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Dos S P Andrade AC, Lacasse E, Dubuc I, Gudimard L, Gravel A, Puhm F, Campolina-Silva G, Queiroz-Junior C, Allaeys I, Prunier J, Azeggouar Wallen O, Dumais É, Belleannée C, Droit A, Flamand N, Boilard É, Flamand L. Deficiency in platelet 12-lipoxygenase exacerbates inflammation and disease severity during SARS-CoV-2 infection. Proc Natl Acad Sci U S A 2025; 122:e2420441122. [PMID: 40100623 DOI: 10.1073/pnas.2420441122] [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: 10/15/2024] [Accepted: 01/27/2025] [Indexed: 03/20/2025] Open
Abstract
Platelets, known for maintaining blood balance, also participate in antimicrobial defense. Upon severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, platelets become hyperactivated, releasing molecules such as cytokines, granule contents, and bioactive lipids. The key effector biolipids produced by platelets include 12-hydroxyeicosatetraenoic acid (12-HETE) and 12-hydroxyeicosatrienoic acid (12-HETrE), produced by 12-lipoxygenase (12-LOX), and prostaglandins and thromboxane, produced by cyclooxygenase-1. While prostaglandin E2 and thromboxane B2 were previously associated with lung inflammation in severe COVID-19, the role of platelet 12-LOX in SARS-CoV-2 infection remains unclear. Using mice deficient for platelets' 12-LOX, we report that SARS-CoV-2 infection resulted in higher lung inflammation characterized by histopathological tissue analysis, increased leukocyte infiltrates, and cytokine production relative to wild-type mice. In addition, distinct platelet and lung transcriptomic changes, including alterations in NOD-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) inflammasome-related gene expression, were observed. Mass spectrometry lipidomic analysis in 12-LOX-deficient-infected mice revealed significant changes in bioactive lipid content, including reduced levels of 12-HETrE that inversely correlated with disease severity. Finally, platelet 12-LOX deficiency was associated with increased morbidity and lower survival rates relative to wild type (WT) mice. Overall, this study highlights the complex interplay between 12-LOX-related lipid metabolism and inflammatory responses during SARS-CoV-2 infection. The findings provide valuable insights into potential therapeutic targets aimed at mitigating severe outcomes, emphasizing the pivotal role of platelet enzymes in the host response to viral infections.
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Affiliation(s)
- Ana Claudia Dos S P Andrade
- Division of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada
| | - Emile Lacasse
- Division of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada
| | - Isabelle Dubuc
- Division of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada
| | - Leslie Gudimard
- Division of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada
| | - Annie Gravel
- Division of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada
| | - Florian Puhm
- Division of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada
| | - Gabriel Campolina-Silva
- Division of Reproduction, mother and youth health, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada
| | - Celso Queiroz-Junior
- Morphology Department, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Isabelle Allaeys
- Division of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada
| | - Julien Prunier
- Division of Endocrinology and Nephrology, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada
| | - Oumaima Azeggouar Wallen
- Centre de recherche de l'Institut Universitaire de cardiologie et pneumologie de Québec, Division of pneumology, Faculty of medicine, Université Laval, Québec City, QC G1V 4G5, Canada
| | - Élizabeth Dumais
- Centre de recherche de l'Institut Universitaire de cardiologie et pneumologie de Québec, Division of pneumology, Faculty of medicine, Université Laval, Québec City, QC G1V 4G5, Canada
| | - Clémence Belleannée
- Division of Reproduction, mother and youth health, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada
| | - Arnaud Droit
- Division of Endocrinology and Nephrology, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada
| | - Nicolas Flamand
- Centre de recherche de l'Institut Universitaire de cardiologie et pneumologie de Québec, Division of pneumology, Faculty of medicine, Université Laval, Québec City, QC G1V 4G5, Canada
- Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health, Université Laval, Québec City, QC G1V 4G5, Canada
| | - Éric Boilard
- Division of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada
- Centre de Recherche ARThrite-Arthrite, Recherche, Traitements, Université Laval, Québec, QC G1V 4G2, Canada
- Department of microbiology, infectious disease and immunology, Faculty of Medicine, Université Laval, Québec City, QC G1V 0A6, Canada
| | - Louis Flamand
- Division of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada
- Centre de Recherche ARThrite-Arthrite, Recherche, Traitements, Université Laval, Québec, QC G1V 4G2, Canada
- Department of microbiology, infectious disease and immunology, Faculty of Medicine, Université Laval, Québec City, QC G1V 0A6, Canada
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2
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Yılmaz M, Mirzaoğlu Ç. Retrospective Cohort Study: Severe COVID-19 Leads to Permanent Blunted Heart Rate Turbulence. Diagnostics (Basel) 2025; 15:621. [PMID: 40075869 PMCID: PMC11899457 DOI: 10.3390/diagnostics15050621] [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: 11/05/2024] [Revised: 12/31/2024] [Accepted: 01/06/2025] [Indexed: 03/14/2025] Open
Abstract
Background: Heart rate turbulence (HRT) is a non-invasive technique that can be used to evaluate autonomic nervous system (ANS) function and cardiac arrhythmia. The objective of this study is to investigate whether COVID-19 can lead to long-term blunted HRT following recovery. Methods: This retrospective cohort study included 253 individuals with a confirmed history of COVID-19, referred to as the recovered COVID-19 group, along with 315 healthy participants who had no history of the virus. The recovered COVID-19 group was categorized into three subgroups based on their chest CT severity scores. The HRT analyses were obtained from a 24-h electrocardiography-Holter recording. Results: This study revealed that the HRT onset value was elevated in the recovered COVID-19 group, while the HRT slope value showed a significant decrease when compared to the control group. Correlation analyses indicated a positive relationship between the chest CT severity score and HRT onset, whereas a negative correlation was observed between the chest CT severity score and HRT slope. Regression analyses identified recovery from severe COVID-19, chest CT severity score, hypertension (HT), and smoking as independent predictors of both abnormal HRT onset and the existence of an abnormal HRT slope. Conclusions: Individuals who have recovered from severe COVID-19 are expected to encounter a permanent blunting of HRT, which is regarded as a significant indicator of an increased risk of ventricular arrhythmias and impaired autonomic nervous system (ANS) function. Recovered severe COVID-19 individuals should be carefully evaluated for HRT with 24-h ECG-Holter.
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Affiliation(s)
- Mücahid Yılmaz
- Department of Cardiology, Elazığ Fethi Sekin City Hospital, University of Health Sciences, 23280 Elazığ, Turkey;
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3
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Soleimani M, Jalilvand A. Spatial analysis of COVID-19 incidence and mortality rates in northwest iran for future epidemic preparedness. Sci Rep 2025; 15:7450. [PMID: 40032988 DOI: 10.1038/s41598-025-91246-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: 10/31/2024] [Accepted: 02/19/2025] [Indexed: 03/05/2025] Open
Abstract
The COVID-19 pandemic has underscored the critical need for effective public health strategies to combat infectious diseases. This study examines the epidemiological characteristics and spatial distribution of COVID-19 incidence and mortality in Zanjan Province, northwest Iran, to inform future epidemic preparedness. Using data from 39,739 hospitalized COVID-19 cases recorded between February 2020 and September 2021, sourced from the Medical Care Monitoring Center, we conducted descriptive and geospatial analyses. Demographic, clinical, and spatial variables were analyzed using logistic regression and advanced spatial techniques, including Kernel Density Estimation and Local Moran's I, to identify risk factors and disease hotspots. Results revealed that women accounted for 52% of cases, with higher incidence rates, while men exhibited higher mortality rates (7.86% vs. 7.80%). Urban areas, particularly the provincial capital, were identified as hotspots, with the highest patient density (20,384 cases per 10 km²). Comorbidities such as HIV/AIDS (OR: 4.85), chronic liver disease (OR: 3.6), chronic blood diseases (OR: 2.8), and cancer (OR: 2.5) significantly increased mortality risk, with ventilator use showing the highest odds ratio for death (OR = 91). Vaccination significantly reduced mortality, with fully vaccinated individuals experiencing a 6.3% mortality rate compared to 8.1% in unvaccinated individuals. Spatial analysis highlighted population density and mobility as key drivers of disease spread. These findings emphasize the importance of integrating spatial and epidemiological data to enhance pandemic preparedness. Targeted interventions in urban hotspots, early detection systems, and prioritizing vaccination for high-risk populations are critical for mitigating future outbreaks. This study provides a foundation for evidence-based public health strategies to strengthen global epidemic response and improve preparedness for future health crises.
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Affiliation(s)
- Mohsen Soleimani
- Assistant Professor of Medical Informatics, Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Ahmad Jalilvand
- Associate Professor of Pathology, Department of Pathology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
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4
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Good K, Joshi R, Snell V. Continuous Glucose Monitoring for Inpatients on Intravenous Insulin. CLIN NURSE SPEC 2025; 39:99-106. [PMID: 39969811 DOI: 10.1097/nur.0000000000000888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2025]
Abstract
PURPOSE This article describes a protocol used to implement a continuous glucose monitoring program for patients treated with intravenous insulin. DESCRIPTION Although continuous glucose monitoring is not indicated for use in hospitalized patients, the COVID-19 pandemic created an immediate need to effectively address the increasing number of people hospitalized with hyperglycemia. The article highlights the implementation process and key glycemic outcomes, discusses the impact of continuous glucose monitoring use on staff time and healthcare resource utilization, and provides information about program expansion. OUTCOME Most patients achieved established glycemic targets. Our program improved staff safety by reducing their exposure to infection. Use of continuous glucose monitoring decreased staff time by almost 2 hours per person per day compared with point-of-care testing and resulted in an average cost savings of $278.00 per patient. CONCLUSION Continuous glucose monitoring is safe and effective in managing glycemia among patients treated with intravenous insulin.
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Affiliation(s)
- Karen Good
- Author Affiliations: Clinical Nurse Specialist (Ms Good), UPMC Central Pa; Endocrinologist, Mount Nittany Medical Center, State College, and Formerly Vice President of Chronic Disease Population Management (Dr Joshi), UPMC Central Pa, Mechanicsburg; and Diabetes Education Program Manager (Ms Snell), UPMC Central Pa, Harrisburg, Pennsylvania
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5
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Venturi G, Gallinaro A, Fortuna C, Pirillo MF, Scoglio A, Di Carlo B, Marsili G, Michelini Z, Amendola A, Carocci A, Dispinseri S, Borghi M, Canitano A, Falce C, Zappitelli A, Scarlatti G, Lixi ML, Aste A, Masala L, Baroncelli S, Cara A, Negri D. Viral and immune profiles during the first wave of SARS-CoV-2 infection in hospitalized patients in Sardinia, Italy. Sci Rep 2025; 15:6660. [PMID: 39994243 PMCID: PMC11850715 DOI: 10.1038/s41598-025-90324-5] [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: 04/05/2024] [Accepted: 02/12/2025] [Indexed: 02/26/2025] Open
Abstract
We performed a retrospective immunological analysis of the antibody response in serum and in nasopharyngeal swabs (NPS) obtained from 46 individuals infected with ancestral SARS-CoV-2 Wuhan-Hu-1 strain during the first COVID-19 wave in Cagliari (Sardinia, Italy), with a 4-month follow-up after the hospital admission. We implemented a comprehensive antibody response in serum and in mucosal samples using assays established in our laboratories. In NPS we evaluated the viral load by real time PCR, presence and kinetics of anti-Spike IgG and IgA by ELISA as well as their anti-Wuhan neutralization activity, showing induction and persistence of anti-viral immunity at the mucosal level. Neutralizing antibodies were measured in serum and NPS using a safe pseudovirus-based assay validated after comparison with a standard neutralization test using live SARS-CoV-2. We evaluated cross-neutralizing antibodies against all the major early variants of concerns (VoC) in sera. Of note, we detected a remarkable reduction of neutralizing activity against BA.1 compared to BA.2 and BA.5 Omicron subvariants, which was confirmed in sera from an analogous cohort of patients at the San Raffaele hospital in Milan, a geographically distant region of Italy, infected with the ancestral virus during the same period of time.
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Affiliation(s)
- Giulietta Venturi
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | | | - Claudia Fortuna
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | | | - Arianna Scoglio
- National Center for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy
| | - Beatrice Di Carlo
- National Center for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy
| | - Giulia Marsili
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Zuleika Michelini
- National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
| | - Antonello Amendola
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Alberto Carocci
- National Center for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy
| | - Stefania Dispinseri
- Viral Evolution and Transmission Unit, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Martina Borghi
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Andrea Canitano
- National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
| | - Chiara Falce
- National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
| | - Alice Zappitelli
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
- Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Rome, Italy
| | - Gabriella Scarlatti
- Viral Evolution and Transmission Unit, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Maria Luisa Lixi
- Laboratory Medicine, Santissima Trinità Hospital, Cagliari, Italy
| | - Alessandra Aste
- Laboratory Medicine, Santissima Trinità Hospital, Cagliari, Italy
| | - Laura Masala
- Laboratory Medicine, Santissima Trinità Hospital, Cagliari, Italy
| | - Silvia Baroncelli
- National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
| | - Andrea Cara
- National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.
| | - Donatella Negri
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
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6
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Zhao Y, Tang Y, Wang QY, Li J. Ocular neuroinflammatory response secondary to SARS-CoV-2 infection-a review. Front Immunol 2025; 16:1515768. [PMID: 39967658 PMCID: PMC11832381 DOI: 10.3389/fimmu.2025.1515768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/13/2025] [Indexed: 02/20/2025] Open
Abstract
With the consistent occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the prevalence of various ocular complications has increased over time. SARS-CoV-2 infection has been shown to have neurotropism and therefore to lead to not only peripheral inflammatory responses but also neuroinflammation. Because the receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), can be found in many intraocular tissues, coronavirus disease 2019 (COVID-19) may also contribute to persistent intraocular neuroinflammation, microcirculation dysfunction and ocular symptoms. Increased awareness of neuroinflammation and future research on interventional strategies for SARS-CoV-2 infection are important for improving long-term outcomes, reducing disease burden, and improving quality of life. Therefore, the aim of this review is to focus on SARS-CoV-2 infection and intraocular neuroinflammation and to discuss current evidence and future perspectives, especially possible connections between conditions and potential treatment strategies.
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Affiliation(s)
| | | | | | - Jia Li
- Department of Glaucoma, The Second Hospital of Jilin University, Changchun, China
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Bruyneel A, Dello S, Dauvergne JE, Kohnen D, Sermeus W. Prevalence and risk factors for burnout, missed nursing care, and intention-to-leave the job among intensive care unit and general ward nurses: A cross-sectional study across six European countries in the COVID-19 era. Intensive Crit Care Nurs 2025; 86:103885. [PMID: 39522308 DOI: 10.1016/j.iccn.2024.103885] [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: 09/04/2024] [Revised: 10/11/2024] [Accepted: 10/27/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVE This study aimed to compare the prevalence of burnout, missed nursing care, and intention-to-leave the job among nurses working in general care units and intensive care units (ICUs), and to analyse the risk factors for these outcomes between the two groups. DESIGN This was a cross-sectional study involving online surveys of nurses at participating hospitals conducted between November 2020 and July 2021 as part of the Magnet4Europe initiative. SETTING AND PARTICIPANTS A convenience sample was recruited, consisting of 67 acute care hospitals in 6 countries: Belgium, England, Germany, Ireland, Norway, and Sweden. In total, data for 1,150 ICU nurses and 5,145 general ward nurses (1,901 from surgical wards and 3,250 from medical wards) were analysed. RESULTS The prevalence of burnout was significantly lower among nurses in ICUs (27.1 % vs. 30.3 %), missed care from care was significantly less frequent (65.5 % vs. 75.4 %), while intention-to-leave was similar (28.1 % vs. 29.2 %) compared with nurses in general wards. Nurses working in a better work environment and with lower workloads had statistically significant lower rates of burnout and intention-to-leave their job compared to those working in a poorer work environment and with higher workloads. Country-specific analysis showed a higher burnout rate and the intention-to-leave the job for nurses working in Germany, Ireland, Scandinavia, and the England compared to Belgium. CONCLUSIONS ICU nurses did not have a higher risk of burnout and had significantly lower risks of missing care and intention-to-leave, compared to nurses in general wards. A better work environment and lower perceived workload were consistently associated with reduced risks for all outcomes studied. IMPLICATIONS FOR CLINICAL PRACTICE National policies should prioritize creating healthy work environments, reducing workloads, and addressing country-specific challenges to lower burnout rates, minimize missed care, and decrease the intention to leave the job among ICU and general ward nurses.
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Affiliation(s)
- Arnaud Bruyneel
- Health Economics, Hospital Management and Nursing Research Dept, School of Public Health, Université Libre de Bruxelles, Belgium.
| | - Simon Dello
- Leuven Institute for Healthcare Policy, KU Leuven, Kapucijnenvoer 35 blok D bus 7001, Leuven 3000, Belgium
| | - Jérôme E Dauvergne
- Nantes Université, CHU Nantes, Department of Anaesthesiology and Critical Care at Laënnec Hospital, University Hospital of Nantes, F-44000 Nantes, France
| | - Dorothea Kohnen
- Leuven Institute for Healthcare Policy, KU Leuven, Kapucijnenvoer 35 blok D bus 7001, Leuven 3000, Belgium
| | - Walter Sermeus
- Leuven Institute for Healthcare Policy, KU Leuven, Kapucijnenvoer 35 blok D bus 7001, Leuven 3000, Belgium
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8
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Willis LD, Spray BJ, Henderson E, Lloyd T, Irby K, Sanders R. Characteristics and Outcomes of Children Hospitalized With COVID-19 During Early Pandemic and Delta Variant. Respir Care 2025. [PMID: 39969916 DOI: 10.1089/respcare.12199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2025]
Abstract
Background: Children were less affected by severe illness as compared to adults at the start of the COVID-19 pandemic. As the pandemic progressed and variants emerged, pediatric hospitalizations increased, and some previously healthy children developed multisystem inflammatory disorder. The aim of this study was to describe the characteristics and outcomes of children hospitalized with COVID-19 from the beginning of the pandemic through the Δ variant. Methods: Data were collected retrospectively for children hospitalized during March 2020-November 2021 with a diagnosis of COVID-19. Admissions were classified as early pandemic or during the delta variant, and outcomes were compared between the time periods. Primary outcome measures were hospital length of stay and use of respiratory support. The number of admissions/month was the secondary outcome. Results: There were 784 hospital admissions: 400 during early pandemic and 378 during the Δ period. Forty-four percent had an underlying medical condition, and 78% were not eligible for COVID-19 vaccination. Oxygen was the most common respiratory support modality and was required more often during Δ (P < .001). Hospital stay was longer during the Δ period (P < .001), and the number of monthly admissions was higher. A statistically significant but low correlation was identified between body mass index (BMI) Z score and stay (P < .001, r = 0.19). Conclusions: The Δ variant was associated with increased hospital length of stay and use of respiratory support compared to the early pandemic period. Children with preexisting medical conditions were more likely to require respiratory support and have longer hospitalization than others. Higher BMI Z score was also weakly associated with longer length of stay. The reason for admission was attributed to causes other than COVID-19 for the majority of admissions except during the Δ period.
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Affiliation(s)
- L Denise Willis
- Mss Willis, Henderson, and Lloyd are affiliated with Respiratory Care Services, Arkansas Children's Hospital, Little Rock, Arkansas
| | - Beverly J Spray
- Dr Spray is affiliated with Arkansas Children's Research Institute, Little Rock, Arkansas
| | - Erin Henderson
- Mss Willis, Henderson, and Lloyd are affiliated with Respiratory Care Services, Arkansas Children's Hospital, Little Rock, Arkansas
| | - Tera Lloyd
- Mss Willis, Henderson, and Lloyd are affiliated with Respiratory Care Services, Arkansas Children's Hospital, Little Rock, Arkansas
| | - Katherine Irby
- Dr Irby is affiliated with Section of Critical Care, Department of Pediatrics, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, Arkansas
| | - Ronald Sanders
- Dr Sanders is affiliated with Respiratory Care Services, Arkansas Children's Hospital, Little Rock, Arkansas; and Section of Critical Care, Department of Pediatrics, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, Arkansas
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Treon SP, Kotton CN, Park DJ, Moranzoni G, Lemvigh CK, Gathe JC, Varughese TA, Barnett CF, Belenchia JM, Clark NM, Farber CM, Abid MB, Ahmed G, Patterson CJ, Guerrera ML, Soumerai JD, Chea VA, Carulli IP, Southard J, Li S, Wu CJ, Livak KJ, Holmgren E, Kim P, Shi C, Lin H, Ramakrishnan V, Ou Y, Olszewski S, Olsen LR, Keskin DB, Hunter ZR, Tankersley C, Zimmerman T, Dhakal B. A randomized, placebo-controlled trial of the BTK inhibitor zanubrutinib in hospitalized patients with COVID-19 respiratory distress: immune biomarker and clinical findings. Front Immunol 2025; 15:1369619. [PMID: 39906744 PMCID: PMC11791645 DOI: 10.3389/fimmu.2024.1369619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 11/04/2024] [Indexed: 02/06/2025] Open
Abstract
Background Cytokine release triggered by a hyperactive immune response is thought to contribute to severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2)-related respiratory failure. Bruton tyrosine kinase (BTK) is involved in innate immunity, and BTK inhibitors block cytokine release. We assessed the next-generation BTK inhibitor zanubrutinib in SARS-CoV-2-infected patients with respiratory distress. Method Cohort 1 had a prospective, randomized, double-blind, placebo-controlled design; cohort 2 had a single-arm design. Adults with SARS-CoV-2 requiring hospitalization (without mechanical ventilation) were randomized in cohort 1. Those on mechanical ventilation ≤24 hours were enrolled in cohort 2. Patients were randomized 1:1 to zanubrutinib 320 mg once daily or placebo (cohort 1), or received zanubrutinib 320 mg once daily (cohort 2). Co-primary endpoints were respiratory failure-free survival rate and time to return to breathing room air at 28 days. Corollary studies to assess zanubrutinib's impact on immune response were performed. Results Sixty-three patients in cohort 1 received zanubrutinib (n=30) or placebo (n=33), with median treatment duration of 8.5 and 7.0 days, respectively. The median treatment duration in cohort 2 (n=4) was 13 days; all discontinued treatment early. In cohort 1, respiratory failure-free survival and the estimated rates of not returning to breathing room air by day 28 were not significantly different between treatments. Importantly, serological response to coronavirus disease 2019 (COVID-19) was not impacted by zanubrutinib. Lower levels of granulocyte colony-stimulating factor, interleukin (IL)-10, monocyte chemoattractant protein-1, IL-4, and IL-13 were observed in zanubrutinib-treated patients. Moreover, single-cell transcriptome analysis showed significant downregulation of inflammatory mediators (IL-6, IL-8, macrophage colony-stimulating factor, macrophage inflammatory protein-1α, IL-1β) and signaling pathways (JAK1, STAT3, TYK2), and activation of gamma-delta T cells in zanubrutinib-treated patients. Conclusions Marked reduction in inflammatory signaling with preserved SARS-CoV-2 serological response was observed in hospitalized patients with COVID-19 respiratory distress receiving zanubrutinib. Despite these immunological findings, zanubrutinib did not show improvement over placebo in clinical recovery from respiratory distress. Concurrent administration of steroids and antiviral therapy to most patients may have contributed to these results. Investigation of zanubrutinib may be warranted in other settings where cytokine release and immune cell exhaustion are important. Clinical Trial Registration https://www.clinicaltrials.gov/study/NCT04382586, identifier NCT04382586.
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Affiliation(s)
| | | | - David J. Park
- Providence St. Jude Medical Center/Providence Medical Foundation, Fullerton, CA, United States
| | - Giorgia Moranzoni
- Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Camilla K. Lemvigh
- Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
| | | | | | | | | | - Nina M. Clark
- Loyola University Stritch School of Medicine, Chicago, IL, United States
| | | | | | - Gulrayz Ahmed
- Medical College of Wisconsin, Milwaukee, WI, United States
| | | | | | | | | | | | | | - Shuqiang Li
- Dana-Farber Cancer Institute, Boston, MA, United States
| | | | | | | | - Pil Kim
- BeiGene USA, Inc., San Mateo, CA, United States
| | - Carrie Shi
- BeiGene USA, Inc., San Mateo, CA, United States
| | - Holly Lin
- BeiGene USA, Inc., San Mateo, CA, United States
| | | | - Ying Ou
- BeiGene USA, Inc., San Mateo, CA, United States
| | | | - Lars Rønn Olsen
- Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Derin B. Keskin
- Dana-Farber Cancer Institute, Boston, MA, United States
- Harvard Medical School, Boston, MA, United States
| | | | | | | | - Binod Dhakal
- Medical College of Wisconsin, Wauwatosa, WI, United States
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10
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Saha A, Choudhary S, Walia P, Kumar P, Tomar S. Transformative approaches in SARS-CoV-2 management: Vaccines, therapeutics and future direction. Virology 2025; 604:110394. [PMID: 39889481 DOI: 10.1016/j.virol.2025.110394] [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: 10/15/2024] [Revised: 12/24/2024] [Accepted: 12/28/2024] [Indexed: 02/03/2025]
Abstract
The global healthcare and economic challenges caused by the pandemic of COVID-19 reinforced the urgent demand for quick and effective therapeutic and preventative interventions. While vaccines served as the frontline of defense, antivirals emerged as adjunctive countermeasures, especially for people who developed infection, were immunocompromised, or were reluctant to be vaccinated. Beyond the serious complications of SARS-CoV-2 infection, the threats of long-COVID and the potential for zoonotic spillover continue to be significant health concerns that cannot be overlooked. Moreover, the incessant viral evolution, clinical safety issues, waning immune responses, and the emergence of drug-resistant variants pinpoint towards more severe viral threats in the future and call for broad-spectrum innovative therapies as a pre-pandemic preparedness measure. The present review provides a comprehensive up-to-date overview of the strategies utilized in the development of classical and next-generation vaccines against SARS-CoV-2, the clinical and experimental data obtained from clinical trials, while addressing safety risks that may arise. Besides vaccines, the review also covers recent breakthroughs in anti-SARS-CoV-2 drug discovery, emphasizing druggable viral and host targets, virus- and host-targeting antivirals, and highlighting mechanistically representative molecules that are either approved or are under clinical investigation. In conclusion, the integration of both vaccines and antiviral therapies, along with swift innovative strategies to address viral evolution and drug resistance is crucial to strengthen our preparedness against future viral outbreaks.
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Affiliation(s)
- Ankita Saha
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Uttarakhand, 247667, India
| | - Shweta Choudhary
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Uttarakhand, 247667, India
| | - Priyanshu Walia
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Uttarakhand, 247667, India
| | - Pravindra Kumar
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Uttarakhand, 247667, India
| | - Shailly Tomar
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Uttarakhand, 247667, India.
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11
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Gasmi A, Kassym L, Menzel A, Anzar W, Dadar M, Semenova Y, Arshad M, Bihunyak T, Meguid NA, Peana M, Bekbergenova Z, Bjørklund G. Genetic and Epigenetic Determinants of COVID-19 Susceptibility: A Systematic Review. Curr Med Chem 2025; 32:753-770. [PMID: 38251695 DOI: 10.2174/0109298673267890231221100659] [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: 06/18/2023] [Revised: 08/04/2023] [Accepted: 11/14/2023] [Indexed: 01/23/2024]
Abstract
BACKGROUND The molecular mechanisms regulating coronavirus pathogenesis are complex, including virus-host interactions associated with replication and innate immune control. However, some genetic and epigenetic conditions associated with comorbidities increase the risk of hospitalization and can prove fatal in infected patients. This systematic review will provide insight into host genetic and epigenetic factors that interfere with COVID-19 expression in light of available evidence. METHODS This study conducted a systematic review to examine the genetic and epigenetic susceptibility to COVID-19 using a comprehensive approach. Through systematic searches and applying relevant keywords across prominent online databases, including Scopus, PubMed, Web of Science, and Science Direct, we compiled all pertinent papers and reports published in English between December 2019 and June 2023. RESULTS The findings reveal that the host's HLA genotype plays a substantial role in determining how viral protein antigens are showcased and the subsequent immune system reaction to these antigens. Within females, genes responsible for immune system regulation are found on the X chromosome, resulting in reduced viral load and inflammation levels when contrasted with males. Possessing blood group A may contribute to an increased susceptibility to contracting COVID-19 as well as a heightened risk of mortality associated with the disease. The capacity of SARS-CoV-2 involves inhibiting the antiviral interferon (IFN) reactions, resulting in uncontrolled viral multiplication. CONCLUSION There is a notable absence of research into the gender-related predisposition to infection, necessitating a thorough examination. According to the available literature, a significant portion of individuals affected by the ailment or displaying severe ramifications already had suppressed immune systems, categorizing them as a group with elevated risk.
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Affiliation(s)
- Amin Gasmi
- Department of Research, Société Francophone de Nutrithérapie et de Nutrigénétique Appliquée, Villeurbanne, France
| | - Laura Kassym
- Department of Research, Astana Medical University, Astana, Kazakhstan
| | - Alain Menzel
- Department of Research, Laboratoires Réunis, Junglinster, Luxembourg
| | - Wajiha Anzar
- Department of Research, Dow University of Health Sciences, Karachi, Pakistan
| | - Maryam Dadar
- Department of Research, CONEM Iran Microbiology Research Group, Tehran, Iran
| | - Yuliya Semenova
- Department of Research, Nazarbayev University School of Medicine, Astana, Kazakhstan
| | - Mehreen Arshad
- Department of Research, National University of Sciences and Technology, Islamabad, Pakistan
| | - Tetyana Bihunyak
- Department of Research, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
| | - Nagwa Abdel Meguid
- Research on Children with Special Needs Department, National Research Centre, Giza, Egypt
- CONEM Egypt Child Brain Research Group, National Research Center, Giza, Egypt
| | - Massimiliano Peana
- Department of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, Sassari, Italy
| | | | - Geir Bjørklund
- Department of Research, Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway
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12
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Jandric M, Zlojutro B, Momcicevic D, Dragic S, Kovacevic T, Djajic V, Stojiljkovic MP, Loncar-Stojiljkovic D, Skrbic R, Djuric DM, Kovacevic P. Do dynamic changes in haematological and biochemical parameters predict mortality in critically ill COVID-19 patients? Technol Health Care 2025; 33:275-286. [PMID: 39302399 DOI: 10.3233/thc-241006] [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: 09/22/2024]
Abstract
BACKGROUND Critically ill COVID-19 patients are usually subjected to clinical, laboratory, and radiological diagnostic procedures resulting in numerous findings. Utilizing these findings as indicators for disease progression or outcome prediction is particularly intriguing. OBJECTIVES Exploring the significance of dynamic changes in haematological and biochemical parameters in predicting the mortality of critically ill COVID-19 patients. METHODS The present study was a prospective and observational study involving mechanically ventilated 75 critically ill adult COVID-19 patients with hypoxemic respiratory failure. The collected data included baseline patient characteristics, treatment options, outcome, and laboratory findings at admission and 7 days after. The dynamics of the obtained findings were compared between survivors and non-survivors. RESULTS The 28-day survival rate was 61.3%. In the group of non-survivors significant dynamic changes were found for C-reactive protein (p= 0.001), interleukin-6 (p< 0.001), lymphocyte (p= 0.003), neutrophil-lymphocyte ratio (p= 0.003), platelets (p< 0.001), haemoglobin (p< 0.001), iron (p= 0.012), and total iron-binding capacity (p< 0.001). Statistically significant changes over time were found for ferritin (p= 0.010), D-dimer (p< 0.001), hs-troponin T (p< 0.002), lactate dehydrogenase (p= 0.001), glucose (p= 0.023), unsaturated iron-binding capacity (p= 0.008), and vitamin D (p< 0.001). CONCLUSION The dynamic changes in inflammatory, haematological and biochemical parameters can predict disease severity, and outcome.
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Affiliation(s)
- Milka Jandric
- University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
| | - Biljana Zlojutro
- University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
- Faculty of Medicine, University of Banja Luka, Banja Luka, The Republic of Srpska, Bosnia and Herzegovina
| | - Danica Momcicevic
- University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
- Faculty of Medicine, University of Banja Luka, Banja Luka, The Republic of Srpska, Bosnia and Herzegovina
| | - Sasa Dragic
- University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
- Faculty of Medicine, University of Banja Luka, Banja Luka, The Republic of Srpska, Bosnia and Herzegovina
| | - Tijana Kovacevic
- University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
- Faculty of Medicine, University of Banja Luka, Banja Luka, The Republic of Srpska, Bosnia and Herzegovina
| | - Vlado Djajic
- University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
- Faculty of Medicine, University of Banja Luka, Banja Luka, The Republic of Srpska, Bosnia and Herzegovina
| | - Milos P Stojiljkovic
- Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, Banja Luka, The Republic of Srpska, Bosnia and Herzegovina
| | | | - Ranko Skrbic
- Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, Banja Luka, The Republic of Srpska, Bosnia and Herzegovina
| | - Dragan M Djuric
- Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Pedja Kovacevic
- University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
- Faculty of Medicine, University of Banja Luka, Banja Luka, The Republic of Srpska, Bosnia and Herzegovina
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13
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Alshahrani MS, Aldahhan R, Macadato NC, Alkhalifah Z, Tahan MRE, Alnimr A, Alnabi MA, Almishkab F, Almusairii J, Asonto LP, Almusawi SM, Almussalam M, Alsanea R, Albakheet MK, Albrahim TA, Alammar MS, Albehair M, Alkhater SA, Alsulaibikh A, Aljumaan M, AlQahtani SM, Abdelhady A, Mapusao C, Attia A, Alzamil IA. Binding Antibodies Responses to SARS-COV-2 Infection in Hospitalized Patients and Vaccinated Subjects: A Longitudinal Prospective Observational Study. SAUDI JOURNAL OF MEDICINE & MEDICAL SCIENCES 2025; 13:39-46. [PMID: 39936001 PMCID: PMC11809754 DOI: 10.4103/sjmms.sjmms_282_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 09/24/2024] [Accepted: 10/06/2024] [Indexed: 02/13/2025]
Abstract
Background Prevalence of seropositivity following SARS-CoV-2 infection is vital in evaluating herd immunity. However, depending on illness severity, it remains unclear whether the breadth and magnitude of immune response to SARS-CoV-2 infection is for short or long term. Objective To test the persistence of humoral antibody responses after SARS-CoV-2 exposure in patients with different illness severity and among volunteers who had been vaccinated. Methods This study was conducted in two Saudi Arabian tertiary hospitals. Participants were categorized as critically ill COVID-19 patients, non-critically ill COVID-19 patients, or vaccinated volunteers. We collected demographic data, COVID-19 exposure history, symptoms, vaccination details, and serum samples to analyze antibody persistence. We evaluated SARS-CoV-2 antibody concentrations in COVID-19 patients with varying disease severity and age groups, as well as in BNT162b2-vaccinated individuals, focusing on IgG levels against the S.FL and S1 domains of the spike protein. Results The study included 172 adults: 92 unvaccinated hospitalized COVID-19 patients and 80 vaccinated volunteers. All vaccinated subjects demonstrated seropositivity to the SARS-CoV-2 spike protein, with nearly 80% having a median antibody titer of 13,500 AU/mL. Notably, vaccinated subjects exhibited significantly higher IgG levels than naturally infected patients (P < 0.001), including higher S.FL and S1 titers, regardless of severity. Age, comorbidities, and previous infections influenced S-specific antibody levels. Among hospitalized patients, 58% required intensive care, with 28- and 90-day mortality rates of 23% and 43%, respectively. Conclusion These findings shed light on the immune response dynamics following SARS-CoV-2 infection compared to vaccinated individuals, where the latter showed significantly higher level of antibodies response, providing crucial insights for evaluating short-term herd immunity and the effectiveness of natural infection-induced immunity.
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Affiliation(s)
- Mohammed Saeed Alshahrani
- Department of Critical Care, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
- Department of Emergency, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Razan Aldahhan
- Nucleic Acid Vaccine Laboratory (NAVL), Department of Epidemic Diseases Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Nabela Calamata Macadato
- Nucleic Acid Vaccine Laboratory (NAVL), Department of Epidemic Diseases Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Zahra Alkhalifah
- Department of Critical Care, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
- Department of Emergency, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Mohamed R. El Tahan
- Department of Anesthesiology, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Amani Alnimr
- Department of Microbiology, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | | | - Fatima Almishkab
- Department of Critical Care, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Jawaher Almusairii
- Department of Critical Care, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Laila Perlas Asonto
- Department of Critical Care, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
- Department of Emergency, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | | | | | - Rawan Alsanea
- Department of Critical Care, Dammam Medical Complex, Dammam, Saudi Arabia
| | | | - Talal Ali Albrahim
- Department of Critical Care, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Moaz Saad Alammar
- Department of Critical Care, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Maan Albehair
- Department of Pediatrics, National Guard Hospital, Dammam, Saudi Arabia
| | - Suzan A. Alkhater
- Department of Pediatrics, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Amal Alsulaibikh
- Department of Emergency, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Mohammed Aljumaan
- Department of Emergency, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Saad M. AlQahtani
- Department of Orthopedic, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Ahmed Abdelhady
- Department of Critical Care, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
- Department of Critical Care, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Charlene Mapusao
- Department of Critical Care, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Ashraf Attia
- Department of Critical Care, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Iman Almansour Alzamil
- Nucleic Acid Vaccine Laboratory (NAVL), Department of Epidemic Diseases Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
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14
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Basilim A, Eljaaly K, Aljuhani O, Korayem GB, Altebainawi AF, Aldhmadi WJ, Alissa A, AlFaifi M, Alharthi AF, Vishwakarma R, Alqahtani R, Alahmari GD, Ibn Khamis AM, Alenazi AA, Alharbi A, Alfaraj L, Alshammari YF, Abdulqader MI, Alharbi MB, Alanazi BM, Alhamazani AE, Al Sulaiman K. Evaluation of Effectiveness and Safety of Dexmedetomidine in non-Mechanically Ventilated COVID-19 Critically ill Patients: A Multicentre Cohort Study. J Intensive Care Med 2025; 40:74-84. [PMID: 39552466 DOI: 10.1177/08850666241268498] [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: 11/19/2024]
Abstract
Background: Dexmedetomidine (DEX) is a highly favored sedative agent in critically ill patients owing to its anxiolytic and analgesic properties, lower risk of delirium, and minimal respiratory depression. Additionally, DEX exhibits anti-inflammatory properties, which have prompted its use in managing COVID-19 patients to mitigate cytokine storm and multi-organ dysfunction. Thus, this study aims to evaluate the safety and effectiveness of DEX use in critically ill patients with COVID-19. Method: This multicenter, retrospective cohort study included adult patients with confirmed COVID-19 who were admitted to the ICUs and did not require invasive mechanical ventilation (MV). Patients were categorized into two groups based on receiving DEX use within 72 h of ICU admission. The primary outcome was respiratory failure requiring invasive MV; other outcomes were considered secondary. Results: A total of 155 patients were included in the study after propensity matching. DEX did not reduce respiratory failure requiring invasive MV (HR 0.66; 95% CI (0.28, 1.53), P = .33). However, the time for invasive MV was statistically significantly shorter in the DEX group compared with the control group (beta coefficient (95%CI): - 1.05 (-2.03, -0.07), P = .03). In contrast, ICU and hospital Length of stay (LOS) were not statistically significant compared to the control group (beta coefficient 0.04 (95% CI -0.29, 0.38), P = .80, and beta coefficient - 0.03 (95% CI -0.33, 0.26), P = .81, respectively). In addition, the 30-day and in-hospital mortality rates were similar between the two groups (HR 1.1; 95% CI 0.97, 1.20, P = .14, and HR 1.01; 95% CI 0.95, 1.06, P = .90, respectively). Conclusion: Dexmedetomidine did not appear to lower the risk of respiratory failure necessitating invasive mechanical ventilation in critically ill patients. However, the mean time for invasive mechanical ventilation was shorter in the DEX group. Future interventional studies are required to confirm our findings.
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Affiliation(s)
- Ahmed Basilim
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Khalid Eljaaly
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ohoud Aljuhani
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ghazwa B Korayem
- Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Ali F Altebainawi
- Department of Clinical Pharmacy, College of Pharmacy, University of Hail, Hail, Saudi Arabia
- Pharmaceutical Care Services, King Salman Specialist Hospital, Hail Health Cluster, Ministry of Health, Hail, Saudi Arabia
| | - Wadha J Aldhmadi
- Department of Clinical Pharmacy, College of Pharmacy, University of Hail, Hail, Saudi Arabia
| | - Abdulrahman Alissa
- Pharmaceutical Care Services, King Abdulla bin Abdulaziz University Hospital, Riyadh, Saudi Arabia
| | - Mashael AlFaifi
- Pharmaceutical Services Administration, King Saud Medical City, Riyadh, Saudi Arabia
| | | | - Ramesh Vishwakarma
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom
| | - Reem Alqahtani
- Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Ghaida D Alahmari
- Pharmaceutical Services Administration, King Saud Medical City, Riyadh, Saudi Arabia
- Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Afnan M Ibn Khamis
- College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Abeer A Alenazi
- Pharmaceutical Care Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Aisha Alharbi
- Pharmaceutical Care Department, King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Lulwa Alfaraj
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | | | - Marwah I Abdulqader
- College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Mada B Alharbi
- College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Bayan M Alanazi
- Pharmaceutical Care Services, King Salman Specialist Hospital, Hail Health Cluster, Ministry of Health, Hail, Saudi Arabia
| | - Atheer E Alhamazani
- Pharmaceutical Care Services, King Salman Specialist Hospital, Hail Health Cluster, Ministry of Health, Hail, Saudi Arabia
| | - Khalid Al Sulaiman
- Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Saudi Critical Care Pharmacy Research (SCAPE) Platform, Riyadh, Saudi Arabia
- Saudi Society for Multidisciplinary Research Development and Education (SCAPE Society), Riyadh, Saudi Arabia
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15
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Boncyk C, Rolfsen ML, Richards D, Stollings JL, Mart MF, Hughes CG, Ely EW. Management of pain and sedation in the intensive care unit. BMJ 2024; 387:e079789. [PMID: 39653416 DOI: 10.1136/bmj-2024-079789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2024]
Abstract
Advances in our approach to treating pain and sedation when caring for patients in the intensive care unit (ICU) have been propelled by decades of robust trial data, knowledge gained from patient experiences, and our evolving understanding of how pain and sedation strategies affect patient survival and long term outcomes. These data contribute to current practice guidelines prioritizing analgesia-first sedation strategies (analgosedation) that target light sedation when possible, use of short acting sedatives, and avoidance of benzodiazepines. Together, these strategies allow the patient to be more awake and able to participate in early mobilization and family interactions. The covid-19 pandemic introduced unique challenges in the ICU that affected delivery of best practices and patient outcomes. Compliance with best practices has not returned to pre-covid levels. After emerging from the pandemic and refocusing our attention on optimal pain and sedation management in the ICU, it is imperative to revisit the data that contributed to our current recommendations, review the importance of best practices on patient outcomes, and consider new strategies when advancing patient care.
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Affiliation(s)
- Christina Boncyk
- Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA
- Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA
| | - Mark L Rolfsen
- Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - Joanna L Stollings
- Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA
- Department of Pharmacy Services, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Matthew F Mart
- Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Geriatric Research, Education, and Clinical Center (GRECC), Tennessee Valley Veterans Affairs Healthcare System, Nashville, TN, USA
| | - Christopher G Hughes
- Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA
- Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA
| | - E Wesley Ely
- Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Geriatric Research, Education, and Clinical Center (GRECC), Tennessee Valley Veterans Affairs Healthcare System, Nashville, TN, USA
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16
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Valderrábano RJ, Wipper B, Pencina KM, Migaud M, Shang YV, Latham NK, Montano M, Cunningham JM, Wilson L, Peng L, Memish‐Beleva Y, Bhargava A, Swain PM, Lehman P, Lavu S, Livingston DJ, Bhasin S. Dysregulated nicotinamide adenine dinucleotide metabolome in patients hospitalized with COVID-19. Aging Cell 2024; 23:e14326. [PMID: 39354697 PMCID: PMC11634700 DOI: 10.1111/acel.14326] [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: 03/14/2024] [Revised: 07/08/2024] [Accepted: 08/01/2024] [Indexed: 10/03/2024] Open
Abstract
Nicotinamide adenine dinucleotide (NAD+) depletion has been postulated as a contributor to the severity of COVID-19; however, no study has prospectively characterized NAD+ and its metabolites in relation to disease severity in patients with COVID-19. We measured NAD+ and its metabolites in 56 hospitalized patients with COVID-19 and in two control groups without COVID-19: (1) 31 age- and sex-matched adults with comorbidities, and (2) 30 adults without comorbidities. Blood NAD+ concentrations in COVID-19 group were only slightly lower than in the control groups (p < 0.05); however, plasma 1-methylnicotinamide concentrations were significantly higher in patients with COVID-19 (439.7 ng/mL, 95% CI: 234.0, 645.4 ng/mL) than in age- and sex-matched controls (44.5 ng/mL, 95% CI: 15.6, 73.4) and in healthy controls (18.1 ng/mL, 95% CI 15.4, 20.8; p < 0.001 for each comparison). Plasma nicotinamide concentrations were also higher in COVID-19 group and in controls with comorbidities than in healthy control group. Plasma concentrations of 2-methyl-2-pyridone-5-carboxamide (2-PY), but not NAD+, were significantly associated with increased risk of death (HR = 3.65; 95% CI 1.09, 12.2; p = 0.036) and escalation in level of care (HR = 2.90, 95% CI 1.01, 8.38, p = 0.049). RNAseq and RTqPCR analyses of PBMC mRNA found upregulation of multiple genes involved in NAD+ synthesis as well as degradation, and dysregulation of NAD+-dependent processes including immune response, DNA repair, metabolism, apoptosis/autophagy, redox reactions, and mitochondrial function. Blood NAD+ concentrations are modestly reduced in COVID-19; however, NAD+ turnover is substantially increased with upregulation of genes involved in both NAD+ biosynthesis and degradation, supporting the rationale for NAD+ augmentation to attenuate disease severity.
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Affiliation(s)
- Rodrigo J. Valderrábano
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence CenterBrigham and Women's Hospital, Harvard Medical SchoolBostonMassachusettsUSA
| | - Benjamin Wipper
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence CenterBrigham and Women's Hospital, Harvard Medical SchoolBostonMassachusettsUSA
| | - Karol Mateusz Pencina
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence CenterBrigham and Women's Hospital, Harvard Medical SchoolBostonMassachusettsUSA
| | - Marie Migaud
- Department of Pharmacology, Mitchell Cancer InstituteUniversity of South AlabamaMobileAlabamaUSA
| | - Yili Valentine Shang
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence CenterBrigham and Women's Hospital, Harvard Medical SchoolBostonMassachusettsUSA
| | - Nancy K. Latham
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence CenterBrigham and Women's Hospital, Harvard Medical SchoolBostonMassachusettsUSA
| | - Monty Montano
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence CenterBrigham and Women's Hospital, Harvard Medical SchoolBostonMassachusettsUSA
| | - James M. Cunningham
- Division of Hematology, Brigham and Women's HospitalHarvard Medical SchoolBostonMassachusettsUSA
| | - Lauren Wilson
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence CenterBrigham and Women's Hospital, Harvard Medical SchoolBostonMassachusettsUSA
| | - Liming Peng
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence CenterBrigham and Women's Hospital, Harvard Medical SchoolBostonMassachusettsUSA
| | - Yusnie Memish‐Beleva
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence CenterBrigham and Women's Hospital, Harvard Medical SchoolBostonMassachusettsUSA
| | - Avantika Bhargava
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence CenterBrigham and Women's Hospital, Harvard Medical SchoolBostonMassachusettsUSA
| | | | - Phoebe Lehman
- Metro International BiotechWorcesterMassachusettsUSA
| | - Siva Lavu
- Metro International BiotechWorcesterMassachusettsUSA
| | | | - Shalender Bhasin
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence CenterBrigham and Women's Hospital, Harvard Medical SchoolBostonMassachusettsUSA
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17
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Vishnoi R, Gaba M, Kumar N, Pandey A, Dewan A. The Relationship Between Predisposing Risk Factors and COVID-19: An Observational Study. Cureus 2024; 16:e75042. [PMID: 39749096 PMCID: PMC11694842 DOI: 10.7759/cureus.75042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/03/2024] [Indexed: 01/04/2025] Open
Abstract
Background Numerous risk factors have been identified for developing severe COVID-19, including sociodemographic variables and concomitant diseases. Individuals with underlying comorbidities such as diabetes, hypertension, asthma, and coronary artery disease are at a greater risk of severe illness and death. This study aimed to observe the association between risk factors and the severity of COVID-19. Methodology A single-center, hospital-based, prospective, observational study was conducted at Max Smart Super Speciality Hospital in Saket, Delhi from October 2020 to December 2021. A total of 1,454 patients admitted under our care in the Department of Internal Medicine were included in this study. Patients were divided into the following three groups: patients without comorbidities, patients with a single comorbidity, and patients with multiple comorbidities. The risk factors under evaluation were age >50 years, obesity, diabetes, hypertension, chronic kidney disease (CKD), heart disease, chronic liver disease (CLD), and immunocompromised status (human immunodeficiency virus, post-transplant, malignancy undergoing chemotherapy). Results In this study, 28.1% (n = 408) of patients did not have comorbidities, 30.1% (n = 438) of patients had a single comorbidity, and 41.8% (n = 608) of patients had multiple comorbidities. Regarding risk factors, 62% (n = 872) of patients were aged >50 years, 7.4% (n = 108) were obese, 30.7% (n = 447) had diabetes, 33% (n = 480) were hypertensive, 1.2% (n = 18) had CKD, 6.8% (n = 99) had heart disease, 0.3% (n = 4) had CLD, and 5.5% (n = 80) were immunocompromised. A statistically significant association was found between increasing age and worsening severity of COVID-19 (p = 0.0001), male gender (p = 0.0001), presence of comorbidities, including diabetes, hypertension, obesity, CKD, CLD, heart disease (p = 0.0001). Patients in the immunocompromised group did not have a statistically significant association with disease severity. A statistically significant association was found between mortality and severity of COVID-19. Overall, 16.7% (n = 48) of the patients in the no comorbidity group, 35.4% (n = 102) in the single comorbidity group, and 47.9% (n = 138) in the multiple comorbidity group (p = 0.0001) presented with severe disease on admission. Conclusions The study shows that the severity of the disease increased as the number of risk factors increased. This information can help us take early and active measures in these groups of patients with multiple comorbid illnesses.
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Affiliation(s)
- Ramnivas Vishnoi
- Internal Medicine, Max Smart Super Speciality Hospital, New Delhi, IND
| | - Manish Gaba
- Internal Medicine, Max Smart Super Speciality Hospital, New Delhi, IND
| | - Naveen Kumar
- Internal Medicine, Max Smart Super Speciality Hospital, New Delhi, IND
| | - Ankita Pandey
- Internal Medicine, Max Smart Super Speciality Hospital, New Delhi, IND
| | - Arun Dewan
- Internal Medicine, Max Smart Super Speciality Hospital, New Delhi, IND
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18
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Sadana D, Granton D, Adhikari NKJ, Pinto R, Murthy S, Fowler RA. Trends in characteristics, interventions, and outcomes of hospitalized patients with COVID-19 in Canada: a multicentre prospective cohort study. Can J Anaesth 2024; 71:1745-1754. [PMID: 39231882 PMCID: PMC11666781 DOI: 10.1007/s12630-024-02826-x] [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: 09/08/2023] [Revised: 03/08/2024] [Accepted: 04/18/2024] [Indexed: 09/06/2024] Open
Abstract
PURPOSE Our objective was to investigate the temporal trends in baseline characteristics, interventions, and clinical outcomes in patients hospitalized with COVID-19 in Canada over five pandemic waves. METHODS We conducted a multicentre prospective cohort study enrolling adults and children admitted with COVID-19 from 47 Canadian hospitals. We compared characteristics, interventions, and outcomes of patients across five distinct pandemic waves. RESULTS We enrolled 5,285 patients between 2 January 2020 and 8 February 2022. The mean (standard deviation) age was 62.6 (21.0) yr; 41.2% (n = 2,176) were female, and 48% (n = 2,539) required admission to an intensive care unit (ICU), of whom 60.3% (n = 1,530) underwent invasive mechanical ventilation. The proportion of vaccinated patients increased over time. The proportion of vaccinated hospitalized patients progressing to require ICU admission fell over pandemic waves while the proportion of unvaccinated hospitalized patients progressing to require ICU admission did not. Patients were most commonly treated with corticosteroids (48.7%; n = 2,575); use of corticosteroids and other evidence-based treatments increased over time. Hospital mortality was 22.1% (n = 1,166) among all patients, 30.2% (n = 766) among those admitted to an ICU, and 37.9% (n = 580) among those requiring invasive mechanical ventilation. Younger age, absence of chronic cardiac or pulmonary disease, severity of illness at admission, and prior vaccination was associated with a lower mortality; however, pandemic wave itself was not. CONCLUSION Among patients hospitalized in Canada with COVID-19, several clinical factors including prior vaccination were associated with lower mortality, but pandemic wave was not.
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Affiliation(s)
- Divyajot Sadana
- Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
- Department of Critical Care Medicine, Respiratory Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
| | - David Granton
- Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Neill K J Adhikari
- Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
- Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Ruxandra Pinto
- Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Srinivas Murthy
- Division of Critical Care, Department of Pediatrics, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada
| | - Robert A Fowler
- Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
- Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
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19
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Kutej M, Sagan J, Ekrtova T, Strakova H, Buzga M, Burda M, Maca J. Role of Alveolar-Arterial Difference in Estimation of Extravascular Lung Water in COVID-19-Related ARDS. Respir Care 2024; 69:1548-1554. [PMID: 39043425 PMCID: PMC11572996 DOI: 10.4187/respcare.11804] [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: 07/25/2024]
Abstract
BACKGROUND The dominant feature of COVID-19-associated ARDS is gas exchange impairment. Extravascular lung water index is a surrogate for lung edema and reflects the level of alveolocapillary disruption. The primary aim was the prediction of extravascular lung water index by the alveolar-arterial oxygen difference. The secondary aims were in determining the relationship between the extravascular lung water index and other oxygenation parameters, the [Formula: see text], end-tidal oxygen concentration, pulmonary oxygen gradient ([Formula: see text] minus end-tidal oxygen concentration), and [Formula: see text]. METHODS This observational prospective single-center study was performed at the Department of Anaesthesiology and Intensive Care, The University Hospital in Ostrava, The Czech Republic, during the COVID-19 pandemic, from March 20, 2020, until May 24, 2021. RESULTS The relationship between the extravascular lung water index and alveolar-arterial oxygen difference showed only a mild-to-moderate correlation (r = 0.33, P < .001). Other extravascular lung water index correlations were as follows: [Formula: see text] (r = 0.33, P < .001), end-tidal oxygen concentration (r = 0.26, P = .0032), [Formula: see text] minus end-tidal oxygen concentration (r = 0.15, P = .0624), and [Formula: see text] (r = -0.15, P = .01). CONCLUSIONS The alveolar-arterial oxygen difference does not reliably correlate with the extravascular lung water index and the degree of lung edema in COVID-19-associated ARDS.
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Affiliation(s)
- Martin Kutej
- Department of Anaesthesiology and Intensive Care Medicine, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
- Department of Pediatric Anaesthesiology and Intensive Care Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Jiri Sagan
- Department of Infectious Diseases, University Hospital Ostrava, Ostrava, Czech Republic
- Department of Surgical Studies, University Hospital Ostrava, Ostrava, Czech Republic
| | - Tereza Ekrtova
- Department of Anaesthesiology and Intensive Care Medicine, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Hana Strakova
- Department of Anaesthesiology and Intensive Care Medicine, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Marek Buzga
- Institute of Physiology and Pathophysiology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Michal Burda
- Institute for Research and Applications of Fuzzy Modeling, Centre of Excellence IT4Innovations, University of Ostrava, Ostrava, Czech Republic
| | - Jan Maca
- Department of Anaesthesiology and Intensive Care Medicine, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
- Institute of Physiology and Pathophysiology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
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20
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Brito ALA, Ferreira ACA, Costa LSP, Silva Júnior EFF, Campos SL. Effect of Continuous Lateral Rotation Therapy on Clinical Outcomes in Mechanically Ventilated Critically Ill Adults. Respir Care 2024; 69:1592-1606. [PMID: 38744476 PMCID: PMC11572998 DOI: 10.4187/respcare.11781] [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: 12/07/2023] [Accepted: 05/10/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND This Population, Intervention, Comparison, and Outcomes-guided systematic review assesses continuous lateral rotation therapy versus conventional position changes in mechanically ventilated critically ill adults, evaluating mortality, ICU length of stay (LOS), and hospital LOS as primary outcomes and respiratory function, mechanical ventilation duration, pulmonary complications, and adverse events as secondary outcomes. METHODS This systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria (International Prospective Register of Systematic Reviews CRD42022384258). Searches spanned databases MEDLINE/PubMed, Embase, Scopus, ScienceDirect, Cochrane, CINAHL, and Web of Science, without language or publication year restrictions. Inclusion criteria involved randomized controlled trials (RCTs) and quasi-randomized trials, comparing continuous lateral rotation therapy (intervention) with conventional position changes (control). Risk of bias and quality of evidence for RCTs were assessed using the Cochrane Collaboration and Grading of Recommendations Assessment, Development, and Evaluation tools. For the quasi-randomized trials, the Risk of Bias in Non-Randomized Studies-of Interventions tool was used. RESULTS In 18 studies with 1,466 participants (intervention, n = 700, 47.7%; control, n = 766, 52.2%), continuous lateral rotation therapy was predominantly used for prophylactic purposes, with protocols varying from 10-24 h/d. Meta-analysis (16 RCTs) favored continuous lateral rotation therapy for reduced mechanical ventilation duration (standardized mean difference [SMD] -0.17 [CI -0.29 to -0.04] d, P = .008) and lower nosocomial pneumonia incidence (odds ratio 0.39 [CI 0.29-0.52], P < .001). Continuous lateral rotation therapy showed no significant impact on mortality (odds ratio 1.04 [CI 0.80-1.34], P = .77), ICU LOS (SMD -0.11 [CI -0.25 to 0.02] d, P = .11), hospital LOS (SMD -0.10 [CI -0.31 to 0.11] d, P = .33), and incidence of pressure ulcers (odds ratio 0.73 [CI 0.34-1.60], P = .44). CONCLUSIONS Continuous lateral rotation therapy showed no significant difference in primary outcomes (mortality, ICU and hospital LOS) but revealed significant differences in secondary outcomes (consistently reduced nosocomial pneumonia, with a minor effect on mechanical ventilation duration), supported by moderate certainty. Very low certainty for other outcomes highlights the need for current studies in diverse clinical settings and protocols to assess continuous lateral rotation therapy effectiveness.
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Affiliation(s)
- Anna Luísa A Brito
- Rehabilitation Sciences Program at the Federal University of Pernambuco, Recife, Pernambuco, Brazil
| | | | - Layane Santana P Costa
- Rehabilitation Sciences Program at the Federal University of Pernambuco, Recife, Pernambuco, Brazil
| | | | - Shirley Lima Campos
- Rehabilitation Sciences Program and the Health-Applied Biology Graduate Program at the Federal University of Pernambuco, Recife, Pernambuco, Brazil.
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21
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Ai N, Zhang Y, Yang J, Zhang Y, Zhao X, Feng H. Genetically predicted blood metabolites mediate the association between circulating immune cells and severe COVID-19: A Mendelian randomization study. Medicine (Baltimore) 2024; 103:e40509. [PMID: 39560514 PMCID: PMC11575977 DOI: 10.1097/md.0000000000040509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 10/24/2024] [Indexed: 11/20/2024] Open
Abstract
Investigating the causal relationship between circulating immune cells, blood metabolites, and severe COVID-19 and revealing the role of blood metabolite-mediated circulating immune cells in disease onset and progression. Genetic variation data of 731 circulating immune cells, 1400 blood metabolites, and severe COVID-19 from genome-wide association study open-access database (https://gwas.mrcieu.ac.uk) were used as instrumental variables for bidirectional and two-step Mendelian randomization analysis. The study identified 11 circulating immune cells with unidirectional causality to severe COVID-19. Two-step Mendelian randomization analysis showed 10 blood metabolites were causally associated with severe COVID-19, and blood Myristate and Citrulline to phosphate ratio mediated the association of circulating effector memory double negative % DN and CD8dim natural killer T cell % T cells, respectively, with severe COVID-19 (Myristate mediated effect ratio was 10.20%, P = .011; Citrulline to phosphate ratio mediated effect ratio was -9.21%, P = .017). This study provides genetic evidence assessing the causal relationship between circulating immune cells, blood metabolites, and severe COVID-19, elucidates the role of blood metabolite-mediated circulating immune cells in severe COVID-19 development, and offers new insights into severe COVID-19 etiology and related preventive and targeted therapeutic strategies.
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Affiliation(s)
- Ning Ai
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yan Zhang
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jing Yang
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yu Zhang
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Xuejing Zhao
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Huifen Feng
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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22
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Wick KD, Ware LB, Matthay MA. Acute respiratory distress syndrome. BMJ 2024; 387:e076612. [PMID: 39467606 DOI: 10.1136/bmj-2023-076612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/30/2024]
Abstract
The understanding of acute respiratory distress syndrome (ARDS) has evolved greatly since it was first described in a 1967 case series, with several subsequent updates to the definition of the syndrome. Basic science advances and clinical trials have provided insight into the mechanisms of lung injury in ARDS and led to reduced mortality through comprehensive critical care interventions. This review summarizes the current understanding of the epidemiology, pathophysiology, and management of ARDS. Key highlights include a recommended new global definition of ARDS and updated guidelines for managing ARDS on a backbone of established interventions such as low tidal volume ventilation, prone positioning, and a conservative fluid strategy. Future priorities for investigation of ARDS are also highlighted.
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Affiliation(s)
- Katherine D Wick
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Lorraine B Ware
- Departments of Medicine and Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Michael A Matthay
- Departments of Medicine and Anesthesia, University of California San Francisco, San Francisco, CA, USA
- Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA
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23
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Atceken Z, Celik Y, Atasoy C, Peker Y. Association of High-Risk Obstructive Sleep Apnea with Artificial Intelligence-Guided, CT-Based Severity Scores in Patients with COVID-19 Pneumonia. J Clin Med 2024; 13:6415. [PMID: 39518554 PMCID: PMC11547013 DOI: 10.3390/jcm13216415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 10/03/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024] Open
Abstract
Background: We have previously demonstrated that high-risk obstructive sleep apnea (HR-OSA), based on a modified Berlin Questionnaire (mBQ), is linked to worse clinical outcomes. Chest computed tomography (CT) imaging with the implementation of an artificial intelligence (AI) analysis program has been a valuable tool for the speedy assessment of huge numbers of patients during the COVID-19 epidemic. In the current study, we addressed how the severity of AI-guided, CT-based total opacity ratio (TOR) scores are associated with high-risk OSA and short-term outcomes in the same cohort. Methods: The ratio of the volume of high opacity areas to that of the total lung volume constituted the TOR. We arbitrarily applied thresholds of <5 (no or mild TOR), ≥5 and <15 (moderate TOR), and ≥15 (severe TOR). Results: In total, 221 patients were included. HR-OSA was observed among 11.0% of the no or mild TOR group, 22.2% of the moderate TOR group, and 38.7% of the severe TOR group (p < 0.001). In a logistic regression analysis, HR-OSA was associated with a severe TOR with an adjusted odds ratio of 3.06 (95% confidence interval [CI] 1.27-7.44; p = 0.01). A moderate TOR predicted clinical worsening with an adjusted hazard ratio (HR) of 1.93 (95% CI 1.00-3.72; p = 0.05) and a severe TOR predicted worsening with an HR of 3.06 (95% CI 1.56-5.99; p = 0.001). Conclusions: Our results offer additional radiological proof of the relationship between HR-OSA and worse outcomes in patients with COVID-19 pneumonia. A TOR may also potentially indicate the individuals that are at higher risk of HR-OSA, enabling early intervention and management strategies. The clinical significance of TOR thresholds needs further evaluation in larger samples.
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Affiliation(s)
- Zeynep Atceken
- Department of Radiology, Koc University School of Medicine, Istanbul 34010, Türkiye; (Z.A.); (C.A.)
| | - Yeliz Celik
- Department of Pulmonary Medicine, Koc University School of Medicine, and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul 34010, Türkiye;
| | - Cetin Atasoy
- Department of Radiology, Koc University School of Medicine, Istanbul 34010, Türkiye; (Z.A.); (C.A.)
| | - Yüksel Peker
- Department of Pulmonary Medicine, Koc University School of Medicine, and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul 34010, Türkiye;
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
- Department of Clinical Sciences, Respiratory Medicine and Allergology, Faculty of Medicine, Lund University, 22185 Lund, Sweden
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
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24
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Miyagishima S, Akatsuka M, Tatsumi H, Takahashi K, Bunya N, Sawamoto K, Narimatsu E, Masuda Y. Neuromuscular Electrical Stimulation Under Deep Sedation Reduces the Incidence of ICU-Acquired Weakness in Critically Ill Patients With COVID-19 With Acute Respiratory Distress Syndrome. Cureus 2024; 16:e71029. [PMID: 39507129 PMCID: PMC11540548 DOI: 10.7759/cureus.71029] [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: 10/07/2024] [Indexed: 11/08/2024] Open
Abstract
BACKGROUND The COVID-19 pandemic has led to an unprecedented increase in cases of acute respiratory distress syndrome (ARDS). In such cases, deep sedation using sedatives and muscle relaxants is commonly used to prevent patient self-inflicted lung injury during the early phase. However, such sedation limits the ability to perform early rehabilitation, leading to ICU-acquired muscle weakness (ICU-AW) and a worse prognosis. SUBJECTS This study aimed to clarify the preventive effect of neuromuscular electrical stimulation (NMES) during deep sedation on ICU-AW and physical function at discharge in critically ill patients with COVID-19 with ARDS. METHODS A retrospective, single-center study was conducted on patients admitted to the ICU or advanced critical care center with severe COVID-19 with ARDS between March 1, 2020, and March 31, 2022. Patients who were managed with the Richmond Agitation-Sedation Scale between -4 and -5 for at least three days were included. Patients in the NMES group received NMES within two days of deep sedation, whereas those in the non-NMES group did not. The primary endpoint was the incidence of ICU-AW at discharge from the ICU, and the secondary endpoints included physical activity levels, skeletal muscle mass index, time to active mobilization, and Barthel index (BI) at discharge. Statistical analyses included Pearson's chi-squared test, Fisher's exact test, and multiple logistic and linear regression analyses. RESULTS Of the 129 patients, 68 (54 males and 14 females) were included after applying the exclusion criteria, with 38 in the NMES group and 30 in the non-NMES group. The incidence of ICU-AW was significantly lower in the NMES group (28.95% vs. 56.67%, p = 0.0211). NMES implementation (OR: 0.20, p = 0.03), ventilator weaning (OR: 0.10, p = 0.01), and duration of deep sedation (OR: 0.81, p < 0.01) were significant predictors of ICU-AW. Higher ICU Mobility Scale scores and shorter time to active mobilization were associated with a higher BI at discharge. CONCLUSIONS Early rehabilitation using NMES during deep sedation may prevent ICU-AW in critically ill patients with COVID-19 with ARDS. NMES is associated with a reduced risk of ICU-AW and improved functional independence at discharge. This procedure can be safely performed in sedated patients and may help prevent ICU-AW, supporting early mobilization strategies in ARDS rehabilitation.
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Affiliation(s)
- Saori Miyagishima
- Department of Rehabilitation, Division of Physical Therapy, Japan Healthcare University Faculty of Health Sciences, Sapporo, JPN
- Division of Rehabilitation, Sapporo Medical University Hospital, Sapporo, JPN
| | - Masayuki Akatsuka
- Department of Intensive Care Medicine, Sapporo Medical University School of Medicine, Sapporo, JPN
| | - Hiroomi Tatsumi
- Department of Intensive Care Medicine, Sapporo Medical University School of Medicine, Sapporo, JPN
| | - Kanako Takahashi
- Department of Nephrology, Sapporo Hokushin Hospital, Sapporo, JPN
| | - Naofumi Bunya
- Department of Emergency Medicine, Sapporo Medical University School of Medicine, Sapporo, JPN
| | - Keigo Sawamoto
- Department of Emergency Medicine, Sapporo Medical University School of Medicine, Sapporo, JPN
| | - Eichi Narimatsu
- Department of Emergency Medicine, Sapporo Medical University School of Medicine, Sapporo, JPN
| | - Yoshiki Masuda
- Department of Intensive Care Medicine, Sapporo Medical University School of Medicine, Sapporo, JPN
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25
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Zhou B, Zong NC, Zhang Y, Huang Y, Youn JY, Cai H. Clinical characteristics of a COVID-19 cohort treated at UCLA Ronald Reagan Medical Center during the breaking phase of the pandemic: A retrospective study. Redox Biol 2024; 75:103178. [PMID: 38986245 PMCID: PMC11280086 DOI: 10.1016/j.redox.2024.103178] [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: 02/26/2024] [Revised: 04/08/2024] [Accepted: 04/29/2024] [Indexed: 07/12/2024] Open
Abstract
To this date, COVID-19 remains an unresolved pandemic, and the impairment of redox homeostasis dictates the severity of clinical outcomes. Here we examined initial UCLA cohort of 440 COVID-19 patients hospitalized between March 1st and April 1st, 2020, representing the first wave of the pandemic. The mean age was 58.88 ± 21.12, among which males were significantly more than females (55.5 % vs. 44.5 %), most distinctively in age group of 50-69. The age groups of 50-69 (33.6 %) and ≥70 (34.8 %) dominated. The racial composition was in general agreement with Census data with slight under-representation of Hispanics and Asians, and over-representation of Caucasians. Smoking was a significant factor (28.8 % vs. 11.0 % in LA population), likewise for obesity (BMI ≥30) (37.4 % vs. 27.7 % in LA population). Patients suffering from obesity or BMI<18.5 checked into ICU at a significantly higher rate. A 74.5 % of the patients had comorbidities including diabetes, chronic kidney disease, chronic pulmonary disease, congestive heart failure and peripheral vascular disease. The levels of d-dimer were drastically upregulated (1159.5 ng/mL), indicating hypercoagulative state. Upregulated LDH (328 IU/L) indicated significant tissue damages. A distorted redox hemeostasis is a common trait associated with these risk factors and clinical markers. A quarter of the patients received antivirals, among which Remdesivir most prescribed (23.6 %). Majority received antithrombotics (75 %), and antibiotics. Upon admission, 67 patients were intubated or received CPR; 177 patients eventually received intensive care (40.2 %). While 290 were discharged alive, 10 remained hospitalized, 73 were transferred, and 36 died with 3 palliatively discharged. In summary, our data fully characterized a Californian cohort of COVID-19 at the breaking phase of the pandemic, indicating that population demographics, biophysical characters, comorbidities and molecular pathological parameters have significant impacts on the evolvement of a pandemic. These provide critical insights into effective management of COVID-19, and future break from another pathogen.
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Affiliation(s)
- Bo Zhou
- Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, California, 90095, USA
| | - Nobel Chenggong Zong
- Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, California, 90095, USA
| | - Yuhan Zhang
- Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, California, 90095, USA
| | - Yuanli Huang
- Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, California, 90095, USA
| | - Ji-Youn Youn
- Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, California, 90095, USA
| | - Hua Cai
- Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, California, 90095, USA.
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Bhowmik L, Hasan MK, Bristy TA, Etu ST, Karim R, Mostaid MS, Shill MC, Reza HM. A comparison of COVID-19 and post-COVID-19 syndrome among symptomatic and asymptomatic patients in Bangladesh: A retrospective cohort study. Heliyon 2024; 10:e36202. [PMID: 39258212 PMCID: PMC11386022 DOI: 10.1016/j.heliyon.2024.e36202] [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: 12/17/2023] [Revised: 08/12/2024] [Accepted: 08/12/2024] [Indexed: 09/12/2024] Open
Abstract
Background The differentiation between COVID-19 and post-COVID-19 syndromes is not properly defined as some patients remain asymptomatic for post-COVID-19. It can be characterized by several signs and symptoms. Risk factors related to post-COVID-19 remain unsolved. Here we aimed to differentiate post-COVID-19 patients among symptomatic and asymptomatic groups to check the percentage among them and the risk factors for post-COVID-19 and the association of different symptoms. Methods This study was conducted in Chittagong division, Bangladesh at different hospitals. Data were collected from the participants either by in person interview or online (email) or mobile phone calls. Follow up was done after 3 months to check the development of post-COVID-19 syndromes. Relevant data were taken, and symptomatic and asymptomatic patients were divided based on the presence and severity of specific symptoms. Results Our results showed that 41.88 % patients develop post-COVID-19 symptoms. Fever and Cough were classified as one of the factors of post-COVID-19, followed by dyspnea, fatigue, cough, rhinitis, sore throat, and muscular discomfort. On the other hand, age, respiratory distress, lethargy, duration of illness and severity were classified as risk factors for post-COVID-19. There was a significant difference between symptomatic and asymptomatic patients as only 16.3 % patients showed post-COVID-19 symptoms. Based on the severity grade, 80.7 % of patients had mild COVID-19. We also found that people with 'B' positive blood group had a higher chance of developing post-COVID-19 syndrome. Conclusion It was concluded that age, duration of illness, presence of respiratory distress, blood group, and disease severity are major risk factors for the development of post-COVID-19 syndrome.
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Affiliation(s)
- Leon Bhowmik
- Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh
| | - Md Kutubul Hasan
- Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh
| | - Tahmina Akter Bristy
- Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh
| | - Sadia Tasnim Etu
- Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh
| | - Reatul Karim
- Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh
| | - Md Shaki Mostaid
- Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh
| | - Manik Chandra Shill
- Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh
| | - Hasan Mahmud Reza
- Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh
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Datta D, Ray S, Martinez L, Newman D, Dalmida SG, Hashemi J, Sareli C, Eckardt P. Feature Identification Using Interpretability Machine Learning Predicting Risk Factors for Disease Severity of In-Patients with COVID-19 in South Florida. Diagnostics (Basel) 2024; 14:1866. [PMID: 39272651 PMCID: PMC11394003 DOI: 10.3390/diagnostics14171866] [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: 07/12/2024] [Revised: 08/16/2024] [Accepted: 08/21/2024] [Indexed: 09/15/2024] Open
Abstract
Objective: The objective of the study was to establish an AI-driven decision support system by identifying the most important features in the severity of disease for Intensive Care Unit (ICU) with Mechanical Ventilation (MV) requirement, ICU, and InterMediate Care Unit (IMCU) admission for hospitalized patients with COVID-19 in South Florida. The features implicated in the risk factors identified by the model interpretability can be used to forecast treatment plans faster before critical conditions exacerbate. Methods: We analyzed eHR data from 5371 patients diagnosed with COVID-19 from South Florida Memorial Healthcare Systems admitted between March 2020 and January 2021 to predict the need for ICU with MV, ICU, and IMCU admission. A Random Forest classifier was trained on patients' data augmented by SMOTE, collected at hospital admission. We then compared the importance of features utilizing different model interpretability analyses, such as SHAP, MDI, and Permutation Importance. Results: The models for ICU with MV, ICU, and IMCU admission identified the following factors overlapping as the most important predictors among the three outcomes: age, race, sex, BMI, diarrhea, diabetes, hypertension, early stages of kidney disease, and pneumonia. It was observed that individuals over 65 years ('older adults'), males, current smokers, and BMI classified as 'overweight' and 'obese' were at greater risk of severity of illness. The severity was intensified by the co-occurrence of two interacting features (e.g., diarrhea and diabetes). Conclusions: The top features identified by the models' interpretability were from the 'sociodemographic characteristics', 'pre-hospital comorbidities', and 'medications' categories. However, 'pre-hospital comorbidities' played a vital role in different critical conditions. In addition to individual feature importance, the feature interactions also provide crucial information for predicting the most likely outcome of patients' conditions when urgent treatment plans are needed during the surge of patients during the pandemic.
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Affiliation(s)
- Debarshi Datta
- Christine E. Lynn College of Nursing, Florida Atlantic University, Boca Raton, FL 33431, USA
| | - Subhosit Ray
- Christine E. Lynn College of Nursing, Florida Atlantic University, Boca Raton, FL 33431, USA
| | - Laurie Martinez
- Christine E. Lynn College of Nursing, Florida Atlantic University, Boca Raton, FL 33431, USA
| | - David Newman
- Christine E. Lynn College of Nursing, Florida Atlantic University, Boca Raton, FL 33431, USA
| | - Safiya George Dalmida
- Christine E. Lynn College of Nursing, Florida Atlantic University, Boca Raton, FL 33431, USA
| | - Javad Hashemi
- College of Engineering & Computer Science, Florida Atlantic University, Boca Raton, FL 33431, USA
| | | | - Paula Eckardt
- Memorial Healthcare System, Hollywood, FL 33021, USA
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Muratsu A, Oda S, Onishi S, Yoshimura J, Matsumoto H, Togami Y, Mitsuyama Y, Ito H, Okuzaki D, Ogura H, Oda J. Bacterial sepsis causes more dramatic pathogenetic changes in the Th1 pathway than does viral (COVID-19) sepsis: a prospective observational study of whole blood transcriptomes. Virol J 2024; 21:190. [PMID: 39160575 PMCID: PMC11334310 DOI: 10.1186/s12985-024-02451-6] [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: 10/11/2023] [Accepted: 07/30/2024] [Indexed: 08/21/2024] Open
Abstract
OBJECTIVES This study aimed to comprehensively compare host responses of patients with bacterial sepsis and those with viral (COVID-19) sepsis by analyzing messenger RNA (mRNA) and microRNA (miRNA) profiles to shed light on their distinct pathophysiological mechanisms. DESIGN Prospective observational study. SETTING Whole blood RNA sequencing was used to analyze mRNA and miRNA profiles of patients diagnosed as having bacterial sepsis or viral (COVID-19) sepsis at the Department of Trauma and Emergency Medicine, Osaka University Graduate School of Medicine. PATIENTS Twenty-two bacterial sepsis patients, 35 viral (COVID-19) sepsis patients, and 15 healthy subjects admitted to the department were included. We diagnosed bacterial sepsis patients according to the sepsis-3 criterion that the Sequential Organ Failure Assessment score must increase to 2 points or more among patients with suspected infections. Viral (COVID-19) sepsis patients were diagnosed using SARS-CoV-2 RT-PCR testing, and presence of pneumonia was assessed through chest computed tomography scans. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS For RNA sequencing, 14,500 mRNAs, 1121 miRNAs, and 2556 miRNA-targeted mRNAs were available for analysis in the bacterial sepsis patients. Numbers of genes showing upregulated: downregulated gene expression (false discovery rate < 0.05, |log2 fold change| > 1.5) were 256:2887 for mRNA, 53:5 for miRNA, and 49:2507 for miRNA-targeted mRNA. Similarly, in viral (COVID-19) sepsis patients, 14,500 mRNAs, 1121 miRNAs, and 327 miRNA-targeted mRNAs were analyzed, with numbers of genes exhibiting upregulated: downregulated gene expression of 672:1147 for mRNA, 3:4 for miRNA, and 165:162 for miRNA-targeted mRNA. This analysis revealed significant differences in the numbers of upregulated and downregulated genes expressed and pathways between the bacterial sepsis and viral (COVID-19) sepsis patients. Bacterial sepsis patients showed activation of the PD-1 and PD-L1 cancer immunotherapy signaling pathway and concurrent suppression of Th1 signaling. CONCLUSION Our study illuminated distinct molecular variances between bacterial sepsis and viral (COVID-19) sepsis. Bacterial sepsis patients had a greater number of upregulated and downregulated genes and pathways compared to viral (COVID-19) sepsis patients. Especially, bacterial sepsis caused more dramatic pathogenetic changes in the Th1 pathway than did viral (COVID-19) sepsis.
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Affiliation(s)
- Arisa Muratsu
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Sayaka Oda
- Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Osaka, Japan
- Laboratory for Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
| | - Shinya Onishi
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Jumpei Yoshimura
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hisatake Matsumoto
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
| | - Yuki Togami
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yumi Mitsuyama
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hiroshi Ito
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Daisuke Okuzaki
- Laboratory for Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
| | - Hiroshi Ogura
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Jun Oda
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
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Silvestri C, Stasi C, Profili F, Bartolacci S, Sessa E, Tacconi D, Villari L, Carrozzi L, Dotta F, Bargagli E, Donnini S, Masotti L, Rasero L, Lavorini F, Pistelli F, Chimera D, Sorano A, Pacifici M, Milli C, Voller F, Group SPRINTS. Retrospective Study on the Features and Outcomes of a Tuscany COVID-19 Hospitalized Patients Cohort: Preliminary Results. J Clin Med 2024; 13:4626. [PMID: 39200770 PMCID: PMC11354555 DOI: 10.3390/jcm13164626] [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: 06/27/2024] [Revised: 07/26/2024] [Accepted: 08/05/2024] [Indexed: 09/02/2024] Open
Abstract
Background: A few months after the COVID-19 pandemic onset, knowledge of SARS-CoV-2 infection and outcomes and treatments blew up. This paper aimed to evaluate the features of a Tuscany COVID-19 hospitalized cohort and to identify risk factors for COVID-19 severity. Methods: This retrospective observational COVID-19 cohort study (1 March 2020-1 March 2021) was conducted on patients ≥ 18 years old, admitted to Tuscany Hospital, and subjected to follow-up within 12 months after discharge. Patients were enrolled at Pisana, Senese and Careggi University Hospitals, and South East, North West, and Center Local Hospitals. Results: 2888 patients (M = 58.5%, mean age = 66.2 years) were enrolled, of whom 14.3% (N = 413) were admitted to an intensive care unit. Smokers were 25%, and overweight and obese 65%. The most used drugs were corticosteroids, antacids, antibiotics, and antithrombotics, all antiviral drugs, with slight differences between 2020 and 2021. A strong association was found between outcomes of evolution towards critical COVID-19 (non-invasive mechanical ventilation (NIV) and/or admission to intensive care) and smoking (RR = 4.91), ex-smoking (RR = 3.48), overweight (RR = 1.30), obese subjects (RR = 1.62), comorbidities (aRR = 1.38). The alteration of liver enzymes (aspartate aminotransferase, alanine aminotransferase, or gamma-glutamyl transpeptidase) was associated with NIV (aOR = 2.28). Conclusions: Our cohort, characterized by patients with a mean age of 66.2 years, showed 65% of patients were overweight and obese. Smoking/ex-smoking, overweight/obesity, and other comorbidities were associated with COVID-19 adverse outcomes. The findings also demonstrated that alterations in liver enzymes were associated with worse outcomes.
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Affiliation(s)
- Caterina Silvestri
- Epidemiology Unit, Regional Health Agency of Tuscany, 50141 Florence, Italy
| | - Cristina Stasi
- Epidemiology Unit, Regional Health Agency of Tuscany, 50141 Florence, Italy
- Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | - Francesco Profili
- Epidemiology Unit, Regional Health Agency of Tuscany, 50141 Florence, Italy
| | - Simone Bartolacci
- Epidemiology Unit, Regional Health Agency of Tuscany, 50141 Florence, Italy
| | - Emiliano Sessa
- Epidemiology Unit, Regional Health Agency of Tuscany, 50141 Florence, Italy
| | - Danilo Tacconi
- Infectious Diseases Unit, PO San Donato, 52100 Arezzo, Italy
| | - Liliana Villari
- Division of Pneumology, AUSL Toscana Nord-Ovest, Apuane Hospital, 54100 Massa, Italy;
| | - Laura Carrozzi
- Pneumology Unit, Pisa University Hospital, 56124 Pisa, Italy
| | - Francesco Dotta
- Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
- Diabetes and Metabolic Diseases Unit, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy
| | - Elena Bargagli
- Respiratory Diseases Unit, Department Medical Sciences, Surgery and Neurological Sciences, Siena University, 53100 Siena, Italy
| | - Sandra Donnini
- Department of Life Sciences, University of Siena, 53100 Siena, Italy
| | - Luca Masotti
- Internal Medicine II and Stroke Unit, San Giuseppe Hospital, 20123 Empoli, Italy
| | - Laura Rasero
- Department of Health Sciences, Clinical Innovations and Research Unit, Careggi University Hospital, University of Florence, 50121 Florence, Italy
| | - Federico Lavorini
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy; (F.L.)
| | | | - Davide Chimera
- Pneumology Unit, Pisa University Hospital, 56124 Pisa, Italy
| | - Alessandra Sorano
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy; (F.L.)
| | - Martina Pacifici
- Epidemiology Unit, Regional Health Agency of Tuscany, 50141 Florence, Italy
| | - Caterina Milli
- Epidemiology Unit, Regional Health Agency of Tuscany, 50141 Florence, Italy
| | - Fabio Voller
- Epidemiology Unit, Regional Health Agency of Tuscany, 50141 Florence, Italy
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Rana R, Akhtar A. Retrospective Comparison of Influenza and COVID-19-Associated Acute Respiratory Distress Syndrome (ARDS): An Experience From a Tertiary Care Hospital. Cureus 2024; 16:e66636. [PMID: 39258093 PMCID: PMC11386436 DOI: 10.7759/cureus.66636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/11/2024] [Indexed: 09/12/2024] Open
Abstract
Background The COVID-19 pandemic has had a profound impact on global healthcare systems, often compared to seasonal influenza due to similarities in clinical presentation. This study aims to compare the clinical characteristics, comorbidities, and outcomes of critically ill patients with COVID-19 and those with influenza admitted to a tertiary care hospital in Islamabad, Pakistan. Methods This retrospective cohort study included 120 patients, 60 with confirmed COVID-19 and 60 with confirmed influenza, all of whom required ICU admission and mechanical ventilation between January 1, 2021, and January 1, 2024. Data were collected from electronic medical records, including demographic information, comorbidities, and clinical outcomes. Descriptive statistics were used to compare the two groups. Results The median age of COVID-19 patients was 55 years (range 30-78), while that of influenza patients was 58 years (range 31-80). Both groups had a slight male predominance (COVID-19: 66.7%, Influenza: 63.3%). Comorbidities were common in both groups, with 75.0% of COVID-19 patients and 83.3% of influenza patients having at least one comorbidity. The most common comorbidities included hypertension (COVID-19: 30.0%, Influenza: 33.3%) and diabetes (COVID-19: 20.0%, Influenza: 25.0%). Clinical outcomes revealed a higher mortality rate among influenza patients (43.3%) compared to COVID-19 patients (28.3%). ICU admission rates were identical for both groups at 66.7%, and mechanical ventilation was required for 66.7% of ICU-admitted patients in both groups. The presence of cardiovascular comorbidities significantly impacted patient outcomes, with higher mortality observed in influenza patients with such comorbidities (44.7%) compared to COVID-19 patients (28.9%). Conclusion This study highlights the significant burden of both COVID-19 and influenza on critically ill patients, particularly those with cardiovascular comorbidities. While influenza patients in this cohort exhibited higher mortality rates, both groups demonstrated substantial ICU admission rates and a need for mechanical ventilation.
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Affiliation(s)
- Rizwana Rana
- Critical Care Medicine, Shifa International Hospital, Islamabad, PAK
- Pulmonary Medicine, College of Physicians and Surgeons of Pakistan, Islamabad, PAK
| | - Aftab Akhtar
- Internal Medicine, Shifa International Hospital, Islamabad, PAK
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Pereira ABN, Pereira FSH, Araújo JÉDL, Brasil RP, Oliveira AMB, Lima SS, Fonseca RRDS, Laurentino RV, Oliveira-Filho AB, Machado LFA. Clinical-Epidemiological Profile of COVID-19 Patients Admitted during Three Waves of the Pandemic in a Tertiary Care Center, in Belém, Pará, Amazon Region of Brazil. Viruses 2024; 16:1233. [PMID: 39205207 PMCID: PMC11359788 DOI: 10.3390/v16081233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 07/21/2024] [Accepted: 07/24/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is a disease with a broad clinical spectrum, which may result in hospitalization in healthcare units, intensive care, and progression to death. This study aimed to describe and compare the clinical and epidemiological profile of COVID-19 during the three waves of the disease, in patients admitted to a public hospital in the city of Belém, Pará, in the Amazon region of Brazil. METHODS This descriptive, observational, and cross-sectional study was population-based on individuals who were hospitalized with a diagnosis of COVID-19, confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR), and who were interviewed and monitored at the public hospital, from February 2020 to April 2022. RESULTS The prevalence was male patients, older than 60 years. The most frequent symptoms were dyspnea, cough, and fever. Systemic arterial hypertension was the most prevalent comorbidity followed by diabetes mellitus. Less than 15% of patients were vaccinated. The nasal oxygen cannula was the most used oxygen therapy interface followed by the non-rebreathing reservoir mask. Invasive mechanical ventilation predominated and the median time of invasive mechanical ventilation ranged from 2 to 6 days among waves. As for the hospital outcome, transfers prevailed, followed by deaths and discharges. CONCLUSION The presence of comorbidities, advanced age, and male sex were important factors in the severity and need for hospitalization of these patients, and the implementation of the vaccination policy was an essential factor in reducing the number of hospital admissions.
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Affiliation(s)
- Ana Beatriz Nunes Pereira
- Biology of Infectious and Parasitic Agents Post-Graduate Program, Federal University of Pará, Belém 66075-110, PA, Brazil;
- Virology Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (S.S.L.); (R.R.d.S.F.); (R.V.L.)
| | - Fernando Sérgio Henriques Pereira
- Belém Health Department, Humberto Maradei Pereira Municipal and Emergency Hospital, Belém 66075-259, PA, Brazil; (F.S.H.P.); (J.É.D.L.A.); (R.P.B.); (A.M.B.O.)
| | - Júlio Éden Davi Lopes Araújo
- Belém Health Department, Humberto Maradei Pereira Municipal and Emergency Hospital, Belém 66075-259, PA, Brazil; (F.S.H.P.); (J.É.D.L.A.); (R.P.B.); (A.M.B.O.)
| | - Rangel Pereira Brasil
- Belém Health Department, Humberto Maradei Pereira Municipal and Emergency Hospital, Belém 66075-259, PA, Brazil; (F.S.H.P.); (J.É.D.L.A.); (R.P.B.); (A.M.B.O.)
| | - Angélica Menezes Bessa Oliveira
- Belém Health Department, Humberto Maradei Pereira Municipal and Emergency Hospital, Belém 66075-259, PA, Brazil; (F.S.H.P.); (J.É.D.L.A.); (R.P.B.); (A.M.B.O.)
| | - Sandra Souza Lima
- Virology Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (S.S.L.); (R.R.d.S.F.); (R.V.L.)
| | - Ricardo Roberto de Souza Fonseca
- Virology Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (S.S.L.); (R.R.d.S.F.); (R.V.L.)
| | - Rogério Valois Laurentino
- Virology Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (S.S.L.); (R.R.d.S.F.); (R.V.L.)
| | - Aldemir Branco Oliveira-Filho
- Study and Research Group on Vulnerable Populations, Institute for Coastal Studies, Federal University of Pará, Bragança 68600-000, PA, Brazil;
| | - Luiz Fernando Almeida Machado
- Biology of Infectious and Parasitic Agents Post-Graduate Program, Federal University of Pará, Belém 66075-110, PA, Brazil;
- Virology Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil; (S.S.L.); (R.R.d.S.F.); (R.V.L.)
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Fernandes Lira JG, Alves de Olinda R, Correia Basto da Silva G, Leal de Oliveira L, de Alencar Neta RL, Vilar Cardoso N, Adami F, da Silva Paiva L. Sociodemographic Profile and Risk Factors for the Evolution of Patients with COVID-19 in ICUs in Brazil: A Cross-Sectional Study. ScientificWorldJournal 2024; 2024:2927407. [PMID: 39040155 PMCID: PMC11262879 DOI: 10.1155/2024/2927407] [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: 03/25/2024] [Revised: 06/24/2024] [Accepted: 07/01/2024] [Indexed: 07/24/2024] Open
Abstract
This is a cross-sectional study, with secondary data from Brazilian hospitals in the state of Paraíba, between January 2021 and January 2022. The evolution of clinical cases configured the dependent variable (cure or death), while the predictive variables were sociodemographic data, risk factors, use of ventilatory support, and vaccination against COVID-19. With the help of R software, the following tests were used: chi-square, Pearson's chi-square, and Fisher's exact adherence. Simple logistic regression models were constructed, and odds ratios (95% CI) were estimated using the LR test and Wald test. 7373 cases were reported, with a mean age of 58.1. Of the reported cases, 63.8% died. The most frequent sociodemographic profile included male people, of mixed race, with less than eight years of schooling. Chronic cardiovascular disease (OR 1.28; 95% CI: 1.13-1.45), diabetes (OR 1.41; 95% CI: 1.24-1.61), lung disease (OR 1.52; 95% CI: 1.11-2.09), and the use of invasive ventilatory support (OR 14.1; 95% CI: 10.56-18.59) were all associated with increased mortality. Nonvaccination was associated with a decreased risk of death (OR 0.74; 95% CI: 0.65-0.84). Male patients, nonwhite, and those with low education were more likely to have a worse clinical outcome. The risk factors studied were related to deaths, and those who did not require ventilatory support were related to cure.
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Affiliation(s)
| | - Ricardo Alves de Olinda
- State University of Paraíba, Baraúnas Street, 351-Universitário, Campina Grande, PB 58429-500, Brazil
| | | | - Luzibênia Leal de Oliveira
- Federal University of Campina Grande, Juvêncio Arruda Avenue, 795-Bodocongó, Campina Grande, PB 58429-600, Brazil
| | | | - Nívea Vilar Cardoso
- Federal University of Campina Grande, Juvêncio Arruda Avenue, 795-Bodocongó, Campina Grande, PB 58429-600, Brazil
| | - Fernando Adami
- ABC Medical School, Lauro Gomes Avenue, 2000-Vila Sacadura Cabral, Santo André, SP 09060-870, Brazil
| | - Laércio da Silva Paiva
- ABC Medical School, Lauro Gomes Avenue, 2000-Vila Sacadura Cabral, Santo André, SP 09060-870, Brazil
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Kim HJ, Jeong S, Song J, Park SJ, Park YJ, Oh YH, Jung J, Park SM. Risk of pulmonary embolism and deep vein thrombosis following COVID-19: a nationwide cohort study. MedComm (Beijing) 2024; 5:e655. [PMID: 39006761 PMCID: PMC11246596 DOI: 10.1002/mco2.655] [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] [Received: 08/06/2023] [Revised: 06/08/2024] [Accepted: 06/12/2024] [Indexed: 07/16/2024] Open
Abstract
Recent studies elucidate that coronavirus disease 2019 (COVID-19) patients may face a higher risk of cardiovascular complications. This study aimed to evaluate association of COVID-19 with the risk of pulmonary embolism (PE) or deep vein thrombosis (DVT). This nationwide population-based retrospective cohort study included Korean adult citizens between January 2021 and March 2022 from the Korea Disease Control and Prevention Agency COVID-19 National Health Insurance Service cohort. The Fine and Gray's regression with all-cause death as a competing event was adopted to evaluate PE and DVT risks after COVID-19. This study included a total of 1,601,835 COVID-19 patients and 14,011,285 matched individuals without COVID-19. The risk of PE (adjusted hazard ratio [aHR], 6.25; 95% confidence interval [CI], 3.67-10.66; p < 0.001) and DVT (aHR, 3.05; 95% CI, 1.75-5.29; p < 0.001) was higher in COVID-19 group in individuals without complete COVID-19 vaccination. In addition, individuals with complete COVID-19 vaccination still had a higher risk of COVID-19-related PE (aHR, 1.48; 95% CI, 1.15-1.88; p < 0.001). However, COVID-19 was not a significant risk factor for DVT among those with complete COVID-19 vaccination. COVID-19 was identified as an independent factor that elevated PE and DVT risks, especially for individuals without complete COVID-19 vaccination.
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Affiliation(s)
- Hye Jun Kim
- Department of Biomedical Sciences Seoul National University College of Medicine Seoul South Korea
| | - Seogsong Jeong
- Department of Biomedical Informatics Korea University College of Medicine Seoul South Korea
| | - Jihun Song
- Department of Biomedical Sciences Seoul National University College of Medicine Seoul South Korea
| | - Sun Jae Park
- Department of Biomedical Sciences Seoul National University College of Medicine Seoul South Korea
| | - Young Jun Park
- Medical Research Center Genomic Medicine Institute Seoul National University Seoul South Korea
| | - Yun Hwan Oh
- Department of Family Medicine Chung-Ang University Gwangmyeong Hospital Chung-Ang University College of Medicine Gwangmyeong South Korea
| | - Jaehun Jung
- Department of Preventive Medicine Gachon University College of Medicine Incheon South Korea
| | - Sang Min Park
- Department of Biomedical Sciences Seoul National University College of Medicine Seoul South Korea
- Department of Family Medicine Seoul National University Hospital Seoul South Korea
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Ramachandran R, Manan A, Kim J, Choi S. NLRP3 inflammasome: a key player in the pathogenesis of life-style disorders. Exp Mol Med 2024; 56:1488-1500. [PMID: 38945951 PMCID: PMC11297159 DOI: 10.1038/s12276-024-01261-8] [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: 11/10/2023] [Revised: 02/27/2024] [Accepted: 03/25/2024] [Indexed: 07/02/2024] Open
Abstract
Proinflammatory cytokines and chemokines play a crucial role in regulating the inflammatory response, which is essential for the proper functioning of our immune system. When infections or threats to the body's defense mechanisms are detected, the innate immune system takes the lead. However, an excessive inflammatory response can lead to the production of high concentrations of cytotoxic molecules, resulting in tissue damage. Inflammasomes are significant contributors to innate immunity, and one of the most extensively studied inflammasome complexes is NOD-like receptor 3 (NLRP3). NLRP3 has a wide range of recognition mechanisms that streamline immune activation and eliminate pathogens. These cytosolic multiprotein complexes are composed of effector, adaptor, and sensor proteins, which are crucial for identifying intracellular bacterial breakdown products and initiating an innate immune cascade. To understand the diverse behavior of NLRP3 activation and its significance in the development of lifestyle-related diseases, one must delve into the study of the immune response and apoptosis mediated by the release of proinflammatory cytokines. In this review, we briefly explore the immune response in the context of lifestyle associated disorders such as obesity, hyperlipidemia, diabetes, chronic respiratory disease, oral disease, and cardiovascular disease.
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Affiliation(s)
- Rajath Ramachandran
- Department of Molecular Science and Technology, Ajou University, Suwon, 16499, Korea.
| | - Abdul Manan
- Department of Molecular Science and Technology, Ajou University, Suwon, 16499, Korea
| | - Jei Kim
- Department of Molecular Science and Technology, Ajou University, Suwon, 16499, Korea
- S&K Therapeutics, Ajou University Campus Plaza 418, 199 Worldcup-ro, Yeongtong-gu, Suwon, 16502, Korea
| | - Sangdun Choi
- Department of Molecular Science and Technology, Ajou University, Suwon, 16499, Korea.
- S&K Therapeutics, Ajou University Campus Plaza 418, 199 Worldcup-ro, Yeongtong-gu, Suwon, 16502, Korea.
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Matthes S, Holl J, Randerath J, Treml M, Sofianos G, Bockover M, Oesterlee U, Herkenrath S, Knoch J, Hagmeyer L, Randerath W. [Prognostic factors in an individualised approach to non-pharmacological therapy of COVID-19: from oxygen and mechanical ventilation to extracorporeal membrane oxygenation]. Pneumologie 2024; 78:515-525. [PMID: 38286417 DOI: 10.1055/a-2235-6357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2024]
Abstract
BACKGROUND Our centre followed a stepwise approach in the nonpharmacological treatment of respiratory failure in COVID-19 in accordance with German national guidelines, escalating non-invasive measures before invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). The aim of this study was to analyse this individualized approach to non-pharmacologic therapy in terms of patient characteristics and clinical features that may help predict more severe disease, particularly the need for intensive care. METHOD This retrospective single-centre study of COVID-19 inpatients between March 2020 and December 2021 analysed anthropometric data, non-pharmacological maximum therapy and survival status via a manual medical file review. RESULTS Of 1052 COVID-19-related admissions, 835 patients were included in the analysis cohort (54% male, median 58 years); 34% (n=284) received no therapy, 40% (n=337) conventional oxygen therapy (COT), 3% (n=22) high flow nasal cannula (NHFC), 9% (n=73) continuous positive airway pressure (CPAP), 7% (n=56) non-invasive ventilation (NIV), 4% (n=34) intermittent mandatory ventilation (IMV), and 3% (n=29) extracorporeal membrane oxygenation (ECMO). Of 551 patients treated with at least COT, 12.3% required intubation. A total of 183 patients required ICU treatment, and 106 (13%) died. 25 (74%) IMV patients and 23 (79%) ECMO patients died. Arterial hypertension, diabetes and dyslipidemia was more prevalent in non-survivors. Binary logistic analysis revealed the following risk factors for increased mortality: an oxygen supplementation of ≥2 L/min at baseline (OR 6.96 [4.01-12.08]), age (OR 1.09 [1.05-1.14]), and male sex (OR 2.23 [0.79-6.31]). CONCLUSION The physician's immediate clinical decision to provide oxygen therapy, along with other recognized risk factors, plays an important role in predicting the severity of the disease course and thus aiding in the management of COVID-19.
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Affiliation(s)
- Sandhya Matthes
- Krankenhaus Bethanien gGmbH, Klinik für Pneumologie und Allergologie, Zentrum für Schlaf- und Beatmungsmedizin, Solingen, Deutschland
- Institut für Pneumologie an der Universität zu Köln, Solingen, Deutschland
| | - Johannes Holl
- Institut für Pneumologie an der Universität zu Köln, Solingen, Deutschland
| | - Johannes Randerath
- Institut für Pneumologie an der Universität zu Köln, Solingen, Deutschland
| | - Marcel Treml
- Institut für Pneumologie an der Universität zu Köln, Solingen, Deutschland
| | - Georgios Sofianos
- Krankenhaus Bethanien gGmbH, Klinik für Pneumologie und Allergologie, Zentrum für Schlaf- und Beatmungsmedizin, Solingen, Deutschland
| | - Michael Bockover
- Krankenhaus Bethanien gGmbH, Klinik für Pneumologie und Allergologie, Zentrum für Schlaf- und Beatmungsmedizin, Solingen, Deutschland
| | - Ulrike Oesterlee
- Krankenhaus Bethanien gGmbH, Klinik für Pneumologie und Allergologie, Zentrum für Schlaf- und Beatmungsmedizin, Solingen, Deutschland
| | - Simon Herkenrath
- Krankenhaus Bethanien gGmbH, Klinik für Pneumologie und Allergologie, Zentrum für Schlaf- und Beatmungsmedizin, Solingen, Deutschland
| | - Johannes Knoch
- Krankenhaus Bethanien gGmbH, Klinik für Pneumologie und Allergologie, Zentrum für Schlaf- und Beatmungsmedizin, Solingen, Deutschland
| | - Lars Hagmeyer
- Krankenhaus Bethanien gGmbH, Klinik für Pneumologie und Allergologie, Zentrum für Schlaf- und Beatmungsmedizin, Solingen, Deutschland
- Institut für Pneumologie an der Universität zu Köln, Solingen, Deutschland
| | - Winfried Randerath
- Krankenhaus Bethanien gGmbH, Klinik für Pneumologie und Allergologie, Zentrum für Schlaf- und Beatmungsmedizin, Solingen, Deutschland
- Institut für Pneumologie an der Universität zu Köln, Solingen, Deutschland
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Liang P, Wei Z, Li R, Zhou E, Chen Z. Predictive value of hematocrit, serum albumin level difference, and fibrinogen-to-albumin ratio for COVID-19-associated acute respiratory failure. Heliyon 2024; 10:e33326. [PMID: 39021974 PMCID: PMC11253537 DOI: 10.1016/j.heliyon.2024.e33326] [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: 08/08/2023] [Revised: 06/16/2024] [Accepted: 06/19/2024] [Indexed: 07/20/2024] Open
Abstract
Background Acute respiratory failure is the main clinical manifestation and a major cause of death in patients with COVID-19. However, few reports on its prevention and control have been published because of the need for laboratory predictive indicators. This study aimed to evaluate the predictive value of hematocrit level, serum albumin level difference, and fibrinogen-to-albumin ratio for COVID-19-associated acute respiratory failure. Material and methods A total of 120 patients with COVID-19 from the First Affiliated Hospital of Anhui Medical University were selected between December 2022 and March 2023. Patients were divided into acute respiratory failure and non-acute respiratory failure groups and compared patient-related indicators between them using univariate and multivariate logistic regression analyses. Receiver operating characteristic analysis was performed to determine the discrimination accuracy. Results In total, 48 and 72 patients were enrolled in the acute respiratory failure and non-acute respiratory failure groups, respectively. The Quick COVID-19 Severity Index scores, fibrinogen-to-albumin ratio, hematocrit and serum albumin level difference, fibrinogen, and hematocrit levels were significantly higher in the acute respiratory failure group than in the non-acute respiratory failure group. A Quick COVID-19 Severity Index >7, fibrinogen-to-albumin ratio >0.265, and hematocrit and serum albumin level difference >12.792 had a 96.14 % positive predictive rate and a 94.06 % negative predictive rate. Conclusion Both fibrinogen-to-albumin ratio and hematocrit and serum albumin level difference are risk factors for COVID-19-associated acute respiratory failure. The Quick COVID-19 Severity Index score combined with fibrinogen-to-albumin ratio, and hematocrit and serum albumin level difference predict high and low risks with better efficacy and sensitivity than those of the Quick COVID-19 Severity Index score alone; therefore, these parameters can be used collectively as a risk stratification method for assessing patients with COVID-19.
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Affiliation(s)
| | | | | | - Enze Zhou
- Department of Emergency Intensive Care Unit, The First Affiliated Hospital of AnHui Medical University, 218 JiXi Avenue, Hefei, 230022, Anhui, China
| | - Zheng Chen
- Department of Emergency Intensive Care Unit, The First Affiliated Hospital of AnHui Medical University, 218 JiXi Avenue, Hefei, 230022, Anhui, China
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37
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Uthaya Kumar A, Ahmad Zan M, Ng CL, Chieng S, Nathan S. Diabetes and Infectious Diseases with a Focus on Melioidosis. Curr Microbiol 2024; 81:208. [PMID: 38833191 DOI: 10.1007/s00284-024-03748-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 05/19/2024] [Indexed: 06/06/2024]
Abstract
Diabetes mellitus (DM) leads to impaired innate and adaptive immune responses. This renders individuals with DM highly susceptible to microbial infections such as COVID-19, tuberculosis and melioidosis. Melioidosis is a tropical disease caused by the bacterial pathogen Burkholderia pseudomallei, where diabetes is consistently reported as the most significant risk factor associated with the disease. Type-2 diabetes is observed in 39% of melioidosis patients where the risk of infection is 13-fold higher than non-diabetic individuals. B. pseudomallei is found in the environment and is an opportunistic pathogen in humans, often exhibiting severe clinical manifestations in immunocompromised patients. The pathophysiology of diabetes significantly affects the host immune responses that play a critical role in fighting the infection, such as leukocyte and neutrophil impairment, macrophage and monocyte inhibition and natural killer cell dysfunction. These defects result in delayed recruitment as well as activation of immune cells to target the invading B. pseudomallei. This provides an advantage for the pathogen to survive and adapt within the immunocompromised diabetic patients. Nevertheless, knowledge gaps on diabetes-infectious disease comorbidity, in particular, melioidosis-diabetes comorbidity, need to be filled to fully understand the dysfunctional host immune responses and adaptation of the pathogen under diabetic conditions to guide therapeutic options.
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Affiliation(s)
- Asqwin Uthaya Kumar
- Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Malaysia
| | - Muhammad Ahmad Zan
- Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Malaysia
| | - Chyan-Leong Ng
- Institute of Systems Biology, Universiti Kebangsaan Malaysia, Bangi, Malaysia
| | - Sylvia Chieng
- Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Malaysia
| | - Sheila Nathan
- Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Malaysia.
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38
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Khatib H, Edwin SB, Paxton R, Hughes C, Hartner C, Al-Samman S, Giuliano C. Enteral Sedation in Patients Requiring Mechanical Ventilation During an Intravenous Analgesic and Sedative Shortage. J Pharm Pract 2024; 37:696-702. [PMID: 37173117 DOI: 10.1177/08971900231175934] [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: 05/15/2023]
Abstract
Background: There is a paucity of data evaluating the use of enteral sedation in mechanical ventilation. A sedative shortage resulted in the use of this approach. Purpose: To evaluate the feasibility of using enteral sedatives to decrease intravenous (IV) analgesia and sedative requirements. Materials/Methods: This single-center, retrospective, observational study compared two groups of patients admitted to the ICU who were mechanically ventilated. One group received a combination of enteral and IV sedatives and the second group received IV monotherapy. Linear mixed model (LMM) analyses were performed to assess the impact of enteral sedatives on IV fentanyl equivalents, IV midazolam equivalents, and propofol. Mann-Whitney U tests were performed on percent of days at goal for Richmond Agitation and Sedation Scale (RASS) and critical care pain observation tool (CPOT) scores. Results: One hundred and four patients were included. The average cohort age was 62 years and 58.7% were male. The median length of mechanical ventilation was 7.1 days and the median length of stay was 11.9 days. The LMM estimated that enteral sedatives reduced IV fentanyl equivalents received per patient by an average of 305.6 mcg/day (P = .04), although did not significantly decrease midazolam equivalents or propofol. There was no statistically significant difference in CPOT scores (P = .57 and P = .46 respectively), however RASS scores in the enteral sedation group were more often at goal (P = .03); oversedation occurred more in the non-enteral sedation group (P = .018). Conclusion: Enteral sedation may be a possible way to decrease IV analgesia requirements during periods of shortage.
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Affiliation(s)
- Hassan Khatib
- Eugene Applebaum College of Pharmacy & Health Sciences, Wayne State University, Detroit, MI, USA
| | - Stephanie B Edwin
- Department of Pharmacy, Ascension St John Hospital, Detroit, MI, USA
| | - Renee Paxton
- Department of Pharmacy, Ascension St John Hospital, Detroit, MI, USA
| | - Christopher Hughes
- Department of Pulmonary and Critical Care Medicine, Ascension St John Hospital, Detroit, MI, USA
| | - Carrie Hartner
- Department of Pharmacy, Ascension St John Hospital, Detroit, MI, USA
| | - Samer Al-Samman
- Department of Pulmonary and Critical Care Medicine, Ascension St John Hospital, Detroit, MI, USA
| | - Christopher Giuliano
- Eugene Applebaum College of Pharmacy & Health Sciences, Wayne State University, Detroit, MI, USA
- Department of Pharmacy, Ascension St John Hospital, Detroit, MI, USA
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39
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Griffin I, King J, Lyons BC, Singleton AL, Deng X, Bruce BB, Griffin PM. Estimates of SARS-CoV-2 Hospitalization and Fatality Rates in the Prevaccination Period, United States. Emerg Infect Dis 2024; 30:1144-1153. [PMID: 38781926 PMCID: PMC11138987 DOI: 10.3201/eid3006.231285] [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: 05/25/2024] Open
Abstract
Few precise estimates of hospitalization and fatality rates from COVID-19 exist for naive populations, especially within demographic subgroups. We estimated rates among persons with SARS-CoV-2 infection in the United States during May 1-December 1, 2020, before vaccines became available. Both rates generally increased with age; fatality rates were highest for persons >85 years of age (24%) and lowest for children 1-14 years of age (0.01%). Age-adjusted case hospitalization rates were highest for African American or Black, not Hispanic persons (14%), and case-fatality rates were highest for Asian or Pacific Islander, not Hispanic persons (4.4%). Eighteen percent of hospitalized patients and 44.2% of those admitted to an intensive care unit died. Male patients had higher hospitalization (6.2% vs. 5.2%) and fatality rates (1.9% vs. 1.5%) than female patients. These findings highlight the importance of collecting surveillance data to devise appropriate control measures for persons in underserved racial/ethnic groups and older adults.
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Haber R, Ghezzawi M, Puzantian H, Haber M, Saad S, Ghandour Y, El Bachour J, Yazbeck A, Hassanieh G, Mehdi C, Ismail D, Abi-Kharma E, El-Zein O, Khamis A, Chakhtoura M, Mantzoros C. Mortality risk in patients with obesity and COVID-19 infection: a systematic review and meta-analysis. Metabolism 2024; 155:155812. [PMID: 38360130 DOI: 10.1016/j.metabol.2024.155812] [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: 09/23/2023] [Revised: 01/13/2024] [Accepted: 01/29/2024] [Indexed: 02/17/2024]
Abstract
Obesity is a risk factor for severe respiratory diseases, including COVID-19 infection. Meta-analyses on mortality risk were inconsistent. We systematically searched 3 databases (Medline, Embase, CINAHL) and assessed the quality of studies using the Newcastle-Ottawa tool (CRD42020220140). We included 199 studies from US and Europe, with a mean age of participants 41.8-78.2 years, and a variable prevalence of metabolic co-morbidities of 20-80 %. Exceptionally, one third of the studies had a low prevalence of obesity of <20 %. Compared to patients with normal weight, those with obesity had a 34 % relative increase in the odds of mortality (p-value 0.002), with a dose-dependent relationship. Subgroup analyses showed an interaction with the country income. There was a high heterogeneity in the results, explained by clinical and methodologic variability across studies. We identified one trial only comparing mortality rate in vaccinated compared to unvaccinated patients with obesity; there was a trend for a lower mortality in the former group. Mortality risk in COVID-19 infection increases in parallel to an increase in BMI. BMI should be included in the predictive models and stratification scores used when considering mortality as an outcome in patients with COVID-19 infections. Furthermore, patients with obesity might need to be prioritized for COVID-19 vaccination.
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Affiliation(s)
- Rachelle Haber
- Department of Internal Medicine, Division of Endocrinology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Malak Ghezzawi
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Houry Puzantian
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Hariri School of Nursing, American University of Beirut, Beirut, Lebanon.
| | - Marc Haber
- Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon
| | - Sacha Saad
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Yara Ghandour
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | | | - Anthony Yazbeck
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | | | - Celine Mehdi
- Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon
| | - Dima Ismail
- Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon
| | - Elias Abi-Kharma
- Department of Internal Medicine, Division of Endocrinology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ola El-Zein
- Saab Medical Library, American University of Beirut, Beirut, Lebanon
| | - Assem Khamis
- Hull York Medical School, University of Hull, York, United Kingdom
| | - Marlene Chakhtoura
- Department of Internal Medicine, Division of Endocrinology, American University of Beirut Medical Center, Beirut, Lebanon.
| | - Christos Mantzoros
- Beth Israel Deaconess Medical Center and Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA
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Spoto S, Basili S, Cangemi R, Yuste JR, Lucena F, Romiti GF, Raparelli V, Argemi J, D’Avanzo G, Locorriere L, Masini F, Calarco R, Testorio G, Spiezia S, Ciccozzi M, Angeletti S. A Focus on the Pathophysiology of Adrenomedullin Expression: Endothelitis and Organ Damage in Severe Viral and Bacterial Infections. Cells 2024; 13:892. [PMID: 38891025 PMCID: PMC11172186 DOI: 10.3390/cells13110892] [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: 04/03/2024] [Revised: 05/03/2024] [Accepted: 05/15/2024] [Indexed: 06/20/2024] Open
Abstract
Adrenomedullin (ADM) is a peptide hormone produced primarily in the adrenal glands, playing a crucial role in various physiological processes. As well as improving vascular integrity and decreasing vascular permeability, ADM acts as a vasodilator, positive inotrope, diuretic, natriuretic and bronchodilator, antagonizing angiotensin II by inhibiting aldosterone secretion. ADM also has antihypertrophic, anti-apoptotic, antifibrotic, antioxidant, angiogenic and immunoregulatory effects and antimicrobial properties. ADM expression is upregulated by hypoxia, inflammation-inducing cytokines, viral or bacterial substances, strength of shear stress, and leakage of blood vessels. These pathological conditions are established during systemic inflammation that can result from infections, surgery, trauma/accidents or burns. The ability to rapidly identify infections and the prognostic, predictive power makes it a valuable tool in severe viral and bacterial infections burdened by high incidence and mortality. This review sheds light on the pathophysiological processes that in severe viral or bacterial infections cause endothelitis up to the development of organ damage, the resulting increase in ADM levels dosed through its more stable peptide mid-regional proadrenomedullin (MR-proADM), the most significant studies that attest to its diagnostic and prognostic accuracy in highlighting the severity of viral or bacterial infections and appropriate therapeutic insights.
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Affiliation(s)
- Silvia Spoto
- Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy; (G.D.); (L.L.); (F.M.); (R.C.); (G.T.); (S.S.)
| | - Stefania Basili
- Department of Translational and Precision Medicine, Sapienza University, Viale dell’Università, 30, 00185 Rome, Italy; (S.B.); (R.C.); (V.R.)
| | - Roberto Cangemi
- Department of Translational and Precision Medicine, Sapienza University, Viale dell’Università, 30, 00185 Rome, Italy; (S.B.); (R.C.); (V.R.)
| | - José Ramón Yuste
- Division of Infectious Diseases, Faculty of Medicine, Clinica Universidad de Navarra, University of Navarra, Avda. Pío XII, 36, 31008 Pamplona, Spain;
- Department of Internal Medicine, Faculty of Medicine, Clinica Universidad de Navarra, University of Navarra, Avda. Pío XII, 36, 31008 Pamplona, Spain
| | - Felipe Lucena
- Departamento de Medicina Interna, Clinica Universidad de Navarra, Avda. Pío XII, 36, 31008 Pamplona, Spain; (F.L.); (J.A.)
| | - Giulio Francesco Romiti
- Department of Translational and Precision Medicine, Sapienza University, Viale dell’Università, 30, 00185 Rome, Italy; (S.B.); (R.C.); (V.R.)
| | - Valeria Raparelli
- Department of Translational and Precision Medicine, Sapienza University, Viale dell’Università, 30, 00185 Rome, Italy; (S.B.); (R.C.); (V.R.)
| | - Josepmaria Argemi
- Departamento de Medicina Interna, Clinica Universidad de Navarra, Avda. Pío XII, 36, 31008 Pamplona, Spain; (F.L.); (J.A.)
| | - Giorgio D’Avanzo
- Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy; (G.D.); (L.L.); (F.M.); (R.C.); (G.T.); (S.S.)
| | - Luciana Locorriere
- Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy; (G.D.); (L.L.); (F.M.); (R.C.); (G.T.); (S.S.)
| | - Francesco Masini
- Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy; (G.D.); (L.L.); (F.M.); (R.C.); (G.T.); (S.S.)
| | - Rodolfo Calarco
- Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy; (G.D.); (L.L.); (F.M.); (R.C.); (G.T.); (S.S.)
| | - Giulia Testorio
- Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy; (G.D.); (L.L.); (F.M.); (R.C.); (G.T.); (S.S.)
| | - Serenella Spiezia
- Diagnostic and Therapeutic Medicine Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy; (G.D.); (L.L.); (F.M.); (R.C.); (G.T.); (S.S.)
| | - Massimo Ciccozzi
- Unit of Medical Statistics and Molecular Epidemiology, Università Campus Bio-Medico di Roma, 00128 Rome, Italy;
| | - Silvia Angeletti
- Unit of Laboratory, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy;
- Research Unit of Clinical Laboratory Science, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy
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Patel MA, Daley M, Van Nynatten LR, Slessarev M, Cepinskas G, Fraser DD. A reduced proteomic signature in critically ill Covid-19 patients determined with plasma antibody micro-array and machine learning. Clin Proteomics 2024; 21:33. [PMID: 38760690 PMCID: PMC11100131 DOI: 10.1186/s12014-024-09488-3] [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: 11/09/2023] [Accepted: 05/06/2024] [Indexed: 05/19/2024] Open
Abstract
BACKGROUND COVID-19 is a complex, multi-system disease with varying severity and symptoms. Identifying changes in critically ill COVID-19 patients' proteomes enables a better understanding of markers associated with susceptibility, symptoms, and treatment. We performed plasma antibody microarray and machine learning analyses to identify novel proteins of COVID-19. METHODS A case-control study comparing the concentration of 2000 plasma proteins in age- and sex-matched COVID-19 inpatients, non-COVID-19 sepsis controls, and healthy control subjects. Machine learning was used to identify a unique proteome signature in COVID-19 patients. Protein expression was correlated with clinically relevant variables and analyzed for temporal changes over hospitalization days 1, 3, 7, and 10. Expert-curated protein expression information was analyzed with Natural language processing (NLP) to determine organ- and cell-specific expression. RESULTS Machine learning identified a 28-protein model that accurately differentiated COVID-19 patients from ICU non-COVID-19 patients (accuracy = 0.89, AUC = 1.00, F1 = 0.89) and healthy controls (accuracy = 0.89, AUC = 1.00, F1 = 0.88). An optimal nine-protein model (PF4V1, NUCB1, CrkL, SerpinD1, Fen1, GATA-4, ProSAAS, PARK7, and NET1) maintained high classification ability. Specific proteins correlated with hemoglobin, coagulation factors, hypertension, and high-flow nasal cannula intervention (P < 0.01). Time-course analysis of the 28 leading proteins demonstrated no significant temporal changes within the COVID-19 cohort. NLP analysis identified multi-system expression of the key proteins, with the digestive and nervous systems being the leading systems. CONCLUSIONS The plasma proteome of critically ill COVID-19 patients was distinguishable from that of non-COVID-19 sepsis controls and healthy control subjects. The leading 28 proteins and their subset of 9 proteins yielded accurate classification models and are expressed in multiple organ systems. The identified COVID-19 proteomic signature helps elucidate COVID-19 pathophysiology and may guide future COVID-19 treatment development.
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Affiliation(s)
- Maitray A Patel
- Epidemiology and Biostatistics, Western University, London, ON, N6A 3K7, Canada
| | - Mark Daley
- Epidemiology and Biostatistics, Western University, London, ON, N6A 3K7, Canada
- Computer Science, Western University, London, ON, N6A 3K7, Canada
| | | | - Marat Slessarev
- Medicine, Western University, London, ON, N6A 3K7, Canada
- Lawson Health Research Institute, London, ON, N6C 2R5, Canada
| | - Gediminas Cepinskas
- Lawson Health Research Institute, London, ON, N6C 2R5, Canada
- Medical Biophysics, Western University, London, ON, N6A 3K7, Canada
| | - Douglas D Fraser
- Lawson Health Research Institute, London, ON, N6C 2R5, Canada.
- Children's Health Research Institute, London, ON, N6C 4V3, Canada.
- Pediatrics, Western University, London, ON, N6A 3K7, Canada.
- Clinical Neurological Sciences, Western University, London, ON, N6A 3K7, Canada.
- Physiology & Pharmacology, Western University, London, ON, N6A 3K7, Canada.
- London Health Sciences Centre, 800 Commissioners Road East, London, ON, N6A 5W9, Canada.
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Feghaly Z, Aoun R, Mouawad C, Chamaa B, Dahboul H, Kassar S, Osseis M, Noun R, Chakhtoura G. The Role of Obesity in the Poor Prognosis of COVID-19 Infection: A Review of 192 Patients. Interdiscip Perspect Infect Dis 2024; 2024:7212355. [PMID: 38770046 PMCID: PMC11105959 DOI: 10.1155/2024/7212355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 04/16/2024] [Accepted: 05/07/2024] [Indexed: 05/22/2024] Open
Abstract
Methods We performed a retrospective study on all patients having COVID-19 infection and admitted to our institution between March 2020 and June 2021. Inclusion criteria included any patient over the age of 18 admitted to our institution's COVID-19 unit, or intensive care unit, with a positive COVID-19 PCR or positive COVID-19 serology (IgM). Results 192 patients met the inclusion criteria, with an average age of 62.68 years and a slight male predominance (64.58%). 76.04% of hospitalized patients and 80% of those admitted to the ICU were either overweight or obese. No statistically significant difference was found regarding the risk of in-hospital mortality and invasive ventilation. The same applies to the length of stay, admission to intensive care, O2 needs, and for the various complications (all p values were >0.05). Patients with obesity type II and III have an increased risk of cardiac arrests and need for intubation and mechanical ventilation. Conclusion Obesity tends to be a major risk factor for a pejorative evolution in the COVID-19 infection.
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Affiliation(s)
- Ziad Feghaly
- Department of Digestive Surgery, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Rany Aoun
- Department of Digestive Surgery, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Christian Mouawad
- Department of Digestive Surgery, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Bilal Chamaa
- Department of Digestive Surgery, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Houssam Dahboul
- Department of Digestive Surgery, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Serge Kassar
- Department of Digestive Surgery, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Michael Osseis
- Department of Digestive Surgery, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Roger Noun
- Department of Digestive Surgery, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Ghassan Chakhtoura
- Department of Digestive Surgery, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
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Yildirim N, Zlotnikov S, Venkat A, Chawla G, Kim J, Bukowski LA, Kahn JM, Mccann J, Zimmerman J. Investigating Why Clinicians Deviate from Standards of Care: Liberating Patients from Mechanical Ventilation in the ICU. PROCEEDINGS OF THE CHI CONFERENCE ON HUMAN FACTORS IN COMPUTING SYSTEMS 2024:1-15. [DOI: 10.1145/3613904.3641982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Affiliation(s)
- Nur Yildirim
- HCI Institute, Carnegie Mellon University, United States
| | - Susanna Zlotnikov
- Integrated Innovation Institute, Carnegie Mellon University, United States
| | | | | | | | - Leigh A. Bukowski
- Department of Critical Care Medicine, University of Pittsburgh School of Medicine, United States
| | - Jeremy M. Kahn
- Department of Critical Care Medicine, University of Pittsburgh, United States
| | - James Mccann
- Robotics Institute, Carnegie Mellon University, United States
| | - John Zimmerman
- HCI Institute, Carnegie Mellon University, United States
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Singh T, Rao Padubidri J, Shetty PH, Antony Manoj M, Mary T, Thejaswi Pallempati B. The top 50 most-cited articles about COVID-19 and the complications of COVID-19: A bibliometric analysis. F1000Res 2024; 13:105. [PMID: 39149509 PMCID: PMC11325134 DOI: 10.12688/f1000research.145713.3] [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] [Accepted: 04/30/2024] [Indexed: 08/17/2024] Open
Abstract
Background This bibliometric analysis examines the top 50 most-cited articles on COVID-19 complications, offering insights into the multifaceted impact of the virus. Since its emergence in Wuhan in December 2019, COVID-19 has evolved into a global health crisis, with over 770 million confirmed cases and 6.9 million deaths as of September 2023. Initially recognized as a respiratory illness causing pneumonia and ARDS, its diverse complications extend to cardiovascular, gastrointestinal, renal, hematological, neurological, endocrinological, ophthalmological, hepatobiliary, and dermatological systems. Methods Identifying the top 50 articles from a pool of 5940 in Scopus, the analysis spans November 2019 to July 2021, employing terms related to COVID-19 and complications. Rigorous review criteria excluded non-relevant studies, basic science research, and animal models. The authors independently reviewed articles, considering factors like title, citations, publication year, journal, impact factor, authors, study details, and patient demographics. Results The focus is primarily on 2020 publications (96%), with all articles being open access. Leading journals include The Lancet, NEJM, and JAMA, with prominent contributions from Internal Medicine (46.9%) and Pulmonary Medicine (14.5%). China played a major role (34.9%), followed by France and Belgium. Clinical features were the primary study topic (68%), often utilizing retrospective designs (24%). Among 22,477 patients analyzed, 54.8% were male, with the most common age group being 26-65 years (63.2%). Complications of COVID-19 affected 13.9% of patients, with a recovery rate of 57.8%. Conclusion Analyzing these top-cited articles offers clinicians and researchers a comprehensive, timely understanding of influential COVID-19 literature. This approach uncovers attributes contributing to high citations and provides authors with valuable insights for crafting impactful research. As a strategic tool, this analysis facilitates staying updated and making meaningful contributions to the dynamic field of COVID-19 research.
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Affiliation(s)
- Tanya Singh
- Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India
| | - Jagadish Rao Padubidri
- Department of Forensic Medicine and Toxicology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India
| | - Pavanchand H Shetty
- Department of Forensic Medicine and Toxicology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India
| | - Matthew Antony Manoj
- Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India
| | - Therese Mary
- Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India
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Albert MC, Uranga-Murillo I, Arias M, De Miguel D, Peña N, Montinaro A, Varanda AB, Theobald SJ, Areso I, Saggau J, Koch M, Liccardi G, Peltzer N, Rybniker J, Hurtado-Guerrero R, Merino P, Monzón M, Badiola JJ, Reindl-Schwaighofer R, Sanz-Pamplona R, Cebollada-Solanas A, Megyesfalvi Z, Dome B, Secrier M, Hartmann B, Bergmann M, Pardo J, Walczak H. Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality. Cell Death Differ 2024; 31:544-557. [PMID: 38514848 PMCID: PMC11093991 DOI: 10.1038/s41418-024-01278-6] [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: 01/15/2024] [Revised: 03/04/2024] [Accepted: 03/08/2024] [Indexed: 03/23/2024] Open
Abstract
The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized that this process might also cause or contribute to inflammatory disease and lung failure following SARS-CoV-2 infection. To test this hypothesis, we developed a novel mouse-adapted SARS-CoV-2 model (MA20) that recapitulates key pathological features of COVID-19. Concomitantly with occurrence of cell death and inflammation, FasL expression was significantly increased on inflammatory monocytic macrophages and NK cells in the lungs of MA20-infected mice. Importantly, therapeutic FasL inhibition markedly increased survival of both, young and old MA20-infected mice coincident with substantially reduced cell death and inflammation in their lungs. Intriguingly, FasL was also increased in the bronchoalveolar lavage fluid of critically-ill COVID-19 patients. Together, these results identify FasL as a crucial host factor driving the immuno-pathology that underlies COVID-19 severity and lethality, and imply that patients with severe COVID-19 may significantly benefit from therapeutic inhibition of FasL.
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Affiliation(s)
- Marie-Christine Albert
- Cell death, inflammation and immunity laboratory, CECAD Cluster of Excellence, University of Cologne, Cologne, 50931, Germany
- Cell death, inflammation and immunity laboratory, Institute of Biochemistry I, Centre for Biochemistry, Faculty of Medicine, University of Cologne, Cologne, 50931, Germany
| | - Iratxe Uranga-Murillo
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, 28029, Spain
- Aragón Health Research Institute (IIS Aragón), San Juan Bosco 13, Zaragoza, 50009, Spain
- Department of Microbiology, Paediatrics, Radiology and Preventive Medicine and Public Health, University of Zaragoza, Zaragoza, 50009, Spain
| | - Maykel Arias
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, 28029, Spain
- Aragón Health Research Institute (IIS Aragón), San Juan Bosco 13, Zaragoza, 50009, Spain
- Department of Microbiology, Paediatrics, Radiology and Preventive Medicine and Public Health, University of Zaragoza, Zaragoza, 50009, Spain
| | - Diego De Miguel
- Aragón Health Research Institute (IIS Aragón), San Juan Bosco 13, Zaragoza, 50009, Spain
| | - Natacha Peña
- Aragón Health Research Institute (IIS Aragón), San Juan Bosco 13, Zaragoza, 50009, Spain
| | - Antonella Montinaro
- Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London, WC1E 6DD, UK
| | - Ana Beatriz Varanda
- Cell death, inflammation and immunity laboratory, CECAD Cluster of Excellence, University of Cologne, Cologne, 50931, Germany
- Cell death, inflammation and immunity laboratory, Institute of Biochemistry I, Centre for Biochemistry, Faculty of Medicine, University of Cologne, Cologne, 50931, Germany
| | - Sebastian J Theobald
- Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, 50931, Germany
- Faculty of Medicine and University Hospital of Cologne, Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, 50931, Germany
- German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, 50931, Germany
| | - Itziar Areso
- Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London, WC1E 6DD, UK
| | - Julia Saggau
- Cell death, inflammation and immunity laboratory, CECAD Cluster of Excellence, University of Cologne, Cologne, 50931, Germany
- Cell death, inflammation and immunity laboratory, Institute of Biochemistry I, Centre for Biochemistry, Faculty of Medicine, University of Cologne, Cologne, 50931, Germany
- Genome instability, inflammation and cell death laboratory, Institute of Biochemistry I, Centre for Biochemistry, Faculty of Medicine, University of Cologne, Cologne, 50931, Germany
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, 50931, Germany
| | - Manuel Koch
- Institue for Dental Research and Oral Musculoskeletal Biology, Faculty of Medicine and University Hospital Cologne, Cologne, 50931, Germany
| | - Gianmaria Liccardi
- Genome instability, inflammation and cell death laboratory, Institute of Biochemistry I, Centre for Biochemistry, Faculty of Medicine, University of Cologne, Cologne, 50931, Germany
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, 50931, Germany
| | - Nieves Peltzer
- Cell death, inflammation and immunity laboratory, CECAD Cluster of Excellence, University of Cologne, Cologne, 50931, Germany
- Faculty of Medicine and University Hospital of Cologne, Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, 50931, Germany
- Department of Translational Genomics, University of Cologne, Cologne, 50931, Germany
| | - Jan Rybniker
- Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, 50931, Germany
- Faculty of Medicine and University Hospital of Cologne, Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, 50931, Germany
- German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, 50931, Germany
| | - Ramón Hurtado-Guerrero
- Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), University of Zaragoza, Zaragoza, 50018, Spain
- Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, 2200, Denmark
- Fundación ARAID, Zaragoza, 50018, Spain
| | - Pedro Merino
- Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), University of Zaragoza, Zaragoza, 50018, Spain
| | - Marta Monzón
- Research Centre for Encephalopaties and Transmissible Emerging Diseases, Institute for Health Research Aragón (IIS), University of Zaragoza, Zaragoza, 50013, Spain
- Department of Human Anatomy and Histology, University of Zaragoza, Zaragoza, 50009, Spain
| | - Juan J Badiola
- Research Centre for Encephalopaties and Transmissible Emerging Diseases, Institute for Health Research Aragón (IIS), University of Zaragoza, Zaragoza, 50013, Spain
| | | | - Rebeca Sanz-Pamplona
- Aragón Health Research Institute (IIS Aragón), San Juan Bosco 13, Zaragoza, 50009, Spain
- Fundación ARAID, Zaragoza, 50018, Spain
- CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid, 28029, Spain
| | - Alberto Cebollada-Solanas
- Aragon Biomedical Research Center (CIBA), Instituto Aragonés de Ciencias de la Salud (IACS), Unidad de Biocomputación, Zaragoza, 50018, Spain
| | - Zsolt Megyesfalvi
- Deparment of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, Austria
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, 1122, Hungary
- National Koranyi Institute of Pulmonology, Budapest, 1121, Hungary
| | - Balazs Dome
- Deparment of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, Austria
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, 1122, Hungary
- National Koranyi Institute of Pulmonology, Budapest, 1121, Hungary
- Department of Translational Medicine, Lund University, Lund, SE-22100, Sweden
| | - Maria Secrier
- UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, WC1E 6BT, United Kingdom
| | - Boris Hartmann
- Virology Group, Institute for Veterinary Disease Control at AGES, Moedling, 2340, Austria
| | - Michael Bergmann
- Div. of Visceral Surgery, Dept. of General Surgery, Comprehensive Cancer Centre, Medical University of Vienna, Vienna, 1090, Austria
| | - Julián Pardo
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, 28029, Spain
- Aragón Health Research Institute (IIS Aragón), San Juan Bosco 13, Zaragoza, 50009, Spain
- Department of Microbiology, Paediatrics, Radiology and Preventive Medicine and Public Health, University of Zaragoza, Zaragoza, 50009, Spain
| | - Henning Walczak
- Cell death, inflammation and immunity laboratory, CECAD Cluster of Excellence, University of Cologne, Cologne, 50931, Germany.
- Cell death, inflammation and immunity laboratory, Institute of Biochemistry I, Centre for Biochemistry, Faculty of Medicine, University of Cologne, Cologne, 50931, Germany.
- Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London, WC1E 6DD, UK.
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Hendi MF, Alrais ZF, Syed F, Elkholy HM, Alsayed H, Moin M, Mukhtar SH. Prevalence of Diabetes, Ketosis, and Ketoacidosis and Their Correlation With Mortality in Critical COVID-19 Patients: A Single-Center Retrospective Study. Cureus 2024; 16:e57551. [PMID: 38707154 PMCID: PMC11068365 DOI: 10.7759/cureus.57551] [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: 04/03/2024] [Indexed: 05/07/2024] Open
Abstract
Aim We aimed to find out the prevalence of diabetes, ketosis, and ketoacidosis in coronavirus disease 2019 (COVID-19) critically ill patients and to explore the clinical impact of the development of ketosis and ketoacidosis on the outcome of COVID-19 critically ill patients and identify them as potential risk factors for these patients. Methods We collected data on COVID-19 patients admitted to the intensive care unit (ICU) retrospectively. The study population will be classified into two groups based on the presence of diabetes or ketosis. Results The study comprises data on 253 ICU patients admitted with COVID-19 pneumonia. Two hundred patients (79.05%) had diabetes or prediabetes on admission. Seventy-six patients (30%) presented with ketosis. Nine patients had progressed to diabetic ketoacidosis during their ICU stay. Concerning the outcome, among 150 patients who died (59.3%), there was significantly higher mortality among the ketotic patients (69.7%) compared to nonketotic patients (54.8%) with a P-value < 0.027. We noted that the peak blood glucose level during ICU stay was statistically significantly higher in nonsurvivors (mean 345 mg/dl) compared to survivors (mean 298 mg/dl) with a P-value of 0.006. Our data showed that peak serum levels of lactate, procalcitonin (PCT), C-reactive protein, white blood cells (WBC), D dimer, and lactate dehydrogenase strongly positively correlated to the length of ICU stay. We used the ROC curve (receiver operating characteristic curve) to assess the relation between many laboratories and mortality. We noted that uncontrolled hyperglycemia and other laboratory variables are significant predictors of mortality of COVID-19 patients (e.g., peak blood glucose (P = 0.004), PCT (P = 0.047), and P < 0.001 of other laboratories (e.g. lactate, PH, WBC, D dimer, ferritin). Conclusion We reported a high prevalence of diabetes and ketosis among COVID-19 patients admitted to the ICU. Ketosis is associated with an increased mortality risk. Uncontrolled hyperglycemia is a significant predictor of mortality in critically ill COVID-19 patients.
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Affiliation(s)
| | | | | | | | | | - Muneeba Moin
- Intensive Care Unit, Rashid Hospital, Dubai, ARE
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Bruyneel A, Bouckaert N, Pirson M, Sermeus W, Van den Heede K. Unfinished nursing care in intensive care units and the mediating role of the association between nurse working environment, and quality of care and nurses' wellbeing. Intensive Crit Care Nurs 2024; 81:103596. [PMID: 38043435 DOI: 10.1016/j.iccn.2023.103596] [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: 02/10/2023] [Revised: 11/13/2023] [Accepted: 11/17/2023] [Indexed: 12/05/2023]
Abstract
OBJECTIVES Unfinished care refers to the situation in which nurses are forced to delay or omit necessary nursing care. The objectives was: 1) to measure the prevalence of unfinished nursing care in intensive care units during the COVID-19 pandemic; 2) to examine whether unfinished nursing care has a mediating role in the relationship between nurse working environment and nurse-perceived quality of care and risk of burnout among nurses. DESIGN A national cross-sectional survey. SETTING Seventy-five intensive care units in Belgium (December 2021 to February 2022). MAIN OUTCOME MEASURES The Practice Environment Scale of the Nursing Work Index was used to measure the work environment. The perception of quality and safety of care was evaluated via a Likert-type scale. The risk of burnout was assessed using the Maslach Burnout Inventory scale. RESULTS A total of 2,183 nurse responses were included (response rate of 47.8%). Seventy-six percent of nurses reported at least one unfinished nursing care activity during their last shift. The staffing and resource adequacy subdimension of the Practice Environment Scale of the Nursing Work Index had the strongest correlation with unfinished nursing care. An increase in unfinished nursing care led to significantly lower perceived quality and safety of care and an increase in high risk of burnout. Unfinished nursing care appears to be a mediating factor for the association between staffing and resource adequacy and the quality and safety of care perceived by nurses and risk of burnout. CONCLUSIONS Unfinished nursing care, which is highly related to staffing and resource adequacy, is associated with increased odds of nurses being at risk of burnout and reporting a lower level of perceived quality of care. IMPLICATIONS FOR CLINICAL PRACTICE The monitoring of unfinished nursing care in the intensive care unit is an important early indicator of problems related to adequate staffing levels, the well-being of nurses, and the perceived quality of care.
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Affiliation(s)
- Arnaud Bruyneel
- Health Economics, Hospital Management and Nursing Research Dept, School of Public Health, Université Libre de Bruxelles, Belgium.
| | | | - Magali Pirson
- Health Economics, Hospital Management and Nursing Research Dept, School of Public Health, Université Libre de Bruxelles, Belgium
| | - Walter Sermeus
- KU Leuven Institute for Healthcare Policy, Leuven, Belgium
| | - Koen Van den Heede
- Belgian Health Care Knowledge Centre (KCE), Brussels, Belgium; KU Leuven Institute for Healthcare Policy, Leuven, Belgium
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Ismaiel A, Birkhahn L, Leucuta DC, Al Srouji N, Popa SL, Dumitrascu DL. Are adipokines related to COVID-19 and its severity? A systematic review and meta-analysis. Med Pharm Rep 2024; 97:120-131. [PMID: 38746027 PMCID: PMC11090279 DOI: 10.15386/mpr-2624] [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: 02/20/2023] [Revised: 05/01/2023] [Accepted: 06/15/2023] [Indexed: 05/16/2024] Open
Abstract
Introduction The relationship between several adipokines and COVID-19 severity has lately been evaluated, results being inconclusive. Therefore, we aimed to assess the association between adipokines in COVID-19 and its severity. Methods A search was performed in PubMed, Scopus, and Embase using predefined keywords. The Newcastle of Ottawa Scale (NOS) was used for the quality assessment of included studies. The main summary outcome was the mean difference (MD) in adipokine levels. Results A total of 8 studies involving 473 individuals were included. A significant MD in serum adiponectin levels was demonstrated in mild vs. severe COVID-19 patients (-5.734 [95% CI -11.215 - -0.252]), with no significant MD in mild vs. moderate (-7.117 [95% CI -19.546 - 5.313]), or moderate vs. severe COVID-19 (-1.846 [95% CI -4.516 - 0.824]). Moreover, no significant MD was found in adiponectin and leptin levels when comparing COVID-19 patients vs. controls (-12.675 [95% CI -36.159 - 10.808]) and (8.034 [95% CI -10.403 - 26.471]), respectively. Conclusion Adiponectin levels were significantly increased in patients with severe compared to mild COVID-19. However, no significant MD was found in adiponectin levels in mild vs. moderate and moderate vs. severe COVID-19 patients, nor in adiponectin and leptin levels in COVID-19 patients vs. controls.
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Affiliation(s)
- Abdulrahman Ismaiel
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Louis Birkhahn
- Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Daniel-Corneliu Leucuta
- Department of Medical Informatics and Biostatistics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Nahlah Al Srouji
- Leon Daniello Clinical Hospital of Pneumology, Cluj-Napoca, Romania
| | - Stefan-Lucian Popa
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Dan L. Dumitrascu
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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50
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Naidu AS, Wang CK, Rao P, Mancini F, Clemens RA, Wirakartakusumah A, Chiu HF, Yen CH, Porretta S, Mathai I, Naidu SAG. Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID. NPJ Sci Food 2024; 8:19. [PMID: 38555403 PMCID: PMC10981760 DOI: 10.1038/s41538-024-00261-2] [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: 10/12/2023] [Accepted: 03/15/2024] [Indexed: 04/02/2024] Open
Abstract
SARS-CoV-2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus-host protein-protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia ('cytokine storm'), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25-70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new 'onset' clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.
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Affiliation(s)
- A Satyanarayan Naidu
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA.
- N-terminus Research Laboratory, 232659 Via del Rio, Yorba Linda, CA, 92887, USA.
| | - Chin-Kun Wang
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- School of Nutrition, Chung Shan Medical University, 110, Section 1, Jianguo North Road, Taichung, 40201, Taiwan
| | - Pingfan Rao
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- College of Food and Bioengineering, Fujian Polytechnic Normal University, No.1, Campus New Village, Longjiang Street, Fuqing City, Fujian, China
| | - Fabrizio Mancini
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- President-Emeritus, Parker University, 2540 Walnut Hill Lane, Dallas, TX, 75229, USA
| | - Roger A Clemens
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- University of Southern California, Alfred E. Mann School of Pharmacy/D. K. Kim International Center for Regulatory & Quality Sciences, 1540 Alcazar St., CHP 140, Los Angeles, CA, 90089, USA
| | - Aman Wirakartakusumah
- International Union of Food Science and Technology (IUFoST), Guelph, ON, Canada
- IPMI International Business School Jakarta; South East Asian Food and Agriculture Science and Technology, IPB University, Bogor, Indonesia
| | - Hui-Fang Chiu
- Department of Chinese Medicine, Taichung Hospital, Ministry of Health & Well-being, Taichung, Taiwan
| | - Chi-Hua Yen
- Department of Family and Community Medicine, Chung Shan Medical University Hospital; School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Sebastiano Porretta
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- President, Italian Association of Food Technology (AITA), Milan, Italy
- Experimental Station for the Food Preserving Industry, Department of Consumer Science, Viale Tanara 31/a, I-43121, Parma, Italy
| | - Issac Mathai
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- Soukya International Holistic Health Center, Whitefield, Bengaluru, India
| | - Sreus A G Naidu
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- N-terminus Research Laboratory, 232659 Via del Rio, Yorba Linda, CA, 92887, USA
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