Espases-Balearic Islands Health Research Institute (IdISBa), Palma, Spain
| | | | | | | | | | | | | | - Javier Lázaro
- Pneumology Service, Hospital Royo Villanova, Zaragoza, Spain
| | - Sarai Quirós
- Pneumology Service, Hospital Basurto, Bilbao, Spain
| | | | - Irene Cano-Pumarega
- Sleep Unit, Pneumology Service, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain
| | - Antoni Torres
- Pneumology Service, Hospital Clínic, Barcelona, Spain
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Chang YH, Wang Y, Liu YC, Chiu CH. Protein disulphide isomerase A4 as a potential biomarker for coronavirus disease 2019: Correlation with cytokine profiles and disease progression. Virulence 2025; 16:2508815. [PMID: 40391685 PMCID: PMC12118414 DOI: 10.1080/21505594.2025.2508815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 05/02/2025] [Accepted: 05/13/2025] [Indexed: 05/22/2025] Open
Abstract
This study investigated the role of protein disulphide isomerase A4 (PDIA4) in the pathogenesis of coronavirus disease 2019 (COVID-19), focusing on its relationship with disease severity and potential as a biomarker. We analysed a cohort of adult COVID-19 patients with varying disease severity, grouped by vaccination status. Serum levels of PDIA4 and cytokines (interleukin [IL]-6, interferon gamma inducible protein-10 [IP-10], IL-16, monocyte chemoattractant protein-1 [MCP-1], and platelet-derived growth factor-BB [PDGF-BB]) were measured using enzyme-linked immunosorbent assay and compared among patients with different disease severities. Statistical analyses were performed to assess the correlation between PDIA4 levels, disease severity, and inflammatory markers. Unvaccinated COVID-19 patients with pneumonia had significantly higher PDIA4 levels than those without pneumonia (517.94 ± 264 vs. 284.86 ± 2.24; p = 0.0022). Although unvaccinated patients requiring oxygen support exhibited higher PDIA4 levels than those not requiring oxygen (519.30 ± 269.67 vs. 420.89 ± 240.49; p = 0.4825), the difference was not statistically significant. No significant difference was observed in the PDIA4 levels between unvaccinated patients with and without respiratory failure. Levels of PDIA4 were positively correlated with the levels of IL-16, MCP-1, IP-10, and IL-6 (correlation coefficients: 0.28-0.62), although this correlation was weaker or absent in vaccinated patients. Our findings suggest that PDIA4 is associated with COVID-19 severity and may serve as a potential biomarker of disease progression. Further studies are needed to elucidate the mechanisms by which PDIA4 influences the immune response and assess its potential for therapeutic exploration in COVID-19.
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Affiliation(s)
- Yu-Hsiu Chang
- Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan
- Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei City, Taiwan
| | - Ying‑Chuan Wang
- Department of Family Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
| | - Yun-Chen Liu
- Institute of Health Data Analytics and Statistics, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Chun-Hsiang Chiu
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
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Pini L, Giordani J, Levi G, Guerini M, Piva S, Peli E, Violini M, Piras S, El Masri Y, Pini A, Visca D, Assanelli D, Muiesan ML, Latronico N, Tantucci C, on behalf of the LOTO Investigators Working Group. Long-term alveolar-capillary diffusion impairments after severe SARS-CoV-2 pneumonia. Ann Med 2025; 57:2483383. [PMID: 40152750 PMCID: PMC11956098 DOI: 10.1080/07853890.2025.2483383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 03/06/2025] [Accepted: 03/10/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Persistent respiratory symptoms and impaired gas exchange are common in patients recovering from COVID-19 pneumonia. The Lung Diffusing Capacity for Carbon Monoxide (DLCO) and Carbon Monoxide Transfer Coefficient (KCO) do not adequately distinguish alveolar membrane dysfunction from vascular abnormalities. This study aimed to characterize persistent diffusion impairment in post-ICU patients with prior SARS-CoV-2 pneumonia and reduced DLCO. METHODS After hospital discharge, patients underwent spirometry, DLCO measurement, and a 6-minute walking test every six months. If DLCO remained impaired at 18-24 months, a combined Lung Diffusing Capacity for Nitric Oxide (DLNO) and DLCO assessment was performed to differentiate alveolar-capillary membrane (DmCO) and pulmonary capillary blood volume (Vc) alterations. RESULTS Among 20 patients with persistent DLCO reduction, 3 had an obstructive ventilatory pattern, 6 had restriction, and 12 had low KCO. In restrictive cases, KCO was reduced but remained within normal limits without compensation. The DLNO/DLCO ratio exceeded 113.5% predicted in all patients. DmCO was impaired in 7 patients, while Vc was reduced in 16. CONCLUSION Both DLCO determinants were affected, with vascular impairment predominating. Vc reduction was present in most patients, with mean values below the lower limit of normality, whereas DmCO was less affected and often normal. The elevated DLNO/DLCO ratio suggests that persistent DLCO reduction is primarily driven by prolonged pulmonary capillary circulation dysfunction rather than alveolar membrane alterations, highlighting the vascular component as the primary site of long-term impairment.
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Affiliation(s)
- Laura Pini
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- Respiratory Physiopathology Unit, ASST – Spedali Civili di Brescia, Brescia, Italy
| | - Jordan Giordani
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Guido Levi
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- Pulmonology Department, ASST – Spedali Civili di Brescia, Brescia, Italy
| | - Michele Guerini
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Simone Piva
- Department of Anesthesia, Critical Care and Emergency, ASST Spedali Civili University Hospital, Brescia, Italy
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Elena Peli
- Department of Anesthesia, Critical Care and Emergency, ASST Spedali Civili University Hospital, Brescia, Italy
| | - Manuela Violini
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Stefano Piras
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Yehia El Masri
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Alessandro Pini
- Department of Emergency, Anaesthesiological and Resuscitation Sciences, University Cattolica Sacro Cuore, Rome, Italy
| | - Dina Visca
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
- Department of Medicine and Cardiopulmonary Rehabilitation, Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy
| | - Deodato Assanelli
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- Internal Medicine Unit, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Maria Lorenza Muiesan
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- Internal Medicine Unit, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Nicola Latronico
- Department of Anesthesia, Critical Care and Emergency, ASST Spedali Civili University Hospital, Brescia, Italy
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Claudio Tantucci
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
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Hood O, Russell SL, Rahman M, Okwose NC, Jakovljevic DG, Roden LC. Respiratory function and sleep parameters in adults following recovery from acute COVID-19. Respir Med 2025; 243:108135. [PMID: 40319929 DOI: 10.1016/j.rmed.2025.108135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 04/24/2025] [Accepted: 04/29/2025] [Indexed: 05/07/2025]
Abstract
The impact of COVID-19 on lung function and sleep in otherwise healthy individuals has been subject to a limited number of studies. The aim of this study was to investigate the effect of COVID-19 on pulmonary function and sleep in adults. Participants, 50-85 years old, who had recovered from COVID-19 (COVID-19 group: n = 48) and those without history of COVID-19 (control group: n = 28) underwent pulmonary function assessment (Forced Vital Capacity, FVC, and Slow Vital Capacity, SVC) using spirometry. Sleep and circadian variables were measured objectively with wrist-worn actigraphy for seven days. Subjective sleep of participants was assessed using the Pittsburgh Sleep Quality Index (PSQI). There were no significant differences in age (60 ± 6 vs 62 ± 6 years), BMI (26.30 ± 4.25 vs 26.48 ± 3.60 kg/m2), or pulmonary function (FVC, 4.02 ± 1.04 vs 3.80 ± 0.98 L, p = 0.36; and SVC, 3.82 ± 1.09 vs 3.89 ± 0.92 L, p = 0.76) between COVID-19 and control groups. The COVID-19 group had significantly reduced sleep efficiency (0.87 ± 0.04 vs 0.91 ± 0.04, p < 0.01), increased sleep disturbance (awakenings, 1.70 ± 1.02 vs 1.15 ± 1.15, p < 0.01; and wakefulness after sleep onset, 35:05 ± 25:37 vs 20:02 ± 12:48 min, p = 0.01) and PSQI score (5.19 ± 2.88 vs 3.93 ± 2.89, p = 0.01), compared to the control group. Individuals with history of COVID-19 demonstrate reduced sleep quality compared to a non-COVID-19 control group.
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Affiliation(s)
- Olivia Hood
- Clinical Sciences and Translational Medicine, Centre for Health and Life Sciences, Coventry University, Coventry, CV1 2DS, UK; School of Biosciences, College of Biomedical and Life Sciences, Cardiff University, UK
| | - Sophie L Russell
- Clinical Sciences and Translational Medicine, Centre for Health and Life Sciences, Coventry University, Coventry, CV1 2DS, UK; Department for Health, University of Bath, Bath, UK; Centre for Nutrition, Exercise and Metabolish, Univeristy of Bath, Bath, UK
| | - Mushidur Rahman
- Clinical Sciences and Translational Medicine, Centre for Health and Life Sciences, Coventry University, Coventry, CV1 2DS, UK
| | - Nduka C Okwose
- Clinical Sciences and Translational Medicine, Centre for Health and Life Sciences, Coventry University, Coventry, CV1 2DS, UK
| | - Djordje G Jakovljevic
- Clinical Sciences and Translational Medicine, Centre for Health and Life Sciences, Coventry University, Coventry, CV1 2DS, UK.
| | - Laura C Roden
- Clinical Sciences and Translational Medicine, Centre for Health and Life Sciences, Coventry University, Coventry, CV1 2DS, UK.
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Vlaming-van Eijk LE, Tang G, Bourgonje AR, den Dunnen WF, Hillebrands JL, van Goor H. Post-COVID-19 condition: clinical phenotypes, pathophysiological mechanisms, pathology, and management strategies. J Pathol 2025. [PMID: 40492581 DOI: 10.1002/path.6443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Revised: 04/11/2025] [Accepted: 05/05/2025] [Indexed: 06/12/2025]
Abstract
Post-COVID-19 condition (PCC), also known as long COVID, is a complex multiple organ system condition that can develop and persist for months after acute COVID-19. PCC encompasses a wide range of symptoms, resulting in heterogeneous clinical manifestations. These manifestations likely arise from diverse underlying pathophysiological mechanisms, which, in turn, are influenced by risk factors such as age, sex, and comorbidities. To this end, characterising clinical phenotypes of PCC is essential for deepening our understanding of its (potentially) distinct pathophysiological mechanisms and for advancing diagnostic and patient-tailored management strategies. PCC is thought to result from a complex interaction of various pathophysiological mechanisms, leading to functional and structural pathological alterations across multiple organ systems. Investigating these alterations is critical to improving our currently incomplete understanding of PCC's complex pathophysiology. This review provides an overview of the main clinical phenotypes of PCC, characterises these phenotypes by examining symptoms and signs, as well as the associated risk factors. The main hypothesised pathophysiological mechanisms are discussed by outlining the current knowledge on PCC pathology, focussing on the most commonly affected organ systems. Current PCC management includes supportive care such as physiotherapy and the repurposing of existing drugs primarily targeting persistence of SARS-CoV-2 (e.g. antivirals, monoclonal antibodies) and immune dysfunction (e.g. antiinflammatory drugs, immunomodulators). To date, prevention of SARS-CoV-2 infection remains critical, which can be achieved through effective public health measures and vaccination strategies. Finally, this review highlights current knowledge gaps and proposes future research directions to advance the understanding and treatment of PCC. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Larissa E Vlaming-van Eijk
- Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Guolu Tang
- Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Arno R Bourgonje
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Wilfred Fa den Dunnen
- Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Jan-Luuk Hillebrands
- Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Harry van Goor
- Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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Pontiroli AE, Ambrosio G, Leoni O, Forlani M, Antonelli B, Gronda E, Palazzuoli A, Bandera F, Galati G, Tagliabue E. Heart failure and co-morbidities confer a negative prognosis in COVID-19 infection. Int J Cardiol 2025:133492. [PMID: 40490033 DOI: 10.1016/j.ijcard.2025.133492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2025] [Revised: 06/01/2025] [Accepted: 06/06/2025] [Indexed: 06/11/2025]
Abstract
BACKGROUND Since early reports, it has been shown that cardiovascular (CV) diseases, including heart failure (HF), represent a risk factor for infection, hospital admissions and mortality from COVID-19. The COVID-19 pandemics has been of major importance in Italy and in the Lombardy Region. Aims of this study were to compare COVID-19 infection in HF and No-HF subjects, and to quantify among HF patients the risk for COVID-19 infection and all-cause mortality. METHODS All consecutive patients (98,549) with at least one hospital discharge of HF (primary diagnosis) during January 1st, 2015, to December 31st, 2019, were identified in the Lombardy Region Database (>10 million inhabitants), and compared with No-HF subjects (394,104 with a lower age limit 40 years), randomly chosen in a 4:1 proportion among hospitalized patients. The whole cohort of cases of COVID-19 infection, laboratory-confirmed by RT-PCR, aged >40 years, diagnosed from the beginning of the epidemic on 21 February 2020 to 1 October 2020 was studied. The study outcomes were: occurrence, hospitalization, and death in COVID-19 cases. RESULTS Incidence of COVID-19 increased with age in both HF (p < 0.001) and No-HF patients (p < 0.001); cases (and incidence rates, IR) were 8648 (IR = 29.653 × 100.000) in HF and 14,256 (IR = 10.195) and in No-HF (p < 0.001); hospital admissions were 4974 (IR = 14.970) and 4943 (IR = 3.484), respectively (p 〈0001); deaths were 7650 (IR = 5.368) and 18,368 (IR = 56.921), respectively (p < 0.001); the incidence rate ratio (IRR) was 2.909 (95 % C.I. 2.908-2.909) for infection (p < 0.001), 4.297 (95 % C.I. 4.296-4.297) for hospital admission (p < 0.001), and 10.603 (95 % C.I.10.602-10.604) for mortality (p < 0.001). The excess IRR for mortality varied from 25.001 (95 % C.I. 24.971-25.032) for the age decade 40-49 to 1.925 (95 % C.I. 1.923-1.926) for the age decade 100-109. Among HF patients, age (OR = 1.087, 95 % C.I.1.05-1.088), male sex (OR = 1.27, 95 % C.I. 1.23-1.31), number of hospital admissions for HF during the period 2015-2019 (OR = 2.22, 95 % C.I. 2.11-2.33), co-morbidities (OR = 1.33, 95 % C.I. 1.32-1.35), or Charlson Index (OR = 1.21, 95 % C.I. 1.20-1.22), were risk factors for both infection and all-cause mortality at univariable and at multivariable analysis. CONCLUSION Infections, hospital admissions, and mortality for COVID-19 increased with age and male sex were more frequent in HF than in No-HF patients. Among HF patients, age and sex, number of hospital admissions for HF, co-morbidities, were risk factors for both infection and mortality. These data are of relevance for prioritizing interventions for prevention of infection, and for assistance to patients with COVID-19, and to inform management of future pandemics.
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Affiliation(s)
- Antonio E Pontiroli
- Università degli Studi di Milano, Dipartimento di Scienze della Salute, Milan, Italy.
| | - Giuseppe Ambrosio
- Università di Perugia, Dipartimento di Medicina - CERICLET, Istituto Nazionale Ricerche Cardiovascolari - INRC, Perugia, Italy; IRCCS MultiMedica, Milan, Italy
| | - Olivia Leoni
- Dipartimento della Salute, Regione Lombardia, Osservatorio Epidemiologico, Milan, Italy.
| | | | | | - Edoardo Gronda
- IRCCS Policlinico, U.O.C. Nefrologia, Dialisi e Trapianti di Rene, Milan, Italy
| | - Alberto Palazzuoli
- Unità Autonoma Malattie Cardiovascolari, Dipartimento Cardio-Toracico e Vascolare, Ospedale le Scotte, Universita di Siena, Siena, Italy.
| | - Francesco Bandera
- IRCCS MultiMedica, Milan, Italy; Università degli Studi di Milano, Dipartimento di Scienze Biomediche per la Salute, Milan, Italy.
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Yan M, Zhan Q, Wu X, Zheng C, Liu D. Hepatic dysfunction in individuals with COVID-19 and its impact on pregnancy outcomes. Medicine (Baltimore) 2025; 104:e42745. [PMID: 40489829 DOI: 10.1097/md.0000000000042745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/11/2025] Open
Abstract
This study aimed to describe the incidence of abnormal liver function tests (LFTs) in pregnant women post-2019 coronavirus disease (COVID-19) and investigate the characteristics of pregnant women with abnormal LFTs and its impact on pregnancy outcomes. The data for 168 pregnant women who were infected with COVID-19 in the late stages of pregnancy were collected in Hefei Maternal and Child Health Hospital from December 2022 to January 2023, and 86 pregnant women with abnormal liver function were divided into the research group and 82 pregnant women with normal liver function into the control group for retrospective analysis. Population and laboratory data were collected and statistical analysis was conducted. Among the 168 pregnant women with COVID-19, 86 (51.2%) had elevated liver enzymes. In the control group, 4 (4.5%) had elevated liver enzymes. Differences between the 2 groups were statistically significant (P < .05). Single-factor analysis revealed that age, gestational week, and body mass index (BMI) exhibited statistically significant differences (P < .001) as potential factors influencing abnormal LFTs. Logistic regression analysis demonstrated that age (OR: 1.526), gestational week (OR: 1.321), and BMI (OR: 1.159) remained independent risk factors for liver injury (P < .05). Furthermore, the cesarean section rate, postpartum hemorrhage rate, rupture of membranes rate, and fetal intrauterine distress rate in the observation group were all significantly higher than those in the control group (P < .05). Additionally, the incidence of neonatal asphyxia, preterm birth, and low birth weight in the observation group were all significantly higher than those in the control group (P < .05). Pregnant individuals are at an elevated risk of hepatic injury following severe acute respiratory syndrome coronavirus 2 infection. Furthermore, the likelihood of hepatic injury escalates with advancing maternal age, gestational age, and BMI. Hepatic functional aberrations in the latter stages of pregnancy may precipitate adverse pregnancy outcomes.
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Affiliation(s)
- Minqin Yan
- Department of Gynecology and Obstetrics, Anhui Women and Children's Medical Center, Hefei Maternal and Child Health Hospital, Hefei, P. R. China
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Chen GS, Lee T, Tsang JL, Binnie A, McCarthy A, Cowan J, Archambault P, Lellouche F, Turgeon AF, Yoon J, Lamontagne F, McGeer A, Douglas J, Daley P, Fowler R, Maslove DM, Winston BW, Lee TC, Tran KC, Cheng MP, Vinh DC, Boyd JH, Walley KR, Singer J, Marshall JC, Russell JA. Machine Learning Accurately Predicts Need for Critical Care Support in Patients Admitted to Hospital for Community-Acquired Pneumonia. Crit Care Explor 2025; 7:e1262. [PMID: 40443788 PMCID: PMC12119046 DOI: 10.1097/cce.0000000000001262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/02/2025] Open
Abstract
OBJECTIVES Hospitalized community-acquired pneumonia (CAP) patients are admitted for ventilation, vasopressors, and renal replacement therapy (RRT). This study aimed to develop a machine learning (ML) model that predicts the need for such interventions and compare its accuracy to that of logistic regression (LR). DESIGN This retrospective observational study trained separate models using random-forest classifier (RFC), support vector machines (SVMs), Extreme Gradient Boosting (XGBoost), and multilayer perceptron (MLP) to predict three endpoints: eventual use of invasive ventilation, vasopressors, and RRT during hospitalization. RFC-based models were overall most accurate in a derivation COVID-19 CAP cohort and were validated in one COVID-19 CAP and two non-COVID-19 CAP cohorts. SETTING This study is part of the Community-Acquired Pneumonia: Toward InnoVAtive Treatment (CAPTIVATE) Research program. PATIENTS Two thousand four hundred twenty COVID-19 and 1909 non-COVID-19 CAP patients over 18 years old hospitalized and not needing invasive ventilation, vasopressors, and RRT on the day of admission were included. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Performance was evaluated with area under the receiver operating characteristic curve (AUROC) and accuracy. RFCs performed better than XGBoost, SVM, and MLP models. For comparison, we evaluated LR models in the same cohorts. AUROC was very high ranging from 0.74 to 0.95 in predicting ventilation, vasopressors, and RRT use in our derivation and validation cohorts. ML used and variables such as Fio2, Glasgow Coma Scale, and mean arterial pressure to predict ventilator, vasopressor use, creatinine, and potassium to predict RRT use. LR was less accurate than ML, with AUROC ranging 0.66 to 0.8. CONCLUSIONS A ML algorithm more accurately predicts need of invasive ventilation, vasopressors, or RRT in hospitalized non-COVID-19 CAP and COVID-19 patients than regression models and could augment clinician judgment for triage and care of hospitalized CAP patients.
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Affiliation(s)
| | - Terry Lee
- Centre for Advancing Health Outcomes, St. Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Jennifer L.Y. Tsang
- Critical Care Medicine, Niagara Health Knowledge Institute, St Catharines, ON, Canada
- Critical Care Medicine, McMaster University, Hamilton, ON, Canada
| | - Alexandra Binnie
- Critical Care Department, William Osler Health System, Brampton, ON, Canada
- Critical Care Medicine, Algarve Biomedical Centre, Faro, Portugal
- Critical Care Medicine, Centro Hospitalar Universitário do Algarve, Faro, Portugal
| | - Anne McCarthy
- Infectious Disease, Ottawa Research Institute, University of Ottawa, Ottawa, ON, Canada
| | - Juthaporn Cowan
- Infectious Disease, Ottawa Research Institute, University of Ottawa, Ottawa, ON, Canada
| | | | - Francois Lellouche
- CHU de Québec-Université Laval Research Center, Population Health and Optimal Health Practices Unit, Trauma- Emergency- Critical Care Medicine, Québec City, QC, Canada
- Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Faculty of Medicine, Université Laval, Québec City, QC, Canada
| | - Alexis F. Turgeon
- CHU de Québec-Université Laval Research Center, Population Health and Optimal Health Practices Unit, Trauma- Emergency- Critical Care Medicine, Québec City, QC, Canada
- Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Faculty of Medicine, Université Laval, Québec City, QC, Canada
| | - Jennifer Yoon
- Critical Care Medicine, Humber River Hospital, Toronto, ON, Canada
| | | | - Allison McGeer
- Mt. Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Josh Douglas
- Critical Care Medicine, Lion’s Gate Hospital, North Vancouver, BC, Canada
| | - Peter Daley
- Infectious Disease, Memorial University of Newfoundland, St. John’s, NL, Canada
| | - Robert Fowler
- Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - David M. Maslove
- Department of Critical Care, Kingston General Hospital and Queen’s University, Kingston, ON, Canada
| | - Brent W. Winston
- Departments of Critical Care Medicine, Medicine and Biochemistry and Molecular Biology, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada
| | - Todd C. Lee
- Division of Infectious Disease, McGill University, Montreal, QC, Canada
| | - Karen C. Tran
- Division of General Internal Medicine, Vancouver General Hospital, Vancouver, BC, Canada
| | - Matthew P. Cheng
- Division of Infectious Disease, McGill University, Montreal, QC, Canada
| | - Donald C. Vinh
- Division of Infectious Disease, McGill University, Montreal, QC, Canada
| | - John H. Boyd
- Centre for Heart Lung Innovation, St. Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada
- Division of Critical Care Medicine, St. Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Keith R. Walley
- Centre for Heart Lung Innovation, St. Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada
- Division of Critical Care Medicine, St. Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Joel Singer
- Centre for Advancing Health Outcomes, St. Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada
| | - John C. Marshall
- Department of Surgery, St. Michael’s Hospital, Toronto, ON, Canada
| | - James A. Russell
- Centre for Heart Lung Innovation, St. Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada
- Division of Critical Care Medicine, St. Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada
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9
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Zhang M, Zhao L, Zeng P, Mu X, Zhao J. Inflammatory and pulmonary function characteristics of bronchial asthma induced by COVID‑19 infection. Biomed Rep 2025; 22:101. [PMID: 40322552 PMCID: PMC12046281 DOI: 10.3892/br.2025.1979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 03/07/2025] [Indexed: 05/08/2025] Open
Abstract
Bronchial asthma, a widely prevalent respiratory disease influencing individuals of all age groups worldwide, has been increasingly recognized as a global concern. While there exists a potentially heightened risk of severe coronavirus disease 2019 (COVID-19) in asthmatic patients, particularly those with non-allergic asthma, it is uncertain whether COVID-19 infection-induced bronchial asthma has its own unique clinical characteristics. The present study aimed to compare and analyze the pulmonary function and eosinophilic inflammation indices of patients with COVID-19 infection-induced bronchial asthma and those with typical bronchial asthma, and further deepen the understanding of COVID-19 infection-induced bronchial asthma. A retrospective analysis was conducted on the pulmonary function and inflammatory characteristics of 116 patients diagnosed with COVID-19 infection-induced bronchial asthma and treated in outpatient clinics after March 2023, as well as 113 patients with typical bronchial asthma diagnosed and treated from January 2022 to November 2022. The main clinical characteristics were cough, sputum, chest tightness, dyspnea and wheezing. There was no significant difference in clinical characteristics between the two groups. The results indicated that there was no significant difference in the total IgE, the absolute value and percentage of eosinophil, transoral FeNO, and trans-nasal FeNO in the peripheral blood samples of patients in the COVID-19 infection-induced bronchial asthma group compared with the typical bronchial asthma group. Although there was no significant difference between the two groups in the rates of impairment in ventilation function, reserve function, and small airway function, significant differences were identified in various indicators, including forced expiratory volume in 1 sec as a percentage of the predicted value (FEV1%), residual volume/total lung capacity (RV/TLC), peak expiratory flow (PEF), maximal expiratory flow rate at 75% (MEF75), maximal voluntary ventilation (MVV), FEV * 30, and residual volume (RV) between the two groups. The findings indicated that patients with COVID-19 infection-induced bronchial asthma exhibited a comparatively inferior pulmonary function versus those with typical bronchial asthma. However, it is important to note that the clinical impact of this disparity was not statistically significant.
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Affiliation(s)
- Mingqiang Zhang
- Department of Respiratory and Critical Care Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, P.R. China
| | - Lina Zhao
- Department of Respiratory and Critical Care Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, P.R. China
| | - Pu Zeng
- Department of Respiratory and Critical Care Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, P.R. China
| | - Xiangdong Mu
- Department of Respiratory and Critical Care Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, P.R. China
| | - Jingquan Zhao
- Department of Respiratory and Critical Care Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, P.R. China
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10
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Melo VLCO, do Brasil PEAA. ACCREDIT: Validation of clinical score for progression of COVID-19 while hospitalized. GLOBAL EPIDEMIOLOGY 2025; 9:100181. [PMID: 39850445 PMCID: PMC11754157 DOI: 10.1016/j.gloepi.2024.100181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 12/19/2024] [Accepted: 12/26/2024] [Indexed: 01/25/2025] Open
Abstract
COVID-19 is no longer a global health emergency, but it remains challenging to predict its prognosis. Objective To develop and validate an instrument to predict COVID-19 progression for critically ill hospitalized patients in a Brazilian population. Methodology Observational study with retrospective follow-up. Participants were consecutively enrolled for treatment in non-critical units between January 1, 2021, to February 28, 2022. They were included if they were adults, with a positive RT-PCR result, history of exposure, or clinical or radiological image findings compatible with COVID-19. The outcome was characterized as either transfer to critical care or death. Predictors such as demographic, clinical, comorbidities, laboratory, and imaging data were collected at hospitalization. A logistic model with lasso or elastic net regularization, a random forest classification model, and a random forest regression model were developed and validated to estimate the risk of disease progression. Results Out of 301 individuals, the outcome was 41.8 %. The majority of the patients in the study lacked a COVID-19 vaccination. Diabetes mellitus and systemic arterial hypertension were the most common comorbidities. After model development and cross-validation, the Random Forest regression was considered the best approach, and the following eight predictors were retained: D-dimer, Urea, Charlson comorbidity index, pulse oximetry, respiratory frequency, Lactic Dehydrogenase, RDW, and Radiologic RALE score. The model's bias-corrected intercept and slope were - 0.0004 and 1.079 respectively, the average prediction error was 0.028. The ROC AUC curve was 0.795, and the variance explained was 0.289. Conclusion The prognostic model was considered good enough to be recommended for clinical use in patients during hospitalization (https://pedrobrasil.shinyapps.io/INDWELL/). The clinical benefit and the performance in different scenarios are yet to be known.
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11
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Wang FD, Chang YH, Chuang HC, Ou TY, Lee MH, Nguyen PA, Phan TP, Burton W, Nguyen TKH, Hsu MH, Lin SM, Yang C, Hsu JC. Nirmatrelvir-ritonavir significantly reduces severe COVID-19 outcomes in diverse Taiwanese populations: Comprehensive evidence from a large-scale longitudinal cohort study in Taiwan. J Infect Public Health 2025; 18:102760. [PMID: 40157333 DOI: 10.1016/j.jiph.2025.102760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 03/11/2025] [Accepted: 03/13/2025] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND Nirmatrelvir-Ritonavir (NR) has proven effective for mild to moderate COVID-19 patients at risk of disease progression. Following its emergency use authorization in Taiwan in January 2022, this study aims to evaluate its impact on severe COVID-19 outcomes across different patient demographics in Taiwan. METHODS We performed a retrospective analysis of a database that includes data from three hospitals in Northern Taiwan. Patients with COVID-19 in 2022 were paired by propensity score matching based on NR prescription. Cox proportional hazard regression analysis calculated hazard ratios (HR), adjusting for confounding factors. Subgroup analysis determined HRs across patient characteristics. RESULTS Among 95,096 patients, 3329 were in the NR group, and 12,807 in the non-NR group. NR users demonstrated significantly better prevention of severe outcomes: intubation (HR=0.296 [95 % CI: 0.187-0.469], p = 0.0482); ICU admission (HR=0.327[0.108-0.991], p < 0.001); mortality (HR=0.195 [0.101-0.378], p < 0.001). Subgroup analysis revealed significantly lower intubation risks for NR users among both sexes, aged 18-65 or ≥ 65 years, BMI < 30, and patients with diabetes mellitus (DM), cardiovascular disease (CVD), or chronic obstructive pulmonary disease (COPD). ICU admission risk was lower for NR users among males, aged ≥ 65 years, and BMI < 30. Mortality risk was lower for NR users among both sexes, aged ≥ 65 years, BMI < 30, and patients with DM, CVD, or COPD. CONCLUSION NR significantly reduces the risk of severe COVID-19, particularly among older adults and those with pre-existing conditions, supporting NR as an essential treatment for high-risk COVID-19 patients.
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Affiliation(s)
- Fu-Der Wang
- Division of Infectious Diseases, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Institute of Public Health, National Yang-Ming Chiao-Tung University, Taipei, Taiwan
| | - Yu-Hui Chang
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Han-Chuan Chuang
- Division of Infectious Diseases, Department of Internal Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
| | - Tsong-Yih Ou
- Division of Infectious Diseases, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Mei-Hui Lee
- Division of Infectious Diseases, Department of Internal Medicine, Shuang Ho Hospital, New Taipei City, Taipei Medical University, Taipei, Taiwan
| | - Phung-Anh Nguyen
- Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei City, Taiwan; Clinical Data Center, Office of Data Science, Taipei Medical University, Taipei, Taiwan; Clinical Big Data Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan; Research Center of Health Care Industry Data Science, College of Management, Taipei Medical University, Taipei, Taiwan
| | - Thanh Phuc Phan
- International PhD Program in Biotech and Healthcare Management, College of Management, Taipei Medical University, Taipei, Taiwan
| | - Whitney Burton
- International PhD Program in Biotech and Healthcare Management, College of Management, Taipei Medical University, Taipei, Taiwan
| | - Thi Kim Hien Nguyen
- Ph.D. Program in School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan
| | - Min-Huei Hsu
- Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei City, Taiwan; Clinical Big Data Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan; Office of Data Science, Taipei Medical University, Taipei, Taiwan
| | - Shiue-Ming Lin
- Research Center of Health Care Industry Data Science, College of Management, Taipei Medical University, Taipei, Taiwan
| | - Chieh Yang
- Research Center of Health Care Industry Data Science, College of Management, Taipei Medical University, Taipei, Taiwan
| | - Jason C Hsu
- Clinical Data Center, Office of Data Science, Taipei Medical University, Taipei, Taiwan; Clinical Big Data Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan; Research Center of Health Care Industry Data Science, College of Management, Taipei Medical University, Taipei, Taiwan; International PhD Program in Biotech and Healthcare Management, College of Management, Taipei Medical University, Taipei, Taiwan.
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12
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Li L, Shi X, Wang R, Fan Y, Xu Z, Mirzaei H, Wei W. Cardiovascular impact of emerging and Re-emerging Viruses: Pathophysiological mechanisms, diagnosis, and management with a pediatric focus. Mol Aspects Med 2025; 104:101371. [PMID: 40424828 DOI: 10.1016/j.mam.2025.101371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2025] [Revised: 05/16/2025] [Accepted: 05/21/2025] [Indexed: 05/29/2025]
Abstract
Emerging and re-emerging viruses are currently known as a major public health issue. These viruses can cause various human complications such as cardiovascular diseases (CVDs), both in adults and pediatric populations. Although various CVDs have been previously reported for emerging and re-emerging viruses, the mechanisms underlying these complications remain relatively unknown. Children and infants, while commonly developing less severe symptoms, may experience notable cardiovascular manifestations during infections caused by emerging and re-emerging viral infections, which can result in both acute and long-term complications. The present review aims to discuss various cardiovascular complications linked to emerging and re-emerging viral pathogens (including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV)) such as arrhythmias, myocarditis, vascular disorders, and thromboembolic conditions, particularly among the pediatric population. This review also addresses the potential mechanisms by which SARS-CoV-2, DENV, ZIKV, and CHIKV may impact the cardiovascular system and their clinical implications. Moreover, it discusses the diagnostic challenges for viral-caused cardiovascular disorders in children, owing to their common subtle or atypical manifestations. Finally, it addresses the present therapeutic specifically used for pediatric cases.
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Affiliation(s)
- Li Li
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, China.
| | - Xu Shi
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Ruiming Wang
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, China; Department of Outpatient, West China Second University Hospital, Sichuan University, China.
| | - Yuxi Fan
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, China; Pediatric Cardiovascular Nursing Unit, West China Second Hospital of Sichuan University, China.
| | - Zhihan Xu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Habibollah Mirzaei
- Hepatitis Research Center, Department of Virology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
| | - Wuran Wei
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.
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13
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Poopipatpab S, Weerayutwattana R, Nuchpramool P, Phairatwet P, Lertwattanachai T, Trongtrakul K. Evaluation of physiological severity scores for predicting COVID-19 disease progression: a retrospective study. BMC Infect Dis 2025; 25:758. [PMID: 40419986 DOI: 10.1186/s12879-025-11127-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 05/15/2025] [Indexed: 05/28/2025] Open
Abstract
BACKGROUND The coronavirus disease (COVID-19) pandemic indeed strains healthcare systems worldwide, resulting in a surge of patients with severe conditions. Numerous physiological severity scores have been assigned to assess critical conditions; however, a comprehensive comparison of these scoring systems remains lacking. Therefore, this study aimed to evaluate the performance of the severity scores upon admission in predicting the progression of COVID-19 patients to a severe condition within 14 days after hospitalization. METHODS Non-critically ill COVID-19 patients admitted to the Faculty of Medicine, Vajira Hospital, between 1 January 2021 and 30 June 2021, were assessed. We compared the discriminated ability of physiological severity scores in predicting disease progression to critical conditions using the area under the receiver operating characteristic curve (AUC). RESULTS Totally, 348 non-critically ill COVID-19 patients were included. Of these, 60 patients (17.2%) progressed to severe conditions within 14 days after hospitalization. The National Early Warning Score 2 with age and body mass index (NEWS2 Plus) was the most outperformed than the National Early Warning Score (NEWS), the National Early Warning Score 2 (NEWS2), the Hamilton Early Warning Score (HEWS), the Modified Early Warning Score (MEWS), and the quick Sepsis-related Organ Failure Assessment (qSOFA) scores, for predicting deterioration to severe conditions [AUC 0.77 (95% CI; 0.72-0.83)]. The NEWS2 Plus with a cutoff point of five exhibited high sensitivity (83.3%) and high negative predictive value (NPV) of 94.7%. CONCLUSIONS NEWS2 Plus score can enhance its utility for triage of COVID-19 patients' clinical status upon admission and guide appropriate management decisions for resource allocation. TRIAL REGISTRATION TCTR20241026001, registered on 26 October 2024.
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Affiliation(s)
- Sujaree Poopipatpab
- Department of Anesthesiology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
| | - Ratchaya Weerayutwattana
- Department of Anesthesiology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
| | - Pruchwilai Nuchpramool
- Department of Anesthesiology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
| | - Piyarat Phairatwet
- Department of Medicine, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
| | - Tospon Lertwattanachai
- Department of Pharmacology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
| | - Konlawij Trongtrakul
- Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
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14
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Bucher AM, Frodl E, Ehrengut C, Müller L, Emrich T, Kloeckner R, Sieren M, Sähn MJ, Fink MA, Móré D, Melekh B, Gottschling S, Meinel F, Schön H, Kornemann N, Renz DM, Lubina N, Wollny C, May MS, Siegler L, Borggrefe J, Meyer HJ, Surov A. Prognostic value of CT-defined coronary sclerosis in COVID-19: results of a multicenter study based on the Weston score. ROFO-FORTSCHR RONTG 2025. [PMID: 40418966 DOI: 10.1055/a-2583-0235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2025]
Abstract
Coronary calcification, as defined by computed tomography (CT), can be quantified with a score (CAC score). It is an established prognostic and predictive imaging marker of the cardiovascular risk profile. The prognostic relevance of the CAC score has been demonstrated for acute diseases, including the coronavirus disease 2019 (COVID-19) in preliminary studies. The aim of the present study was to prove the prognostic relevance of the CAC score in patients with coronavirus disease 2019.The present study used a nationwide radiological research platform to conduct a multicenter retrospective study. The study included a total of 541 patients, 176 of whom were female (32.5%). The mean age of the patients was 61.2 years ± 15.6 years. The coronavirus (SARS-COV-2) disease was confirmed in all patients by PCR testing. The CAC score was calculated using the Weston score, which is a semiquantitative method. The primary outcome of the study was 30-day mortality.The overall mortality rate within the 30-day period was 21.2%, with 115 patients dying. The mean Weston score was 3.0 ± 3.6. 128 patients (23.7%) exhibited no evidence of coronary calcifications, as indicated by a Weston Score of 0. In the univariable regression analysis, the presence of calcifications was found to be associated with mortality, with an odds ratio of 1.68 (95% confidence interval 1.08-2.59, p=0.01). However, this result did not remain statistically significant in the multivariable analysis (p=0.49). The Weston score was found to be associated with mortality in the univariable analysis, with an odds ratio (OR) of 1.10 (95% CI 1.04-1.14, p < 0.001), and in the multivariable analysis, with an OR of 1.06 (95% CI 1.005-1.138, p = 0.036).The imaging marker CAC score has been demonstrated to have a significant prognostic impact on 30-day mortality in patients diagnosed with coronavirus disease 2019 (COVID-19). It is incumbent upon the radiologist to acknowledge the sole presence of coronary calcifications as a relevant prognostic factor. The prognostic relevance of the calcifications was found to be greater in cases where more extensive calcification was present. · Coronary calcifications assessed by CT are prognostic markers for 30-day COVID-19 mortality.. · Calcification extent has greater prognostic value than the mere presence of calcifications.. · The study highlights the need to integrate coronary calcifications into clinical risk scores.. · Bucher AM, Frodl E, Ehrengut C et al. Prognostic value of CT-defined coronary sclerosis in COVID-19: results of a multicenter study based on the Weston score. Rofo 2025; DOI 10.1055/a-2583-0235.
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Affiliation(s)
- Andreas Michael Bucher
- University Hospital, Institute for Diagnostic and Interventional Radiology, Goethe University Frankfurt Faculty 16 Medicine, Frankfurt am Main, Germany
| | - Eric Frodl
- University Hospital, Institute for Diagnostic and Interventional Radiology, Goethe University Frankfurt Faculty 16 Medicine, Frankfurt am Main, Germany
| | | | - Lukas Müller
- Department for Diagnostic and Interventional Radiology, University Medical Center Mainz, Mainz, Germany
| | - Tilman Emrich
- Department for Diagnostic and Interventional Radiology, University Medical Center Mainz, Mainz, Germany
| | - Roman Kloeckner
- Department of Radiology, University Hospital Schleswig-Holstein Campus Lübeck, Lübeck, Germany
| | - Malte Sieren
- Department of Radiology, University Hospital Schleswig-Holstein Campus Lübeck, Lübeck, Germany
| | - Marwin-Jonathan Sähn
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Aachen, Germany
| | - Matthias A Fink
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Dorottya Móré
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Bohdan Melekh
- Department of Radiology and Nuclear Medicine, University Hospital of Magdeburg, Magdeburg, Germany
| | - Sebastian Gottschling
- Department of Radiology and Nuclear Medicine, University Hospital of Magdeburg, Magdeburg, Germany
| | - Felix Meinel
- Institute of Diagnostic and Interventional Radiology, Pediatric Radiology and Neuroradiology, University Hospital of Rostock, Rostock, Germany
| | - Hanna Schön
- Institute of Diagnostic and Interventional Radiology, Pediatric Radiology and Neuroradiology, University Hospital of Rostock, Rostock, Germany
| | - Norman Kornemann
- Department of Radiology, Hannover Medical School, Hanover, Germany
| | | | - Nora Lubina
- Clinic for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Augsburg, Augsburg, Germany
| | - Claudia Wollny
- Clinic for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Augsburg, Augsburg, Germany
| | | | - Lisa Siegler
- Department of Radiology, University Hospital of Erlangen, Erlangen, Germany
| | - Jan Borggrefe
- Institute of Radiology, Neuroradiology and Nuclear Medicine Minden, Ruhr-University-Bochum, Minden, Germany
| | - Hans-Jonas Meyer
- Department of Radiology, University Hospital Leipzig, Leipzig, Germany
| | - Alexey Surov
- Institute of Radiology, Neuroradiology and Nuclear Medicine Minden, Ruhr-University-Bochum, Minden, Germany
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15
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Partouche N, Maumy M, Chamaraux-Tran TN, Bertrand F, Schneider F, Meyer N, Solis M, Fafi-Kremer S, Noll E, Pottecher J. Does the IL-6/KL-6 ratio distinguish different phenotypes in COVID-19 Acute Respiratory Distress Syndrome? An observational study stemmed from prospectively derived clinical, biological, and computed tomographic data. PLoS One 2025; 20:e0321533. [PMID: 40397955 DOI: 10.1371/journal.pone.0321533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 03/07/2025] [Indexed: 05/23/2025] Open
Abstract
BACKGROUND As new SARS-CoV-2 variants emerge and as treatment of COVID-19 ARDS remains exclusively supportive, there is an unmet need to better characterize its different phenotypes to tailor personalized treatments. Clinical, biological, spirometric and CT data hardly allow deciphering of Heavy (H), Intermediate (I) and Light (L) phenotypes of COVID-19 ARDS and the implementation of tailored specific strategies (prone positioning, PEEP settings, recruitment maneuvers). We hypothesized that the ratio of two pivotal COVID-19 biomarkers (interleukin 6 [IL-6] and Krebs von den Lungen 6 [KL-6], related to inflammation and pneumocyte repair, respectively) would provide a biologic insight into the disease timeline allowing 1) to differentiate H, I and L phenotypes, 2) to predict outcome and 3) to reflect some of CT findings. METHODS AND FINDINGS This was a retrospective analysis of prospectively acquired data (COVID HUS cohort). Inclusion concerned any patient with severe COVID-19 pneumonia admitted to two intensive care units between March 1st and May 1st, 2020, in a high-density cluster of the first epidemic wave (Strasbourg University Hospital, France). Demographic, clinical, biological (standard, IL-6 [new generation ELISA], KL-6 [CLEIA technique]), spirometric (driving pressure, respiratory system compliance) and CT data were collected longitudinally. CT analysis included semi-automatic and automatic lung measurements and allowed segmentation of lung volumes into 4 (poorly aerated, non-aerated, overinflated and normally aerated) and 3 (ground-glass, restricted normally aerated, and overinflated) zones, respectively. The primary outcome was to challenge the IL-6/KL-6 ratio capacity to decipher the three COVID-19 ARDS phenotypes (H, I and L) defined on clinical, spirometric and radiologic grounds. Secondary outcomes were the analysis of the prognostic value of the IL-6/KL-6 ratio and its correlates with CT-acquired data. Multivariate analysis was based on principal component analysis. One hundred and forty-eight ventilated COVID-19 ICU patients from the COVID HUS cohort were assessed for eligibility and 77 were included in the full analysis. Most were male, all were under invasive mechanical ventilation and vasopressor therapy and displayed high severity scores (SAPSII: 48 [42-56]; SOFA: 8 [7-10]). The L, I and H COVID ARDS phenotypes were identified in 11, 15 and 48 patients, respectively. In three patients, the phenotype could not be defined precisely. Thirty patients (39%) died in the ICU and the number of ventilator-free days was 2 [0-2] days. The IL-6/KL-6 ratio was not significantly different between the L, I and H phenotypes and evolved according to similar patterns over time. Surviving and deceased patients displayed an inverse kinetic of KL-6. IL-6 and the IL-6/KL-6 ratio were linearly associated with ground-glass volume on semi-automatic and automatic CT lung measurements. CONCLUSIONS In our population of severe ventilated COVID ARDS patients, the IL-6/KL-6 ratio was not clue to differentiate the H, I and L phenotypes and tailor a personalized ventilatory approach. There was an interesting correlation between IL-6/KL-6 ratio and ground-glass volume as determined by automated lung CT analysis. Such correlation deserves more in-depth pathophysiological study, at best gathered from a prospective cohort with a larger sample size and histological analysis. TRIAL REGISTRATION COVID HUS Trial registration number: NCT04405726.
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Affiliation(s)
- Nicolas Partouche
- Service d'Anesthésie-Réanimation & Médecine Péri-Opératoire, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, UR3072, FMTS, FHU Omicare, Faculté de Médecine, Maïeutique et Sciences de la Santé, Université de Strasbourg, Strasbourg, France
| | - Myriam Maumy
- LIST3N, University of Technology of Troyes, Troyes, France
| | - Thien-Nga Chamaraux-Tran
- Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104, INSERM U1258, Université de Strasbourg, 1 Rue Laurent Fries, Illkirch-Graffenstaden, France
| | | | - Francis Schneider
- Service de Médecine Intensive-Réanimation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - Nicolas Meyer
- Service de santé Publique, GMRC, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - Morgane Solis
- Faculté de Médecine, Laboratoire de Virologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France - INSERM, UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Fédération Hospitalo-Universitaire (FHU) OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France
| | - Samira Fafi-Kremer
- Faculté de Médecine, Laboratoire de Virologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France - INSERM, UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Fédération Hospitalo-Universitaire (FHU) OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France
| | - Eric Noll
- Service d'Anesthésie-Réanimation & Médecine Péri-Opératoire, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, UR3072, FMTS, FHU Omicare, Faculté de Médecine, Maïeutique et Sciences de la Santé, Université de Strasbourg, Strasbourg, France
| | - Julien Pottecher
- Service d'Anesthésie-Réanimation & Médecine Péri-Opératoire, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, UR3072, FMTS, FHU Omicare, Faculté de Médecine, Maïeutique et Sciences de la Santé, Université de Strasbourg, Strasbourg, France
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16
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Mahmodi MA, Akbari A, Hosseini SMR, Amouzeshi Z. Risk perception of emergency medical technicians in biological disasters: a comparison between COVID-19 and Non-COVID-19 cases. BMC Emerg Med 2025; 25:82. [PMID: 40399782 PMCID: PMC12096615 DOI: 10.1186/s12873-025-01239-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Accepted: 05/13/2025] [Indexed: 05/23/2025] Open
Abstract
BACKGROUND Emergency medical technicians (EMTs), positioned at the forefront of medical services, are at greater risk of contracting COVID-19 and passing it on to their families and communities than others. Recognizing the risks associated with this disease can play a crucial role in the care and prevention process. Consequently, this study evaluated the level of risk perception (RP) regarding COVID-19 among EMTs and compared it between those who have contracted the disease and those who have not. METHODS This was a cross-sectional descriptive-analytical study conducted in 2021. This study employed simple random sampling to select 200 EMTs affiliated with Birjand University of Medical Sciences. The sample included 100 EMTs who had contracted COVID-19 and 100 who had not. Data were collected through a researcher-designed questionnaire, distributed online via WhatsApp and Telegram groups among the participants. The data were analyzed using SPSS version 16, utilizing descriptive statistical methods (frequency, mean, and standard deviation) along with inferential statistical tests such as independent t-tests, chi-square, and two-way analysis of variance (ANOVA). RESULTS The infected EMTs exhibited a moderate perception of the risk of COVID-19, while the non-infected EMTs reported a high level of RP. The independent t-test confirmed that the mean total score for COVID-19 RP was significantly lower in the infected EMTs compared to the non-infected group (mean RP score: infected 150.82 ± 32.24 vs. non-infected 161.54 ± 22.50, P = 0.007). Additionally, ANOVA revealed that none of the demographic variables individually had a significant impact on the level of COVID-19 RP (P > 0.05). Furthermore, the interaction effect between the demographic variables and the groups was also insignificant (P > 0.05). CONCLUSION EMTs who contracted COVID-19 had a significantly lower RP compared to their non-infected counterparts. This reduced awareness of COVID-19 risks likely contributed to their infection, highlighting the critical role of RP in disease prevention. Targeted educational programs to enhance RP among EMTs could foster stronger adherence to preventive measures, ultimately reducing infection rates during future biological disasters. Therefore, this study not only contributes to expanding existing knowledge in this field but also assists policymakers and health administrators in improving decision-making to strengthen epidemic preparedness.
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Affiliation(s)
- Mohammad Azim Mahmodi
- Department of Health in Emergencies and Disasters, School of Nursing and Midwifery, Birjand University of Medical Sciences, Birjand, Iran
- Health in Emergency and Disaster Research Center, Social Health Research Institute, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Ayob Akbari
- School of Nursing and Midwifery, Birjand University of Medical Sciences, Birjand, Iran
| | - Seyyed Mohammad Reza Hosseini
- Department of Health in Emergencies and Disasters, School of Nursing and Midwifery, Birjand University of Medical Sciences, Birjand, Iran
| | - Zahra Amouzeshi
- Department of Nursing, School of Nursing and Midwifery, Birjand University of Medical Sciences, Birjand, Iran.
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17
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Hsieh LL, Thompson EA, Jairam NP, Roznik K, Figueroa A, Aytenfisu T, Zhou W, Gour N, Chao KH, Milstone AM, Egbert E, D'Alessio F, Karakousis PC, Ordoñez A, Scully EP, Pekosz A, Karaba AH, Cox AL. SARS-CoV-2 induces neutrophil degranulation and differentiation into myeloid-derived suppressor cells associated with severe COVID-19. Sci Transl Med 2025; 17:eadn7527. [PMID: 40397714 DOI: 10.1126/scitranslmed.adn7527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 11/18/2024] [Accepted: 04/01/2025] [Indexed: 05/23/2025]
Abstract
Severe COVID-19 presents with a distinct immunological profile, characterized by elevated neutrophil and reduced lymphocyte counts, seen commonly in fungal and bacterial infections. This study demonstrates that patients hospitalized with COVID-19 show evidence of neutrophil degranulation and have increased expression of neutrophil surface lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a marker of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Both early LOX-1 and programmed death-ligand 1 (PD-L1) expression on neutrophils were associated with development of severe disease. To determine whether tissue damage or inflammation is required to induce PMN-MDSCs or whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly activates neutrophils to become PMN-MDSCs, we incubated healthy human neutrophils with SARS-CoV-2. SARS-CoV-2 rapidly induced LOX-1 surface expression in healthy neutrophils independent of productive infection. LOX-1 induction was dependent on granule exocytosis and promoted up-regulation of reactive oxygen species, CD63, and PD-L1, enabling LOX-1+ neutrophils to suppress autologous T cell proliferation in vitro. These results support a role for PMN-MDSCs in mediating severe COVID-19, and inhibition of PD-L1 represents a potential therapeutic strategy for enhancing the immune response in acute SARS-CoV-2 infection.
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Affiliation(s)
- Leon L Hsieh
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA
| | - Elizabeth A Thompson
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA
| | - Nirvani P Jairam
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Katerina Roznik
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA
| | - Alexis Figueroa
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Tihitina Aytenfisu
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Weiqiang Zhou
- Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA
| | - Naina Gour
- Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Kuan-Hao Chao
- Center for Computational Biology, Johns Hopkins University, Baltimore, MD 21287, USA
| | - Aaron M Milstone
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Emily Egbert
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Franco D'Alessio
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Petros C Karakousis
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21287, USA
| | - Alvaro Ordoñez
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Eileen P Scully
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Andrew Pekosz
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA
| | - Andrew H Karaba
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Andrea L Cox
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA
- Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
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18
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Song XY, Mou YK, Wang HR, Wang Y, Liu WC, Yang T, Sun CY, Ren C, Song XC. IL-6 and Olfactory Dysfunction: Focus on Changes, Effects, and Mechanisms. Mediators Inflamm 2025; 2025:5891188. [PMID: 40420944 PMCID: PMC12105899 DOI: 10.1155/mi/5891188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 04/28/2025] [Indexed: 05/28/2025] Open
Abstract
The sense of smell is vital for human life and risk identification. Many diseases can cause olfactory disorders, and early identification and intervention of olfactory disorders are crucial. Currently, the diagnosis of olfactory disorders in clinical practice mostly relies on subjective visual analog scale (VAS) evaluations, expensive and complex imaging, and neurophysiological examinations, which lead to poor patient compliance and low completion rates. Therefore, there is an urgent need to identify novel, objective, easily detectable biological indicators. Interleukin-6 (IL-6) is an inflammatory factor that is closely associated with olfactory dysfunction in various diseases. However, the role of IL-6 in the occurrence and development of olfactory disorders is not yet clear, which limits its clinical application. This article reviews the changes and possible mechanisms of IL-6 in various diseases associated with olfactory disorders, with the aim of providing a reference for the clinical application of IL-6 as a biomarker for olfactory disorders and promoting an in-depth exploration of its mechanism in the occurrence and development of olfactory disorders.
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Affiliation(s)
- Xiao-Yu Song
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
| | - Ya-Kui Mou
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
| | - Han-Rui Wang
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
| | - Yao Wang
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
| | - Wan-Chen Liu
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
| | - Ting Yang
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
| | - Cai-Yu Sun
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
| | - Chao Ren
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
- Department of Neurology, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
| | - Xi-Cheng Song
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
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Mauricio LFS, Campanharo CRV, Piacezzi LHV, Lopes MCBT, Batista REA. Quick Sequential Organ Failure Assessment to identify clinical deterioration in adults with COVID-19: a retrospective cohort. Rev Lat Am Enfermagem 2025; 33:e4530. [PMID: 40396841 DOI: 10.1590/1518-8345.7239.4530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 11/22/2024] [Indexed: 05/22/2025] Open
Abstract
to evaluate the performance of qSOFA in identifying deterioration in patients with COVID-19. retrospective cohort study conducted between February and August 2020 in the Emergency Department of a private hospital, involving 813 adults. The variables studied included sociodemographic data, clinical characteristics, deterioration, qSOFA on admission and before the event, and outcomes. The performance of qSOFA at both moments was analyzed using the area under the ROC curve. the average age was 69 years. There was a predominance of men (61.5%), white (97.2%), catholic (73.7%), married (89.6%) and employed (66%). Comorbidities were present in 69.7%, and 58.8% were classified as "urgent" upon admission. The most frequent deterioration was respiratory failure (16.7%), and the outcome was discharge (68%). Patients with positive qSOFA on admission had a higher percentage of respiratory failure, cardiopulmonary arrest, and "very urgent" risk classification, and those with negative qSOFA showed a higher percentage of discharge (p< 0.0001). Upon admission, qSOFA showed 66% sensitivity and 55% specificity, and prior to the event it showed 48% sensitivity and 88% specificity for identifying clinical deterioration. Patients with positive qSOFA on admission were 350 times more likely to experience deterioration. qSOFA showed low sensitivity for identifying deterioration at both moments and high specificity before the event.
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20
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Lin HF, Jiang RD, Qin RX, Yao B, Zeng WT, Gao Y, Shi AM, Li JM, Liu MQ. Characterization of a SARS-CoV-2 Infection Model in Golden Hamsters with Diabetes Mellitus. Virol Sin 2025:S1995-820X(25)00059-8. [PMID: 40389095 DOI: 10.1016/j.virs.2025.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Accepted: 05/12/2025] [Indexed: 05/21/2025] Open
Abstract
Being widespread across the globe, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and generating new variants and continuously poses threat to public health, especially to the population with chronic comorbidities. Diabetes mellitus is one of high-risk factors for severe outcome of coronavirus disease 2019 (COVID-19). Establishment of animal models that parallel the clinical and pathological features of COVID-19 complicated with diabetes is thus highly essential. Here, in this study, we constructed leptin receptor gene knockout hamsters with the phenotype of diabetes mellitus (db/db), and revealed that the diabetic hamsters were more susceptible to SARS-CoV-2 and its variants than wild-type hamsters. SARS-CoV-2 and its variants induced a stronger immune cytokine response in the lungs of diabetic hamsters than in wild-type hamsters. Comparative histopathology analyses also showed that infection of SARS-CoV-2 and the variants caused more severe lung tissue injury in diabetic hamsters, and may induce serious complications such as diabetic kidney disease and cardiac lesions. Our findings demonstrated that despite the decreased respiratory pathogenicity, the SARS-CoV-2 variants were still capable of impairing other organs such as kidney and heart in diabetic hamsters, suggesting that the risk of evolving SARS-CoV-2 variants to diabetic patients should never be neglected. This hamster model may help better understand the pathogenesis mechanism of severe COVID-19 in patients with diabetes. It will also aid in development and testing of effective therapeutics and prophylactic treatments against SARS-CoV-2 variants among these high-risk populations.
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Affiliation(s)
- Hao-Feng Lin
- The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Laboratory Clinical Base, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510120, China
| | - Ren-Di Jiang
- State Key Laboratory of Genetic Engineering, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200433, China
| | - Rui-Xin Qin
- State Key Laboratory of Reproductive Medicine and Offspring Health, Jiangsu Laboratory Animal Center, Jiangsu Animal Experimental Center of Medicine and Pharmacy, Department of Cell Biology, Animal Core facility, Key Laboratory of Model Animal, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing 211166, China
| | - Bing Yao
- Jinling Hospital Department Reproductive Medical Center, Nanjing Medical University, Nanjing 211166, China
| | - Wen-Tao Zeng
- State Key Laboratory of Reproductive Medicine and Offspring Health, Jiangsu Laboratory Animal Center, Jiangsu Animal Experimental Center of Medicine and Pharmacy, Department of Cell Biology, Animal Core facility, Key Laboratory of Model Animal, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing 211166, China
| | - Yun Gao
- State Key Laboratory of Reproductive Medicine and Offspring Health, Jiangsu Laboratory Animal Center, Jiangsu Animal Experimental Center of Medicine and Pharmacy, Department of Cell Biology, Animal Core facility, Key Laboratory of Model Animal, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing 211166, China.
| | - Ai-Min Shi
- State Key Laboratory of Reproductive Medicine and Offspring Health, Jiangsu Laboratory Animal Center, Jiangsu Animal Experimental Center of Medicine and Pharmacy, Department of Cell Biology, Animal Core facility, Key Laboratory of Model Animal, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing 211166, China.
| | - Jian-Min Li
- State Key Laboratory of Reproductive Medicine and Offspring Health, Jiangsu Laboratory Animal Center, Jiangsu Animal Experimental Center of Medicine and Pharmacy, Department of Cell Biology, Animal Core facility, Key Laboratory of Model Animal, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing 211166, China.
| | - Mei-Qin Liu
- The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Laboratory Clinical Base, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510120, China.
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21
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Argano C, Torres A, Orlando V, Cangialosi V, Maggio D, Pollicino C, Corrao S. Molecular Insight into the Role of Vitamin D in Immune-Mediated Inflammatory Diseases. Int J Mol Sci 2025; 26:4798. [PMID: 40429939 PMCID: PMC12112522 DOI: 10.3390/ijms26104798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2025] [Revised: 05/04/2025] [Accepted: 05/06/2025] [Indexed: 05/29/2025] Open
Abstract
In the last decades, it has become increasingly evident that the role of vitamin D extends beyond the regulation of calcium homeostasis and the maintenance of bone health. A significant extraskeletal function of vitamin D is its role in modulating the immune system, particularly highlighted in the context of immune-mediated inflammatory diseases, where correlations between vitamin D status and genetic variations in the vitamin D receptor have been observed about the incidence and severity of these conditions. Additionally, different studies have reported the existence of immunomodulatory effects of vitamin D, particularly the effects of vitamin D on dendritic cell function, maturation, cytokine production, and antigen presentation, and that its deficiency may be associated with a sub-inflammatory state. In this sense, different clinical trials have been conducted to assess the therapeutic efficacy of vitamin D in different immune-mediated inflammatory disorders, including asthma, atopic dermatitis (AD), rheumatoid arthritis (RA), psoriasis, thyroid diseases, infectious diseases, and systemic lupus erythematosus (SLE). This review will provide a comprehensive overview of the current understanding of the molecular mechanisms underlying vitamin D's immunomodulatory properties, its role, and innovative therapeutic applications in patients with immune-mediated inflammatory diseases.
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Affiliation(s)
- Christiano Argano
- Department of Internal Medicine, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, 90127 Palermo, Italy;
| | - Alessandra Torres
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90133 Palermo, Italy; (A.T.); (V.O.); (V.C.); (D.M.); (C.P.)
| | - Valentina Orlando
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90133 Palermo, Italy; (A.T.); (V.O.); (V.C.); (D.M.); (C.P.)
| | - Virginia Cangialosi
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90133 Palermo, Italy; (A.T.); (V.O.); (V.C.); (D.M.); (C.P.)
| | - Dalila Maggio
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90133 Palermo, Italy; (A.T.); (V.O.); (V.C.); (D.M.); (C.P.)
| | - Chiara Pollicino
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90133 Palermo, Italy; (A.T.); (V.O.); (V.C.); (D.M.); (C.P.)
| | - Salvatore Corrao
- Department of Internal Medicine, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, 90127 Palermo, Italy;
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90133 Palermo, Italy; (A.T.); (V.O.); (V.C.); (D.M.); (C.P.)
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22
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Pei T, Li W, Zhou Z, Zhang Q, Yu G, Yin S, Chen H, Tang J. The relationship between tryptophan metabolism and gut microbiota: Interaction mechanism and potential effects in infection treatment. Microbiol Res 2025; 298:128211. [PMID: 40393170 DOI: 10.1016/j.micres.2025.128211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 04/29/2025] [Accepted: 05/05/2025] [Indexed: 05/22/2025]
Abstract
Human health is influenced by the gut microbiota, particularly in aspects of host immune homeostasis and intestinal immune response. Tryptophan (Trp) not only acts as a nutrient enhancer but also plays a critical role in the balance between host immune tolerance and gut microbiota maintenance. Both endogenous and bacterial metabolites of Trp, exert significant effects on gut microbial composition, microbial metabolism, the host immunity and the host-microbiome interface. Trp metabolites regulate host immunity by activating aryl hydrocarbon receptor (AhR), thereby contributing to immune homeostasis. Among Trp metabolites, AhR ligands include endogenous metabolites (such as kynurenine), and bacterial metabolites (such as indole and its derivatives). Here, we present a comprehensive analysis of the relationships between Trp metabolism and 14 key microbiota, encompassing fungi (e.g., Candida albicans, Aspergillus), bacteria (e.g., Ruminococcus gnavus, Bacteroides, Prevotella copri, Clostridium difficile, Escherichia coli, lactobacilli, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, Helicobacter. Pylori), and viruses (e.g., SARS-CoV-2, influenza virus). This review clarifies how the gut microbiota regulates Trp metabolism and uncovers the underlying mechanisms of these interactions. And increased mechanistic insight into how the microbiota modulate the host immune system through Trp metabolism may allow for the identification of innovative therapies that are specifically designed to target Trp absorption, Trp metabolites, the gut microbiota, or interactions between Trp and gut microbiota to treat both intestinal and extra-intestinal inflammation as well as microbial infections.
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Affiliation(s)
- Tongchao Pei
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China
| | - Wenweiran Li
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China
| | - Ziyang Zhou
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China
| | - Qinyu Zhang
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China
| | - Guohong Yu
- Department of Emergency Medicine, Baoshan Second People's Hospital, Baoshan College of Traditional Chinese Medicine, Baoshan 678000, China
| | - Sokun Yin
- Department of Emergency Medicine, Luoping County People's Hospital, Qujing 655800, China
| | - Hui Chen
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China.
| | - Jianguo Tang
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China.
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Wang X, Li Y, Wang Q, Xia F, Chen W, You C, Ma L. Glucose concentration predicting mortality in patients with COVID-19: A propensity score-matched study. Am J Med Sci 2025:S0002-9629(25)01035-3. [PMID: 40374008 DOI: 10.1016/j.amjms.2025.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 05/11/2025] [Accepted: 05/12/2025] [Indexed: 05/17/2025]
Abstract
BACKGROUND Patients with coronavirus disease-19 (COVID-19) often develop systemic inflammation, which is associated with increased mortality. Elevated blood glucose levels can exacerbate the cytokine storm, further worsening disease severity and accelerating patient death. Therefore, this study aims to investigate the association between glucose levels and mortality in hospitalized patients, providing insights into the importance of optimizing glucose management in hospitalized COVID-19 patients. METHODS A retrospective cohort study was conducted, involving adult COVID-19 patients in a university hospital. The primary outcome was in-hospital mortality. Propensity score matching (PSM) was utilized to match patients' baseline characteristics. Discrimination capacity of different models was assessed using C-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Trends in blood glucose over time were detected using the ordinary least squares model. RESULTS Among the 4583 COVID-19 patients during the study period, 2147 (46.8%) exhibited normal glycemia, while 2436 (53.2%) had admission hyperglycemia. After adjusting for confounding factors through multivariate regression analysis, patients with hyperglycemia showed significantly higher odds of in-hospital mortality (adjusted odds ratio [aOR]: 3.10, 95% CI: 2.25 to 4.28; P < 0.001). PSM analysis yielded similar results (aOR: 2.66, 95% CI: 2.09 to 3.41; P < 0.001). The incorporation of admission glucose significantly improved C-statistics (P < 0.001), IDI (P < 0.001), and NRI (P < 0.001) for predicting mortality. CONCLUSION This study concludes that blood glucose levels ≥ 6.1 mmol/L can independently predict all-cause mortality and clinical sequelae in COVID-19 patients. Furthermore, even a mild increase in blood glucose was associated with a significantly higher risk of mortality in these patients. These findings underscore the importance of managing hyperglycemia and monitoring blood glucose in individuals with COVID-19.
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Affiliation(s)
- Xing Wang
- Traumatic Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yue Li
- Research Core Facility of West China Hospital, Sichuan University
| | - Qiao Wang
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Fan Xia
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wuqian Chen
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chao You
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lu Ma
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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24
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Yang X, Zhu W. Effects of coronavirus disease 2019 on the incidence, mortality, and prognosis of ischemic stroke: a systematic review and meta-analysis. Front Neurol 2025; 16:1486887. [PMID: 40433610 PMCID: PMC12106046 DOI: 10.3389/fneur.2025.1486887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 04/28/2025] [Indexed: 05/29/2025] Open
Abstract
Objective The objective of this study was to conduct a systematic review on the effect of coronavirus disease 2019 (COVID-19) on the incidence, mortality, and prognosis of ischemic stroke. The systematic review also ascertained the relationship between COVID-19 and the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) typing of ischemic stroke, as well as the risk factors for ischemic stroke in patients with COVID-19. Methods The relevant literature between COVID-19 and ischemic stroke incidence, mortality, and prognosis up to January 2024 were systematically reviewed. Searches were carried out PubMed, Embase, Web of Science, and Cochrane databases. Utilizing the Meta-analysis of observational studies in epidemiology (MOOSE) declaration list, a systematic review and meta-analysis were carried out. Heterogeneity and publication bias were assessed. Results Twenty-one studies encompassed 505,864 participants across 13 countries. In total, 1.1% of patients with COVID-19 infection had an ischemic stroke (odds ratio [OR], 0.011; 95% confidence interval [CI], 0.007-0.017; p < 0.001). COVID-19 was related to in-hospital mortality (OR, 2.76; 95% CI, 1.90-4.02; p < 0.001), mortality 3 months following the beginning of an ischemic stroke (OR, 2.54; 95% CI, 1.80-3.58; p < 0.001), and modified Rankin scale (mRS) score ≤2 at hospital discharge (OR, 0.62; 95% CI, 0.54-0.72; p < 0.001). mRS ≤ 2 at 3 months after the onset of ischemic stroke did not show any correlation significantly with COVID-19 (OR, 0.67; 95% CI, 0.43-1.06; p = 0.086). Longer hospital stays (OR, 0.13; 95% CI, 0.06-0.20; p < 0.001) and increased incidence of large-artery atherosclerosis and small-vessel disease phenotypes of ischemic stroke were observed in patients with both COVID-19 and ischemic stroke (p < 0.05). In patients with COVID-19, ischemic stroke was substantially linked with hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, coronary artery disease, chronic kidney disease, and chronic obstructive pulmonary disease (p < 0.05). Conclusion COVID-19 is linked with increased incidence and mortality rates for ischemic stroke, as well as a worsening prognosis for the condition. With the data obtained from this study, targeted strategies to prevent and treat ischemic stroke in the context of the COVID-19 can be developed. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42024524016, identifier: CRD42024524016.
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Affiliation(s)
- Xinyue Yang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Wenhao Zhu
- Department of Encephalopathy, Zibo Hospital of Traditional Chinese Medicine, Zibo, Shandong, China
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25
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Che W, Guo S, Wang Y, Wan X, Tan B, Li H, Alifu J, Zhu M, Chen Z, Li P, Zhang L, Zhang Z, Wang Y, Huang X, Wang X, Zhu J, Pan X, Zhang F, Wang P, Sui SF, Zhao J, Xu Y, Liu Z. SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations. J Adv Res 2025:S2090-1232(25)00306-6. [PMID: 40354933 DOI: 10.1016/j.jare.2025.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Revised: 05/04/2025] [Accepted: 05/08/2025] [Indexed: 05/14/2025] Open
Abstract
INTRODUCTION With the COVID-19 pandemic becoming endemic, vigilance for Long COVID-related cardiovascular issues remains essential, though their specific pathophysiology is largely unexplored. OBJECTIVES Our study investigates the persistent cardiovascular symptoms observed in individuals long after contracting SARS-CoV-2, a condition commonly referred to as "Long COVID", which has significantly affected millions globally. METHODS We meticulously describe the cardiovascular outcomes in five patients, encompassing a range of severe conditions such as sudden cardiac death during exercise, coronary atherosclerotic heart disease, palpitation, chest tightness, and acute myocarditis. RESULTS All five patients were diagnosed with myocarditis, confirmed through endomyocardial biopsy and histochemical staining, which identified inflammatory cell infiltration in their heart tissue. Crucially, electron microscopy revealed widespread mitochondrial vacuolations and the presence of myofilament degradation within the cardiomyocytes of these patients. These findings were mirrored in SARS-CoV-2-infected mice, suggesting a potential underlying cellular mechanism for the cardiac effects associated with Long COVID. CONCLUSION Our findings demonstrate a profound impact of SARS-CoV-2 on mitochondrial integrity, shedding light on the cardiovascular implications of Long COVID.
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Affiliation(s)
- Wenliang Che
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Shuai Guo
- Cryo-electron Microscopy Center, Southern University of Science and Technology, Shenzhen, China; School of Life Science, Southern University of Science and Technology, Shenzhen, China
| | - Yanqun Wang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xiaohua Wan
- School of Medical Technology, Beijing Institute of Technology, Beijing, China
| | - Bingyu Tan
- Shanghai NanoPort, Thermo Fisher Scientific Inc., Shanghai, China
| | - Hailing Li
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jiasuer Alifu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Mengyun Zhu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zesong Chen
- Cryo-electron Microscopy Center, Southern University of Science and Technology, Shenzhen, China
| | - Peiyao Li
- Cryo-electron Microscopy Center, Southern University of Science and Technology, Shenzhen, China
| | - Lei Zhang
- Cryo-electron Microscopy Center, Southern University of Science and Technology, Shenzhen, China
| | - Zhaoyong Zhang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yiliang Wang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xiaohan Huang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xinsheng Wang
- School of Medical Technology, Beijing Institute of Technology, Beijing, China
| | - Jian Zhu
- Cryo-electron Microscopy Center, Southern University of Science and Technology, Shenzhen, China
| | - Xijiang Pan
- Shanghai NanoPort, Thermo Fisher Scientific Inc., Shanghai, China
| | - Fa Zhang
- School of Medical Technology, Beijing Institute of Technology, Beijing, China
| | - Peiyi Wang
- Cryo-electron Microscopy Center, Southern University of Science and Technology, Shenzhen, China
| | - Sen-Fang Sui
- Cryo-electron Microscopy Center, Southern University of Science and Technology, Shenzhen, China; School of Life Science, Southern University of Science and Technology, Shenzhen, China.
| | - Jincun Zhao
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou National Laboratory, Bio-Island, Guangzhou, China.
| | - Yawei Xu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
| | - Zheng Liu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Cryo-electron Microscopy Center, Southern University of Science and Technology, Shenzhen, China.
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Shekarnabi M, Guillien A, Terzi N, Sigaud F, Bitker L, Roux E, Ahaouari T, Serrano EED, Boussel L, Ferretti G, Yonis H, Mezidi M, Noirot I, Chauvelot L, Dhelft F, Gaillet M, Siroux V, Orkisz M, Richard JC, Bayat S. Prognostic value of functional CT imaging in COVID-ARDS: a two-centre prospective observational study. Respir Res 2025; 26:177. [PMID: 40346553 PMCID: PMC12065372 DOI: 10.1186/s12931-025-03232-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 04/11/2025] [Indexed: 05/11/2025] Open
Abstract
BACKGROUND Patients with ARDS have heterogeneous lungs which exposes them to the risk of lung injury exacerbation by mechanical ventilation. Functional lung CT imaging gives a comprehensive description of regional lung mechanical behaviour. Here, we investigated whether CT registration-based regional lung function parameters are associated with survival in patients with COVID-ARDS. METHODS We conducted a two-centre prospective observational study of adult COVID-ARDS patients with an indication for CT within 72 h of onset. Dual volume CT images were aligned using image-registration. Regional lung functional parameters, and their spatial distributions, were analysed by univariable Cox proportional hazard models with survival as the main outcome. Selected variables based on the univariable analysis were included in a stepwise Cox model adjusted for age, sex, body mass index and SAPSII. RESULTS 94 patients were included in the study. Recruitment was associated with a higher (HR = 1.45, p = 0.023) hazard of death, while apical (sΔVz) and central (sΔVx) displacement of specific volume change centre-of-mass were associated with a lower hazard of death (HR = 0.72, p = 0.041; HR = 0.68, p = 0.031, respectively). CONCLUSIONS Our data show that in addition to recruitment, the spatial distribution of specific volume change, a surrogate measure of regional lung ventilation, is associated with the risk of death in mechanically ventilated COVID-19 ARDS patients. Our findings suggest that CT image-registration based functional biomarkers may have prognostic value in COVID-ARDS patients. TRIAL REGISTRATION This study was retrospectively registered in Clinical Trials under NCT06113276 ( https://clinicaltrials.gov/study/NCT06113276 ) on 27/10/2023.
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Affiliation(s)
- Mehdi Shekarnabi
- Synchrotron Radiation for Biomedicine Laboratory (STROBE), INSERM UA07, Univ. Grenoble Alpes, Grenoble, France
- INSA-Lyon, CNRS, INSERM, CREATIS UMR 5220, U1294, Univ. Lyon, Université Claude Bernard Lyon 1, Villeurbanne, U1294, France
| | - Alicia Guillien
- Team of environmental epidemiology applied to development and respiratory health, Institute for Advanced Biosciences, Univ Grenoble Alpes, Inserm U1209, CNRS, Grenoble, France
| | - Nicolas Terzi
- Service de Médecine Intensive Réanimation, CHU Grenoble-Alpes, Grenoble, France
| | - Florian Sigaud
- Service de Médecine Intensive Réanimation, CHU Grenoble-Alpes, Grenoble, France
| | - Laurent Bitker
- INSA-Lyon, CNRS, INSERM, CREATIS UMR 5220, U1294, Univ. Lyon, Université Claude Bernard Lyon 1, Villeurbanne, U1294, France
- Service de Médecine Intensive Réanimation, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Emmanuel Roux
- INSA-Lyon, CNRS, INSERM, CREATIS UMR 5220, U1294, Univ. Lyon, Université Claude Bernard Lyon 1, Villeurbanne, U1294, France
| | - Touria Ahaouari
- Synchrotron Radiation for Biomedicine Laboratory (STROBE), INSERM UA07, Univ. Grenoble Alpes, Grenoble, France
| | - Eduardo Enrique Dávila Serrano
- INSA-Lyon, CNRS, INSERM, CREATIS UMR 5220, U1294, Univ. Lyon, Université Claude Bernard Lyon 1, Villeurbanne, U1294, France
| | - Loic Boussel
- INSA-Lyon, CNRS, INSERM, CREATIS UMR 5220, U1294, Univ. Lyon, Université Claude Bernard Lyon 1, Villeurbanne, U1294, France
- Service de Radiologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Gilbert Ferretti
- Service de Radiologie Diagnostique Et Interventionnelle, Université Grenoble Alpes, CHU Grenoble-Alpes, Grenoble, France
| | - Hodane Yonis
- Service de Médecine Intensive Réanimation, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Mehdi Mezidi
- Service de Médecine Intensive Réanimation, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
- Université Claude Bernard Lyon 1, Villeurbanne, France
| | - Ines Noirot
- Service de Médecine Intensive Réanimation, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Louis Chauvelot
- Service de Médecine Intensive Réanimation, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - François Dhelft
- Service de Médecine Intensive Réanimation, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
- Université Claude Bernard Lyon 1, Villeurbanne, France
| | - Maxime Gaillet
- Service de Médecine Intensive Réanimation, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
- Université Claude Bernard Lyon 1, Villeurbanne, France
| | - Valérie Siroux
- Team of environmental epidemiology applied to development and respiratory health, Institute for Advanced Biosciences, Univ Grenoble Alpes, Inserm U1209, CNRS, Grenoble, France
| | - Maciej Orkisz
- INSA-Lyon, CNRS, INSERM, CREATIS UMR 5220, U1294, Univ. Lyon, Université Claude Bernard Lyon 1, Villeurbanne, U1294, France
| | - Jean-Christophe Richard
- INSA-Lyon, CNRS, INSERM, CREATIS UMR 5220, U1294, Univ. Lyon, Université Claude Bernard Lyon 1, Villeurbanne, U1294, France
- Service de Médecine Intensive Réanimation, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Sam Bayat
- Synchrotron Radiation for Biomedicine Laboratory (STROBE), INSERM UA07, Univ. Grenoble Alpes, Grenoble, France.
- Department of Pulmonology & Physiology, Grenoble University Hospital, Grenoble, France.
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Singh A, Yazid NBM, Morales RF, Ejima K, Chia PY, Fong SW, Ng LFP, Renia L, Lye DC, Sun LJ, Tan SY, Chai LYA, Kalimuddin S, Young BE, Yeo TW, Teo A. Early neutrophil responses are potential biomarkers to predict severe COVID-19 in adults. J Leukoc Biol 2025; 117:qiaf035. [PMID: 40402813 DOI: 10.1093/jleuko/qiaf035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 01/16/2025] [Accepted: 03/18/2025] [Indexed: 03/22/2025] Open
Abstract
In the early COVID-19 pandemic, the strain on healthcare facilities highlighted the need for reliable biomarkers to predict progression to severe COVID-19. Neutrophils, the most abundant leukocytes in circulation, are early defenders against pathogens. In a Singaporean adult cohort, early neutrophil mediators were assessed for their suitability as prognostic biomarkers of COVID-19 complications. Plasma levels of myeloperoxidase (MPO), elastase, soluble urokinase plasminogen activator receptor (suPAR), and soluble suppressor of tumorigenicity 2 (sST2) in 35 nonsevere and 14 severe cases were measured twice, 2 to 7 d apart after hospitalization. Nineteen controls were included. The levels of MPO, elastase, suPAR, and sST2 were significantly higher in patients with severe COVID-19 compared with those with mild and healthy controls. At baseline sampling, MPO and suPAR predicted severe COVID-19 and had AUROCs of 0.76 and 0.87, respectively. MPO and suPAR at cut-off values of 26.41 ng/mL and 3.19 ng/mL, respectively showed approximately 71% sensitivity and 81% to 84% specificity to differentiate severe COVID-19. In contrast, elastase and neutrophil counts were less predictive of severe disease. In adult COVID-19, MPO and suPAR may be reliable prognostic biomarkers of severe disease during acute COVID-19. Further validation of these markers in a larger cohort and in other infectious diseases is warranted.
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Affiliation(s)
- Ananya Singh
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| | | | | | - Keisuke Ejima
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| | - Po Ying Chia
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
- National Centre for Infectious Diseases, Singapore 308442, Singapore
- Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore 308442, Singapore
| | - Siew Wai Fong
- A*STAR Infectious Diseases Lab, Agency for Science and Technology and Research (A*STAR), Singapore 138648, Singapore
| | - Lisa F P Ng
- A*STAR Infectious Diseases Lab, Agency for Science and Technology and Research (A*STAR), Singapore 138648, Singapore
- Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7ZX, United Kingdom
- National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool L69 7ZX, United Kingdom
| | - Laurent Renia
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
- A*STAR Infectious Diseases Lab, Agency for Science and Technology and Research (A*STAR), Singapore 138648, Singapore
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
| | - David Chien Lye
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
- National Centre for Infectious Diseases, Singapore 308442, Singapore
- Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore 308442, Singapore
- Department of Medicine, Yong Loo Ling School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Lousia Jin Sun
- Infectious Diseases, Alexandra Hospital, National University Health System, Singapore 119228, Singapore
| | - Seow Yen Tan
- National Centre for Infectious Diseases, Singapore 308442, Singapore
- Changi General Hospital, Singapore 529889, Singapore
| | - Louis Yi Ann Chai
- Department of Medicine, Yong Loo Ling School of Medicine, National University of Singapore, Singapore 119228, Singapore
- Division of Infectious Diseases, Department of Medicine, National University Health System, Singapore 119228, Singapore
| | - Shirin Kalimuddin
- Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Barnaby Edward Young
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
- National Centre for Infectious Diseases, Singapore 308442, Singapore
- Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore 308442, Singapore
| | - Tsin Wen Yeo
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| | - Andrew Teo
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
- National Centre for Infectious Diseases, Singapore 308442, Singapore
- Department of Medicine, The Doherty Institute, University of Melbourne, Melbourne 3000, Australia
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Lehtisalo J, Sääskilahti M, Härkänen T, Kulmala J, Hemiö K, Siltanen S, Zhi Z, Mangialasche F, Laatikainen T, Strandberg T, Antikainen R, Tuomilehto J, Soininen H, Kivipelto M, Ngandu T. Changes in older persons' lifestyle and perceived health over time and during the COVID-19 pandemic: findings from the extended follow-up of the FINGER randomized controlled trial from 2009 to 2020. BMC Geriatr 2025; 25:308. [PMID: 40319270 PMCID: PMC12048948 DOI: 10.1186/s12877-025-05979-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 04/22/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND Multidomain lifestyle trials have been shown to be effective in changing people's behaviour during the intervention, but less is known about long-term effects of such interventions. The aim of this study was to investigate how self-reported lifestyle and self-evaluated health changed over a 10-year period in older adults participating in the FINGER randomised controlled trial. Effects of the initial lifestyle intervention and the COVID-19 pandemic on these behaviour changes were evaluated. METHODS A two-year multicentre FINGER trial recruited community-dwelling people aged 60-77 years at risk of cognitive impairment (n=1259). Participants were randomised to a multidomain lifestyle intervention or regular health advice (control). They underwent study visits annually during the original trial period (at baseline, one, and two years) and twice during the follow-up (five and seven years), and responded to a survey during the COVID-19 pandemic at approximately 10 years. Generalised estimating equations (GEE) and linear mixed-effects regression model were used to analyse physical, cognitive, and social activity, food consumption, smoking, alcohol consumption, and self-evaluated health. RESULTS People in the intervention group were better able to maintain their level of physical activity up to the five-year follow-up. The intervention group also improved their diet quality: difference in fish consumption was maintained up to the seventh year, and consumption of vegetables and fruits increased during the active intervention. Cognitive and social activities increased and self-evaluated health and memory improved during the active period, but decreased thereafter, without a group difference. During the COVID-19 pandemic, physical and cognitive activities increased. CONCLUSION Multidomain lifestyle intervention was beneficial for improving physical activity and healthy food choices in older people both in the short and long term, but had no effect on other activities, smoking, alcohol use, or self-evaluated health. Increased physical activity was the most evident pandemic-associated change in older adults' lifestyle. TRIAL REGISTRATION ClinicalTrials.gov, NCT01041989. Registered 04/01/2010 - Retrospectively registered, https://clinicaltrials.gov/ .
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Affiliation(s)
- Jenni Lehtisalo
- Department of Public Health, Lifestyles and Living Environments, Finnish Institute for Health and Welfare, Helsinki, 00271, Finland.
- Department of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, 70211, Finland.
| | - Maria Sääskilahti
- Department of Public Health, Lifestyles and Living Environments, Finnish Institute for Health and Welfare, Helsinki, 00271, Finland
| | - Tommi Härkänen
- Department of Public Health, Lifestyles and Living Environments, Finnish Institute for Health and Welfare, Helsinki, 00271, Finland
| | - Jenni Kulmala
- Department of Public Health, Lifestyles and Living Environments, Finnish Institute for Health and Welfare, Helsinki, 00271, Finland
- Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Solna, Stockholm, 171 64, Sweden
- Faculty of Social Sciences (Health Sciences) and Gerontology Research Center (GEREC), Tampere, Finland
| | - Katri Hemiö
- Department of Public Health, Lifestyles and Living Environments, Finnish Institute for Health and Welfare, Helsinki, 00271, Finland
| | - Sini Siltanen
- Department of Public Health, Lifestyles and Living Environments, Finnish Institute for Health and Welfare, Helsinki, 00271, Finland
| | - Zhou Zhi
- Department of Public Health, Lifestyles and Living Environments, Finnish Institute for Health and Welfare, Helsinki, 00271, Finland
| | - Francesca Mangialasche
- Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Solna, Stockholm, 171 64, Sweden
- FINGERS Brain Health Institute, Stockholm, Sweden
- Theme Inflammation and Aging, Medical Unit Aging, Karolinska University Hospital, Stockholm, Sweden
| | - Tiina Laatikainen
- Department of Public Health, Lifestyles and Living Environments, Finnish Institute for Health and Welfare, Helsinki, 00271, Finland
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Timo Strandberg
- University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Unit of Population Health/Geriatrics, University of Oulu, Oulu, FI-90014, Finland
| | - Riitta Antikainen
- Research Unit of Population Health/Geriatrics, University of Oulu, Oulu, FI-90014, Finland
- Center for Geriatrics and General Medicine, Oulu University Hospital, Pohde Wellbeing Services County of North Ostrobothnia, Oulu, Finland
- Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland
| | - Jaakko Tuomilehto
- Department of Public Health, Lifestyles and Living Environments, Finnish Institute for Health and Welfare, Helsinki, 00271, Finland
- South Ostrobothnia Central Hospital, Seinäjoki, Finland
- Department of Public Health, University of Helsinki, Helsinki, Finland
- Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hilkka Soininen
- Department of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, 70211, Finland
- Department of Neurology, Kuopio University Hospital, Kuopio, Finland
| | - Miia Kivipelto
- Department of Public Health, Lifestyles and Living Environments, Finnish Institute for Health and Welfare, Helsinki, 00271, Finland
- Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Solna, Stockholm, 171 64, Sweden
- FINGERS Brain Health Institute, Stockholm, Sweden
- Theme Inflammation and Aging, Medical Unit Aging, Karolinska University Hospital, Stockholm, Sweden
- The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, London, UK
| | - Tiia Ngandu
- Department of Public Health, Lifestyles and Living Environments, Finnish Institute for Health and Welfare, Helsinki, 00271, Finland
- Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Solna, Stockholm, 171 64, Sweden
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
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Vanderkamp SG, Niazy M, Stegelmeier AA, Stinson KJ, Ricker N, Bridle BW. Cytokine, chemokine, and acute-phase protein profiles in plasma as correlative biomarkers of clinical outcomes for patients with COVID-19. Sci Rep 2025; 15:15397. [PMID: 40316702 PMCID: PMC12048561 DOI: 10.1038/s41598-025-99248-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 04/17/2025] [Indexed: 05/04/2025] Open
Abstract
Coronavirus disease identified in 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2, had a global impact on human health and the economy. The aim of this study was to quantify cytokines, chemokines, and acute phase proteins in the plasma of patients with COVID-19 to elucidate potential biomarkers to inform prognostic and treatment decisions. Clustering analysis using the K-prototypes method identified underlying biological patterns in patients with COVID-19. The penalized multinomial logistic regression analysis identified two comorbidities (hypertension, congestive heart failure) and thirteen analytes as potential risk factors for COVID-19 progression with 88.2% accuracy. Based on a patient's age, high concentrations of interleukin (IL)-6, monocyte chemoattractant protein-1, and pentraxin 3 were important biomarkers for lethal COVID-19. Decreased concentrations of interferon gamma-induced protein-10, IL-10, and soluble tumor necrosis factor receptor I were found to be associated with mild COVID-19, while increasing concentrations of these analytes could be used to predict COVID-19 severity.
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Affiliation(s)
- Sierra G Vanderkamp
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada
| | - Maysa Niazy
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada
| | - Ashley A Stegelmeier
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada
| | | | - Nicole Ricker
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada.
| | - Byram W Bridle
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada.
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Zhao J, Dong L, Jiao X, Xia F, Shan Q, Tang J, Wang S, Lyu X. Longitudinal Assessment of Pulmonary Involvement and Prognosis in Different Subtypes of COVID-19 Patients After One Year Using Low-Dose CT: A Prospective Observational Study. Acad Radiol 2025; 32:3006-3022. [PMID: 39864985 DOI: 10.1016/j.acra.2025.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 01/06/2025] [Accepted: 01/08/2025] [Indexed: 01/28/2025]
Abstract
RATIONALE AND OBJECTIVES Severe COVID-19 typically results in pulmonary sequelae. However, current research lacks clarity on the differences in these sequelae among various clinical subtypes. This study aimed to evaluate the changing lung imaging features and predictive factors in patients with COVID-19 pneumonia in northern China over a 12-month follow-up period after the relaxation of COVID-19 restrictions in 2022. MATERIALS AND METHODS Imaging and clinically relevant data from three groups (moderate, severe, and critical) of patients with varying severity were prospectively analyzed. Low-dose CT scans were conducted at 3, 6, and 12 months after discharge, with chest CT images evaluated at baseline and each follow-up using qualitative and quantitative analyses. Clinical symptoms and pulmonary function recovery at 12 months were documented. The correlation between lung function and CT results was analyzed. Univariate and multivariable logistic regression analyses were employed to examine factors influencing prognosis, while a post-hoc analysis model was utilized to investigate the relationships among different groups, time points, and chest CT findings. RESULTS Among the 103 hospitalized patients with COVID-19 pneumonia, 64 completed the 12-month evaluation. The median age was 63.70 ± 12.15%, and 62.5% (40/64) were men. During the follow-up period, while 67.19% (43/64) showed abnormalities, including fibrotic changes in 9.38% (6/64). Multivariable logistic regression identified age ≥ 65 (OR: 8.66; 95% CI: 1.86, 40.34; P = 0.006), length of hospital stays (OR: 1.23; 95% CI: 1.03, 1.47; P = 0.022), and baseline consolidation volume as a percentage of the whole lung (OR: 56.95; 95% CI: 1.198, 2706.782; P = 0.04) as independent risk factors for persistent CT lung abnormalities at 1 year. After 1 year, 34.38% (22/64) of patients still had abnormal lung function, and 9.38% (6/64) had pulmonary fibrosis and restrictive ventilatory dysfunction. The relationship between lung function and CT findings is weak correlation. The mixed model analysis revealed significant differences between groups, particularly between the moderate and severe groups, and significant changes in CT values over time. CONCLUSION One year after infection, more than one third of even moderate patients with mild symptoms had persistent pulmonary abnormalities. In our study, fibrotic changes were seen in severe and critically ill patients and remained stable 6 months after discharge from hospital. Imaging parameters can predict the prognosis. The larger the extent of baseline consolidation, the worse the prognosis of elderly patients.
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Affiliation(s)
- Jinyang Zhao
- Radiology Department, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China (J.Z., F.X., Q.S., J.T., S.W., X.L.)
| | - Liang Dong
- School of Electrical Engineering, Liaoning University of Technology, Jinzhou, China (L.D.)
| | - Xue Jiao
- Respiratory Department, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China (X.J.)
| | - Fan Xia
- Radiology Department, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China (J.Z., F.X., Q.S., J.T., S.W., X.L.)
| | - Qi Shan
- Radiology Department, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China (J.Z., F.X., Q.S., J.T., S.W., X.L.)
| | - Jiawen Tang
- Radiology Department, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China (J.Z., F.X., Q.S., J.T., S.W., X.L.)
| | - Sihan Wang
- Radiology Department, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China (J.Z., F.X., Q.S., J.T., S.W., X.L.)
| | - Xiaohong Lyu
- Radiology Department, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China (J.Z., F.X., Q.S., J.T., S.W., X.L.).
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Ljujic B, Maksimovic N, Damnjanovic T, Novakovic I, Grk M, Gulic M, Dusanovic-Pjevic M, Popovska Jovicic B, Rakovic I, Gazdic Jankovic M, Miletic Kovacevic M, Jekic B. HIF-1A Gene Polymorphisms are Associated With Clinical and Biochemical Parameters in COVID-19 Patients in Serbian Population. Clin Nurs Res 2025; 34:153-159. [PMID: 39781996 DOI: 10.1177/10547738241308972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
The hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a major regulator of adaptive response to hypoxia, common in patients with severe coronavirus disease 2019 (COVID-19). In addition, HIF-1 alpha regulates the expression of the most important proteins necessary for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of cells. The study included 129 hospitalized COVID-19 patients. Genotypes of HIF-1A gene polymorphisms rs11549465 and rs2057482 were determined by the RT-PCR method. We have observed lower mean platelet counts in carriers of HIF-1A rs11549465CC genotype (p = .050) and a significant association of thrombocytopenia with rs11549465CC/rs2057482CT HIF-1A genotypes combination (p = .037) in the group of patients under the age of 40. HIF-1A rs11549465CC genotype and rs11549465CC/rs2057482CT genotype combination could be predictive markers for thrombocytopenia in COVID-19 patients. Identification of such predictive markers for severe disease may contribute to a more efficient response of health systems to the SARS-CoV-2 pandemic.
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Affiliation(s)
- Biljana Ljujic
- Department of Genetics, Faculty of Medical Sciences, University of Kragujevac, Serbia
- Center for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, Serbia
| | - Nela Maksimovic
- Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Serbia
| | - Tatjana Damnjanovic
- Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Serbia
| | - Ivana Novakovic
- Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Serbia
| | - Milka Grk
- Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Serbia
| | - Milica Gulic
- Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Serbia
| | | | - Biljana Popovska Jovicic
- Department of Infectious diseases, Faculty of Medical Sciences, University of Kragujevac, Serbia
| | - Ivana Rakovic
- Department of Infectious diseases, Faculty of Medical Sciences, University of Kragujevac, Serbia
| | - Marina Gazdic Jankovic
- Department of Genetics, Faculty of Medical Sciences, University of Kragujevac, Serbia
- Center for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, Serbia
| | - Marina Miletic Kovacevic
- Center for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, Serbia
- Department of Histology and Embryology, Faculty of Medical Sciences, University of Kragujevac, Serbia
| | - Biljana Jekic
- Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Serbia
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Hachimi A, El-Mansoury B, Merzouki M. Incidence, pathophysiology, risk factors, histopathology, and outcomes of COVID-19-induced acute kidney injury: A narrative review. Microb Pathog 2025; 202:107360. [PMID: 39894232 DOI: 10.1016/j.micpath.2025.107360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 01/28/2025] [Accepted: 01/30/2025] [Indexed: 02/04/2025]
Abstract
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to a significant burden on global healthcare systems. COVID-19-induced acute kidney injury (AKI) is among one of the complications, that has emerged as a critical and frequent condition in COVID-19 patients. This AKI among COVID-19 patients is associated with poor outcomes, and high mortality rates, especially in those with severe AKI or requiring renal replacement therapy. COVID-19-induced AKI represents a significant complication with complex pathophysiology and multifactorial risk factors. Indeed, several pathophysiological mechanisms, including direct viral invasion of renal cells, systemic inflammation, endothelial and thrombotic abnormalities as well as nephrotoxic drugs and rhabdomyolysis are believed to underlie this condition. Moreover, histopathological and immunohistopathological findings commonly observed in postmortem studies include acute tubular necrosis, glomerular injury, and the presence of viral particles within renal tissue and urine. Identified risk factors for developing AKI vary among studies, depending on regions, underlying conditions, and the severity of the disease. Moreover, histopathological and immunohistopathological findings commonly observed in postmortem studies include show acute tubular necrosis, glomerular injury, and viral particles within renal tissue and urine. While, identified risk factors for developing AKI vary among studies, according to regions, underlying conditions, and the gravity of the disease. This narrative review aims to synthesize current knowledge on the incidence, pathophysiology, risk factors, histopathology, and outcomes of AKI induced by COVID-19.
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Affiliation(s)
- Abdelhamid Hachimi
- Medical ICU, Mohammed VI(th) University Hospital of Marrakech, Marrakech, Morocco; Morpho-Science Research Laboratory, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech, Morocco; Life Sciences Department, Bioengineering Laboratory, Faculty of Sciences and Technics, Sultan Moulay Slimane University, Beni Mellal, Morocco
| | - Bilal El-Mansoury
- Nutritional Physiopathologies, Neuroscience and Toxicology Team, Laboratory of Anthropogenic, Biotechnology and Health, Faculty of Sciences, Chouaib Doukkali University, El Jadida, Morocco
| | - Mohamed Merzouki
- Life Sciences Department, Bioengineering Laboratory, Faculty of Sciences and Technics, Sultan Moulay Slimane University, Beni Mellal, Morocco.
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McCullough MD, Spencer BR, Shi J, Plumb ID, Haynes JM, Shah M, Briggs-Hagen M, Stramer SL, Jones JM, Midgley CM. Coronavirus Disease 2019 Symptoms by Immunity Status and Predominant-Variant Period Among US Blood Donors. Open Forum Infect Dis 2025; 12:ofaf185. [PMID: 40322271 PMCID: PMC12048779 DOI: 10.1093/ofid/ofaf185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 03/24/2025] [Indexed: 05/08/2025] Open
Abstract
Background Amid changing variant and immunity landscapes since early in the coronavirus disease 2019 (COVID-19) pandemic, common COVID-19 symptoms need better understanding in relation to prior immunity or infecting variant. Methods American Red Cross blood donors were surveyed during February-April 2022 about prior COVID-19 vaccinations and symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Donations were tested for anti-nucleocapsid antibodies to inform infection history. Restricting analysis to donors with survey-reported infections during the Omicron BA.1-predominant period (19 December 2021 through 19 March 2022), we used multivariable logistic regression to compare symptoms by existing immunity from prior infection or vaccination. Restricting analysis to those with no existing immunity, we compared symptoms by variant-predominant period of their first reported infection (BA.1 vs before). Results Among 9505 donors with a BA.1-predominant period infection, donors with prior infection (n = 1115), vaccination (n = 5888), or both (n = 1738) were less likely than those without prior immunity (n = 764) to report loss of taste or smell, lower respiratory tract, constitutional, or gastrointestinal symptoms and more likely to report upper respiratory tract symptoms. Stronger associations followed recent prior infection, vaccination, or more vaccine doses. Among 8539 donors without prior immunity, those with survey-reported infections during the BA.1-predominant period (n = 764) were less likely to report loss of taste or smell, or lower respiratory tract symptoms than those with infections before this period (n = 7775). Conclusions Our data suggest that both prior immunity and Omicron predominance redistributed COVID-19 symptoms toward upper respiratory tract presentations and likely both contributed to a decrease in COVID-19 severity over time. These findings may better inform COVID-19 identification in high-immunity settings and demonstrate additional benefits of vaccination.
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Affiliation(s)
- Matthew D McCullough
- Coronavirus and Other Respiratory Viruses Division, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia USA
| | - Bryan R Spencer
- American Red Cross, Scientific Affairs, Dedham, Massachusetts, USA
| | - Jianrong Shi
- Coronavirus and Other Respiratory Viruses Division, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia USA
| | - Ian D Plumb
- Coronavirus and Other Respiratory Viruses Division, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia USA
| | - James M Haynes
- American Red Cross, Scientific Affairs, Rockville, Maryland, USA
| | - Melisa Shah
- Coronavirus and Other Respiratory Viruses Division, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia USA
| | - Melissa Briggs-Hagen
- Coronavirus and Other Respiratory Viruses Division, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia USA
| | - Susan L Stramer
- American Red Cross, Scientific Affairs, Rockville, Maryland, USA
| | - Jefferson M Jones
- Coronavirus and Other Respiratory Viruses Division, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia USA
| | - Claire M Midgley
- Coronavirus and Other Respiratory Viruses Division, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia USA
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Sasaki K, Garcia-Manero G, Nigo M, Jabbour E, Ravandi F, Wierda WG, Jain N, Takahashi K, Montalban-Bravo G, Daver NG, Thompson PA, Pemmaraju N, Kontoyiannis DP, Sato J, Karimaghaei S, Soltysiak KA, Raad II, Kantarjian HM, Carter BW. Artificial Intelligence Assessment of Chest Radiographs for COVID-19. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2025; 25:319-327. [PMID: 39710565 PMCID: PMC11993350 DOI: 10.1016/j.clml.2024.11.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 10/21/2024] [Accepted: 11/25/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND The sensitivity of reverse-transcription polymerase chain reaction (RT-PCR) is limited for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Chest computed tomography (CT) is reported to have high sensitivity; however, given the limited availability of chest CT during a pandemic, the assessment of more readily available imaging, such as chest radiographs, augmented by artificial intelligence may substitute for the detection of the features of coronavirus disease 2019 (COVID-19) pneumonia. METHODS We trained a deep convolutional neural network to detect SARS-CoV-2 pneumonia using publicly available chest radiography imaging data including 8,851 normal, 6,045 pneumonia, and 200 COVID-19 pneumonia radiographs. The entire cohort was divided into training (n = 13,586) and test groups (n = 1510). We assessed the accuracy of prediction with independent external data. RESULTS The sensitivity and positive predictive values of the assessment by artificial intelligence were 96.8% and 90.9%, respectively. In the first external validation of 204 chest radiographs among 107 patients with confirmed COVID-19, the artificial intelligence algorithm correctly identified 174 (85%) chest radiographs as COVID-19 pneumonia among 97 (91%) patients. In the second external validation with 50 immunocompromised patients with leukemia, the higher probability of the artificial intelligence assessment for COVID-19 was correlated with suggestive features of COVID-19, while the normal chest radiographs were closely correlated with the likelihood of normal chest radiographs by the artificial intelligence prediction. CONCLUSIONS The assessment method by artificial intelligence identified suspicious lung lesions on chest radiographs. This novel approach can identify patients for confirmatory chest CT before the progression of COVID-19 pneumonia.
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Affiliation(s)
- Koji Sasaki
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
| | | | - Masayuki Nigo
- Division of Infectious Diseases, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX
| | - Elias Jabbour
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Farhad Ravandi
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - William G Wierda
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Nitin Jain
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Koichi Takahashi
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | - Naval G Daver
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Philip A Thompson
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Naveen Pemmaraju
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Dimitrios P Kontoyiannis
- Department of Infectious Disease, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Junya Sato
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Sam Karimaghaei
- McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX
| | - Kelly A Soltysiak
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Issam I Raad
- Department of Infectious Disease, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Hagop M Kantarjian
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Brett W Carter
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
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Atçeken Z, Çelik Y, Atasoy Ç, Peker Y. Artificial Intelligence-guided Total Opacity Scores and Obstructive Sleep Apnea in Adults with COVID-19 Pneumonia. THORACIC RESEARCH AND PRACTICE 2025; 26:107-114. [PMID: 39930690 PMCID: PMC12047196 DOI: 10.4274/thoracrespract.2024.24090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 12/30/2024] [Indexed: 05/03/2025]
Abstract
OBJECTIVE We previously demonstrated that artificial intelligence (AI)-directed chest computed tomography (CT)-based total opacity scores (TOS) are associated with high-risk obstructive sleep apnea (OSA) based on the Berlin Questionnaire. In the current study, we examined the association between TOS severity and OSA severity based on polysomnography (PSG) recordings among participants with a history of Coronavirus disease-2019 (COVID-19) infection. MATERIAL AND METHODS This was a post-hoc analysis of 56 patients who underwent CT imaging after being diagnosed with COVID-19 pneumonia as well as overnight PSG for a validation study with a median of 406 days after the initial COVID-19 onset. The AI software quantified the overall opacity scores, which included consolidation and ground-glass opacity regions on CT scans. TOS was defined as the volume of high-opacity regions divided by the volume of the entire lung, and severe TOS was defined as the score ≥15. OSA was defined as an apnea-hypopnea index (AHI) of at least 15 events/h. RESULTS In total, 21 participants had OSA and 35 had no OSA. The median TOS was 10.5 [interquartile range (IQR) 1.6-21.2] in the OSA group and 2.8 (IQR 1.4-9.0) in the non-OSA group (P = 0.047). In a multivariate logistic regression analysis, OSA, AHI, and oxygen desaturation index were associated with severe TOS (P < 0.05 for all, respectively) adjusted for age, sex, body mass index, and hypertension. CONCLUSION AI-directed CT-based TOS severity in patients with COVID-19 pneumonia was associated with OSA severity based on PSG recordings. These results support our previous findings suggesting an association between questionnaire-based high-risk OSA and worse outcomes in COVID-19 pneumonia.
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Affiliation(s)
- Zeynep Atçeken
- Department of Radiology, Koç University Faculty of Medicine, İstanbul, Türkiye
| | - Yeliz Çelik
- Department of Pulmonary Medicine, Koç University Faculty of Medicine; Koç University Research Center for Translational Medicine (KUTTAM), İstanbul, Türkiye
| | - Çetin Atasoy
- Department of Radiology, Koç University Faculty of Medicine, İstanbul, Türkiye
| | - Yüksel Peker
- Department of Pulmonary Medicine, Koç University Faculty of Medicine; Koç University Research Center for Translational Medicine (KUTTAM), İstanbul, Türkiye
- Department of Molecular and Clinical Medicine/Cardiology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Sciences, Respiratory Medicine and Allergology, Lund University Faculty of Medicine, Lund, Sweden
- Department of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pennsylvania, USA
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Tang C, Xu M, Ruan R, Pan B, Luo J, Huang J, Cheng J, Li H, Zhang Y, Zhang Z. The relationship between COVID-19 and stroke and its risk factors, a Mendelian randomization analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2025:1-12. [PMID: 40304158 DOI: 10.1080/09603123.2025.2490187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 04/03/2025] [Indexed: 05/02/2025]
Abstract
BACKGROUND It remains unclear about the association between stroke and Coronavirus disease 2019 (COVID-19). Therefore, a Mendelian randomization (MR) analysis was conducted to explore the relationship between them. METHODS In this study, the most recent large-scale genome-wide association studies (GWASs) were selected from the publicly available COVID-19 GWAS meta-analysis (Round 7) as the exposure. Data from a recent original stroke GWAS were used as the outcome for the experimental group, while the stroke GWAS data from the IEU GWAS database were used as the validation group. In addition, an MR analysis was conducted to explore the causal relationships of susceptibility, hospitalization, and severity of COVID-19 with stroke and its subtypes. In addition, the results of the experimental and validation groups were integrated to perform a meta-analysis. RESULTS The MR analysis results corroborated that there was a positively causal relationship between the hospitalization (OR, 1.11; p = 0.015) (ORmeta, 1.11; p < 0.001), and severity (OR, 1.06; p = 0.043) (ORmeta, 1.07; p = 0.002) of COVID-19 and cardioembolic stroke (CES). This result is supported by the validation group and sensitivity analysis. CONCLUSION This study demonstrates for the first time that COVID-19 hospitalization and COVID-19 severity are risk factors for CES.
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Affiliation(s)
- Chao Tang
- Jinzhou Medical University, Jinzhou, China
| | | | | | - Bingxiao Pan
- The Second Affiliated Hospital of China Medical University, Shenyang, China
| | - Jia Luo
- Shenyang University of technology, Shenyang, China
| | - Jing Huang
- Jinzhou Medical University, Jinzhou, China
| | - Junyao Cheng
- The People's hospital of Yuechi County, Yuechi, China
| | - Hangxu Li
- The Third Clinical Medical College of Jinzhou Medical University, Jinzhou, China
| | - Yinan Zhang
- Department of Neurosurgery, General Hospital of Fushun Mining Bureau of Liaoning Health Industry Group, Fushun, China
| | - Zhenxing Zhang
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
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Guo F, Wang Y, Chen J, Wang R, Wang L, Hong W, Du Y, Yang G. Construction and application of macrophage-based extracellular drug-loaded delivery systems. Int J Pharm 2025; 675:125462. [PMID: 40101875 DOI: 10.1016/j.ijpharm.2025.125462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 02/17/2025] [Accepted: 03/10/2025] [Indexed: 03/20/2025]
Abstract
Given their unique phagocytic function, inflammatory site tropism, and ability to penetrate deep into the lesion sites, macrophages are considered to have promising application potential in the field of living-cell drug delivery. The methods of drug delivery using macrophages primarily include intracellular phagocytic and extracellular drug loading. Comparatively, extracellular drug loading is potential less cytotoxicity and has minimal effects on the motility and orientation of cells. In this review, we provide an overview of the methods of extracellular drug loading, and examine the effects of the different properties of nanoformulations on extracellular drug-loaded delivery systems. In addition, we assess the prospects and challenges of a self-propelled macrophage-based drug delivery system. We hope this research contributes to optimizing the design of these drug delivery systems.
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Affiliation(s)
- Fangyuan Guo
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; Research Institute of Pharmaceutical Particle Technology, Zhejiang University of Technology, Hangzhou 310014, China
| | - Yujia Wang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
| | - Jialin Chen
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
| | - Ruorong Wang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
| | - Lianyi Wang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
| | - Weiyong Hong
- Department of Pharmacy, Taizhou Municipal Hospital Affiliated to Taizhou University, Taizhou 318000, China
| | - Yinzhou Du
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
| | - Gensheng Yang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; Research Institute of Pharmaceutical Particle Technology, Zhejiang University of Technology, Hangzhou 310014, China.
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Wang X, Ma H, He X, Gu X, Ren Y, Yang H, Tong Z. Efficacy of early pulmonary rehabilitation in severe and critically ill COVID-19 patients: a retrospective cohort study. BMC Pulm Med 2025; 25:203. [PMID: 40301769 PMCID: PMC12039096 DOI: 10.1186/s12890-025-03678-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Accepted: 04/21/2025] [Indexed: 05/01/2025] Open
Abstract
BACKGROUND Respiratory sequelae, induced by lung injury, reduced muscle strength, and nutritional disturbance, are common in hospitalized patients with coronavirus disease 2019 (COVID-19). Therefore, optimal treatment is essential for reducing the mortality in severe forms of the disease and critically ill patients. Pulmonary rehabilitation (PR) has been used in many chronic respiratory diseases, but the role of early PR in severe and critically ill COVID-19 patients remains to be fully understood. METHODS Hospitalized severe to critically ill COVID-19 patients were recruited from Beijing Chaoyang Hospital between December 1, 2022, and June 30, 2023. In all, we recruited 272 patients, with 39 in the PR group and 233 in the control group. The PR intervention consisted of the prone position, airway clearance therapy (ACT), and resistance respiratory training (RRT). The primary outcome was the composite disease progression outcome rate, defined as death or intensive care unit (ICU) admission. Adverse events (AEs) and serious adverse events (SAEs) were recorded in the PR group. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) was used to balance confounding bias, generating weighting cohort and matched cohort. RESULTS The rate of the primary outcome was lower in the PR group (28.2% [11/39] in the PR group vs. 48.9% [114/233] in the control group). Significant differences were observed in both the original and weighting cohorts. Subgroup analyses showed that receiving ≥ 2 types of PR, receiving RRT, length from admission to intervention ≤ 4 days, and baseline P/F ≤ 150 mmHg were associated with lower rates of progression. Total rates of 2.6% (1/39) for AEs and 10.26% (4/39) for SAEs were reported. CONCLUSIONS Early pulmonary rehabilitation may prevent disease progression and reduce mortality in patients with severe COVID-19. These findings may be helpful for formulating an optimal rehabilitation strategy.
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Affiliation(s)
- Xue Wang
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Haomiao Ma
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Xiaoya He
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
- Sports and Medicine Integrative Innovation Center, Capital University of Physical Education and Sports, Beijing, China
| | - Xiaomeng Gu
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Yi Ren
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Huqin Yang
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
| | - Zhaohui Tong
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
- Beijing Research Center for Respiratory Infectious Diseases, Beijing, China.
- Laboratory for Clinical Medicine, Capital Medical University, Beijing, China.
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Zhao X, Huang H, Zeng G, Shi Q, Zhu P, Zhang L, Li L, Liu L, Huang N, Liu W, Yu K. Research on the online service mechanism of internet hospital in infectious disease prevention and control. Exp Biol Med (Maywood) 2025; 250:10349. [PMID: 40351479 PMCID: PMC12061786 DOI: 10.3389/ebm.2025.10349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 04/15/2025] [Indexed: 05/14/2025] Open
Abstract
Infectious diseases can sometimes lead to pandemics, often transmitted through public and social gatherings, including in-person hospital visits. Consequently, there is an urgent need for innovative approaches to prevent their spread. Taking COVID-19 as an example, we have explored a remote, contactless hospital online model that offers the public online medical consultations, professional psychological counseling, and chronic disease management consultations, thereby mitigating the risk of new transmissions resulting from hospital visits. This model was implemented, validated, and practiced at West China Hospital in China from 29 January 2020, to 12 March 2020. It was also applicable to other infectious diseases, such as influenza A. In this research, we utilized the hospital's internet platform, supplemented by telephone services, to offer the following to the public: 1) General medical education and consultation related to epidemics and psychological anxiety; 2) Online screening for at-risk populations; 3) Online prescription and medication delivery services for patients with chronic diseases. Consequently, over a period of more than 1 month, the online epidemic platform completed a total of 32,755 cases, including 8,783 internet consultations and 1,082 telephone consultations for the public, as well as 22,890 internet consultations for chronic disease patients. Among these, 289 high-risk individuals were identified, with 3 cases confirmed as COVID-19 during follow-up diagnoses, while no infections were detected in the remaining individuals. In conclusion, this innovative medical model serves as a significant supplement to existing healthcare systems and has the potential to be expanded to other hospitals and other infectious diseases. It is particularly beneficial in scenarios where medical resources are limited, populations are under quarantine, and there is a large demand for medical services and anxiety management during infectious disease pandemics.
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Affiliation(s)
- Xin Zhao
- Emergency Office, West China Hospital, Sichuan University, Chengdu, China
| | - Haitao Huang
- Department of Computer Application, Chengdu College of University of Electronic Science and Technology of China, Chengdu, China
| | - Guojun Zeng
- Division of Vascular Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Vascular Surgery, The People’s Hospital of Leshan, Leshan, China
| | - Qingke Shi
- Information Center, West China Hospital, Sichuan University, Chengdu, China
| | - Peijia Zhu
- Department of Science and Technology, West China Hospital, Sichuan University, Chengdu, China
| | - Longhao Zhang
- Double First-Class Construction Office, West China Hospital, Sichuan University, Chengdu, China
| | - Lei Li
- Department of Clinical Research Management, West China Hospital, Sichuan University, Chengdu, China
| | - Lunxu Liu
- Department of Thoracic Surgery, and President’s Office, West China Hospital, Sichuan University, Chengdu, China
| | - Nan Huang
- Department of Dermatology and Venerology, West China Hospital, Sichuan University, Chengdu, China
| | - Wenguang Liu
- Department of Computer Application, Chengdu College of University of Electronic Science and Technology of China, Chengdu, China
| | - Kexin Yu
- Department of Computer Application, Chengdu College of University of Electronic Science and Technology of China, Chengdu, China
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da Silva-Neto PV, de Carvalho JCS, Toro DM, Oliveira BTM, Cominal JG, Castro RC, Almeida MA, Prado CM, Arruda E, Frantz FG, Ramos AP, Ciancaglini P, Martins RB, da Silveira JC, Almeida F, Malmegrim KCR, Sorgi CA. TREM-1-Linked Inflammatory Cargo in SARS-CoV-2-Stimulated Macrophage Extracellular Vesicles Drives Cellular Senescence and Impairs Antibacterial Defense. Viruses 2025; 17:610. [PMID: 40431622 PMCID: PMC12115590 DOI: 10.3390/v17050610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/29/2025] [Accepted: 04/19/2025] [Indexed: 05/29/2025] Open
Abstract
The COVID-19 pandemic, caused by SARS-CoV-2, has significantly affected global health, with severe inflammatory responses leading to tissue damage and persistent symptoms. Macrophage-derived extracellular vesicles (EVs) are involved in the modulation of immune responses, but their involvement in SARS-CoV-2-induced inflammation and senescence remains unclear. Triggering receptors expressed on myeloid cell-1 (TREM-1) are myeloid cell receptors that amplify inflammation, described as a biomarker of the severity and mortality of COVID-19. This study investigated the composition and effects of macrophage-derived EVs stimulated by SARS-CoV-2 (MφV-EVs) on the recipient cell response. Our results, for the first time, show that SARS-CoV-2 stimulation modifies the cargo profile of MφV-EVs, enriching them with TREM-1 and miRNA-155 association, along with MMP-9 and IL-8/CXCL8. These EVs carry senescence-associated secretory phenotype (SASP) components, promote cellular senescence, and compromise antibacterial defenses upon internalization. Our findings provide evidence that MφV-EVs are key drivers of inflammation and immune dysfunction, underscoring their potential as therapeutic targets in COVID-19.
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Affiliation(s)
- Pedro V. da Silva-Neto
- Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto-FFCLRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-901, SP, Brazil; (P.V.d.S.-N.); (J.C.S.d.C.); (J.G.C.); (A.P.R.); (P.C.)
- Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-FCFRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil; (R.C.C.); (F.G.F.); (R.B.M.); (K.C.R.M.)
| | - Jonatan C. S. de Carvalho
- Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto-FFCLRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-901, SP, Brazil; (P.V.d.S.-N.); (J.C.S.d.C.); (J.G.C.); (A.P.R.); (P.C.)
- Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-FCFRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil; (R.C.C.); (F.G.F.); (R.B.M.); (K.C.R.M.)
| | - Diana M. Toro
- Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil; (D.M.T.); (E.A.)
| | - Bianca T. M. Oliveira
- Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil; (B.T.M.O.); (F.A.)
| | - Juçara G. Cominal
- Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto-FFCLRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-901, SP, Brazil; (P.V.d.S.-N.); (J.C.S.d.C.); (J.G.C.); (A.P.R.); (P.C.)
| | - Ricardo C. Castro
- Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-FCFRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil; (R.C.C.); (F.G.F.); (R.B.M.); (K.C.R.M.)
| | - Maria A. Almeida
- Departamento de Medicina Veterinária, Faculdade de Zootecnia e Engenharia de Alimentos-FZEA, Universidade de São Paulo-USP, Pirassununga 13635-900, SP, Brazil; (M.A.A.); (C.M.P.); (J.C.d.S.)
| | - Cibele M. Prado
- Departamento de Medicina Veterinária, Faculdade de Zootecnia e Engenharia de Alimentos-FZEA, Universidade de São Paulo-USP, Pirassununga 13635-900, SP, Brazil; (M.A.A.); (C.M.P.); (J.C.d.S.)
| | - Eurico Arruda
- Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil; (D.M.T.); (E.A.)
| | - Fabiani G. Frantz
- Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-FCFRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil; (R.C.C.); (F.G.F.); (R.B.M.); (K.C.R.M.)
| | - Ana P. Ramos
- Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto-FFCLRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-901, SP, Brazil; (P.V.d.S.-N.); (J.C.S.d.C.); (J.G.C.); (A.P.R.); (P.C.)
| | - Pietro Ciancaglini
- Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto-FFCLRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-901, SP, Brazil; (P.V.d.S.-N.); (J.C.S.d.C.); (J.G.C.); (A.P.R.); (P.C.)
- Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil; (B.T.M.O.); (F.A.)
| | - Ronaldo B. Martins
- Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-FCFRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil; (R.C.C.); (F.G.F.); (R.B.M.); (K.C.R.M.)
| | - Juliano C. da Silveira
- Departamento de Medicina Veterinária, Faculdade de Zootecnia e Engenharia de Alimentos-FZEA, Universidade de São Paulo-USP, Pirassununga 13635-900, SP, Brazil; (M.A.A.); (C.M.P.); (J.C.d.S.)
| | - Fausto Almeida
- Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil; (B.T.M.O.); (F.A.)
| | - Kelen C. R. Malmegrim
- Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-FCFRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil; (R.C.C.); (F.G.F.); (R.B.M.); (K.C.R.M.)
| | - Carlos A. Sorgi
- Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto-FFCLRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-901, SP, Brazil; (P.V.d.S.-N.); (J.C.S.d.C.); (J.G.C.); (A.P.R.); (P.C.)
- Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil; (B.T.M.O.); (F.A.)
- Programa de Pós-graduação em Imunologia Básica e Aplicada-PPGIBA, Instituto de Ciências Biológicas, Universidade Federal do Amazonas-UFAM, Manaus 69080-900, AM, Brazil
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Pohl R, Wolff D, Özkan E, Sprenger AA, Hasenpusch C, Wesenberg J, Düzel E, Apfelbacher C. Prevalence and incidence of cognitive impairment following acute respiratory distress syndrome of any cause: a systematic review and meta-analysis. Crit Care 2025; 29:164. [PMID: 40269971 PMCID: PMC12020237 DOI: 10.1186/s13054-025-05375-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 03/16/2025] [Indexed: 04/25/2025] Open
Abstract
OBJECTIVES The aim of this systematic review and meta-analysis is to synthesize and appraise the evidence on prevalence of cognitive impairment following acute respiratory distress syndrome (ARDS) of any cause. METHODS We systematically searched PubMed, Scopus, and Web of Science for observational studies focused on cognitive impairment in adult survivors of ARDS. Risk of bias and certainty of evidence (GRADE) were assessed. A meta-analysis using a random effects model was performed to estimate the overall prevalence of cognitive impairment after ARDS, with subgroup analyses for COVID-19-related ARDS (C-ARDS). Additionally, a meta-regression was conducted to assess the influence of demographic and clinical predictors on cognitive outcomes. Heterogeneity was assessed using τ2 and the I2 statistic. RESULTS We identified 14 studies with 1451 participants, with 650 participants (range: 13-98) included in the analyses. In the subgroup of C-ARDS, 12 studies with 563 participants (range: 13-98) were considered. The pooled prevalence of cognitive impairment following ARDS was 36% (95% CI 26-46%), with high heterogeneity between studies (I2 = 92%, τ2 = 0.03). In C-ARDS cohorts, the prevalence was 34% (95% CI 22-45%), with similar levels of heterogeneity (I2 = 92.7%, τ2 = 0.03). Meta-regression analysis showed that older age predicted a higher prevalence of cognitive impairment following ARDS (b = 0.02, p = 0.033), reducing between-study heterogeneity (I² = 60.04%, τ² = 0.01). ICU stay, sex, and time from ICU discharge to cognitive assessment showed no significant associations (p > 0.05). CONCLUSIONS This meta-analysis corroborates previous findings that cognitive impairment remains a persistent issue for ARDS survivors. The prevalence of cognitive impairments following ARDS highlights the importance of future research to unravel the complex underlying mechanisms contributing to these deficits and to develop targeted strategies for prevention and rehabilitation in survivors.
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Affiliation(s)
- Robert Pohl
- Institute of Social Medicine and Health Systems Research, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
| | - Doreen Wolff
- Institute of Social Medicine and Health Systems Research, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Ebru Özkan
- Institute of Social Medicine and Health Systems Research, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Antonia A Sprenger
- Institute of Social Medicine and Health Systems Research, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Claudia Hasenpusch
- Institute of Social Medicine and Health Systems Research, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Judith Wesenberg
- Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Emrah Düzel
- Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Christian Apfelbacher
- Institute of Social Medicine and Health Systems Research, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
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Chen Y, Ma J. The construction and validation of a prediction model of hypertensive disease in pregnancy. Sci Rep 2025; 15:13406. [PMID: 40251427 PMCID: PMC12008367 DOI: 10.1038/s41598-025-98416-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 04/11/2025] [Indexed: 04/20/2025] Open
Abstract
The HDP prediction model was constructed and validated by using the demographic characteristics, blood routine and biochemical screening indicators in early pregnancy to reduce the incidence of HDP. 16,112 pregnant women admitted to Yuyao People's Hospital from May 1, 2018 to April 30, 2022 were randomly divided into modeling group (n = 11279) and validation group (n = 4833) according to a ratio of 7:3. Demographic characteristics, blood routine and biochemical screening data of 8-12+ 6 weeks gestation were obtained from Ningbo Health Records system. Univariate analysis and multivariate binary Logistic regression analysis were used to determine the independent risk factors of HDP, and the scoring system was established by using the nomogram. Univariate analysis and multivariate binary Logistic regression analysis showed that Age, BMI, previous medical history, HB, TG, HDL and ALB were independent risk factors for HDP (P < 0.001). In the modeling group, AUC = 0.809, sensitivity = 74.30%, specificity = 73.10%, and in the validation group, AUC = 0.801, sensitivity = 77.60%, specificity = 68.90%. Hosmer-Lemeshow goodness of fit test showed that modeling group: P = 0.195 > 0.05, validation group: P = 0.775 > 0.05. The prediction model of early pregnancy Age, BMI, previous medical history, HB, TG, HDL and ALB can effectively predict the occurrence of HDP.
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Affiliation(s)
- Yuanyuan Chen
- Department of Obstetrics and Gynecology, Yuyao People's Hospital, Yuyao, 315400, Zhejiang, China
| | - Jianting Ma
- Department of Obstetrics and Gynecology, Yuyao People's Hospital, Yuyao, 315400, Zhejiang, China.
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Nie J, Zhou L, Tian W, Liu X, Yang L, Yang X, Zhang Y, Wei S, Wang DW, Wei J. Deep insight into cytokine storm: from pathogenesis to treatment. Signal Transduct Target Ther 2025; 10:112. [PMID: 40234407 PMCID: PMC12000524 DOI: 10.1038/s41392-025-02178-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 12/22/2024] [Accepted: 02/12/2025] [Indexed: 04/17/2025] Open
Abstract
Cytokine storm (CS) is a severe systemic inflammatory syndrome characterized by the excessive activation of immune cells and a significant increase in circulating levels of cytokines. This pathological process is implicated in the development of life-threatening conditions such as fulminant myocarditis (FM), acute respiratory distress syndrome (ARDS), primary or secondary hemophagocytic lymphohistiocytosis (HLH), cytokine release syndrome (CRS) associated with chimeric antigen receptor-modified T (CAR-T) therapy, and grade III to IV acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. The significant involvement of the JAK-STAT pathway, Toll-like receptors, neutrophil extracellular traps, NLRP3 inflammasome, and other signaling pathways has been recognized in the pathogenesis of CS. Therapies targeting these pathways have been developed or are currently being investigated. While novel drugs have demonstrated promising therapeutic efficacy in mitigating CS, the overall mortality rate of CS resulting from underlying diseases remains high. In the clinical setting, the management of CS typically necessitates a multidisciplinary team strategy encompassing the removal of abnormal inflammatory or immune system activation, the preservation of vital organ function, the treatment of the underlying disease, and the provision of life supportive therapy. This review provides a comprehensive overview of the key signaling pathways and associated cytokines implicated in CS, elucidates the impact of dysregulated immune cell activation, and delineates the resultant organ injury associated with CS. In addition, we offer insights and current literature on the management of CS in cases of FM, ARDS, systemic inflammatory response syndrome, treatment-induced CRS, HLH, and other related conditions.
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Grants
- 82070217, 81873427 National Natural Science Foundation of China (National Science Foundation of China)
- 82100401 National Natural Science Foundation of China (National Science Foundation of China)
- 81772477, 81201848, 82473220 National Natural Science Foundation of China (National Science Foundation of China)
- 82330010,81630010,81790624 National Natural Science Foundation of China (National Science Foundation of China)
- National High Technology Research and Development Program of China, Grant number: 2021YFA1101500.
- The Hubei Provincial Natural Science Foundation (No.2024AFB050)
- Project of Shanxi Bethune Hospital, Grant Numbber: 2023xg02); Fundamental Research Program of Shanxi Province, Grant Numbber: 202303021211224
- The Key Scientific Research Project of COVID-19 Infection Emergency Treatment of Shanxi Bethune Hospital (2023xg01), 2023 COVID-19 Research Project of Shanxi Provincial Health Commission (No.2023XG001, No. 2023XG005), Four “Batches” Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province (2023XM003), Cancer special Fund research project of Shanxi Bethune Hospital (No. 2020-ZL04), and External Expert Workshop Fund Program of Shanxi Provincial Health Commission(Proteomics Shanxi studio for Huanghe professor)
- Fundamental Research Program of Shanxi Province(No.202303021221192); 2023 COVID-19 Emergency Project of Shanxi Health Commission (Nos.2023XG001,2023XG005)
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Affiliation(s)
- Jiali Nie
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
| | - Ling Zhou
- Department of Respiratory and Critical Care Medicine, National Health Commission (NHC) Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Branch of National Clinical Research Center for Infectious Diseases, Wuhan Pulmonary Hospital (Wuhan Tuberculosis Prevention and Control Institute), Wuhan, China
| | - Weiwei Tian
- Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
- Sino-German Joint Oncological Research Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China
| | - Xiansheng Liu
- Department of Respiratory and Critical Care Medicine, National Health Commission (NHC) Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Branch of National Clinical Research Center for Infectious Diseases, Wuhan Pulmonary Hospital (Wuhan Tuberculosis Prevention and Control Institute), Wuhan, China
- Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
- Sino-German Joint Oncological Research Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China
| | - Liping Yang
- Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
- Sino-German Joint Oncological Research Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China
| | - Xingcheng Yang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yicheng Zhang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shuang Wei
- Department of Respiratory and Critical Care Medicine, National Health Commission (NHC) Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Hubei Branch of National Clinical Research Center for Infectious Diseases, Wuhan Pulmonary Hospital (Wuhan Tuberculosis Prevention and Control Institute), Wuhan, China.
| | - Dao Wen Wang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China.
| | - Jia Wei
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Zhang T, Ouyang Z, Zhang Y, Sun H, Kong L, Xu Q, Qu J, Sun Y. Marine Natural Products in Inflammation-Related Diseases: Opportunities and Challenges. Med Res Rev 2025. [PMID: 40202793 DOI: 10.1002/med.22109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 03/14/2025] [Accepted: 03/18/2025] [Indexed: 04/11/2025]
Abstract
In recent decades, the potentiality of marine natural products (MNPs) in the medical field has been increasingly recognized. Natural compounds derived from marine microorganisms, algae, and invertebrates have shown significant promise for treating inflammation-related diseases. In this review, we cover the three primary sources of MNPs and their diverse and unique chemical structures and bioactivities. This review aims to summarize the progress of MNPs in combating inflammation-related diseases. Moreover, we cover the functions and mechanisms of MNPs in diseases, highlighting their functions in regulating inflammatory signaling pathways, cellular stress responses, and gut microbiota, among others. Meanwhile, we focus on key technologies and scientific methods to address the current limitations and challenges in MNPs.
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Affiliation(s)
- Tao Zhang
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, China
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Zijun Ouyang
- School of Food and Drug, Shenzhen Polytechnic University, Shenzhen, China
| | - Yueran Zhang
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, China
| | - Haiyan Sun
- School of Food and Drug, Shenzhen Polytechnic University, Shenzhen, China
| | - Lingdong Kong
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, China
| | - Qiang Xu
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, China
| | - Jiao Qu
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, China
| | - Yang Sun
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, China
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
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Liao M, Zhang LT, Bai LJ, Wang RY, Liu Y, Han J, Liu LH, Qi BL. Xuebijing injection reduces COVID-19 patients' mortality as influenced by the neutrophil to lymphocyte platelet ratio. JOURNAL OF INTEGRATIVE MEDICINE 2025:S2095-4964(25)00046-9. [PMID: 40251040 DOI: 10.1016/j.joim.2025.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 01/21/2025] [Indexed: 04/20/2025]
Abstract
OBJECTIVE Xuebijing injection has been recommended as a therapeutic approach for individuals with severe and critical COVID-19. This study aims to explore the correlation of neutrophil to lymphocyte platelet ratio (NLPR) with the severity and prognosis of COVID-19, and the effect of XBJ on the prognosis of patients with COVID-19 in different inflammatory states. METHODS This was a retrospective study conducted at Wuhan Union Hospital in China. COVID-19 patients admitted between November 1, 2022 and February 1, 2023 were included. In predicting prognosis for individuals with COVID-19, new inflammatory indicators were used, and their prognostic value was assessed by using Cox regression models and receiver operating characteristic curves. Furthermore, a calculation was made to determine the cutoff value for NLPR. Relative risk and Cox regression models were used to examine the effects of Xuebijing injection on prognosis in patient cohorts that had been stratified by the NLPR cutoff. RESULTS This research included 455 participants with COVID-19, with a mean age of 72 years. Several inflammatory indicators were found to be strongly correlated with prognosis, and NLPR shows the greatest predictive power. Patients with NLPR > 3.29 exhibited a mortality rate of 17.3%, which was 6.2 times higher than in patients with NLPR ≤ 3.29. Importantly, providing Xuebijing injection to patients with NLPR > 3.29 was associated with a lower risk of 60-day all-cause mortality. However, there was no discernible improvement in survival among patients with NLPR ≤ 3.29 who received Xuebijing injection. CONCLUSION NLPR is the most reliable inflammatory marker for predicting prognosis among individuals with COVID-19, and can accurately identify individuals who may benefit from Xuebijing injection. Please cite this article as: Liao M, Zhang LT, Bai LJ, Wang RY, Liu Y, Han J, Liu LH, Qi BL. Xuebijing injection reduces COVID-19 patients mortality as influenced by the neutrophil to lymphocyte platelet ratio. J Integr Med. 2025; Epub ahead of print.
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Affiliation(s)
- Man Liao
- Department of General Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 Hubei Province, China
| | - Li-Ting Zhang
- Department of General Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 Hubei Province, China
| | - Li-Juan Bai
- Department of General Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 Hubei Province, China
| | - Rui-Yun Wang
- Department of General Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 Hubei Province, China
| | - Yun Liu
- Department of General Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 Hubei Province, China
| | - Jing Han
- Department of General Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 Hubei Province, China
| | - Li-Hua Liu
- Department of General Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 Hubei Province, China.
| | - Ben-Ling Qi
- Department of General Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 Hubei Province, China.
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Xu Y, Tang M, Guo Z, Lin Y, Guo H, Fang F, Lin L, Shi Y, Lai L, Pan Y, Tang X, You W, Li Z, Song J, Wang L, Cai W, Fu Y. A model based on PT-INR and age serves as a promising predictor for evaluating mortality risk in patients with SARS-CoV-2 infection. Front Cell Infect Microbiol 2025; 15:1499154. [PMID: 40248368 PMCID: PMC12003402 DOI: 10.3389/fcimb.2025.1499154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 03/03/2025] [Indexed: 04/19/2025] Open
Abstract
COVID-19 caused by the coronavirus SARS-CoV-2 has resulted in a global pandemic. Considering some patients with COVID-19 rapidly develop respiratory distress and hypoxemia, early assessment of the prognosis for COVID-19 patients is important, yet there is currently a lack of research on a comprehensive multi-marker approach for disease prognosis assessment. Here, we utilized a large sample of hospitalized individuals with COVID-19 to systematically compare the clinical characteristics at admission and developed a nomogram model that was used to predict prognosis. In all cases, those with pneumonia, older age, and higher PT-INR had a poor prognosis. Besides, pneumonia patients with older age and higher PT-INR also had a poor prognosis. A nomogram model incorporating presence of pneumonia, age and PT-INR could evaluate the prognosis in all patients with SARS-CoV-2 infections well, while a nomogram model incorporating age and PT-INR could evaluate the prognosis in those with pneumonia well. Together, our study establishes a prognostic prediction model that aids in the timely identification of patients with poor prognosis and helps facilitate the improvement of treatment strategies in clinical practice in the future.
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Affiliation(s)
- Yongjie Xu
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Blood Transfusion, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Minjie Tang
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Blood Transfusion, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Zhaopei Guo
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yanping Lin
- Department of Laboratory Medicine, The Third Hospital of Xiamen, Xiamen, China
| | - Hongyan Guo
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Fengling Fang
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Lin Lin
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yue Shi
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Lu Lai
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yan Pan
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Xiangjun Tang
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Weiquan You
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Zishun Li
- Department of Laboratory Medicine, The Third Hospital of Xiamen, Xiamen, China
| | - Jialin Song
- Medical Research Center, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, China
| | - Liang Wang
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Weidong Cai
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Blood Transfusion, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Ya Fu
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
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Reimer M, Lee V, Obadeyi O, Reimer KS, Tarver C, Tran DA, Pak E. Pain Complaints and Intubation Risk in COVID-19 Patients: A Retrospective Cross-Sectional Analysis. Cureus 2025; 17:e81585. [PMID: 40322436 PMCID: PMC12045755 DOI: 10.7759/cureus.81585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/01/2025] [Indexed: 05/08/2025] Open
Abstract
Purpose In late 2019, the SARS-CoV-2 virus spread to become a worldwide pandemic with continued impact today. The disease severity is categorized based on age, comorbid conditions, and respiratory symptoms, but the clinical significance of pain reports and their correlation with life-sustaining treatment is not addressed much in the literature. The purpose of this study is to investigate the relationship between pain reports in patients with COVID-19 and the likelihood of intubation. Methods A retrospective cross-sectional analysis was performed compiling representative billing codes for pain complaints using the Epic Cosmos data set, a HIPAA limited data set of more than 226 million patients from 236 health systems using Epic software. For validation of this method, three months of institutional-specific Cosmos billing code data were compared to chart-reviewed pain complaints at a university health system. After validation, the data was broadened to include the entire Cosmos database from February 1, 2020 through April 15, 2023 for patients with confirmed COVID-19 infections seen in emergency rooms or an inpatient ward. Using billing codes, these patients were divided into different pain groups: abdominal pain, chest pain, myalgia, headache, or none of these, and then further subdivided based on intubation status. Lastly, patients were divided by age: <18 years, 18 to <40 years, 40 to <50 years, 50 to 65 years, and ≥65 years of age. Pearson's chi-square analyses were performed to investigate the relationship between pain symptoms and intubation and further performed to assess variations by age subgroup. Odds ratios (ORs) of the data were calculated in the same manner. Results We investigated 2,491,770 data points in our analysis of COVID-19 positive emergency room and inpatient cases. When comparing the presence of all pain types combined and intubation by the chi-square test, the p-value (p) was <0.00001, suggesting that a relationship exists between pain and intubation. OR analysis showed that those with pain complaints were less likely to be intubated with OR 0.58 (95% confidence interval (CI) 0.57 to 0.59, p <0.0001). Pain subgroups similarly showed reduced likelihood of intubation: abdominal pain, OR of 0.61 (95% Cl: 0.59 - 0.62), chest pain, OR of 0.86 (95% Cl: 0.85 - 0.88), myalgia, OR of 0.26 (95% Cl: 0.24 - 0.27) and headache, OR of 0.31 (95% CI: 0.29 - 0.32). Conclusions Due to the wide variability in COVID-19 infection symptoms, it is difficult to identify a single risk factor that correlates with an increased likelihood of intubation. Our cross-sectional examination of 2.4 million data points for COVID-19 patients in the emergency department or inpatient settings found that pain complaints were negatively correlated with emergency intubation. Given this, the absence of pain reports in hospitalized COVID-19 patients may imply poor prognosis; however, further research is needed to determine whether the absence of pain is indeed a poor prognostic indicator and if so, hospitalized COVID-19 patients without pain warrant close monitoring.
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Affiliation(s)
- Michael Reimer
- Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, USA
| | - Victor Lee
- Emergency Medicine, Loma Linda University Medical Center, Loma Linda, USA
| | - Oluseyi Obadeyi
- Pain Medicine, Loma Linda University Medical Center, Loma Linda, USA
| | | | - Christopher Tarver
- Physical Medicine and Rehabilitation, Loma Linda University Medical Center, Loma Linda, USA
| | - Duc A Tran
- Physical Medicine and Rehabilitation, Loma Linda University Medical Center, Loma Linda, USA
| | - Eugene Pak
- Pain Medicine, Loma Linda University Medical Center, Loma Linda, USA
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Matin MA, Sami CA, Anjan MAH, Rashed HM, Hoque A, Hasan MN, Arafat SM, Biswas SK, Chowdhury FR. Dynamics of SARS-CoV-2 Immunoglobulin G Antibody Among Hospitalized Patients and Healthcare Workers During the Delta Wave in Bangladesh. Cureus 2025; 17:e82175. [PMID: 40370886 PMCID: PMC12076252 DOI: 10.7759/cureus.82175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/12/2025] [Indexed: 05/16/2025] Open
Abstract
BACKGROUND A reliable marker of COVID-19 past infection is the anti-spike IgG antibody (Ab) titer of the SARS-CoV-2 virus, which may be identified even one year from diagnosis. Serology can be effective in diagnosing asymptomatic infection and patients with negative reverse transcription polymerase chain reaction. Exploring these dynamics and the persistence of antibodies is vital to understanding the disease process. MATERIALS AND METHODS We designed this observational study to compare the seroconversion status of COVID-19 patients to healthy healthcare workers. The total number of participants was 272, including 58 hospitalized (recovered) patients, 153 healthcare workers (HCWs), and 61 control populations from the community. A total of 404 samples were taken for IgG titer measurements using the enzyme-linked immunosorbent assay method. RESULTS Among 58 COVID-19 patients, 58.6% were men, and the male-to-female ratio was 1:1.41. All hospitalized patients had three months of persistence of Ab titer. The median IgG titer (interquartile range) optical density values for the hospitalized severe group on day 0, as well as during the fourth, eighth, and twelfth weeks, were 9.25 (6.01-11.893), 8.95 (5.52-12.42), 13.19 (12.26-13.26), and 12.99 (9.23-13.24), respectively. In comparison, the nonsevere group exhibited median values of 4.19 (3.08-9.89), 6.99 (4.32-9.75), 8.65 (5.83-13.08), and 12.48 (7.88-13.16), respectively. However, seroprevalence was higher in the control group (83.3%); in the HCWs, it was 54.9%. Although patients with severe disease had higher antispike IgG titers, no difference in titers was seen among age, gender, body mass index, or diabetes subgroups. CONCLUSION We observed Ab titer persistence up to three months in cases of COVID-19-recovered patients, whereas seroprevalence was high among HCWs and the control group during the Delta wave.
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Affiliation(s)
- Md Abdul Matin
- Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
| | - Chowdhury Adnan Sami
- Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
| | | | - Hasan M Rashed
- Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
| | - Ashraful Hoque
- Department of Blood Transfusion, Sheikh Hasina National Institute of Burn and Plastic Surgery, Dhaka, BGD
| | - Md Nazmul Hasan
- Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
| | - Shohael Mahmud Arafat
- Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
| | - Sunil K Biswas
- Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
| | - Fazle R Chowdhury
- Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
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Barrachina-Esteve O, Anguita A, Reverter A, Espinosa J, Lafuente C, Rubio-Roy M, Crosas M, Vila-Sala C, Acero C, Navarro M, Cánovas D, Ribera G, Jodar M, Estela J. Neurologic features in hospitalized patients with COVID-19: a prospective cohort in a catalan hospital. Neurol Sci 2025; 46:1477-1488. [PMID: 39951175 PMCID: PMC11920300 DOI: 10.1007/s10072-025-08031-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Accepted: 01/27/2025] [Indexed: 03/19/2025]
Abstract
OBJECTIVES To study the prevalence and timing of neurological manifestations, including cognitive involvement, in patients hospitalized for Coronavirus disease 2019 (COVID-19). To analyze the pathogenic mechanisms and any association they have with disease severity. METHODS Longitudinal cohort study with prospective follow-up of patients who required hospitalization. Patients under 65 who had no pre-existing cognitive impairment and did not require an ICU stay were evaluated 3 and 12 months after discharge using a battery of neuropsychological tests. RESULTS Of 205 patients hospitalized for COVID-19, 153 (74.6%) presented with neurological manifestations. The most frequent were myalgia (32.7%), headache (31.7%), dysgeusia (29.2%), and anosmia (24.9%). Patients with more severe illness at the time of hospitalization presented fewer neurological manifestations. Of the 62 patients who underwent neuropsychological examination 3 months after discharge, 22.6% had impaired attention, 19.4% impaired working memory, 16.1% impaired learning and retrieval, 9.7% impaired executive functions, and 8.2% impaired processing speed. Patients with anosmia also presented with more headache (OR 5.45; p < 0.001) and greater risk of working memory impairment (OR 5.87; p 0.03). At follow-up 12 months after hospital discharge, 14.3% of patients still showed impaired attention, 2.4% impaired working memory, 2.5% impaired executive functions, and 2.5% impaired processing speed. DISCUSSION Neurological manifestations are common in patients hospitalized for COVID-19 regardless of severity. The high prevalence of anosmia and its association with headache and working memory impairment at 3 months, suggest potential direct or indirect damage to the prefrontal cortex via invasion of the olfactory bulb by COVID-19.
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Affiliation(s)
- Oriol Barrachina-Esteve
- Department of Neurology, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain.
- Department of Neurology, Manacor Hospital, Manacor, Mallorca, Spain.
| | - A Anguita
- Department of Neurology, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain
- Department of Neurology, Sant Joan de Déu Hospital, Althaia Foundation, Manresa, Spain
| | - A Reverter
- Department of Neurology, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain
| | - J Espinosa
- Department of Neurology, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain
| | - C Lafuente
- Department of Neurology, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain
| | - M Rubio-Roy
- Department of Neurology, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain
| | - M Crosas
- Department of Neurology, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain
| | - C Vila-Sala
- Department of Neurology, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain
| | - C Acero
- Department of Ophthalmology, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain
| | - M Navarro
- Department of Infectious Diseases, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain
| | - D Cánovas
- Department of Neurology, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain
| | - G Ribera
- Department of Neurology, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain
| | - M Jodar
- Department of Neurology, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain
- Department of Clinical and Health Psychology, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centre for Biomedical Research in the Mental Health Network (CIBERSAM), National Institute of Health Carlos III, Madrid, Spain
| | - J Estela
- Department of Neurology, Parc Taulí University Hospital, Parc Taulí Research and Innovation Institute Foundation (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain
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Nurisyah S, Iyori M, Hasyim AA, Amru K, Itani K, Nakamura K, Zainal KH, Halik H, Djaharuddin I, Bukhari A, Asih PBS, Syafruddin D, Yoshida S, Idris I, Yusuf Y. Evaluation of an E. coli-expressed spike protein-based in-house ELISA system for assessment of antibody responses after COVID-19 infection and vaccination. NARRA J 2025; 5:e1250. [PMID: 40352206 PMCID: PMC12059849 DOI: 10.52225/narra.v5i1.1250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 02/18/2025] [Indexed: 05/14/2025]
Abstract
Evaluating long-term immunity after COVID-19 infection and vaccination is critical for managing potential outbreaks. The aim of this study was to develop a cost-effective in-house enzyme-linked immunosorbent assay (ELISA) based on Escherichia coli-expressed SARS-CoV-2 spike protein (E-S1) for antibody detection and to evaluate its performance. The system was validated by comparing the in-house ELISA results with those obtained using a commercial ELISA with HEK293-expressed spike protein (H-S1). Recombinant SARS-CoV-2 spike protein was produced in E. coli, purified, and validated for antigenicity via ELISA. Indirect ELISAs with both E-S1 and H-S1 antigens were performed on 386 serum samples from COVID-19 survivors, vaccinated individuals, and pre-pandemic controls collected at different time points. The E-S1 ELISA showed a statistically significant but weak correlation with H-S1 ELISA across all samples (r=0.205; p=0.0001). Stronger correlations were observed among vaccinated individuals with prior infection on day 90 (r=0.6017; p<0.001) and in naïve vaccine recipients on day 30 (r=0.5361; p=0.0003). Pre-pandemic sera from a rural population in Sumba Island exhibited high background reactivity in E-S1 ELISA, likely due to anti-E. coli antibodies, while urban pre-pandemic sera from Jakarta showed a stronger correlation with H-S1 ELISA. This suggests potential regional or immune background differences influencing assay performance. Although E-S1 retained antigenic properties, its diagnostic utility is limited by non-specific reactivity and reduced sensitivity compared to H-S1. In conclusion, E. coli expression systems may not be ideal for producing spike protein-based ELISA antigens specific to SARS-CoV-2. Alternative expression systems, such as human or baculovirus, could enhance diagnostic accuracy and specificity for COVID-19 antibody detection.
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Affiliation(s)
- Sitti Nurisyah
- Department of Pulmonology and Respiratory Medicine, Universitas Hasanuddin, Makassar, Indonesia
- Dr. Tadjuddin Chalid Hospital, Makassar, Indonesia
| | - Mitsuhiro Iyori
- Research Institute of Pharmaceutical Science, Musashino University, Nishitokyo, Japan
| | - Ammar A. Hasyim
- Laboratory of Vaccinology and Applied Immunology, Kanazawa University, Ishikawa, Japan
| | - Khaeriah Amru
- Dr. Tadjuddin Chalid Hospital, Makassar, Indonesia
- Department of Medical Education, Universitas Hasanuddin, Makassar, Indonesia
| | - Kei Itani
- Laboratory of Vaccinology and Applied Immunology, Kanazawa University, Ishikawa, Japan
| | - Kurumi Nakamura
- Laboratory of Vaccinology and Applied Immunology, Kanazawa University, Ishikawa, Japan
| | - Kartika H. Zainal
- Laboratory of Vaccinology and Applied Immunology, Kanazawa University, Ishikawa, Japan
| | | | - Irawaty Djaharuddin
- Department of Pulmonology and Respiratory Medicine, Universitas Hasanuddin, Makassar, Indonesia
- Dr. Wahidin Soedirohusodo Hospital, Makassar, Indonesia
| | - Agussalim Bukhari
- Department of Clinical Nutrition, Universitas Hasanuddin, Makassar, Indonesia
| | - Puji BS. Asih
- National Research and Innovation Agency, Jakarta, Indonesia
| | - Din Syafruddin
- Department of Parasitology, Universitas Hasanuddin, Makassar, Indonesia
| | - Shigeto Yoshida
- Laboratory of Vaccinology and Applied Immunology, Kanazawa University, Ishikawa, Japan
| | - Irfan Idris
- Department of Physiology, Universitas Hasanuddin, Makassar, Indonesia
| | - Yenni Yusuf
- Department of Parasitology, Universitas Hasanuddin, Makassar, Indonesia
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