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Fokam J, Kengni Ngueko AM, Nka AD, Chenwi CA, Ngoufack Jagni Semengue E, Bouba Y, Takou D, Fainguem N, Tommo Tchouaket MC, Ka'e AC, Beloumou GA, Djupsa Ndjeyep SC, Togna Pabo WL, Gouissi Anguechia DH, Etame NK, Molimbou E, Nayang Mundo RA, Abba A, Sosso SM, Otshudiema Otokoye J, Ngongang Ouankou C, Alteri C, Colagrossi L, Santoro MM, Ceccherini-Silberstein F, Boum Y, Halle Ekane EG, Njamnshi AK, Colizzi V, Ndembi N, Ndjolo A, Perno CF. Viral dynamics and factors associated with duration of COVID-19 positivity: evidence from the first-three epidemiological waves in Cameroon. BMC Infect Dis 2025; 25:660. [PMID: 40325359 PMCID: PMC12054280 DOI: 10.1186/s12879-025-11048-5] [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: 07/02/2023] [Accepted: 04/25/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND Coronavirus 2019 (COVID-19) disease progression evidence and viral clearance time remain limited in tropical settings. Understanding this is crucial for public health control measures at community-level. We evaluated the viral dynamics of SARS-CoV-2 infection and factors associated with positivity duration in COVID-19 cases in Cameroon. MATERIAL AND METHODS We conducted a retrospective cohort-study of SARS-CoV-2 positive cases from the first to third wave (March 2020-October 2021) in Yaounde-Cameroon. RT-PCR was carried out on the participants using nasopharyngeal swabs after every 7 days. SARS-CoV-2 positivity duration was evaluated from the first to last positive PCR-test before a negative result. Epi-info V.7.0 was used for data analyses with p < 0.05 considered statistically significant. RESULTS A total of 282 participants were enrolled. The mean age was 41 ± 14 years, with male predominant (62.1%). We had 15.6% symptomatic participants of which 59% had cough. The overall median positivity duration was 15[IQR: 9-23] days with 15[IQR: 13-22] in the first, 17[IQR: 12-26] in the second and 9[IQR: 6-12] in the third wave (p < 0.0001). Positivity duration was significantly higher in males (16 versus 14 days, p = 0.03) those aged [35-45] years (16 days) followed by those ≥ 46 years(15 days); p = 0.008). Positivity duration was not affected by presence or absence of symptoms (p = 0.80). No significant correlation was found with viral load (r = 0.03; p = 0.61). Considering baseline (24.7 ± 7.2Ct) and last viral load (29.3 ± 5.9 Ct), the ΔCt (4.6 ± 1.3) and positivity duration (15 days) revealed a kinetic in viral decay of 0.3 ± 0.087 Ct/day. CONCLUSIONS A median positivity duration of 15 days is in accordance with viral clearance around 2 weeks for optimal confinement at community-level. Men and/or the elderly stand at higher risk of prolonged infection. Given the viral decay (0.3 Ct daily), we suggest personalized confinement periods. The variability of positivity duration according to waves could be function of strains which could be a factor influencing positivity duration.
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Affiliation(s)
- Joseph Fokam
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon.
- Faculty of Health Sciences, University of Buea, Buea, Cameroon.
- COVID-19 National Public Health Emergency Operations Coordination Centre, Yaounde, Cameroon.
- School of Health Sciences, Catholic University of Central Africa, Yaounde, Cameroon.
| | - Aurelie Minelle Kengni Ngueko
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon.
- School of Health Sciences, Catholic University of Central Africa, Yaounde, Cameroon.
- University of Rome "Tor Vergata", Rome, Italy.
| | - Alex Durand Nka
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
- University of Rome "Tor Vergata", Rome, Italy
- Evangelical University of Cameroon, Bandjoun, Cameroon
| | - Collins Ambe Chenwi
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
- University of Rome "Tor Vergata", Rome, Italy
| | - Ezechiel Ngoufack Jagni Semengue
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
- University of Rome "Tor Vergata", Rome, Italy
- Evangelical University of Cameroon, Bandjoun, Cameroon
| | - Yagai Bouba
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
- University of Rome "Tor Vergata", Rome, Italy
- National AIDS Control Committee (NACC), Yaoundé, Cameroon
| | - Désiré Takou
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
| | - Nadine Fainguem
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
| | - Michel Carlos Tommo Tchouaket
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
- School of Health Sciences, Catholic University of Central Africa, Yaounde, Cameroon
| | - Aude Christelle Ka'e
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
- University of Rome "Tor Vergata", Rome, Italy
| | - Grace Angong Beloumou
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
| | - Sandrine Claire Djupsa Ndjeyep
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
| | - Willy Leroi Togna Pabo
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
- Faculty of Health Sciences, University of Buea, Buea, Cameroon
| | | | - Naomi-Karell Etame
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
- School of Health Sciences, Catholic University of Central Africa, Yaounde, Cameroon
| | - Evariste Molimbou
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
- Evangelical University of Cameroon, Bandjoun, Cameroon
| | - Rachel Audrey Nayang Mundo
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
| | - Aissatou Abba
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
| | - Samuel Martin Sosso
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
| | | | | | - Claudia Alteri
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
- Multimodal Research Area, Microbiology and Diagnostics of Immunology Unit, IRCCS Bambino Gesu Pediatric Hospital, Rome, Italy
| | - Luna Colagrossi
- Multimodal Research Area, Microbiology and Diagnostics of Immunology Unit, IRCCS Bambino Gesu Pediatric Hospital, Rome, Italy
| | | | | | - Yap Boum
- COVID-19 National Public Health Emergency Operations Coordination Centre, Yaounde, Cameroon
- Faculty of Medicine and Biomedical Sciences, University of Yaounde I, Yaounde, Cameroon
| | | | - Alfred K Njamnshi
- Brain Research Africa Initiative (BRAIN)Neuroscience LabFaculty of Medicine and Biomedical Sciences, The University of Yaoundé I, Yaoundé, Cameroon
| | - Vittorio Colizzi
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
- University of Rome "Tor Vergata", Rome, Italy
- Evangelical University of Cameroon, Bandjoun, Cameroon
| | - Nicaise Ndembi
- Africa Centres for Disease Control and Prevention (A-CDC), Addis Ababa, Ethiopia
| | - Alexis Ndjolo
- Chantal BIYA International Reference Centre for Research On HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
| | - Carlo-Federico Perno
- Multimodal Research Area, Microbiology and Diagnostics of Immunology Unit, IRCCS Bambino Gesu Pediatric Hospital, Rome, Italy
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Giorgi F, Tedeschi R. Breathe better, live better: the science of slow breathing and heart rate variability. Acta Neurol Belg 2025:10.1007/s13760-025-02789-w. [PMID: 40252198 DOI: 10.1007/s13760-025-02789-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Accepted: 04/14/2025] [Indexed: 04/21/2025]
Abstract
BACKGROUND Slow breathing and heart rate variability (HRV) biofeedback have gained attention as non-invasive methods for enhancing autonomic regulation and promoting vagal tone. These techniques are associated with improvements in cardiovascular, respiratory, and neural outcomes, offering potential therapeutic applications for stress-related and chronic conditions. METHODS A scoping review was conducted by analyzing six studies focusing on slow breathing and HRV biofeedback. The included studies involved healthy adults aged between 18 and 60 years, free from major cardiovascular, respiratory, or neurological disorders. Studies were identified through systematic searches in MEDLINE (PubMed), Scopus, Web of Science, and other databases. Population characteristics, intervention protocols, and outcomes related to HRV, respiratory sinus arrhythmia (RSA), baroreflex sensitivity, and neural synchronization were extracted and synthesized. Interventions were applied both acutely (single or short-term sessions) and chronically (ranging from daily sessions over 4-8 weeks). RESULTS All six studies demonstrated significant improvements in HRV parameters, particularly the high-frequency (HF) band, reflecting enhanced parasympathetic activity. RSA increased significantly in studies utilizing tailored breathing patterns, especially those emphasizing longer exhalations. Baroreflex sensitivity improved in interventions combining HRV biofeedback and slow breathing, indicating better cardiovascular adaptability. One study reported neural synchronization between HRV and cortical potentials with decelerated breathing. Across studies, these interventions promoted relaxation, enhanced autonomic flexibility, and stabilized cardiovascular function. Autonomic flexibility refers to the dynamic ability of the autonomic nervous system to adapt to internal and external stressors by shifting between sympathetic and parasympathetic dominance. CONCLUSIONS Slow breathing and HRV biofeedback are effective, non-invasive interventions for improving autonomic regulation, vagal tone, and stress resilience. These techniques hold promise for managing chronic conditions and enhancing cardiovascular and mental health. Standardization of protocols and long-term evaluations are needed to optimize clinical implementation.
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Affiliation(s)
- Federica Giorgi
- Pediatric Physical Medicine and Rehabilitation Unit, IRCCS Institute of Neurological Sciences, Bologna, Italy
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3
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Bejm K, Wojtkiewicz S, Pastuszak Z, Liebert A. Oxygen-dependent functional brain haemodynamic response. BIOMEDICAL OPTICS EXPRESS 2025; 16:1457-1470. [PMID: 40322006 PMCID: PMC12047717 DOI: 10.1364/boe.545722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 01/17/2025] [Accepted: 01/24/2025] [Indexed: 05/08/2025]
Abstract
The influence of hypoxia - a condition where tissues are under oxygen deficiency - on the human brain under functional load has not been fully understood yet. This study aims to analyse the effects of hypoxia on the brain's haemodynamic response under visual stimulation, using the in-house developed functional near-infrared spectroscopy system and to quantify the hemodynamic response. Our results (median, 25th and 75th percentile) demonstrate the amplitude of the oxygenated haemoglobin functional response during hypoxia 0.30 µM (0.27, 0.41) was lower compared with the normoxia 0.63 µM (0.54, 0.93) and hyperoxia 0.73 µM (0.43, 1.09). No statistical significance is observed for the deoxygenated haemoglobin changes. The hypoxia has a statistically significant effect on the amplitude of the haemodynamic response (p < 0.001).
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Affiliation(s)
- Karolina Bejm
- Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland
| | - Stanislaw Wojtkiewicz
- Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland
| | - Zanna Pastuszak
- Laboratory of Preclinical Research and Environmental Agents, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
| | - Adam Liebert
- Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland
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Kneeland IJ, Biesen JN, Fink BC, Keeling LA, Lindsey L. The Association Between COVID-fear with Psychological Distress and Substance Use: the Moderating Effect of Treatment Engagement. J Behav Health Serv Res 2025; 52:231-248. [PMID: 39187735 DOI: 10.1007/s11414-024-09905-3] [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] [Accepted: 08/06/2024] [Indexed: 08/28/2024]
Abstract
The purpose of this brief report was to examine the association between COVID-fear with psychiatric symptoms severity and substance use risk in an outpatient population with co-occurring substance use and mental health disorders and whether these associations were moderated by treatment engagement, especially after providers had shifted from an in-person care model to a telehealth format. A total of 136 patients receiving outpatient treatment for comorbid substance use and mental health disorders completed self-report questionnaires on their psychiatric symptoms, substance use, and treatment engagement (i.e., frequency, length, and helpfulness of phone and video sessions with a mental health counselor, psychiatrist, or primary care provider) in the past month between November 2020 and March 2021. Results showed that COVID-fear was significantly associated with psychiatric symptom severity, but not substance use risk. Additionally, perceived helpfulness of phone counseling sessions moderated the associations between COVID-fear and global psychiatric symptom severity, such that COVID-fear and global psychiatric symptom severity were positively associated when perceived helpfulness was low, and not associated if perceived helpfulness was high. The present results highlight the importance of directly addressing fears specific to a national emergency, as well as for providers to build strong rapport with their clients.
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Affiliation(s)
| | - Judith N Biesen
- Department of Mental Health Law and Policy, University of South Florida, Tampa, FL, 33604, USA.
| | - Brandi C Fink
- Department of Psychiatry and Behavioral Science, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | | | - Larissa Lindsey
- Addictions and Substance Abuse Program, University of New Mexico Hospitals, Albuquerque, NM, USA
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Ay Karadas Y, Yilmaz Sahin S, Dönmez E, Temiz G. Effect of the coronavirus disease 2019 pandemic on beliefs and practices regarding hand hygiene among intensive care nurses: A repeated cross-sectional study. Medicine (Baltimore) 2025; 104:e41903. [PMID: 40128050 PMCID: PMC11936649 DOI: 10.1097/md.0000000000041903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Accepted: 02/28/2025] [Indexed: 03/26/2025] Open
Abstract
Hand hygiene is an important factor in the prevention of healthcare-associated infections. Studies show healthcare professionals' hand hygiene practices vary and are not at sufficient levels. This study aimed to examine the effect of the COVID-19 pandemic on the beliefs and practices of nurses working in intensive care units (ICU) towards hand hygiene. This was longitudinal, repeated, and cross-sectional study. The study was conducted in 2 phases between January 2,2020 and March 10,2021 in the intensive care unit of a university hospital in northern Turkey. No sampling method was used. The objective was to reach the entire population. The first phase of this study was completed with 119 (76% of the population) ICU nurses and the second phase with 85 (70% of the population) ICU nurses. The data were collected with the personal information form, hand hygiene belief scale (HHBS), hand hygiene practices inventory (HHPI) and the views of the intensive care nurses related to COVID-19. Descriptive statistics such as mean and standard deviations, frequency, and percentages and analytical statistics such as t-test, Mann-Whitney U test, Kruskal-Wallis test were used for data analysis at the significance level of P < .05. The majority of the nurses who participated in the study were female (75.6%; 69.4%), with a mean age of 30.82 ± 5.51 and 30.58 ± 5.51 years, respectively. There was a significant difference (P < .05) between the median HHBS (P = .002) and HHPI (P = .001) scores before and after COVID-19. All nurses (100%) reported that the pandemic was effective in hand hygiene practices. In this study, it was determined that the hand hygiene beliefs and practices of nurses were high, and the scores of nurses' hand hygiene beliefs and practices after COVID-19 increased significantly. Healthcare professionals must always adhere to stringent standards of hand hygiene, rather than merely during periods of heightened challenges. To ensure the sustainability of optimal hand hygiene practices, it is recommended that motivational interventions that strengthen beliefs and practices related to hand hygiene should be implemented and that studies should be conducted to evaluate their effectiveness.
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Affiliation(s)
- Yasemin Ay Karadas
- Department of Medical Services and Techniques, Bayburt University Vocational School of Health Services, Bayburt, Turkey
| | - Sibel Yilmaz Sahin
- Department of Surgical Diseases Nursing, University of Health Sciences, Hamidiye Faculty of Nursing, Istanbul, Turkey
| | - Elif Dönmez
- Hamidiye Faculty of Nursing, Oncology Nursing Department, University of Health Sciences, Istanbul, Turkey
| | - Gamze Temiz
- Hamidiye Faculty of Nursing, Oncology Nursing Department, University of Health Sciences, Istanbul, Turkey
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6
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Simioni C, Sanz JM, Gafà R, Cenacchi G, Occhionorelli S, Passaro A, Neri LM. Increase of VEGF and Fibronectin expression and ultrastructural alterations of intercellular junctions in a swab negative patient after SARS-COV-2 infection. Virol J 2025; 22:82. [PMID: 40114185 PMCID: PMC11927238 DOI: 10.1186/s12985-025-02701-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 03/09/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND SARS-CoV-2 infection has been responsible of COrona VIrus Disease (COVID-19) pandemia and can cause a variety of symptoms including gastrointestinal disorders, abdominal pain and liver injury. The host receptor for SARS-CoV-2, ACE2, is expressed in gut and SARS-CoV-2 infection could induce vascular damage and immune system dysregulation, creating an inflammatory and hypercoagulable state, as widely described at the lung level. CASE PRESENTATION This work presents the case of a middle-aged Caucasian man admitted to the Hospital Emergency Department from the University Hospital of Ferrara (Italy), complaining of pain in the upper and middle region of the abdomen. The patient tested negative to the nose-oropharyngeal swab for SARS-CoV-2 four weeks after recovering from viral infection. The patient required resection of a segment of ileum and an ulcer of the bowel wall was recognized and sampled. Previous published results had confirmed the presence of the SARS-CoV-2 nucleocapsid protein, an increased human leukocyte antigen (HLA-G) and an altered morphology of microvilli in the ulcerated ileum of the patient when compared to the non-ulcerated ileum. The present study sought to deepen the consequences of SARS-CoV-2 infection. To this end, we evaluated the expression and co-expression of Vascular Endothelial Growth Factor (VEGF) and Fibronectin by immunohistochemical techniques. VEGF immunohistochemical expression was higher in the ulcer than in the control ileum sample and the non-ulcerated ileum areas and co-expressed with the SPIKE protein. Fibronectin staining was lower in control sample than in non-ulcerated and ulcerated ileum. Electron microscopy analysis showed alterations of the integrity of the intestinal barrier in the ulcerated area when compared to the non-ulcerated ileum or to the control sample. CONCLUSIONS Although the patient was tested negative to nose-oropharyngeal swab for SARS-CoV-2, the SPIKE protein was detected in his terminal ileum, especially in the ulcerated areas. The presence of the viral protein was also associated with an increase of VEGF and Fibronectin. In addition to vascular changes, the SARS-CoV-2 infection altered the junctional apparatus among epithelial cells, making the tissue even more fragile and thus susceptible to the entry of pathogens and the development of further infections.
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Affiliation(s)
- Carolina Simioni
- Department of Life Sciences and Biotechnology, University of Ferrara, Via Luigi Borsari 46, Ferrara, I-44121, Italy
- Laboratory for Technologies of Advanced Therapies (LTTA)-Electron Microscopy Center, University of Ferrara, Via Luigi Borsari 46, Ferrara, I-44121, Italy
| | - Juana Maria Sanz
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari 46, Ferrara, I-44121, Italy
| | - Roberta Gafà
- Department of Translational Medicine, University of Ferrara, Via Luigi Borsari 46, Ferrara, I-44121, Italy
- Integrated Activity Department of Onco-Hematology, University Hospital of Ferrara Arcispedale, Sant'Anna - Via Aldo Moro 8, Ferrara, I-44124, Italy
| | - Giovanna Cenacchi
- Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Bologna, 40126, Italy
| | - Savino Occhionorelli
- Department of Translational Medicine, University of Ferrara, Via Luigi Borsari 46, Ferrara, I-44121, Italy
- Emergency Surgery Department, University Hospital of Ferrara Arcispedale Sant'Anna, Via Aldo Moro 8, Ferrara, I-44124, Italy
| | - Angelina Passaro
- Department of Translational Medicine, University of Ferrara, Via Luigi Borsari 46, Ferrara, I-44121, Italy.
| | - Luca Maria Neri
- Laboratory for Technologies of Advanced Therapies (LTTA)-Electron Microscopy Center, University of Ferrara, Via Luigi Borsari 46, Ferrara, I-44121, Italy.
- Department of Translational Medicine, University of Ferrara, Via Luigi Borsari 46, Ferrara, I-44121, Italy.
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Zhang G, Wang N, Ma S, Zhang Y, Tao P, Cai H. Comprehensive Analysis of Potential Common Pathogenic Mechanisms for COVID-19 Infection and Gastric Cancer. Anal Cell Pathol (Amst) 2025; 2025:5106674. [PMID: 40224213 PMCID: PMC11991771 DOI: 10.1155/ancp/5106674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 12/16/2024] [Accepted: 01/25/2025] [Indexed: 04/15/2025] Open
Abstract
A growing body of data suggests that the prevalence of COVID-19 pneumonia in patients with stomach cancer is much higher than in the general population. However, these mechanisms are still not fully understood. After a thorough examination of shared differentially expressed genes (DEGs) for gastric cancer (GC) and COVID-19 pneumonia, we performed functional annotation, protein-protein interaction (PPI) networks, module design, and pivot gene identification. qPCR was used to verify the expression of hub genes in GC. Finally, a pivotal gene transcription factor-gene regulatory network was created and validated. According to functional enrichment analysis, common genes are mainly enriched in biological processes such as extracellular matrix tissue and extracellular structural tissue. Finally, five genes were found to be pivotal genes in the pathogenesis of GC and COVID-19 pneumonia: BGN (biglycan), UBE2C (ubiquitin-conjugating enzymes 2C), SPP1 (secreted phosphoprotein 1), THBS2 (thrombospondin 2), and COL1A1 (type I collagen alpha 1). These shared pathways and pivotal genes could provide new insights for more mechanistic studies.
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Affiliation(s)
- Guiqian Zhang
- Otorhinolaryngology Head and Neck Surgery, The 940th Hospital of Joint Logistics Support Force of People's Liberation Army, Lanzhou, China
| | - Ning Wang
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Shixun Ma
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China
| | - Yan Zhang
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China
| | - Pengxian Tao
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- Cadre Ward of General Surgery Department, Gansu Provincial Hospital, Lanzhou, China
| | - Hui Cai
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China
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8
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Chavhan RL, Jaybhaye SG, Hinge VR, Deshmukh AS, Shaikh US, Jadhav PK, Kadam US, Hong JC. Emerging applications of gene editing technologies for the development of climate-resilient crops. Front Genome Ed 2025; 7:1524767. [PMID: 40129518 PMCID: PMC11931038 DOI: 10.3389/fgeed.2025.1524767] [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: 11/08/2024] [Accepted: 01/07/2025] [Indexed: 03/26/2025] Open
Abstract
Climate change threatens global crop yield and food security due to rising temperatures, erratic rainfall, and increased abiotic stresses like drought, heat, and salinity. Gene editing technologies, including CRISPR/Cas9, base editors, and prime editors, offer precise tools for enhancing crop resilience. This review explores the mechanisms of these technologies and their applications in developing climate-resilient crops to address future challenges. While CRISPR/enables targeted modifications of plant DNA, the base editors allow for direct base conversion without inducing double-stranded breaks, and the prime editors enable precise insertions, deletions, and substitutions. By understanding and manipulating key regulator genes involved in stress responses, such as DREB, HSP, SOS, ERECTA, HsfA1, and NHX; crop tolerance can be enhanced against drought, heat, and salt stress. Gene editing can improve traits related to root development, water use efficiency, stress response pathways, heat shock response, photosynthesis, membrane stability, ion homeostasis, osmotic adjustment, and oxidative stress response. Advancements in gene editing technologies, integration with genomics, phenomics, artificial intelligence (AI)/machine learning (ML) hold great promise. However, challenges such as off-target effects, delivery methods, and regulatory barriers must be addressed. This review highlights the potential of gene editing to develop climate-resilient crops, contributing to food security and sustainable agriculture.
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Affiliation(s)
- R. L. Chavhan
- Vilasrao Deshmukh College of Agricultural Biotechnology, Vasantrao Naik Marathwada Krishi Vidyapeeth, Latur, India
| | - S. G. Jaybhaye
- Vilasrao Deshmukh College of Agricultural Biotechnology, Vasantrao Naik Marathwada Krishi Vidyapeeth, Latur, India
| | - V. R. Hinge
- Vilasrao Deshmukh College of Agricultural Biotechnology, Vasantrao Naik Marathwada Krishi Vidyapeeth, Latur, India
| | - A. S. Deshmukh
- Vilasrao Deshmukh College of Agricultural Biotechnology, Vasantrao Naik Marathwada Krishi Vidyapeeth, Latur, India
| | - U. S. Shaikh
- Vilasrao Deshmukh College of Agricultural Biotechnology, Vasantrao Naik Marathwada Krishi Vidyapeeth, Latur, India
| | - P. K. Jadhav
- Vilasrao Deshmukh College of Agricultural Biotechnology, Vasantrao Naik Marathwada Krishi Vidyapeeth, Latur, India
| | - U. S. Kadam
- Division of Applied Life Science (BK21 Four), Division of Life Science, Plant Molecular Biology and Biotechnology Research Centre (PMBBRC), Gyeongsang National University, Jinju, Republic of Korea
| | - J. C. Hong
- Division of Applied Life Science (BK21 Four), Division of Life Science, Plant Molecular Biology and Biotechnology Research Centre (PMBBRC), Gyeongsang National University, Jinju, Republic of Korea
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Khan S, Hussain Timraz J, Al Ghamdi NA, Metwali NY, Yaseen FA, Alshaqha AM, Alamri SH, Turkistani H, Dwaima A, Ali Algarni I. COVID-19 and Its Effects on the Hepatobiliary System: A Literature Review. Cureus 2025; 17:e80231. [PMID: 40190856 PMCID: PMC11972666 DOI: 10.7759/cureus.80231] [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: 03/07/2025] [Indexed: 04/09/2025] Open
Abstract
COVID-19 encompasses a wide clinical spectrum, from mild influenza-like illness to severe pneumonia and systemic complications. There is emerging literature on hepatobiliary involvement in COVID-19, especially elevation in liver enzymes as surrogate markers of liver injury. Angiotensin-converting enzyme 2 receptors within the hepatobiliary system are a portal of entry for SARS-CoV-2, after which injury may be perpetuated through hypoxia and cytokine storms. This literature review covers studies published before 2024 from databases such as PubMed, Google Scholar, Springer, and BMC Library. The keywords used were "COVID-19", "liver", "SARS-CoV-2", "chronic liver disease", and other relevant terms to ensure a wide scope of investigation. The most common liver enzymes elevated among COVID-19 patients include aspartate transaminase, alanine transaminase, and alkaline phosphatase, all of which are associated with the severity of the disease. Chronic liver disease (CLD) and hepatocellular carcinoma (HCC) patients have worse outcomes with increased ICU admission rates and increased mortality. COVID-19 vaccination in CLD and liver transplant recipients is very often associated with suboptimal antibody responses, adding to the risks. SARS-CoV-2 causes liver involvement through direct viral cytopathic effects, immune-mediated injury, and systemic hypoxia. Individuals with CLD are particularly vulnerable to severe illness.
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Affiliation(s)
- Sariya Khan
- General Medicine and Surgery, Batterjee Medical College, Jeddah, SAU
| | | | | | - Nada Y Metwali
- Obstetrics and Gynecology, Batterjee Medical College, Jeddah, SAU
| | - Faten A Yaseen
- Medicine and Surgery, Batterjee Medical College, Jeddah, SAU
| | | | - Sarah H Alamri
- Internal Medicine, Batterjee Medical College, Jeddah, SAU
| | | | - Anas Dwaima
- Internal Medicine, International Medical Center Hospital, Jeddah, SAU
| | - Ibraheem Ali Algarni
- Family Medicine, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, SAU
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10
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Singh D. The Impact of the COVID-19 Pandemic on Women’s Health: A Review. CURRENT WOMEN S HEALTH REVIEWS 2025; 21. [DOI: 10.2174/0115734048273722231201080837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 11/16/2023] [Accepted: 11/20/2023] [Indexed: 01/04/2025]
Abstract
:
During any crisis, whether it is health, economic, or environmental, people are more
likely to experience stress, anxiety, and other psychological issues that jeopardize their general
well-being. The Coronavirus, or COVID-19, is considered a global pandemic that affects millions
of persons. Many people of different ages have significantly suffered from mental illness as a result
of COVID-19, especially women affected vulnerable. As per the report, the death rates of
men have doubled in comparison with women; this epidemic shows a bigger influence on the
health of women than men. Even quarantine impacts make the females afraid, bewildered, and
feel alone, which is terrible for them, as it also disturbs their health, such as pregnancy, sexual
life, postpartum depression, etc. This review article reveals the COVID-19 impact on the health of
women and finds a way to prevent and manage the health implications in women at various periods
throughout their lives.
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Affiliation(s)
- Deepika Singh
- Department of Pharmaceutical Sciences, Shalom Institute of Health and Allied Sciences, Sam Higginbottom University
of Agriculture, Technology and Sciences, Prayagraj, India
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11
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Ramli Y, Prawiroharjo P, Wiratman W, Tenda E, Ibrahim N, Susilaradeya D, Reza A, Agatha J, Siagian R, Fauhan H, Evelyn F, Ugawa Y, Yusuf P. The relationship between cognitive function and neuropsychiatric disorders with quantitative electroencephalogram (qEEG) on long COVID syndrome patients. Brain Behav Immun Health 2025; 44:100954. [PMID: 39990283 PMCID: PMC11847274 DOI: 10.1016/j.bbih.2025.100954] [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: 06/23/2024] [Revised: 12/25/2024] [Accepted: 01/22/2025] [Indexed: 02/25/2025] Open
Abstract
Background The COVID-19 pandemic has resulted in long-term consequences for a subset of affected individuals, known as long COVID syndrome. The neurological and psychiatric effects of this condition remain incompletely understood. This study aims to evaluate heightened common mental disorders in long COVID through assessing psychiatric, cognitive, neurophysiological aspects, and emphasizing lasting mental health impacts. Methods This cross-sectional study compared patients with long COVID to those who had recovered from COVID-19 without residual symptoms using quantitative electroencephalogram (qEEG) analysis. We conducted qEEG analyses, and Montreal Cognitive Assessment (MoCA) and Self-Rating Questionnaire (SRQ) tests on participants. Analyses included brain spectrum examination, hemispheric asymmetry, and inter-electrode connectivity. Results Analyses revealed lower MoCA scores in the memory domain were lower in the long COVID group (Mann Whitney Utest), indicating that individuals with long COVID experience more substantial cognitive deficits. There is no statistical difference for spectrum examination and hemispheric asymmetry observed in the qEEG data between the COVID and long COVID groups. Connectivity analysis showed statistically significant higher connectivity in temporal-occipital (T6-O2) in long COVID groups (Mann Whitney Utest). Conclusion Our findings underscore the persistent neuropsychiatric impact of COVID-19, particularly in long COVID patients. Notably, working memory deficits in MoCA scores were identified as one of the most frequent neuropsychological symptoms in these individuals. Decreased brain connectivity indicates cognitive-sensorimotor decline and is confirmed by the frequent brain fog symptoms in long COVID.
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Affiliation(s)
- Yetty Ramli
- Department of Neurology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- Medical Technology IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Pukovisa Prawiroharjo
- Department of Neurology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- Medical Technology IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Winnugroho Wiratman
- Department of Neurology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- Medical Technology IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Eric Tenda
- Medical Technology IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Nurhadi Ibrahim
- Medical Technology IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- Department of Medical Physiology and Biophysics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Damar Susilaradeya
- Medical Technology IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- Department of Medical Physiology and Biophysics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Abdi Reza
- Department of Neurosurgery, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Jennifer Agatha
- Medical Technology IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Rejoel Siagian
- Medical Technology IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Hazrina Fauhan
- Medical Technology IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | | | - Yoshikazu Ugawa
- Department of Department of Human Neurophysiology, Institute of Brain Medical Sciences, Fukushima Medical University, Japan
| | - Prasandhya Yusuf
- Medical Technology IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- Department of Medical Physiology and Biophysics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
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12
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Kim J, Kim YR, Lee SM, Lee J, Lee S, Yong D, Park HG. Novel Isothermal Amplification Integrated with CRISPR/Cas13a and Its Applications for Ultrasensitive Detection of SARS-CoV-2. ACS Synth Biol 2025; 14:463-469. [PMID: 39834214 DOI: 10.1021/acssynbio.4c00605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2025]
Abstract
We herein developed an ultrasensitive and rapid strategy to identify genomic nucleic acids by integrating a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 13a (Cas13a) into our recently developed isothermal technique, nicking and extension chain reaction system-based amplification (NESBA) reaction. In this technique, named CESBA, the NESBA reaction isothermally produces a large amount of RNA amplicons from the initial target genomic RNA (gRNA). The RNA amplicons bind to the crispr RNA (crRNA) and activate the collateral cleavage activity of Cas13a, which would then cleave the reporter probe nearby, consequently producing the final signals. Based on this design principle, we successfully detected SARS-CoV-2 gRNA as a model target very sensitively down to even a single copy (0.05 copies/μL) in both fluorescence- and lateral flow assay (LFA)-based modes with excellent specificity against other human coronaviruses (H-CoVs). We further validated the clinical applicability of CESBA by testing the 20 clinical samples with 100% clinical sensitivity and specificity. This work represents a potent and innovative strategy for the identification of genomic nucleic acids in molecular diagnostics, delivering exceptional levels of sensitivity.
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Affiliation(s)
- Jaemin Kim
- Department of Chemical and Biomolecular Engineering (BK21 Four), Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
| | - Yo Rim Kim
- Department of Chemical and Biomolecular Engineering (BK21 Four), Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
| | - Sang Mo Lee
- Department of Chemical and Biomolecular Engineering (BK21 Four), Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
| | - Jinhwan Lee
- Department of Chemical and Biomolecular Engineering (BK21 Four), Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
| | - Seoyoung Lee
- Department of Chemical and Biomolecular Engineering (BK21 Four), Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
| | - Dongeun Yong
- Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Hyun Gyu Park
- Department of Chemical and Biomolecular Engineering (BK21 Four), Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
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13
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Shehzadi K, Kalsoom I, Yu MJ, Liang JH. Design and in-silico evaluation of PNA-based novel pronucleotide analogues targeting RNA-dependent RNA polymerase to combat COVID-19. J Biomol Struct Dyn 2025:1-23. [PMID: 39937582 DOI: 10.1080/07391102.2024.2335287] [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: 11/10/2023] [Accepted: 03/19/2024] [Indexed: 02/13/2025]
Abstract
The emergence of highly contagious SARS-CoV-2 variants emphasizes the need for antiviral drugs that can adapt to evolving viral mutations. Despite widespread vaccination efforts, novel variants and recurrence cases raise concerns about COVID-19. Although repurposed drugs like Remdesivir, a nucleoside inhibitor, offer treatment, there is still a critical need for alternative drugs. Inhibiting viral RdRp function remains a key strategy. Structural analysis highlights the importance of pyrrolo-triazine and pyrimidine scaffolds in nucleoside inhibitors. Our study designed Peptide Nucleic Acid (PNA) antisense pronucleotides by combining these scaffolds using structure-guided drug design. Molecular modeling, including molecular docking, pharmacokinetics, molecular dynamics simulations, and MMPBSA binding energy calculations, predicts that modified PNAs can disrupt ribosome assembly at the RdRp translation start site. The neutral backbone of PNAs may enhance sequence-specific RNA binding. MD simulations revealed that complexes of Remdesivir and L14 remained stable throughout, with the phosphate tail of L14 stabilized by a positive amino acid pocket near the RdRp-RNA entry channel, similar to Remdesivir. Additionally, L14's guanine motif interacted with U20, A19, and U18 on the primer RNA strand. The lead PNA analog (L14) showed superior binding free energy to both RdRp (-47.26 kcal/mol) and RdRp-RNA (-85.66 kcal/mol), outperforming Remdesivir. Key amino acid residues critical for binding affinity were identified, providing valuable insights for drug development. This promising PNA-mimetic compound offers dual-target specificity, presenting a compelling avenue for developing potent anti-SARS-CoV-2 agents.
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Affiliation(s)
- Kiran Shehzadi
- Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, China
| | - Iqra Kalsoom
- Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, China
| | - Ming-Jia Yu
- Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, China
| | - Jian-Hua Liang
- Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, China
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14
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Assis GMCCD, Veiga IGD, Reis RDNR, Menezes DCD, Xavier SS, Chaves ECR, Sousa JRD, Quaresma JAS, Falcão LFM, Lima PDLD. Investigation of renal function in patients with long COVID in the Amazon region: a cross-sectional study. BMC Infect Dis 2025; 25:202. [PMID: 39934662 PMCID: PMC11817966 DOI: 10.1186/s12879-024-10355-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Accepted: 12/16/2024] [Indexed: 02/13/2025] Open
Abstract
BACKGROUND COVID-19 became a pandemic disease in 2020, with multisystem involvement and high renal morbidity during the acute phase. Some affected patients began to present new or persistent symptoms in a condition known as Long COVID. The study aimed to evaluate renal function using clinical and laboratory findings, and to establish the frequency and staging of renal function decline in Long COVID patients, as well as the associated factors. METHODS This is a cross-sectional observational study that selected participants from a Long COVID clinical care program between 2020 and 2022. RESULTS A total of 246 patients were selected for this study, and renal function decline was found in 83 (33.7%). Patients over 60 years (29.6%) and those who developed glycaemic alterations (41.8%) exhibited a higher prevalence of renal outcomes in long COVID. Some laboratory test as LDH levels and glycated hemoglobin seems to have a statistic relation with a decrease in renal function (p < 0.05). CONCLUSION A decline in renal function was common in patients with Long COVID in this study, and older age and glycaemic alterations were relevant to this condition. Some laboratory markers can be used to predict this outcome.
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Affiliation(s)
| | - Ian Gonçalves da Veiga
- Department of Center for Biological Health Sciences (CCBS), State University of Pará (UEPA), Belém, Pará, 66087-670, Brazil
| | - Rita de Nazaré Rayol Reis
- Department of Center for Biological Health Sciences (CCBS), State University of Pará (UEPA), Belém, Pará, 66087-670, Brazil
| | - Daniel Carvalho de Menezes
- Department of Center for Biological Health Sciences (CCBS), State University of Pará (UEPA), Belém, Pará, 66087-670, Brazil
| | - Stanley Soares Xavier
- Department of Center for Biological Health Sciences (CCBS), State University of Pará (UEPA), Belém, Pará, 66087-670, Brazil
| | - Elem Cristina Rodrigues Chaves
- Department of Center for Biological Health Sciences (CCBS), State University of Pará (UEPA), Belém, Pará, 66087-670, Brazil
| | - Jorge Rodrigues de Sousa
- Department of Morphology and Physiological Sciences (DMCF), State University of Pará (UFPA), Belém, Pará, 66087-670, Brazil
| | - Juarez Antônio Simões Quaresma
- Department of Center for Biological Health Sciences (CCBS), State University of Pará (UEPA), Belém, Pará, 66087-670, Brazil
- School of Medicine, São Paulo University (USP), São Paulo, 01246903, Brazil
| | - Luiz Fábio Magno Falcão
- Department of Center for Biological Health Sciences (CCBS), State University of Pará (UEPA), Belém, Pará, 66087-670, Brazil
- School of Medicine, São Paulo University (USP), São Paulo, 01246903, Brazil
| | - Patrícia Danielle Lima de Lima
- Department of Center for Biological Health Sciences (CCBS), State University of Pará (UEPA), Belém, Pará, 66087-670, Brazil.
- Department of Center for Biological Health Sciences (CCBS), Graduate Program in Parasitic Biology in Amazonia (PPGBPA), State University of Pará (UEPA), Belém, Pará, Marco-66087-670, Brazil.
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15
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Yazbeck A, Akika R, Awada Z, Zgheib NK. The role of candidate genetic polymorphisms in covid-19 susceptibility and outcomes. BMC Med Genomics 2025; 18:30. [PMID: 39920651 PMCID: PMC11806658 DOI: 10.1186/s12920-025-02094-8] [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: 09/26/2024] [Accepted: 01/28/2025] [Indexed: 02/09/2025] Open
Abstract
BACKGROUND This study aims to investigate the association between candidate host genetic polymorphisms and COVID-19 susceptibility, severity, hospitalization, hypoxia, and their combined effect, measured by the polygenic risk score (PRS). METHODS Three hundred and seventy-six Lebanese participants, comprising 151 controls and 225 cases, were included. Clinical data were obtained from questionnaires and medical records. DNA isolated from peripheral blood was genotyped for ACE1 rs1799752, ACE2 rs2074192, TMPRSS2 rs75603675 and OAS1 rs107746771 using TaqMan assays, and for TMPRSS2 rs35074065 using Sanger Sequencing. Candidate genetic variants were analyzed in association with COVID-19 susceptibility, severity, hospitalization and hypoxia, using univariate and multivariate models. PRS constructed from the weighted sum of variants was evaluated in association with COVID-19 outcomes. RESULTS In this study, there were no statistically significant differences in the frequencies of candidate variant alleles between cases, controls and within disease outcomes subgroups, after adjustment for confounders. PRS was not associated with COVID-19 susceptibility and hospitalization, it however significantly predicted COVID-19 severity (P = 0.01). CONCLUSION This study highlights the importance of genetic testing for key host genes involved in COVID-19 life cycle and eventually measuring the PRS which proves to be an important tool for prognosis assessment in vulnerable individuals, potentially enhancing patient care.
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Affiliation(s)
- Anthony Yazbeck
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Reem Akika
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Zainab Awada
- Research Department, Sidra Medicine, Doha, Qatar
| | - Nathalie K Zgheib
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
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16
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Zhang N, Luo X, Ji X, Tian T, Wu R, Zhao S, Wang G. Genomic Patterns are Associated with Different Sequelae of Patients with Long-Term COVID-19. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2407342. [PMID: 39741349 PMCID: PMC11848565 DOI: 10.1002/advs.202407342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 12/15/2024] [Indexed: 01/02/2025]
Abstract
In the post-large era, various COVID-19 sequelae are getting more and more attention to health problems. Although the mortality rate of the COVID-19 infection is now declining, it is often accompanied by new clinical sequelae with different symptoms such as fatigue after infection, loss of smell. The degree of age, gender, virus infection seems to be weakly correlated with clinical symptoms. Human genetic variation plays a significant role in the sequelae of the COVID-19 infection. This study aims to analyze the genomic differences between individuals with different COVID-19 sequelae. In this study, the exomes of 97 patients with Omicron with 8 unique clinical manifestations are sequenced, and conducted a systematic analysis. Based on non-negative matrix factorization algorithms, the trinucleotide mutation spectrum of four long-term COVID-19 genomes is summarized and found that individuals with different clinical symptoms have unique DNA mutation patterns and indel patterns. By constructing a Genomic Fingerprinting Framework, the driver genes of variation in each symptomatic population are deciphered and analyzed. This study showed that population-specific mutational fingerprint differences are the main cause of heterogeneity in long-term COVID-19 sequelae. This study provides new ideas and insights into the causes of the long-term COVID-19 sequelae.
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Affiliation(s)
- Nan Zhang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious DiseasesKey Laboratory of Pathobiology Ministry of EducationChina‐Japan Union Hospital of Jilin UniversityChangchun130033China
- College of MathematicsJilin UniversityChangchun130012China
| | - Xizi Luo
- State Key Laboratory for Zoonotic DiseasesKey Laboratory for Zoonosis Research of the Ministry of EducationCollege of Veterinary MedicineJilin UniversityChangchun130062China
- College of Basic Medical SciencesJilin UniversityChangchun130021China
| | - Xiangwen Ji
- Department of Cardiology and Institute of Vascular MedicinePeking University Third Hospital49 Huayuanbei RoadBeijing100191China
| | - Tian Tian
- College of Basic Medical SciencesJilin UniversityChangchun130021China
| | - Runze Wu
- College of MathematicsJilin UniversityChangchun130012China
| | - Shishun Zhao
- College of MathematicsJilin UniversityChangchun130012China
| | - Guoqing Wang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious DiseasesKey Laboratory of Pathobiology Ministry of EducationChina‐Japan Union Hospital of Jilin UniversityChangchun130033China
- College of Basic Medical SciencesJilin UniversityChangchun130021China
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17
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Zhang P, Xin M, Bai Y, Ren X, Li N. Severe central nervous system injury in 9 children with COVID-19. BMC Pediatr 2025; 25:63. [PMID: 39871225 PMCID: PMC11771022 DOI: 10.1186/s12887-025-05436-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 01/16/2025] [Indexed: 01/29/2025] Open
Abstract
PURPOSE To investigate the clinical features and prognosis of severe central nervous system (CNS) injury in children caused by coronavirus disease 2019 (COVID-19). METHOD We retrospectively studied confirmed pediatric cases of COVID-19 complicated with CNS injury. RESULTS Nine patients diagnosed with COVID-19 complicated with severe CNS injury were admitted to the pediatric intensive care unit of the Affiliated Hospital of Jining University from December 1, 2022 to January 12, 2023. Of the nine patients, seven were male (77.78%). Five children were aged ≥ 10 years, and the others were 1-2 years old. All children had fever, eight had convulsions, seven had progressed to multiple organ failure, and all suffered varying degrees of coma. Most of the children had elevated interleukin-6 (100%), lactic acid (100%), alanine transaminase (87.5%), aspartate transaminase (87.5%), creatine kinase MB (87.5%), and lactate dehydrogenase (85.7%) levels. Four children had cerebrospinal fluid proteinnacell separation. The cranial imaging results of five children were abnormal. One child had lost his vital signs when admitted to hospital, and the remaining eight received hormonal shock, human immunoglobulin transfusion, antinainfection, cranial pressure reduction, and tracheal intubation, among others, during hospitalization. Ultimately, eight children died, and the remaining child has serious neurological sequelae and is undergoing rehabilitation. CONCLUSIONS Severe CNS injury caused by COVID-19 has an acute onset, rapid progression, high disability rate, and high fatality rate. A low cerebrospinal fluid protein level may be a protective factor for children with severe nervous system injury caused by COVID-19.
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Affiliation(s)
- Peipei Zhang
- Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, 272007, Shandong, China
| | - Meiyun Xin
- Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, 272007, Shandong, China
| | - Yingge Bai
- Surrey College, Dongbei University of Finance and Economics, Dalian, 116025, Liaoning, China
| | - Xueyun Ren
- Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, 272007, Shandong, China
| | - Na Li
- Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, 272007, Shandong, China.
- Postdoctoral Mobile Station of Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China.
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18
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Thuy La VN, Kang L, Minh DDL. Enzyme kinetics model for the coronavirus main protease including dimerization and ligand binding. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.01.631001. [PMID: 39803422 PMCID: PMC11722214 DOI: 10.1101/2025.01.01.631001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/22/2025]
Abstract
The coronavirus main protease (MPro) plays a pivotal role in viral replication and is the target of several antivirals against SARS-CoV-2. In some species, CRCs of MPro enzymatic activity can exhibit biphasic behavior in which low ligand concentrations activate the enzyme whereas higher ones inhibit it. While this behavior has been attributed to ligand-induced dimerization, quantitative enzyme kinetics models have not been fit to it. Here, we develop a kinetic model integrating dimerization and ligand binding. We perform a Bayesian regression to globally fit the model to multiple types of biochemical and biophysical data. The reversible covalent inhibitor GC376 strongly induces dimerization and binds to the dimer with no cooperativity. In contrast, the fluorescent peptide substrate has a minor effect on dimerization but binds to the dimer with positive cooperativity. The biphasic concentration response curve occurs because compared to substrate, the inhibitor accelerates turnover in the opposite catalytic site.
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Affiliation(s)
- Van Ngoc Thuy La
- Department of Biology, Illinois Institute of Technology, Chicago, IL 60616, USA
| | - Lulu Kang
- Department of Mathematics and Statistics, University of Massachusetts Amherst, Amherst, MA, 01003, USA
| | - David D L Minh
- Department of Chemistry, Illinois Institute of Technology, Chicago, IL 60616, USA
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19
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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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20
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Mailani F, Huriani E, Krisdianto BF, Oktarina E. Nurses' Experiences at the Intensive Care Unit for COVID-19 in Indonesia: A Study of Hermeneutic Phenomenology. IRANIAN JOURNAL OF NURSING AND MIDWIFERY RESEARCH 2025; 30:25-33. [PMID: 40052038 PMCID: PMC11881967 DOI: 10.4103/ijnmr.ijnmr_447_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 09/14/2024] [Accepted: 09/17/2024] [Indexed: 03/09/2025]
Abstract
Background Nurses working in Intensive Care Unit (ICU) for COVID-19 are more at risk as they interact more with infected patients. Therefore, this study aimed to explore the experience of Indonesian nurses who work in ICU for COVID-19 patients. Materials and Methods A qualitative hermeneutic phenomenological approach was used. A total of 20 nurses working in the respective ICUs of eight COVID-19 referral tertiary hospitals in Indonesia were recruited using purposive sampling. Semistructured individual video call interviews were conducted in June-September 2021; then, Diekelmann's hermeneutic phenomenological approach was used to analyze and interpret the data. Results Thirteen subthemes describing the following four themes, namely, the pleasing and bad feelings, new challenges of working, nursing professional growth, and nurse resource management for COVID-19. Conclusions This study describes nurses' experiences working in ICUs during the COVID-19 crisis, such as their feelings, perceived challenges, and received support. Nurse leaders play a significant role in providing adequate Personal Protective Equipment (PPE), flexible work shifts, and a caring and healing work environment. However, being aware of the limit of pressure that an individual can manage and providing adequate allowance as rewards for work in risky areas are essential to avoid burnout.
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Affiliation(s)
- Fitri Mailani
- Medical-Surgical Department, Faculty of Nursing, Universitas Andalas, Padang, West Sumatera, Indonesia
| | - Emil Huriani
- Medical-Surgical Department, Faculty of Nursing, Universitas Andalas, Padang, West Sumatera, Indonesia
| | - Boby Febri Krisdianto
- Medical-Surgical Department, Faculty of Nursing, Universitas Andalas, Padang, West Sumatera, Indonesia
| | - Elvi Oktarina
- Medical-Surgical Department, Faculty of Nursing, Universitas Andalas, Padang, West Sumatera, Indonesia
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21
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Delibaş L, Polat F, Ekren Çakici A. Adults' State of Using Complementary and Alternative Medicine During the COVID-19 Pandemic: Complementary and Alternative Medicine During the COVID-19 Pandemic. Holist Nurs Pract 2025; 39:59-65. [PMID: 35435866 DOI: 10.1097/hnp.0000000000000506] [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: 11/27/2022]
Abstract
This study aimed to explore the attitudes of adults living in Turkey toward complementary and alternative medicine in the period of the coronavirus disease-2019 (COVID-19) pandemic and identify whether Turkish adults used complementary and alternative medicine during the pandemic. The cross-sectional study covered 3242 adults across Turkey. The data were collected via a Personal Information Form and the Holistic Complementary and Alternative Medicine Questionnaire. The participants had positive attitudes toward complementary and alternative medicine (33.8 ± 4.7). The results indicated that the Turkish adults widely used complementary and alternative treatment methods (70.5%) during the COVID-19 pandemic, and they were more oriented toward the use of herbal treatment (35.5%). It was identified that the primary reasons for using complementary and alternative medicine were to be protected from COVID-19, and if infected with COVID-19, to recover from it quickly with only mild symptoms.
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Affiliation(s)
- Leyla Delibaş
- Author Affiliations: Hasan Kalyoncu University Vocational School, Gaziantep, Turkey (Dr Delibaş and Ms Çakici); and Faculty of Nursing, Osmaniye Korkut Ata University, Osmaniye, Turkey (Dr Polat)
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22
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Rengiiyiler S, Teközel M. Visual attention is not attuned to non-human animal targets' pathogenicity: an evolutionary mismatch perspective. THE JOURNAL OF GENERAL PSYCHOLOGY 2025; 152:36-57. [PMID: 38733318 DOI: 10.1080/00221309.2024.2349005] [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: 09/17/2023] [Accepted: 04/23/2024] [Indexed: 05/13/2024]
Abstract
A considerable amount of research has revealed that there exists an evolutionary mismatch between ancestral environments and conditions following the rise of agriculture regarding the contact between humans and animal reservoirs of infectious diseases. Based on this evolutionary mismatch framework, we examined whether visual attention exhibits adaptive attunement toward animal targets' pathogenicity. Consistent with our predictions, faces bearing heuristic infection cues held attention to a greater extent than did animal vectors of zoonotic infectious diseases. Moreover, the results indicated that attention showed a specialized vigilance toward processing facial cues connoting the presence of infectious diseases, whereas it was allocated comparably between animal disease vectors and disease-irrelevant animals. On the other hand, the pathogen salience manipulation employed to amplify the participants' contextual-level anti-pathogen motives did not moderate the selective allocation of attentional resources. The fact that visual attention seems poorly equipped to detect and encode animals' zoonotic transmission risk supports the idea that our evolved disease avoidance mechanisms might have limited effectiveness in combating global outbreaks originating from zoonotic emerging infectious diseases.
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Affiliation(s)
| | - Mert Teközel
- Department of Psychology, Ege University, Izmir, Turkey
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23
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Chelly S, Jaziri S, Ammar A, Ezzi O, Douss N, Saffar S, Tritar M, Njah M, Mahjoub M. Safety and efficiency of COVID-19 vaccine in North Africa. Hum Vaccin Immunother 2024; 20:2306703. [PMID: 38304972 PMCID: PMC10841012 DOI: 10.1080/21645515.2024.2306703] [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: 10/17/2023] [Accepted: 01/15/2024] [Indexed: 02/03/2024] Open
Abstract
Background In the absence of a specific treatment for COVID-19, preventive measures have been implemented to control this pandemic and vaccination is one of them. However, it is crucial to verify the safety and efficiency of every vaccine. The aim was to determinate the predictive factors of side effects and reinfection after COVID-19 vaccine. Methods A cross-sectional study was conducted in February 2022 among Tunisians infected with COVID-19 between March 2020 and February 2022, using an online self-administered questionnaire. We conducted univariate and multivariate analyses using binary stepwise logistic regression. Results A total of 1541 was selected from 1911 individuals. Comorbidities affected a quarter of the population (22.3%). Before the initial infection, 39.3% had received full vaccination, and 8.7% had received partial vaccination. By February 2022, the majority (82.9%) had received at least two vaccine doses. The reinfection rate was 30.6%. All vaccines prior to the first infection was identified as a protective factor against reinfection. Inactivated virus vaccinations were less likely to induce adverse effects. Conclusion ach vaccine has its own set of advantages and disadvantages: mRNA-based vaccines had a higher incidence of side effects but all vaccines provided better protection against reinfection.
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Affiliation(s)
- Souhir Chelly
- Faculty of Medicine of Sousse, Infection Prevention and Control Department, Farhat Hached University Hospital, University of Sousse, Sousse, Tunisia
| | - Shayma Jaziri
- Faculty of Medicine of Sousse, Infection Prevention and Control Department, Farhat Hached University Hospital, University of Sousse, Sousse, Tunisia
| | - Asma Ammar
- Faculty of Medicine of Sousse, Infection Prevention and Control Department, Farhat Hached University Hospital, University of Sousse, Sousse, Tunisia
| | - Olfa Ezzi
- Faculty of Medicine of Sousse, Infection Prevention and Control Department, Farhat Hached University Hospital, University of Sousse, Sousse, Tunisia
| | - Nour Douss
- Faculty of Medicine of Sousse, Infection Prevention and Control Department, Farhat Hached University Hospital, University of Sousse, Sousse, Tunisia
| | - Sonia Saffar
- Faculty of Medicine of Sousse, Infection Prevention and Control Department, Farhat Hached University Hospital, University of Sousse, Sousse, Tunisia
| | - Marouen Tritar
- Faculty of Medicine of Sousse, Infection Prevention and Control Department, Farhat Hached University Hospital, University of Sousse, Sousse, Tunisia
| | - Mansour Njah
- Faculty of Medicine of Sousse, Infection Prevention and Control Department, Farhat Hached University Hospital, University of Sousse, Sousse, Tunisia
| | - Mohamed Mahjoub
- Faculty of Medicine of Sousse, Infection Prevention and Control Department, Farhat Hached University Hospital, University of Sousse, Sousse, Tunisia
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24
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Li X, Zhu H, Xu P, Zhang J, Wang Z, He H, Shen F, Jiang Y, Shen L, Xiang J, Yang L, Yang C, Jiang H, Gao G, Jin J, Shen H, Wang Y, Wu L, Qian C, Liu D, Qiu W, Li Q, Chen Y, Lin F, Liu Y. A comprehensive immune repertoire signature distinguishes pulmonary infiltration in SARS-CoV-2 Omicron variant infection. Front Immunol 2024; 15:1486352. [PMID: 39742285 PMCID: PMC11685115 DOI: 10.3389/fimmu.2024.1486352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 11/27/2024] [Indexed: 01/03/2025] Open
Abstract
Introduction The coronavirus disease 2019 (COVID-19) global pandemic has been the most severe public health emergency since 2019. Currently, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the most dominant. The most prominent symptom of SARS-CoV-2 infection is respiratory. Meanwhile, the fatality of COVID-19 was mainly from pneumonia. However ,in patients with SARS-CoV-2 infection who have pneumonia and those who do not, the differences in the immune repertoire still require further investigation. Methods We conducted seven-chain adaptome immune repertoire analyses on patients with SARS-CoV-2 Omicron infection, both with and without pulmonary infiltration. Results Patients with pulmonary infiltration exhibit lymphopenia, a decreased proportion of the overall TCR repertoire alongside an increased BCR repertoire, reduced IGHD and IGHM isotype expression, a shorter mean CDR3 length for TRG, and a longer mean length for TRD, as well as diminished clonality and diversity in the TCR/BCR repertoire. Meanwhile, patients with pulmonary infiltration have distinct V-J gene usage and unique CDR3 signature, as well as BCR class switch recombination pattern. Finally, prior vaccination triggered less BCR IGHM/IGHD somatic hypermutation response, preserved the diversity of the entire adaptive immune repertoire, and provided clinical protection against severe or critical conditions following Omicron infection. Discussion We report a unique, comprehensive adaptive immune system signature in patients with pulmonary infiltration, which may serve as potential immunological biomarkers and therapeutic targets.
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Affiliation(s)
- Xuechuan Li
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Hongyi Zhu
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Peipei Xu
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Jie Zhang
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Zhe Wang
- Tilcure Biotherapeutics, Shanghai, China
| | - Hui He
- Department of Training Department, China Medical University Benxi Central Hospital Postgraduate Training Workstation, Shanghai, China
| | - Fang Shen
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Yi Jiang
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Lijuan Shen
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Jing Xiang
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Linhua Yang
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Chao Yang
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Hao Jiang
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Ganglong Gao
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Junshuo Jin
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Huojian Shen
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Yinping Wang
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Linshi Wu
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Changlin Qian
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Dejun Liu
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Weiqing Qiu
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Qiwei Li
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Yuanwen Chen
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Fujun Lin
- Renal Division, Department of Internal Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yun Liu
- Shanghai Cancer Institute, Shanghai, China
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25
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Zhu N, Ye R, Liu F, Li D, Lin Y, Li W, Wu G, Zhuang D, Huang X. Comparing clinical and biochemical characteristics of febrile seizures in children with and without COVID-19: a retrospective study. BMC Infect Dis 2024; 24:1389. [PMID: 39639218 PMCID: PMC11622598 DOI: 10.1186/s12879-024-10287-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 11/27/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND Transmission of COVID-19 is now normalized. There is an association between it and increased incidence of febrile seizures in children. Exploring whether COVID-19 has a specific effect on the clinical and biochemical features of febrile seizures is critical for the development of clinical treatment and prevention strategies. This study is to compare the differences in clinical features, hematological features, and cerebrospinal fluid characteristics between COVID-19 and non-COVID-19 children with febrile seizures and to provide a new perspective for further exploring the impact of COVID-19 on the nervous system of children. METHODS This was a retrospective case-control study. The cases included children with COVID-19 and non-COVID-19 febrile seizures admitted to Xiamen Children's Hospital from December 2022 to December 2023. The age, gender, length of hospital stay, peak body temperature, presence or absence of other viral infections, hematological characteristics, and cerebrospinal fluid characteristics were compared between children with COVID-19 febrile seizures and non-COVID-19 febrile seizures. RESULTS A total of 50 COVID-19 children with febrile seizures and 192 non-COVID-19 children with febrile seizures were enrolled in this study. Multivariate analysis showed that age (OR = 0.715, P = 0.031), blood urea nitrogen (OR = 0.454, P = 0.029), platelet count (OR = 0.987, P = 0.009) and magnesium ion concentration (OR = 0.109, P < 0.001) were negatively correlated with COVID-19 febrile seizures. Albumin (OR = 1.840, P < 0.001) was positively correlated. The concentration of potassium ion in cerebrospinal fluid (OR = 0.334, P = 0.012) was negatively correlated with COVID-19 febrile seizures, and the concentration of sodium ion (OR = 4.383, P = 0.022) was positively correlated with COVID-19 febrile seizures. CONCLUSION There were differences in age, blood urea nitrogen, platelet count, magnesium ion concentration, albumin, potassium ion concentration in cerebrospinal fluid, and sodium ion concentration in the cerebrospinal fluid between children with COVID-19 febrile seizures and non-COVID-19 febrile seizures. This study may provide valuable insights into the potential mechanisms of COVID-19 damage to the nervous system in children, and the long-term neurological prognosis of these children requires long-term follow-up.
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Affiliation(s)
- Nanxi Zhu
- Children's Hospital of Fudan University (Xiamen Branch), Xiamen Children's Hospital, No. 92-98, Yibin Road, Huli District, Xiamen, 361006, China
- Fujian Provincial Key Laboratory of Neonatal Diseases, Xiamen, 361006, China
| | - Ruming Ye
- Children's Hospital of Fudan University (Xiamen Branch), Xiamen Children's Hospital, No. 92-98, Yibin Road, Huli District, Xiamen, 361006, China
- Fujian Provincial Key Laboratory of Neonatal Diseases, Xiamen, 361006, China
| | - Fangyi Liu
- Jinjiang Municipal Hospital, Jinjiang, 362200, China
| | - Dan Li
- Children's Hospital of Fudan University (Xiamen Branch), Xiamen Children's Hospital, No. 92-98, Yibin Road, Huli District, Xiamen, 361006, China
- Fujian Provincial Key Laboratory of Neonatal Diseases, Xiamen, 361006, China
| | - Ying Lin
- Children's Hospital of Fudan University (Xiamen Branch), Xiamen Children's Hospital, No. 92-98, Yibin Road, Huli District, Xiamen, 361006, China
- Fujian Provincial Key Laboratory of Neonatal Diseases, Xiamen, 361006, China
| | - Wanting Li
- Children's Hospital of Fudan University (Xiamen Branch), Xiamen Children's Hospital, No. 92-98, Yibin Road, Huli District, Xiamen, 361006, China
- Fujian Provincial Key Laboratory of Neonatal Diseases, Xiamen, 361006, China
| | - Guanhong Wu
- Children's Hospital of Fudan University (Xiamen Branch), Xiamen Children's Hospital, No. 92-98, Yibin Road, Huli District, Xiamen, 361006, China
- Fujian Provincial Key Laboratory of Neonatal Diseases, Xiamen, 361006, China
| | - Deyi Zhuang
- Children's Hospital of Fudan University (Xiamen Branch), Xiamen Children's Hospital, No. 92-98, Yibin Road, Huli District, Xiamen, 361006, China.
- Fujian Provincial Key Laboratory of Neonatal Diseases, Xiamen, 361006, China.
| | - Xianghui Huang
- Children's Hospital of Fudan University (Xiamen Branch), Xiamen Children's Hospital, No. 92-98, Yibin Road, Huli District, Xiamen, 361006, China.
- Fujian Provincial Key Laboratory of Neonatal Diseases, Xiamen, 361006, China.
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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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27
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Karofi DH, Lawal N, Bello MB, Imam MU. Immunogenicity and Protective Efficacy of Nucleic Acid-Based Vaccines Against COVID-19: A Systematic Review. Mol Biotechnol 2024; 66:3438-3448. [PMID: 38006520 DOI: 10.1007/s12033-023-00965-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 10/25/2023] [Indexed: 11/27/2023]
Abstract
To overcome the COVID-19 pandemic, the development of safe and effective vaccines is crucial. With the enormous information available on vaccine development for COVID-19, there are still grey areas to be considered when designing a potential vaccine. The rapid regulatory approval of nucleic acid-based vaccines was unique to the COVID-19; these vaccines were rapidly produced cost-effectively and with lesser risk of infectivity. Additionally, they demonstrated relative stability at room temperature (DNA). However, a comparative understanding of the immunogenic impact and efficacy of these vaccines is lacking. Immunogenicity is essential for developing and maintaining effective and long-lasting post-vaccination immunity to pathogenic microorganisms. This systematic review aims to assess and summarize the immunogenicity and protective efficacy of the nucleic acid-based vaccines against COVID-19. The Preferred Reporting Items for Systematic Reviews (PRISMA) recommendations were followed in this review. CASP tool was used for quality assessment of randomized controlled trials. All included studies employed a randomized control method, and the results demonstrated promising immune responses and effectiveness that provided high-level protection against COVID-19 infection. This study offers vital insights for advancing vaccine technology. Furthermore, it guides formulation, informs personalized vaccination strategies, and enhances global health preparedness, particularly in regions with limited vaccine access.
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Affiliation(s)
- Dahiru Hafiz Karofi
- Department of Veterinary Microbiology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria
| | - Nafi'u Lawal
- Department of Veterinary Microbiology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria
| | - Muhammad Bashir Bello
- Department of Veterinary Microbiology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria
| | - Mustapha Umar Imam
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria.
- Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, P.M.B 2254, Sokoto, Nigeria.
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28
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Aldiabat M, Aleyadeh W, Muzammil T, Adewuyi K, Alahmad M, Jabri A, Alhuneafat L, Kilani Y, Alsakarneh S, Bilal M. Rates, Risk Factors, and Outcomes of Nonvariceal Upper Gastrointestinal Bleeding in Patients Hospitalized for COVID-19 in the United States. Curr Med Sci 2024; 44:1202-1209. [PMID: 39673580 DOI: 10.1007/s11596-024-2838-6] [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: 06/15/2023] [Accepted: 12/11/2023] [Indexed: 12/16/2024]
Abstract
OBJECTIVE This study aimed to investigate the incidence and predictors of non-variceal upper gastrointestinal bleeding (NVUGIB) in hospitalized patients with coronavirus disease 2019 (COVID-19), as well as the inpatient outcomes associated with this complication. METHODS This was an analysis of the National Inpatient Sample Database from January to December 2020. Adult COVID-19 patients were categorized into two groups based on NVUGIB development during hospitalization. Multivariate logistic analysis was performed to identify predictors and outcomes associated with NVUGIB in hospitalized COVID-19 patients in the US, after adjusting for age, sex, race, and Charlson Comorbidity Index (CCI) score, using Stata/BE 17.0. RESULTS Among 1 050 045 hospitalized patients, 1.87% developed NVUGIB. Asian Americans had the highest risk, followed by Native Americans, Hispanics, and African Americans, with odds ratios (ORs) of 1.70, 1.59, 1.40, and 1.14, respectively. Patients with higher CCI scores were also at greater risk (with ORs of 1.47, 2.09, and 3.45 for CCI scores of 1, 2, and 3, respectively). COVID-19 patients with NVUGIB had a higher risk of inpatient mortality (OR=3.84), acute kidney injury (OR=3.12), hypovolemic shock (OR=13.7), blood transfusion (OR=7.02), and in-hospital cardiac arrest (OR=4.02). CONCLUSION NVUGIB occurred in 1.87% of hospitalized COVID-19 patients and was associated with a threefold increase in mortality. Further research is necessary to identify strategies for reducing its incidence in COVID-19 patients with multiple risk factors.
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Affiliation(s)
- Mohammad Aldiabat
- Harvard T.H. Chan School of Public Health, Harvard University, Boston, 02115, USA.
| | - Wesam Aleyadeh
- Department of Medicine, Cleveland Clinic Akron General, Akron, 44307, USA
| | - Taimur Muzammil
- Department of Medicine, Allegheny Health Network, Pittsburgh, 15212, USA
| | - Kemi Adewuyi
- Department of Medicine, Allegheny Health Network, Pittsburgh, 15212, USA
| | - Majd Alahmad
- Department of Medicine, University of Pittsburgh, Pittsburgh, 15261, USA
| | - Ahmad Jabri
- Heart and Vascular Center, MetroHealth Medical Center, Cleveland, 44109, USA
| | - Laith Alhuneafat
- Department of Medicine, Allegheny Health Network, Pittsburgh, 15212, USA
| | - Yassine Kilani
- Department of Medicine, Lincoln Medical Center/Weil Cornell Medicine, Bronx, 10451, USA
| | - Saqr Alsakarneh
- Department of Medicine, University of Missouri-Kansas City, Kansas City, 64108, USA
| | - Mohammad Bilal
- Department of Medicine, University of Minnesota/Minneapolis VA Medical Center, Minneapolis, 55417, USA
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Barozi V, Chakraborty S, Govender S, Morgan E, Ramahala R, Graham SC, Bishop NT, Tastan Bishop Ö. Revealing SARS-CoV-2 M pro mutation cold and hot spots: Dynamic residue network analysis meets machine learning. Comput Struct Biotechnol J 2024; 23:3800-3816. [PMID: 39525081 PMCID: PMC11550722 DOI: 10.1016/j.csbj.2024.10.031] [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: 08/15/2024] [Revised: 10/19/2024] [Accepted: 10/19/2024] [Indexed: 11/16/2024] Open
Abstract
Deciphering the effect of evolutionary mutations of viruses and predicting future mutations is crucial for designing long-lasting and effective drugs. While understanding the impact of current mutations on protein drug targets is feasible, predicting future mutations due to natural evolution of viruses and environmental pressures remains challenging. Here, we leveraged existing mutation data during the evolution of the SARS-CoV-2 protein drug target main protease (Mpro) to test the predictive power of dynamic residue network (DRN) analysis in identifying mutation cold and hot spots. We conducted molecular dynamics simulations on the Mpro of SARS-CoV-2 (Wuhan strain) and calculated eight DRN metrics (averaged BC, CC, DC, EC, ECC, KC, L, PR), each of which identifies a unique network feature within the protein. The sets of residues with the highest and lowest values for each metric, comprising potential cold and hot spots, were compared to published biochemical analyses and per residue mutation frequencies observed across five SARS-CoV-2 lineages, encompassing a total of 191,878 sequences. Individual DRN metrics displayed only modest power to predict the mutation frequency of individual residues. However, integrating the eight DRN metrics with additional structural and sequence-derived metrics allowed us to develop machine learning models which significantly improved the prediction of residue mutation frequency. While further refinements should enhance accuracy, we demonstrated a robust method to understand pathogen evolution. This approach can also guide the development of long-lasting drugs by targeting functional residues located in and near active site, and allosteric sites, that are less prone to mutations.
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Affiliation(s)
- Victor Barozi
- Research Unit in Bioinformatics (RUBi), Department of Biochemistry, Microbiology and Bioinformatics, Rhodes University, Makhanda 6139, South Africa
| | - Shrestha Chakraborty
- Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
| | - Shaylyn Govender
- Research Unit in Bioinformatics (RUBi), Department of Biochemistry, Microbiology and Bioinformatics, Rhodes University, Makhanda 6139, South Africa
| | - Emily Morgan
- Research Unit in Bioinformatics (RUBi), Department of Biochemistry, Microbiology and Bioinformatics, Rhodes University, Makhanda 6139, South Africa
| | - Rabelani Ramahala
- Research Unit in Bioinformatics (RUBi), Department of Biochemistry, Microbiology and Bioinformatics, Rhodes University, Makhanda 6139, South Africa
| | - Stephen C. Graham
- Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
| | - Nigel T. Bishop
- Department of Pure and Applied Mathematics, Rhodes University, Makhanda 6139, South Africa
- National Institute for Theoretical and Computational Sciences (NITheCS), South Africa
| | - Özlem Tastan Bishop
- Research Unit in Bioinformatics (RUBi), Department of Biochemistry, Microbiology and Bioinformatics, Rhodes University, Makhanda 6139, South Africa
- National Institute for Theoretical and Computational Sciences (NITheCS), South Africa
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Ameni G, Zewude A, Tulu B, Derara M, Bayissa B, Mohammed T, Degefa BA, Hamad ME, Tibbo M, Barigye R. A Narrative Review on the Pandemic Zoonotic RNA Virus Infections Occurred During the Last 25 Years. J Epidemiol Glob Health 2024; 14:1397-1412. [PMID: 39378018 PMCID: PMC11652441 DOI: 10.1007/s44197-024-00304-7] [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: 06/22/2024] [Accepted: 09/21/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND Pandemic zoonotic RNA virus infections have continued to threaten humans and animals worldwide. The objective of this review was to highlight the epidemiology and socioeconomic impacts of pandemic zoonotic RNA virus infections that occurred between 1997 and 2021. METHODS Literature search was done from Web of Science, PubMed, Google Scholar and Scopus databases, cumulative case fatalities of individual viral infection calculated, and geographic coverage of the pandemics were shown by maps. RESULTS Seven major pandemic zoonotic RNA virus infections occurred from 1997 to 2021 and were presented in three groups: The first group consists of highly pathogenic avian influenza (HPAI-H5N1) and swine-origin influenza (H1N1) viruses with cumulative fatality rates of 53.5% and 0.5% in humans, respectively. Moreover, HPAI-H5N1 infection caused 90-100% death in poultry and economic losses of >$10 billion worldwide. Similarly, H1N1 caused a serious infection in swine and economic losses of 0.5-1.5% of the Gross Domestic Product (GDP) of the affected countries. The second group consists of severe acute respiratory syndrome-associated coronavirus infection (SARS-CoV), Middle East Respiratory Syndrome (MERS-CoV) and Coronavirus disease 2019 (COVID-19) with case fatalities of 9.6%, 34.3% and 2.0%, respectively in humans; but this group only caused mild infections in animals. The third group consists of Ebola and Zika virus infections with case fatalities of 39.5% and 0.02%, respectively in humans but causing only mild infections in animals. CONCLUSION Similar infections are expected in the near future, and hence strict implementation of conventional biosecurity-based measures and development of efficacious vaccines would help minimize the impacts of the next pandemic infection.
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Affiliation(s)
- Gobena Ameni
- College of Agriculture and Veterinary Medicine, United Arab Emirates University, PO Box 15551, Al Ain, United Arab Emirates.
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, PO Box 1176, Addis Ababa, Ethiopia.
| | - Aboma Zewude
- College of Agriculture and Veterinary Medicine, United Arab Emirates University, PO Box 15551, Al Ain, United Arab Emirates
| | - Begna Tulu
- College of Medicine and Health Sciences, Bahir Dar University, P.O. Box 79, Bahir City, Ethiopia
| | - Milky Derara
- Department of Dentistry, College of Medicine and Health Sciences, Ambo University, Ambo, Ethiopia
| | - Berecha Bayissa
- Vaccine Production and Drug Formulation Directorate, National Veterinary Institute, PO Box 35, Debre Zeit, Ethiopia
| | - Temesgen Mohammed
- College of Agriculture and Veterinary Medicine, United Arab Emirates University, PO Box 15551, Al Ain, United Arab Emirates
| | - Berhanu Adenew Degefa
- College of Agriculture and Veterinary Medicine, United Arab Emirates University, PO Box 15551, Al Ain, United Arab Emirates
| | - Mohamed Elfatih Hamad
- College of Agriculture and Veterinary Medicine, United Arab Emirates University, PO Box 15551, Al Ain, United Arab Emirates
| | - Markos Tibbo
- Sub Regional Office for the Gulf-cooperation Council States and Yemen-SNG, Food and Agricultural Organization of the United Nations, Al Qala-id Street, PO Box 62027, Abu Dhabi, United Arab Emirates
| | - Robert Barigye
- College of Agriculture and Veterinary Medicine, United Arab Emirates University, PO Box 15551, Al Ain, United Arab Emirates
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Chang F, Wu Q, Hu Y, Pan Z, Liu YC, Li YZ, Bostina M, Liu W, Zhao P, Qu X, Li YP. Engineered bispecific antibodies with enhanced breadth and potency against SARS-CoV-2 variants and SARS-related coronaviruses. Med Microbiol Immunol 2024; 213:24. [PMID: 39520579 DOI: 10.1007/s00430-024-00809-9] [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: 05/02/2024] [Accepted: 11/02/2024] [Indexed: 11/16/2024]
Abstract
The concern of COVID-19 persists due to the continuous emergence of variants and the potential spillover of animal coronaviruses. The broad-spectrum neutralizing antibodies play a pivotal role in the prevention and treatment of coronavirus (CoV) infections. Here, we constructed 18 bi-specific antibodies (bsAbs) using 9 antibodies isolated from COVID-19 convalescents and vaccinated individuals, designed as dual variable domain immunoglobulin (DVD-Ig). A bsAb 5-HI showed a high binding capability to the S1 subunit of spike and exhibited breadth and potency against pseudotyped SARS-CoV-2 variants of concerns (VOCs) and SARS-related-CoVs (SARSr-CoVs), with half maximal effective concentration (EC50) of 0.028-3.444 nM and 50% inhibitory concentration (IC50) of 0.008-0.800 nM. In addition, it retained neutralization potency against the peudotyped virus of recently prevalent JN.1 strain (IC50, 12.74 nM). We found that the parental antibodies showed weak or no binding to the receptor binding domain (RBD) of the SARS-CoV, EG.5.1, and JN.1. However, the 5-HI maintained the binding with RBD and prevented the binding between hACE2 and RBD (IC50 for the RBD of SARS-CoV, 1.067 nM; EG.5.1, 0.423 nM; JN.1, 0.223 nM). In neutralization assays with the authentic virus, we found that the 5-HI effectively neutralized Omicron variants XBB.1.5 (IC50, 0.308 nM), EG.5.1 (IC50, 0.129 nM), and JN.1 (IC50, 13.692 nM), while its parental antibodies showed weakened or no neutralization. Therefore, the 5-HI represents a promising candidate for further development in the treatment and prevention of ongoing evolved SARS-CoV-2 VOCs and other SARSr-CoVs that potentially emerge in the future.
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Affiliation(s)
- Fangfang Chang
- Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Qian Wu
- Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Yabin Hu
- Translational Medicine Institute, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, China
| | - Zhendong Pan
- Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai, China
| | - Yong-Chen Liu
- Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Yue-Zhou Li
- Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Mihnea Bostina
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
| | - Wenpei Liu
- College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases, Hengyang, China
| | - Ping Zhao
- Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai, China.
| | - Xiaowang Qu
- College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases, Hengyang, China.
| | - Yi-Ping Li
- Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
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Elkhawaga H, Kamel AM, Badr M, Gamiel A, Basheer AA. Impact of the COVID-19 Pandemic on Physical Therapy Clinical Practice in Egypt: A Cross-Sectional Study. Cureus 2024; 16:e73507. [PMID: 39669811 PMCID: PMC11635885 DOI: 10.7759/cureus.73507] [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: 09/18/2024] [Accepted: 11/10/2024] [Indexed: 12/14/2024] Open
Abstract
Background The coronavirus disease 2019 (COVID-19) was an expanding pandemic caused by a new strain of the coronavirus family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). No previous studies have examined the impact of COVID-19 pandemic on physical therapy practice in Egypt. Objectives This study aimed to assess the impact of COVID-19 pandemic on physical therapy clinical practice in Egypt five months after the pandemic declaration. The study investigated how Egyptian physical therapists interacted during the pandemic and the effect of the pandemic on precautionary measures. Additionally, this study assessed the knowledge of physical therapists about COVID-19. Methods A cross-sectional study with a convenient sample was conducted in Egypt through an online structured questionnaire. Data were collected between August 28, 2020, and October 10, 2020. Results A total of 409 physical therapists from 23 Egyptian governorates completed the survey. At some point during the COVID-19 pandemic, 249 (60.9%) physical therapists left their work. Only 131 (32%) visited patients' homes. The majority of respondents, 330 (80.7%), reported that they were afraid to catch any infection from patients during assessment and treatment. Moreover, 330 (80.7%) reported feeling anxious about the COVID-19 pandemic, and 220 (53.8%) reported that their mental health and well-being were not okay. The majority of the participants committed to precautionary measures of physical therapists during the COVID-19 pandemic. The mean knowledge score was 18.29±1.99 out of 23. Conclusions The COVID-19 pandemic affected physical therapy clinical practice in Egypt. It had a psychological impact on Egyptian physical therapists. Egyptian physical therapists committed to precautionary measures against COVID-19 and demonstrated a very good knowledge about COVID-19. Physical therapists should be aware of precautionary measures against infectious diseases, which help can prevent the spread of disease if any new pandemic occurs.
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Affiliation(s)
- Hosny Elkhawaga
- Faculty of Physical Therapy, Cairo University, Giza, EGY
- Medical Research Group of Egypt, Negida Academy, Arlington, USA
| | - Abdallah M Kamel
- Department of Physical Therapy for Musculoskeletal Disorders and Its Surgeries, Faculty of Physical Therapy, Cairo University, Giza, EGY
| | - Mohamed Badr
- Department of Physical Therapy for Neuromuscular Disorders and Its Surgery, Faculty of Physical Therapy, Al Hayah University in Cairo, Cairo, EGY
| | - Abdallah Gamiel
- Department of Physical Therapy for Musculoskeletal Disorders and Its Surgery, Faculty of Physical Therapy, Modern University for Technology and Information (MTI) University, Cairo, EGY
| | - Ahmed A Basheer
- Department of Physical Therapy for Musculoskeletal Disorders, Faculty of Physical Therapy, Beni Suef University, Beni Suef, EGY
- Medical Research Group of Egypt, Negida Academy, Arlington, USA
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Imai M, Kawakami F, Uematsu T, Matsumoto T, Kawashima R, Kurosaki Y, Tamaki S, Maehana S, Ichikawa T, Hanaki H, Kitazato H, Kubo M. SARS-CoV-2 propagation to the TPH2-positive neurons in the ventral tegmental area induces cell death via GSK3β-dependent accumulation of phosphorylated tau. PLoS One 2024; 19:e0312834. [PMID: 39475992 PMCID: PMC11524480 DOI: 10.1371/journal.pone.0312834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 10/14/2024] [Indexed: 11/02/2024] Open
Abstract
COVID-19, an infectious disease caused by SARS-CoV-2, was declared a pandemic by the WHO in 2020. Psychiatric symptoms including sleep disturbance, memory impairment, and depression are associated with SARS-CoV-2 infection. These symptoms are causes long-term mental and physical distress in recovering patients; however, the underlying mechanism is unclear. In this study, we determined the effects of SARS-CoV-2 infection on brain tissue using k18hACE2 mice. Using brain tissue from 18hACE2 mice infected with SARS-CoV-2 through intranasal administration, SARS-CoV-2 spike protein and RNA were analyzed by immunohistochemical staining and in-situ hybridization. Immunohistochemical analysis revealed that Tryptophan hydroxylase 2 (TPH2)-positive cells and SARS-CoV-2 spike protein were co-localized in the ventral tegmental area of SARS-CoV-2-infected mice. We observed decreased TPH2 expression and increased accumulation of phosphorylated tau protein and Phospho-Histone H2A.X (γH2AX) expression in the ventral tegmental region. In addition, activation of glycogen synthase kinase 3β (GSK3β) was induced by SARS-CoV-2 infection. Overall, our results suggest that SARS-CoV-2 infection of TPH2-positive cells in the ventral tegmental area induces neuronal cell death through increased accumulation of phosphorylated tau. Attenuation of the GSK3β pathway and decreased serotonin synthesis through suppression of TPH2 expression may contribute to the development of neurological symptoms.
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Affiliation(s)
- Motoki Imai
- Department of Molecular Diagnostics, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
| | - Fumitaka Kawakami
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Health Administration, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
| | - Takayuki Uematsu
- Biomedical Laboratory, Division of Biomedical Research, Kitasato University Medical Center, Kitamoto, Saitama, Japan
| | - Toshihide Matsumoto
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Pathology, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
| | - Rei Kawashima
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Biochemistry, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
| | - Yoshifumi Kurosaki
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Clinical Chemistry, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
| | - Shun Tamaki
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Biochemistry, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
| | - Shotaro Maehana
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Environmental Microbiology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan
| | - Takafumi Ichikawa
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Biochemistry, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
| | - Hideaki Hanaki
- Infection Control Research Center, Ōmura Satoshi Memorial Institute, Kitasato University, Minato-Ku, Tokyo, Japan
| | - Hidero Kitazato
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Environmental Microbiology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan
| | - Makoto Kubo
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
- Department of Environmental Microbiology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan
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Wilar G, Suhandi C, Fukunaga K, Kawahata I. Efficacy and safety of tofacitinib on COVID-19 patients: A systematic review and meta-analysis. Heliyon 2024; 10:e38229. [PMID: 39381111 PMCID: PMC11456853 DOI: 10.1016/j.heliyon.2024.e38229] [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: 07/03/2024] [Revised: 09/19/2024] [Accepted: 09/20/2024] [Indexed: 10/10/2024] Open
Abstract
The use of drugs off-label for managing COVID-19 offers a potential approach. Among these potential drugs, tofacitinib, a JAK inhibitor, is strongly implicated in its ability to mitigate mortality by attenuating the cytokine storm syndrome. This study systematically reviewed and quantitatively assessed the effectiveness and safety profile of tofacitinib use through meta-analysis. Through searches of the PubMed, Scopus, and the Cochrane Library databases up to May 31, 2024, six articles meeting inclusion criteria were identified, encompassing 669 patients diagnosed with COVID-19. The review findings indicate that tofacitinib use demonstrates significant clinical efficacy, as evidenced by a reduced risk of mortality (P = 0.003), and a decreased need for invasive mechanical ventilation (P = 0.0002). Furthermore, tofacitinib use is not correlated with an increased risk of adverse drug reactions (P = 0.98), indicating a favorable safety profile. In conclusion, the evidence supports the clinical efficacy of tofacitinib for COVID-19 patients without concomitant risks of adverse effects. Further clinical studies, especially larger-scale randomized controlled trials, are necessary to validate the findings of this study.
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Affiliation(s)
- Gofarana Wilar
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia
| | - Cecep Suhandi
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia
| | - Kohji Fukunaga
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan
- Department of CNS Drug Innovation, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan
| | - Ichiro Kawahata
- Department of CNS Drug Innovation, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan
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Liu Y, Zhang W, Sun M, Liang X, Wang L, Zhao J, Hou Y, Li H, Yang X. The severity assessment and nucleic acid turning-negative-time prediction in COVID-19 patients with COPD using a fused deep learning model. BMC Pulm Med 2024; 24:515. [PMID: 39402509 PMCID: PMC11476205 DOI: 10.1186/s12890-024-03333-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 10/07/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND Previous studies have shown that patients with pre-existing chronic obstructive pulmonary diseases (COPD) were more likely to be infected with coronavirus disease (COVID-19) and lead to more severe lung lesions. However, few studies have explored the severity and prognosis of COVID-19 patients with different phenotypes of COPD. PURPOSE The aim of this study is to investigate the value of the deep learning and radiomics features for the severity evaluation and the nucleic acid turning-negative time prediction in COVID-19 patients with COPD including two phenotypes of chronic bronchitis predominant patients and emphysema predominant patients. METHODS A total of 281 patients were retrospectively collected from Hohhot First Hospital between October 2022 and January 2023. They were divided to three groups: COVID-19 group of 95 patients, COVID-19 with emphysema group of 94 patients, COVID-19 with chronic bronchitis group of 92 patients. All patients underwent chest computed tomography (CT) scans and recorded clinical data. The U-net model was pretrained to segment the pulmonary involvement area on CT images and the severity of pneumonia were evaluated by the percentage of pulmonary involvement volume to lung volume. The 107 radiomics features were extracted by pyradiomics package. The Spearman method was employed to analyze the correlation of the data and visualize it through a heatmap. Then we establish a deep learning model (model 1) and a fusion model (model 2) combined deep learning with radiomics features to predict nucleic acid turning-negative time. RESULTS COVID-19 patients with emphysema was lowest in the lymphocyte count compared to COVID-19 patients and COVID-19 companied with chronic bronchitis, and they have the most extensive range of pulmonary inflammation. The lymphocyte count was significantly correlated with pulmonary involvement and the time for nucleic acid turning negative (r=-0.145, P < 0.05). Importantly, our results demonstrated that model 2 achieved an accuracy of 80.9% in predicting nucleic acid turning-negative time. CONCLUSION The pre-existing emphysema phenotype of COPD severely aggravated the pulmonary involvement of COVID-19 patients. Deep learning and radiomics features may provide more information to accurately predict the nucleic acid turning-negative time, which is expected to play an important role in clinical practice.
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Affiliation(s)
- Yanhui Liu
- Medical Imaging Department, Hohhot First Hospital, Inner Mongolia, P.R. China
| | - Wenxiu Zhang
- Institute of Research and Clinical Innovations, Neusoft Medical Systems Co., Ltd, Shanghai, P.R. China
| | - Mengzhou Sun
- Institute of Research and Clinical Innovations, Neusoft Medical Systems Co., Ltd, Beijing, P.R. China
| | - Xiaoyun Liang
- Institute of Research and Clinical Innovations, Neusoft Medical Systems Co., Ltd, Shanghai, P.R. China
| | - Lu Wang
- Medical Imaging Department, Hohhot First Hospital, Inner Mongolia, P.R. China
| | - Jiaqi Zhao
- Medical Imaging Department, Hohhot First Hospital, Inner Mongolia, P.R. China
| | - Yongquan Hou
- Respiratory and Critical Care Medicine Department, Hohhot First Hospital, Inner Mongolia, P.R. China
| | - Haina Li
- Medical Imaging Department, Hohhot First Hospital, Inner Mongolia, P.R. China
| | - Xiaoguang Yang
- Medical Imaging Department, Hohhot First Hospital, Inner Mongolia, P.R. China.
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Arévalo-Romero JA, López-Cantillo G, Moreno-Jiménez S, Marcos-Alcalde Í, Ros-Pardo D, Camacho BA, Gómez-Puertas P, Ramírez-Segura CA. In Silico Design of miniACE2 Decoys with In Vitro Enhanced Neutralization Activity against SARS-CoV-2, Encompassing Omicron Subvariants. Int J Mol Sci 2024; 25:10802. [PMID: 39409131 PMCID: PMC11476394 DOI: 10.3390/ijms251910802] [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: 09/14/2024] [Revised: 10/02/2024] [Accepted: 10/04/2024] [Indexed: 10/20/2024] Open
Abstract
The COVID-19 pandemic has overwhelmed healthcare systems and triggered global economic downturns. While vaccines have reduced the lethality rate of SARS-CoV-2 to 0.9% as of October 2024, the continuous evolution of variants remains a significant public health challenge. Next-generation medical therapies offer hope in addressing this threat, especially for immunocompromised individuals who experience prolonged infections and severe illnesses, contributing to viral evolution. These cases increase the risk of new variants emerging. This study explores miniACE2 decoys as a novel strategy to counteract SARS-CoV-2 variants. Using in silico design and molecular dynamics, blocking proteins (BPs) were developed with stronger binding affinity for the receptor-binding domain of multiple variants than naturally soluble human ACE2. The BPs were expressed in E. coli and tested in vitro, showing promising neutralizing effects. Notably, miniACE2 BP9 exhibited an average IC50 of 4.9 µg/mL across several variants, including the Wuhan strain, Mu, Omicron BA.1, and BA.2 This low IC50 demonstrates the potent neutralizing ability of BP9, indicating its efficacy at low concentrations.Based on these findings, BP9 has emerged as a promising therapeutic candidate for combating SARS-CoV-2 and its evolving variants, thereby positioning it as a potential emergency biopharmaceutical.
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Affiliation(s)
- Jenny Andrea Arévalo-Romero
- Unidad de Ingeniería Celular y Molecular, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud, IDCBIS, Bogotá 111611, Colombia; (J.A.A.-R.); (G.L.-C.); (S.M.-J.); (B.A.C.)
- Instituto de Errores Innatos del Metabolismo, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá 110231, Colombia
| | - Gina López-Cantillo
- Unidad de Ingeniería Celular y Molecular, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud, IDCBIS, Bogotá 111611, Colombia; (J.A.A.-R.); (G.L.-C.); (S.M.-J.); (B.A.C.)
| | - Sara Moreno-Jiménez
- Unidad de Ingeniería Celular y Molecular, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud, IDCBIS, Bogotá 111611, Colombia; (J.A.A.-R.); (G.L.-C.); (S.M.-J.); (B.A.C.)
| | - Íñigo Marcos-Alcalde
- Grupo de Modelado Molecular del Centro de Biología Molecular Severo Ochoa, 14 CSIC-UAM, 28049 Madrid, Spain; (Í.M.-A.); (D.R.-P.)
| | - David Ros-Pardo
- Grupo de Modelado Molecular del Centro de Biología Molecular Severo Ochoa, 14 CSIC-UAM, 28049 Madrid, Spain; (Í.M.-A.); (D.R.-P.)
| | - Bernardo Armando Camacho
- Unidad de Ingeniería Celular y Molecular, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud, IDCBIS, Bogotá 111611, Colombia; (J.A.A.-R.); (G.L.-C.); (S.M.-J.); (B.A.C.)
| | - Paulino Gómez-Puertas
- Grupo de Modelado Molecular del Centro de Biología Molecular Severo Ochoa, 14 CSIC-UAM, 28049 Madrid, Spain; (Í.M.-A.); (D.R.-P.)
| | - Cesar A. Ramírez-Segura
- Unidad de Ingeniería Celular y Molecular, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud, IDCBIS, Bogotá 111611, Colombia; (J.A.A.-R.); (G.L.-C.); (S.M.-J.); (B.A.C.)
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Zhu M, Huang F, Sun H, Liu K, Chen Z, Yu B, Hao H, Liu H, Ding S, Zhang X, Liu L, Zhang K, Ren J, Liu Y, Liu H, Shan C, Guan W. Characterization of ACTN4 as a novel antiviral target against SARS-CoV-2. Signal Transduct Target Ther 2024; 9:243. [PMID: 39289355 PMCID: PMC11408661 DOI: 10.1038/s41392-024-01956-4] [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: 11/01/2023] [Revised: 08/13/2024] [Accepted: 08/27/2024] [Indexed: 09/19/2024] Open
Abstract
The various mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose a substantial challenge in mitigating the viral infectivity. The identification of novel host factors influencing SARS-CoV-2 replication holds potential for discovering new targets for broad-spectrum antiviral drugs that can combat future viral mutations. In this study, potential host factors regulated by SARS-CoV-2 infection were screened through different high-throughput sequencing techniques and further identified in cells. Subsequent analysis and experiments showed that the reduction of m6A modification level on ACTN4 (Alpha-actinin-4) mRNA leads to a decrease in mRNA stability and translation efficiency, ultimately inhibiting ACTN4 expression. In addition, ACTN4 was demonstrated to target nsp12 for binding and characterized as a competitor for SARS-CoV-2 RNA and the RNA-dependent RNA polymerase complex, thereby impeding viral replication. Furthermore, two ACTN4 agonists, YS-49 and demethyl-coclaurine, were found to dose-dependently inhibit SARS-CoV-2 infection in both Huh7 cells and K18-hACE2 transgenic mice. Collectively, this study unveils the pivotal role of ACTN4 in SARS-CoV-2 infection, offering novel insights into the intricate interplay between the virus and host cells, and reveals two potential candidates for future anti-SARS-CoV-2 drug development.
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Affiliation(s)
- Miao Zhu
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Fang Huang
- Hubei Jiangxia Laboratory, Wuhan, Hubei, 430200, China
| | - Huize Sun
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Kunpeng Liu
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Zhen Chen
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
| | - Baocheng Yu
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Haojie Hao
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
| | - Haizhou Liu
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
| | - Shuang Ding
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
| | - Xueyan Zhang
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
| | - Lishi Liu
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Kui Zhang
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Jierao Ren
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yi Liu
- Hubei Jiangxia Laboratory, Wuhan, Hubei, 430200, China
| | - Haibin Liu
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
- Hubei Jiangxia Laboratory, Wuhan, Hubei, 430200, China
| | - Chao Shan
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
- Hubei Jiangxia Laboratory, Wuhan, Hubei, 430200, China
| | - Wuxiang Guan
- Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China.
- Hubei Jiangxia Laboratory, Wuhan, Hubei, 430200, China.
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Abu Bakar SF, Md Isa Z, Ibrahim R, Ismail A, Daud F, Ibrahim R. Knowledge, attitudes, and practices towards COVID-19 prevention among indigenous population in Malaysia: A cross-sectional study. Sci Rep 2024; 14:21428. [PMID: 39271935 PMCID: PMC11399268 DOI: 10.1038/s41598-024-72519-4] [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: 04/24/2024] [Accepted: 09/09/2024] [Indexed: 09/15/2024] Open
Abstract
The COVID-19 pandemic has become a significant challenge to humanity, especially marginalized groups such as indigenous people. This study aimed to assess the knowledge, attitude, and practice towards COVID-19 prevention among the indigenous population in Lipis district, Pahang, Malaysia. A cross-sectional study was conducted among the indigenous population and the data were collected through face-to-face interviews using a validated questionnaire. The mean score of knowledge, attitude, and practice were 2.35 (SD 1.104), 32.84 (SD 4.756), and 9.64 (SD 3.227), respectively. In the bivariable analysis, the younger the age (p < 0.001), and the higher the education level (p = 0.001) of the participants, the higher the knowledge score on COVID-19. Meanwhile, the female participants (p = 0.043) and the higher the household income, the higher the attitude score of the participants (p = 0.006). Factors that contributed to a higher score of practice towards COVID-19 prevention were younger age (p = 0.013), female (p < 0.001), no religion (p = 0.026), unemployed (p < 0.001), and higher household income (p = 0.012). There was a positive correlation between knowledge score and practice score (p = 0.001) and a positive correlation between attitude score and practice score (p < 0.001), respectively. Multivariable regression analysis showed that the younger age (p < 0.001) was significantly associated with a higher knowledge score. Furthermore, female (p = 0.018), unemployed (p = 0.001), higher knowledge score (p < 0.001), and higher attitude score (p < 0.001) were significantly associated with a higher score of practice towards COVID-19 prevention among the participants, respectively. Indigenous people in Malaysia have a good knowledge, attitude, and practice towards COVID-19. However, strategic planning and programmes related to preventive practices against infectious disease outbreaks need to be conducted continuously to reduce the outbreaks in the future.
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Affiliation(s)
- Siti Fairuz Abu Bakar
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000, Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia
| | - Zaleha Md Isa
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000, Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia.
| | - Roszita Ibrahim
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000, Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia
| | - Aniza Ismail
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000, Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia
- Faculty of Public Health, Universitas Sumatera Utara, Jalan Universitas No. 21, Kampus USU, Medan, 20155, North Sumatra, Indonesia
| | - Faiz Daud
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000, Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia
| | - Rozita Ibrahim
- Centre for Liberal Studies (Pusat Pengajian Citra Universiti), Universiti Kebangsaan Malaysia, 43600, Bangi, Selangor, Malaysia
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Istifli ES, Okumus N, Sarikurkcu C, Kuhn ER, Netz PA, Tepe AS. Comparative docking and molecular dynamics studies of molnupiravir (EIDD-2801): implications for novel mechanisms of action on influenza and SARS-CoV-2 protein targets. J Biomol Struct Dyn 2024; 42:8202-8214. [PMID: 37811782 DOI: 10.1080/07391102.2023.2267696] [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: 05/11/2023] [Accepted: 07/27/2023] [Indexed: 10/10/2023]
Abstract
Molnupiravir (EIDD-2801) (MLN) is an oral antiviral drug for COVID-19 treatment, being integrated into viral RNA through RNA-dependent RNA polymerase (RdRp). Upon ingestion, MLN is transformed into two active metabolites: β-d-N4-hydroxycytidine (NHC) (EIDD-1931) in the host plasma, and EIDD-1931-triphosphate (MTP) within the host cells. However, recent studies provide increasing evidence of MLN's interactions with off-target proteins beyond the viral genome, suggesting that the complete mechanisms of action of MLN remain unclear. The aim of this study was therefore to investigate the molecular interactions of MLN in the form of NHC and MTP with the non-RNA structural components of avian influenza (hemagglutinin, neuraminidase) and SARS-CoV-2 (spike glycoprotein, Mpro, and RdRp) viruses and to elucidate whether these two metabolites possess the ability to form stable complexes with these major viral components. Molecular docking of NHC and MTP was performed using AutoDock 4.2.6 and the obtained protein-drug complexes were submitted to 200-ns molecular dynamics simulations in triplicate with subsequent free energy calculations using GROMACS. Docking scores, molecular dynamics and MM/GBSA results showed that MTP was tightly bound within the active site of SARS-CoV-2 RdRp and remained highly stable throughout the 200-ns simulations. Besides, it was also shown that NHC and MTP formed moderately-to-highly stable molecular complexes with off-target receptors hemagglutinin, neuraminidase and Mpro, but rather weak interactions with spike glycoprotein. Our computational findings suggest that NHC and MTP may directly inhibit these receptors, and propose that additional studies on the off-target effects of MLN, i.e. real-time protein binding assays, should be performed.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Erman Salih Istifli
- Faculty of Science and Literature, Department of Biology, Cukurova University, Adana, Turkey
| | - Nurullah Okumus
- Faculty of Medicine, Department of Pediatrics, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey
| | - Cengiz Sarikurkcu
- Faculty of Pharmacy, Department of Analytical Chemistry, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey
| | - Eduardo Ramires Kuhn
- Theoretical Chemistry Group, Institute of Chemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Paulo A Netz
- Theoretical Chemistry Group, Institute of Chemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Arzuhan Sihoglu Tepe
- Department of Pharmacy Services, Kilis 7 Aralik University, Vocational High School of Health Services, Kilis, Turkey
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Thaveesangsakulthai I, Chatdarong K, Somboonna N, Pombubpa N, Palaga T, Makmuang S, Wongravee K, Hoven V, Somboon P, Torvorapanit P, Nhujak T, Kulsing C. A large scale study of portable sweat test sensor for accurate, non-invasive and rapid COVID-19 screening based on volatile compound marker detection. Sci Rep 2024; 14:20148. [PMID: 39209886 PMCID: PMC11362290 DOI: 10.1038/s41598-024-68250-9] [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: 02/24/2024] [Accepted: 07/22/2024] [Indexed: 09/04/2024] Open
Abstract
This study established a novel infield sensing approach based on detection of the volatile compound markers in skin secretions. This was based on analysis of volatile compounds in axillary sweat samples collected from RT-PCR-proven Coronavirus disease 2019 (COVID-19) positive and negative populations using gas chromatography-mass spectrometry (GC-MS). The analysis proposed the possible markers of the monoaromatic compounds and ethyl hexyl acrylate. A portable photo ionization detector (PID) incorporated with the selective material towards the marker compounds was then developed with the pressurized injection approach. This provided the accuracy of 100% in the research phase (n = 125). The developed approach was then applied for screening of 2207 COVID-19 related cases covering the periods of the Alpha, Beta, Delta and Omicron variants of SARS-CoV-2 infection in Bangkok, Thailand. This offered the sensitivity, specificity and accuracy ranges of 92-99, 93-98 and 95-97%, respectively.
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Affiliation(s)
| | - Kaywalee Chatdarong
- Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand
| | - Naraporn Somboonna
- Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
- Microbiome Research Unit for Probiotics in Food and Cosmetics, Chulalongkorn University, Bangkok, 10330, Thailand
- Multi-Omics for Functional Products in Food, Cosmetics and Animals Research Unit, Chulalongkorn University, Bangkok, Thailand
| | - Nuttapon Pombubpa
- Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
- Microbiome Research Unit for Probiotics in Food and Cosmetics, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Tanapat Palaga
- Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Sureerat Makmuang
- Sensor Research Unit (SRU), Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
| | - Kanet Wongravee
- Sensor Research Unit (SRU), Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
| | - Voravee Hoven
- Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
- Center of Excellence in Materials and Bio-Interfaces, Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok, 10330, Thailand
| | - Pakpum Somboon
- Department of Electrical Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Pattama Torvorapanit
- Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Thai Red Cross Emerging Infectious Diseases Clinical Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Thumnoon Nhujak
- Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Chadin Kulsing
- Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
- Electrochemistry and Optical Spectroscopy Center of Excellence (EOSCE), Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
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Alqahtani SAM. Mucosal immunity in COVID-19: a comprehensive review. Front Immunol 2024; 15:1433452. [PMID: 39206184 PMCID: PMC11349522 DOI: 10.3389/fimmu.2024.1433452] [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: 05/15/2024] [Accepted: 07/19/2024] [Indexed: 09/04/2024] Open
Abstract
Mucosal immunity plays a crucial role in defending against coronaviruses, particularly at respiratory sites, serving as the first line of defense against viral invasion and replication. Coronaviruses have developed various immune evasion strategies at the mucosal immune system, hindering the recognition of infected cells and evading antibody responses. Understanding the immune mechanisms and responses is crucial for developing effective vaccines and therapeutics against coronaviruses. The role of mucosal immunity in COVID-19 is significant, influencing both local and systemic immune responses to the virus. Although most clinical studies focus on antibodies and cellular immunity in peripheral blood, mucosal immune responses in the respiratory tract play a key role in the early restriction of viral replication and the clearance of SARS-CoV-2. Identification of mucosal biomarkers associated with viral clearance will allow monitoring of infection-induced immunity. Mucosally delivered vaccines and those under clinical trials are being compared and contrasted to understand their effectiveness in inducing mucosal immunity against coronaviruses. A greater understanding of lung tissue-based immunity may lead to improved diagnostic and prognostic procedures and novel treatment strategies aimed at reducing the disease burden of community-acquired pneumonia, avoiding the systemic manifestations of infection and excess morbidity and mortality. This comprehensive review article outlines the current evidence about the role of mucosal immune responses in the clearance of SARS-CoV-2 infection, as well as potential mucosal mechanisms of protection against (re-)infection. It also proposes that there is a significant role for mucosal immunity and for secretory as well as circulating IgA antibodies in COVID-19, and that it is important to elucidate this in order to comprehend especially the asymptomatic and mild states of the infection, which appear to account for the majority of cases. Moreover, it is possible that mucosal immunity can be exploited for beneficial diagnostic, therapeutic, or prophylactic purposes. The findings from recent studies on mucosal immunity in COVID-19 can be used to develop effective vaccines and treatments that can effectively target both mucosal and systemic immune responses.
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Liu Y, Guo Y, Zhan H, Liu X, Li X, Cui J, Li H, Feng S, Cheng L, Li X, Guo S, Li Y. Immune and inflammation features of severe and critical Omicron infected patients during Omicron wave in China. BMC Infect Dis 2024; 24:809. [PMID: 39123106 PMCID: PMC11316362 DOI: 10.1186/s12879-024-09652-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 07/23/2024] [Indexed: 08/12/2024] Open
Abstract
OBJECTIVE The current study aimed to investigate the baseline immune and inflammatory features and in-hospital outcomes of patients infected with the Omicron variant (PIWO) who presented with different disease severities during the first wave of mass Omicron infections in the Chinese population has occurred. METHOD A cross-sectional study was conducted on 140 hospitalized PIWO between December 11, 2022, and February 16, 2023. The clinical features, antibodies against SARS-CoV-2, immune cells, and inflammatory cytokines among mildly, severely, and critically ill PIWO at baseline and during follow-up period were compared. RESULT Patients with severe (n = 49) and critical (n = 35) disease were primarily male, needed invasive mechanical ventilation treatment, and exhibited higher mortality than those with mild disease (n = 56). During acute infection, SARS-CoV-2-specific antibody levels fluctuated with disease severity, serum antibodies increased and the incidence of severe cases decreased in critically ill PIWO over time. Antibody titers in severe or critical PIWO with no antibody responses at baseline did not increase significantly over time. Meanwhile, CD4+T cell, CD8+T cell, and natural killer cell counts were negatively correlated with disease severity, whereas interleukin (IL)-6 and IL-10 levels were positively correlated. In addition, combined diabetes, immunosuppressive therapy before infection, serum amyloid A, IL-10 and neutrophil counts were independently associated with severe and critical illness in PIWO. Among the 11 nonsurvivors, 8, 2, 1 died of respiratory failure, sudden cardiac death, and renal failure, respectively. Compared with survivors, nonsurvivors exhibited lower seropositivity of SARS-CoV-2-specific antibody, reduced CD3+T and CD4+T cell counts, and higher IL-2R, IL-6, IL-8, and IL-10 levels. Of note, lactate dehydrogenase was a significant risk factor of death in severe or critically ill PIWO. CONCLUSION This present study assessed the dynamic changes of SARS-CoV-2-specific antibodies, immune cells and inflammatory indexes between severely and critically ill PIWO. Critical and dead PIWO featured compromised humoral immune response and excessive inflammation, which broadened the understanding of the pathophysiology of Omicron infection and provides warning markers for severe disease and poor prognosis.
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Affiliation(s)
- Yongmei Liu
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100010, China
| | - Yaping Guo
- Department of Clinical Laboratory, Baoding First Central HospitalBaoding NO.1 Central Hospital, No. 320, Great Wall North Street, Baoding, Hebei, 071000, China
| | - Haoting Zhan
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100010, China
| | - Xin Liu
- Department of Clinical Laboratory, Baoding First Central HospitalBaoding NO.1 Central Hospital, No. 320, Great Wall North Street, Baoding, Hebei, 071000, China
| | - Xiaomeng Li
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100010, China
- Department of Clinical Laboratory, Peking University People's Hospital, NO.11, Xizhimen South Street, Beijing, 100035, China
| | - Jingjing Cui
- Department of Clinical Laboratory, Baoding First Central HospitalBaoding NO.1 Central Hospital, No. 320, Great Wall North Street, Baoding, Hebei, 071000, China
| | - Haolong Li
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100010, China
| | - Sha Feng
- Department of Clinical Laboratory, Baoding First Central HospitalBaoding NO.1 Central Hospital, No. 320, Great Wall North Street, Baoding, Hebei, 071000, China
| | - Linlin Cheng
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100010, China
| | - Xiaoyan Li
- Department of Clinical Laboratory, Baoding First Central HospitalBaoding NO.1 Central Hospital, No. 320, Great Wall North Street, Baoding, Hebei, 071000, China
| | - Shuqin Guo
- Department of Endocrinology, Baoding NO.1 Central Hospital, No. 320, Great Wall North Street, Baoding, Hebei, 071000, China.
| | - Yongzhe Li
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100010, China.
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Beckman CKDC, Luppieri V, Pereira LM, Silva CR, Castelo PM, Cadenaro M, Rontani RMP, Castilho ARFD. Impact of COVID-19 on pediatric dental care in two epicenters: Italy and Brazil. Braz Oral Res 2024; 38:e068. [PMID: 39109765 PMCID: PMC11376669 DOI: 10.1590/1807-3107bor-2024.vol38.0068] [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: 08/21/2023] [Accepted: 03/06/2024] [Indexed: 09/20/2024] Open
Abstract
The study aimed to compare the adherence of Brazilian and Italian pediatric dentists to the biosafety measures and operative protocols recommended by the health authorities during COVID-19 pandemic and to classify the participants according to their risk of infection. An online questionnaire with 34 questions about sociodemographic and occupational data, dental practice organization, biological risk management, and clinical operative protocols was sent to Brazilian and Italian pediatric dentists using a convenience sampling strategy. Chi-square test and multivariate analysis (two-step cluster) were performed (α = 5%). Of 641 respondents (377 Brazilians and 264 Italians), most were female (94% and 70%, respectively), aged 20-39 years (63%), with over 10 years of professional experience (58% and 49%, respectively). Based on adherence to recommended biosafety measures, participants were classified as "safer" (n = 219) or "less safe" (n = 422). Adherence to recommended protocols by the majority of participants resulted in low contagion rates (Brazilians = 5%; Italians = 12.5%). Participants with extensive professional experience in the dental setting exhibited a greater tendency to implement multiple adaptations (three or more) in their practice. Most participants (Brazilians = 92%; Italians = 80.7%) adopted the recommended minimal intervention dentistry approaches, with the use of fissure sealants and the use of non-rotary instruments for caries removal the most frequently techniques used among Brazilians (36%) and Italians (66%), respectively. Two different profiles of pediatric dentists were identified based on the biosafety protocols adopted during the pandemic. In addition, changes were implemented in the dental care provided to children, with focus on the minimal intervention dentistry.
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Affiliation(s)
- Camilla Karoline de Carvalho Beckman
- Universidade Estadual de Campinas - Unicamp, Faculdade de Odontologia de Piracicaba, Departamento de Ciências da Saúde e Odontologia Infantil, Piracicaba, SP, Brazil
| | - Valentina Luppieri
- Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy
| | - Letícia Martins Pereira
- Universidade Estadual de Campinas - Unicamp, Faculdade de Odontologia de Piracicaba, Departamento de Ciências da Saúde e Odontologia Infantil, Piracicaba, SP, Brazil
| | - Camila Ribeiro Silva
- Universidade Estadual de Campinas - Unicamp, Faculdade de Odontologia de Piracicaba, Departamento de Odontologia Restauradora, Piracicaba, SP, Brazil
| | - Paula Midori Castelo
- Universidade Federal de São Paulo, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Departamento de Ciências Farmacêuticas, Diadema, SP, Brazil
| | - Milena Cadenaro
- University of Trieste, Department of Medicine, Surgery and Health Sciences, Trieste, Italy
| | - Regina Maria Puppin Rontani
- Universidade Estadual de Campinas - Unicamp, Faculdade de Odontologia de Piracicaba, Departamento de Ciências da Saúde e Odontologia Infantil, Piracicaba, SP, Brazil
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da Fonseca AM, Caluaco BJ, Madureira JMC, Cabongo SQ, Gaieta EM, Djata F, Colares RP, Neto MM, Fernandes CFC, Marinho GS, Dos Santos HS, Marinho ES. Screening of Potential Inhibitors Targeting the Main Protease Structure of SARS-CoV-2 via Molecular Docking, and Approach with Molecular Dynamics, RMSD, RMSF, H-Bond, SASA and MMGBSA. Mol Biotechnol 2024; 66:1919-1933. [PMID: 37490200 DOI: 10.1007/s12033-023-00831-x] [Citation(s) in RCA: 37] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 07/17/2023] [Indexed: 07/26/2023]
Abstract
Severe Acute Respiratory Syndrome caused by a coronavirus is a recent viral infection. There is no scientific evidence or clinical trials to indicate that possible therapies have demonstrated results in suspected or confirmed patients. This work aims to perform a virtual screening of 1430 ligands through molecular docking and to evaluate the possible inhibitory capacity of these drugs about the Mpro protease of Covid-19. The selected drugs were registered with the FDA and available in the virtual drug library, widely used by the population. The simulation was performed using the MolAiCalD algorithm, with a Lamarckian genetic model (GA) combined with energy estimation based on rigid and flexible conformation grids. In addition, molecular dynamics studies were also performed to verify the stability of the receptor-ligand complexes formed through analyses of RMSD, RMSF, H-Bond, SASA, and MMGBSA. Compared to the binding energy of the synthetic redocking coupling (-6.8 kcal/mol/RMSD of 1.34 Å), which was considerably higher, it was then decided to analyze the parameters of only three ligands: ergotamine (-9.9 kcal/mol/RMSD of 2.0 Å), dihydroergotamine (-9.8 kcal/mol/RMSD of 1.46 Å) and olysio (-9.5 kcal/mol/RMSD of 1.5 Å). It can be stated that ergotamine showed the best interactions with the Mpro protease of Covid-19 in the in silico study, showing itself as a promising candidate for treating Covid-19.
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Affiliation(s)
- Aluísio Marques da Fonseca
- Mestrado Acadêmico em Sociobiodiversidades e Tecnologias Sustentáveis - MASTS, Instituto de Engenharias e Desenvolvimento Sustentável, Universidade da Integração Internacional da Lusofonia Afro-Brasileira, Acarape, CE, Brazil
| | - Bernardino Joaquim Caluaco
- Instituto de Ciências Exatas e da Natureza, Universidade da Integração Internacional da Lusofonia Afro-Brasileira, Acarape, CE, Brazil
| | | | - Sadrack Queque Cabongo
- Instituto de Ciências Exatas e da Natureza, Universidade da Integração Internacional da Lusofonia Afro-Brasileira, Acarape, CE, Brazil
| | - Eduardo Menezes Gaieta
- Fundação Oswaldo Cruz - Fiocruz, R. São José, S/N - Precabura, Eusébio, Ceará, 61773-270, Brazil
| | - Faustino Djata
- Instituto de Ciências Exatas e da Natureza, Universidade da Integração Internacional da Lusofonia Afro-Brasileira, Acarape, CE, Brazil
| | - Regilany Paulo Colares
- Instituto de Ciências Exatas e da Natureza, Universidade da Integração Internacional da Lusofonia Afro-Brasileira, Acarape, CE, Brazil
| | - Moises Maia Neto
- Curso de Graduação Em Farmácia, Centro Universitário Fametro, Fortaleza, CE, Brazil
| | | | - Gabrielle Silva Marinho
- Faculdade de Filosofia, Dom Aureliano Matos - FAFIDAM, Universidade Estadual Do Ceará, Centro, Limoeiro Do Norte, CE, Brazil
| | | | - Emmanuel Silva Marinho
- Faculdade de Filosofia, Dom Aureliano Matos - FAFIDAM, Universidade Estadual Do Ceará, Centro, Limoeiro Do Norte, CE, Brazil
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Banerjee T, Gosai A, Yousefi N, Garibay OO, Seal S, Balasubramanian G. Examining sialic acid derivatives as potential inhibitors of SARS-CoV-2 spike protein receptor binding domain. J Biomol Struct Dyn 2024; 42:6342-6358. [PMID: 37424217 DOI: 10.1080/07391102.2023.2234044] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 07/01/2023] [Indexed: 07/11/2023]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has been the primary reason behind the COVID-19 global pandemic which has affected millions of lives worldwide. The fundamental cause of the infection is the molecular binding of the viral spike protein receptor binding domain (SP-RBD) with the human cell angiotensin-converting enzyme 2 (ACE2) receptor. The infection can be prevented if the binding of RBD-ACE2 is resisted by utilizing certain inhibitors or drugs that demonstrate strong binding affinity towards the SP RBD. Sialic acid based glycans found widely in human cells and tissues have notable propensity of binding to viral proteins of the coronaviridae family. Recent experimental literature have used N-acetyl neuraminic acid (Sialic acid) to create diagnostic sensors for SARS-CoV-2, but a detailed interrogation of the underlying molecular mechanisms is warranted. Here, we perform all atom molecular dynamics (MD) simulations for the complexes of certain Sialic acid-based molecules with that of SP RBD of SARS CoV-2. Our results indicate that Sialic acid not only reproduces a binding affinity comparable to the RBD-ACE2 interactions, it also assumes the longest time to dissociate completely from the protein binding pocket of SP RBD. Our predictions corroborate that a combination of electrostatic and van der Waals energies as well the polar hydrogen bond interactions between the RBD residues and the inhibitors influence free energy of binding.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Tanumoy Banerjee
- Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, PA, USA
| | | | - Niloofar Yousefi
- Industrial Engineering and Management Systems, University of Central Florida, Orlando, FL, USA
| | - Ozlem Ozmen Garibay
- Industrial Engineering and Management Systems, University of Central Florida, Orlando, FL, USA
| | - Sudipta Seal
- College of Medicine, Bionix Cluster, University of Central Florida, Orlando, FL, USA
- Advanced Materials Processing and Analysis Center, Dept. of Materials Science and Engineering, University of Central Florida, Orlando, FL, USA
| | - Ganesh Balasubramanian
- Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, PA, USA
- Institute of Functional Materials & Devices and College of Health, Lehigh University, Bethlehem, PA, USA
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Sharma S, Caputi M, Asghar W. Development of a Diagnostic Microfluidic Chip for SARS-CoV-2 Detection in Saliva and Nasopharyngeal Samples. Viruses 2024; 16:1190. [PMID: 39205164 PMCID: PMC11360425 DOI: 10.3390/v16081190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 07/15/2024] [Accepted: 07/16/2024] [Indexed: 09/04/2024] Open
Abstract
The novel coronavirus SARS-CoV-2 was first isolated in late 2019; it has spread to all continents, infected over 700 million people, and caused over 7 million deaths worldwide to date. The high transmissibility of the virus and the emergence of novel strains with altered pathogenicity and potential resistance to therapeutics and vaccines are major challenges in the study and treatment of the virus. Ongoing screening efforts aim to identify new cases to monitor the spread of the virus and help determine the danger connected to the emergence of new variants. Given its sensitivity and specificity, nucleic acid amplification tests (NAATs) such as RT-qPCR are the gold standard for SARS-CoV-2 detection. However, due to high costs, complexity, and unavailability in low-resource and point-of-care (POC) settings, the available RT-qPCR assays cannot match global testing demands. An alternative NAAT, RT-LAMP-based SARS-CoV-2 detection offers scalable, low-cost, and rapid testing capabilities. We have developed an automated RT-LAMP-based microfluidic chip that combines the RNA isolation, purification, and amplification steps on the same device and enables the visual detection of SARS-CoV-2 within 40 min from saliva and nasopharyngeal samples. The entire assay is executed inside a uniquely designed, inexpensive disposable microfluidic chip, where assay components and reagents have been optimized to provide precise and qualitative results and can be effectively deployed in POC settings. Furthermore, this technology could be easily adapted for other novel emerging viruses.
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Affiliation(s)
- Sandhya Sharma
- Department of Electrical Engineering and Computer Science, Florida Atlantic University, Boca Raton, FL 33431, USA
- Asghar-Lab, Micro and Nanotechnology in Medicine, College of Engineering and Computer Science, Boca Raton, FL 33431, USA
| | - Massimo Caputi
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA;
| | - Waseem Asghar
- Department of Electrical Engineering and Computer Science, Florida Atlantic University, Boca Raton, FL 33431, USA
- Asghar-Lab, Micro and Nanotechnology in Medicine, College of Engineering and Computer Science, Boca Raton, FL 33431, USA
- Department of Biological Sciences (Courtesy Appointment), Florida Atlantic University, Boca Raton, FL 33431, USA
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Rodriguez Lima DR, Rubio Ramos C, Diaz Quiroz MA, Rodríguez Aparicio EE, Gómez Cortes LA, Otálora González L, Hernández-Herrera G, Pinzón Rondón ÁM, Ruiz Sternberg ÁM. Resilience and quality of life in patients who underwent mechanical ventilation due to COVID-19, one year after discharge: a cross-sectional study. J Patient Rep Outcomes 2024; 8:70. [PMID: 38995437 PMCID: PMC11245452 DOI: 10.1186/s41687-024-00748-2] [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: 03/05/2024] [Accepted: 06/22/2024] [Indexed: 07/13/2024] Open
Abstract
BACKGROUND Patients with COVID-19 often experience severe long-term sequelae. This study aimed to assess resilience and Quality of Life (QoL) of patients who underwent mechanical ventilation due to COVID-19, one year after discharge. METHODS This cross-sectional study enrolled patients who received mechanical ventilation for severe COVID-19 and were assessed one-year post-discharge. Participants completed a structured questionnaire via telephone comprising the Connor-Davidson Resilience Scale (CD-RISC) and the Post-COVID-19 Functional Status scale (PCFS). To establish the association between QoL and resilience, Spearman correlations were calculated between the PCFS and the CD-RISC. Linear regression models were adjusted to evaluate which factors were associated with QoL, with the total score of PCFS as the dependent variable. RESULTS A total of 225 patients were included in the analysis. The CD-RISC had a median score of 83 (IQR 74-91). The PCFS results showed that 61.3% (n = 138) of the patients were able to resume their daily activities without limitations. Among them, 37.3% (n = 84) were classified as Grade 0 and 24% (n = 54) as Grade 1. Mild and moderate functional limitations were found in 33.7% of the patients, with 24.8% (n = 56) classified as Grade 2 and 8.8% (n = 20) as Grade 3. Severe functional limitations (Grade 4) were observed in 4.8% (n = 11) of the patients. High CD-RISC scores were associated with lower levels of PCFS score (p < 0.001). CONCLUSIONS In this cohort of critically ill patients who underwent mechanical ventilation due to COVID-19, 38% of patients experienced a significant decline in their QoL one year after hospital discharge. Finally, a high level of resilience was strongly associated with better QoL one year after discharge.
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Affiliation(s)
- David Rene Rodriguez Lima
- Critical and Intensive Care Medicine, Hospital Universitario Mayor-Méderi, Bogotá, Colombia.
- Grupo de Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.
- Doctorado Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.
| | - Cristhian Rubio Ramos
- Critical and Intensive Care Medicine, Hospital Universitario Mayor-Méderi, Bogotá, Colombia
| | - Mateo Andrés Diaz Quiroz
- Grupo de Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
| | | | | | - Laura Otálora González
- Facultad de Medicina, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
| | - Gilma Hernández-Herrera
- Doctorado Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
| | - Ángela María Pinzón Rondón
- Grupo de Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
- Doctorado Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
| | - Ángela María Ruiz Sternberg
- Grupo de Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
- Doctorado Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
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Alsaffar SF, Baqer NN. Association between Methylenetetrahydrofolate Reductase ( MTHFR) and 5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase ( MTRR) Polymorphisms in Iraqi Patients with COVID-19. IRANIAN JOURNAL OF MEDICAL SCIENCES 2024; 49:430-440. [PMID: 39114635 PMCID: PMC11300940 DOI: 10.30476/ijms.2023.99555.3162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 08/20/2023] [Accepted: 09/15/2023] [Indexed: 08/10/2024]
Abstract
Background The methylenetetrahydrofolate reductase (MTHFR) gene is an essential gene in the metabolism of folate-homocysteine. Recently, the level of homocysteine was found to be a significant marker in the follow-up of COVID-19 infection. Thus, this study aimed to detect the effect of genetic polymorphisms for single nucleotide polymorphisms (SNPs) (c.66A>G, c.1298A>C, and c.677CT) on COVID-19 infection. Methods Blood samples were collected from 270 patients with COVID-19 in the medical center of Al-Shifa (Baghdad, Iraq) from November 2020 to March 2021. Tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique was used for the detection of genotypes of SNPs. The odds ratio (OR) was used to detect the relationship between SNPs and COVID-19 infections. Haplotype analysis was performed by SHEsis software. Results There was a significant difference between mild/moderate cases and severe/critical cases for ages (35-45), (46-55), and (56-65) years (P<0.0001, P=0.01, and P=0.006, respectively). The results showed significant differences in the T allele for SNP c.677>C (P<0.0001 and OR=4.58). The C allele for SNP c.1298A>C indicated significant differences (P<0.001 and OR=3.15). Besides, the G allele for SNP c.677C>T showed significant differences (P<0.001 and OR=6.64). Consequently, these SNPs showed a predisposition to the development of COVID-19 infection. With regard to the C-A-A, T-A-A and T-C-G haplotypes indicated significant differences between the control and patient groups. The C-A-A was related to a decreased risk and indicated a protective effect against COVID-19 infection development (P<0.0001 and OR=0.218). The increased risk was associated with T-A-A and T-C-G haplotypes and indicated the risk impact on COVID-19 infection development (P<0.0001, P=0.004, and OR=15.5, OR=6.772, respectively). Furthermore, the linkage disequilibrium (LD) for SNPs was studied, and the complete D' value was 99. Conclusion The genetic polymorphisms of SNPs (c.66A>G, c.1298A>C, and c.677C>T) in the Iraqi population were associated with COVID-19 infection.
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Affiliation(s)
- Sura F. Alsaffar
- Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq
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Siami Z, Rasooli A, Zebardast J, Jalali I, Jamalimoghadamsiahkali S. Clinical outcomes and considerations in outpatient with COVID-19 receiving remdesivir therapy. Health Sci Rep 2024; 7:e2252. [PMID: 39044845 PMCID: PMC11262996 DOI: 10.1002/hsr2.2252] [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: 07/01/2023] [Revised: 05/13/2024] [Accepted: 05/27/2024] [Indexed: 07/25/2024] Open
Abstract
Introduction This retrospective cross-sectional study aimed to assess the outcomes of Covid-19 patients who received remdesivir therapy at the outpatient department of Ziaian Hospital. Method A total of 514 eligible patients were included between May and September 2021. Covid-19 diagnosis was confirmed through positive SARS-COV-2 PCR tests or chest CT scans. Due to limited hospital beds, patients received remdesivir on an outpatient basis. Results Patients received six daily doses of remdesivir for 5 days. Those referred to a physician within 7 days of symptom onset had similar hospitalization rates compared to later referrals. Lower blood saturation levels were associated with a higher likelihood of hospital admission, indicating that earlier administration of remdesivir may be more effective. Patients with over 50% lung involvement had higher rates of disease progression despite treatment. Corticosteroids did not significantly improve outcomes in patients with saturation above 90%. Discontinuation of remdesivir due to side effects was rare, with only 1% experiencing increased liver enzymes, 1.2% facial redness and tremors, and 1.5% allergies. After 1 week of treatment, patients commonly reported symptoms such as hair loss, fatigue, body pain, lethargy, and anorexia, particularly among hospitalized patients. Discussion Patients generally preferred outpatient treatment over hospitalization. Body mass index (BMI) did not significantly impact hospitalization rates, although average weight tended to be higher among inpatients. The study confirmed the effectiveness of remdesivir therapy with a low occurrence of side effects. Conclusion This retrospective study evaluated the outcomes of Covid-19 patients receiving remdesivir at an outpatient department. Early administration of remdesivir showed better outcomes, while corticosteroids had limited benefits. Outpatient treatment was favored, and BMI did not significantly influence hospitalization rates. Remdesivir demonstrated efficacy with a low incidence of side effects.
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Affiliation(s)
- Zeinab Siami
- Department of Infectious Disease, School of Medicine, Ziaeian HospitalTehran University of Medical SciencesTehranIran
| | - Aziz Rasooli
- Department of Emergency MedicineTehran University of Medical, SciencesTehranIran
| | - Jayran Zebardast
- Department of Cognitive LinguisticsInstitute for Cognitive Science Studies (ICSS)TehranIran
| | - Illahay Jalali
- Department of Infectious Disease, School of MedicineTehran University of Medical, SciencesTehranIran
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Dietz TK, Brondstater KN. Long COVID management: a mini review of current recommendations and underutilized modalities. Front Med (Lausanne) 2024; 11:1430444. [PMID: 38947233 PMCID: PMC11211541 DOI: 10.3389/fmed.2024.1430444] [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: 05/09/2024] [Accepted: 06/04/2024] [Indexed: 07/02/2024] Open
Abstract
Long COVID is a condition that develops in a subset of patients after COVID-19 infection comprising of symptoms of varying severity encompassing multiple organ systems. Currently, long COVID is without consensus on a formal definition, identifiable biomarkers, and validated treatment. Long COVID is expected to be a long-term chronic condition for a subset of patients and is associated with suffering and incapacity. There is an urgent need for clear management guidelines for the primary care provider, who is essential in bridging the gap with more specialized care to improve quality of life and functionality in their patients living with long COVID. The purpose of this mini review is to provide primary care providers with the latest highlights from existing literature regarding the most common long COVID symptoms and current management recommendations. This review also highlights the underutilized interventions of stellate ganglion blocks and low-dose naltrexone, both with well-established safety profiles demonstrated to improve quality of life and functionality for patients suffering with some symptoms of long COVID, and encourages prompt referral to interventional pain management.
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Affiliation(s)
- Tiffany K. Dietz
- School of Health Professions, Shenandoah University, Winchester, VA, United States
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