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1
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Nguyen THV, Ferron F, Murakami K. Neurotoxic Implications of Human Coronaviruses in Neurodegenerative Diseases: A Perspective from Amyloid Aggregation. ACS Chem Biol 2025; 20:983-992. [PMID: 40272376 DOI: 10.1021/acschembio.5c00153] [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: 04/25/2025]
Abstract
Human coronaviruses (HCoVs) include seven species: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1, and SARS-CoV-2. The last three, classified as Betacoronaviruses, are highly transmissible and have caused severe pandemics. HCoV infections primarily affect the respiratory system, leading to symptoms such as dry cough, fever, and breath shortness, which can progress to acute respiratory failure and death. Beyond respiratory effects, increasing evidence links HCoVs to neurological dysfunction. However, distinguishing direct neural complications from preexisting disorders, particularly in the elderly, remains challenging. This study examines the association between HCoVs and neurodegenerative diseases like Alzheimer disease, Parkinson disease, Lewy body dementia, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease. It also presents the long-term neurological effects of HCoV infections and their differential impact across age groups and sexes. A key aspect of this study is the investigation of the sequence and structural similarities between amyloidogenic and HCoV spike proteins, which can provide insights into potential neuropathomechanisms.
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Affiliation(s)
- Thi Hong Van Nguyen
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan
| | - Francois Ferron
- Aix Marseille Univ, CNRS-Architecture et Fonction des Macromolécules Biologiques (AFMB) UMR7257, Marseille 13288, France
- European Virus Bioinformatics Center, Jena 07743, Germany
| | - Kazuma Murakami
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan
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2
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Breugem TI, Riesebosch S, Zhang J, Mykytyn AZ, Krabbendam L, Groen N, Baptista Varela S, Schipper D, van den Doel PB, van Acker R, Stadhouders R, Lamers MM, Haagmans BL. Variable DPP4 expression in multiciliated cells of the human nasal epithelium as a determinant for MERS-CoV tropism. Proc Natl Acad Sci U S A 2025; 122:e2410630122. [PMID: 40048293 PMCID: PMC11929475 DOI: 10.1073/pnas.2410630122] [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: 05/29/2024] [Accepted: 12/21/2024] [Indexed: 03/25/2025] Open
Abstract
Transmissibility of respiratory viruses is a complex viral trait that is intricately linked to tropism. Several highly transmissible viruses, including severe acute respiratory syndrome coronavirus 2 and Influenza viruses, specifically target multiciliated cells in the upper respiratory tract to facilitate efficient human-to-human transmission. In contrast, the zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) generally transmits poorly between humans, which is largely attributed to the absence of its receptor dipeptidyl peptidase 4 (DPP4) in the upper respiratory tract. At the same time, MERS-CoV epidemiology is characterized by occasional superspreading events, suggesting that some individuals can disseminate this virus effectively. Here, we utilized well-differentiated human pulmonary and nasal airway organoid-derived cultures to further delineate the respiratory tropism of MERS-CoV. We find that MERS-CoV replicated to high titers in both pulmonary and nasal airway cultures. Using single-cell messenger-RNA sequencing, immunofluorescence, and immunohistochemistry, we show that MERS-CoV preferentially targeted multiciliated cells, leading to loss of ciliary coverage. MERS-CoV cellular tropism was dependent on the differentiation of the organoid-derived cultures, and replication efficiency varied considerably between donors. Similarly, variable and focal expression of DPP4 was revealed in human nose tissues. This study indicates that the upper respiratory tract tropism of MERS-CoV may vary between individuals due to differences in DPP4 expression, providing an explanation for the unpredictable transmission pattern of MERS-CoV.
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Affiliation(s)
- Tim I. Breugem
- Viroscience Department, Erasmus University Medical Center, Rotterdam3015 GD, The Netherlands
| | - Samra Riesebosch
- Viroscience Department, Erasmus University Medical Center, Rotterdam3015 GD, The Netherlands
| | - Jingshu Zhang
- Viroscience Department, Erasmus University Medical Center, Rotterdam3015 GD, The Netherlands
| | - Anna Z. Mykytyn
- Viroscience Department, Erasmus University Medical Center, Rotterdam3015 GD, The Netherlands
| | - Lisette Krabbendam
- Pulmonary Medicine Department, Erasmus University Medical Center, Rotterdam3015 GD, The Netherlands
| | - Nathalie Groen
- Single Cell Discoveries, Utrecht3584 BW, The Netherlands
| | - Sivana Baptista Varela
- Viroscience Department, Erasmus University Medical Center, Rotterdam3015 GD, The Netherlands
| | - Debby Schipper
- Viroscience Department, Erasmus University Medical Center, Rotterdam3015 GD, The Netherlands
| | - Petra B. van den Doel
- Viroscience Department, Erasmus University Medical Center, Rotterdam3015 GD, The Netherlands
| | - Romy van Acker
- Viroscience Department, Erasmus University Medical Center, Rotterdam3015 GD, The Netherlands
| | - Ralph Stadhouders
- Pulmonary Medicine Department, Erasmus University Medical Center, Rotterdam3015 GD, The Netherlands
| | - Mart M. Lamers
- Viroscience Department, Erasmus University Medical Center, Rotterdam3015 GD, The Netherlands
- Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore169857, Singapore
| | - Bart L. Haagmans
- Viroscience Department, Erasmus University Medical Center, Rotterdam3015 GD, The Netherlands
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Adilović M, Hromić-Jahjefendić A, Mahmutović L, Šutković J, Rubio-Casillas A, Redwan EM, Uversky VN. Intrinsic Factors Behind the Long-COVID: V. Immunometabolic Disorders. J Cell Biochem 2025; 126:e30683. [PMID: 39639607 DOI: 10.1002/jcb.30683] [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: 07/07/2024] [Revised: 11/02/2024] [Accepted: 11/15/2024] [Indexed: 12/07/2024]
Abstract
The complex link between COVID-19 and immunometabolic diseases demonstrates the important interaction between metabolic dysfunction and immunological response during viral infections. Severe COVID-19, defined by a hyperinflammatory state, is greatly impacted by underlying chronic illnesses aggravating the cytokine storm caused by increased levels of Pro-inflammatory cytokines. Metabolic reprogramming, including increased glycolysis and altered mitochondrial function, promotes viral replication and stimulates inflammatory cytokine production, contributing to illness severity. Mitochondrial metabolism abnormalities, strongly linked to various systemic illnesses, worsen metabolic dysfunction during and after the pandemic, increasing cardiovascular consequences. Long COVID-19, defined by chronic inflammation and immune dysregulation, poses continuous problems, highlighting the need for comprehensive therapy solutions that address both immunological and metabolic aspects. Understanding these relationships shows promise for effectively managing COVID-19 and its long-term repercussions, which is the focus of this review paper.
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Affiliation(s)
- Muhamed Adilović
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Altijana Hromić-Jahjefendić
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Lejla Mahmutović
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Jasmin Šutković
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Alberto Rubio-Casillas
- Autlan Regional Hospital, Health Secretariat, Autlan, Mexico
- Biology Laboratory, Autlan Regional Preparatory School, University of Guadalajara, Autlan, Mexico
| | - Elrashdy M Redwan
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
- Centre of Excellence in Bionanoscience Research, King Abdulaziz University, Jeddah, Saudi Arabia
- Therapeutic and Protective Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), New Borg EL-Arab, Alexandria, Egypt
| | - Vladimir N Uversky
- Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
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4
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Ye F, Wang N, Guan Q, Wang M, Sun J, Zhai D, Huang B, Zhao Y, Tan W. Rapid generation and characterization of recombinant HCoV-OC43-VR1558 infectious clones expressing reporter Renilla luciferase. BIOSAFETY AND HEALTH 2024; 6:350-360. [PMID: 40078980 PMCID: PMC11894994 DOI: 10.1016/j.bsheal.2024.11.006] [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: 08/16/2024] [Revised: 11/17/2024] [Accepted: 11/17/2024] [Indexed: 03/14/2025] Open
Abstract
Viral infectious clones (ICs) serve as robust platforms for studying viral biology and screening antiviral agents using reverse genetics. However, the molecular profiles and complex limitations of human coronaviruses (HCoVs) pose a challenge to ICs development. In this study, we report a novel platform to develop the ICs for HCoV-OC43-VR1558 using a one-step assembly method in yeast by transformation-associated recombination (TAR) technology. Recombinant HCoV-OC43-VR1558, named as rOC43(1558)-WT, was rapidly generated by TAR. In addition, recombinant HCoV-OC43-VR1558-expressing reporter genes, named as rOC43(1558)-ns2FusionRluc, was also generated based on TAR by inserting the ns2 region of the IC with Renilla luciferase (Rluc). We further characterized their replication through virus titration using 50 % tissue culture infective dose (TCID50) and indirect immunofluorescence assay (IFA), luciferase reporter assay, and western blotting (WB) assay. The genetic stability of the recombinant HCoV-OC43 was assessed through viral genome sequencing following passaging in BHK-21 cells. These reporter viruses were validated as screening tools for inhibitors in vitro by evaluating the antiviral activities of remdesivir and chloroquine. The phenotypes of HCoV-OC43-VR1558 and HCoV-OC43-VR759 were compared in vitro and in vivo. The TAR-based one-step assembly of IC was successfully applied, facilitating the rapid generation of recombinant HCoV-OC43 and providing a useful platform for the investigation of biological mechanisms, development of vaccines and diagnostic tests, and screening inhibitors of HCoVs.
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Affiliation(s)
- Fei Ye
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Na Wang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
- School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China
| | - Qiongge Guan
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
- School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China
| | - Mengwei Wang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
- School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China
| | - Jiewei Sun
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
- School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China
| | - Desheng Zhai
- School of Public Health, Xinxiang Medical University, Xinxiang 453003, China
| | - Baoying Huang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Ying Zhao
- School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China
| | - Wenjie Tan
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
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Rajan MV, Sharma V, Upadhyay N, Murali A, Bandyopadhyay S, Hariprasad G. Serum proteomics for the identification of biomarkers to flag predilection of COVID19 patients to various organ morbidities. Clin Proteomics 2024; 21:61. [PMID: 39487396 PMCID: PMC11531188 DOI: 10.1186/s12014-024-09512-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 10/23/2024] [Indexed: 11/04/2024] Open
Abstract
BACKGROUND COVID19 is a pandemic that has affected millions around the world since March 2020. While many patients recovered completely with mild illness, many patients succumbed to various organ morbidities. This heterogeneity in the clinical presentation of COVID19 infection has posed a challenge to clinicians around the world. It is therefore crucial to identify specific organ-related morbidity for effective treatment and better patient outcomes. We have carried out serum-based proteomic experiments to identify protein biomarkers that can flag organ dysfunctions in COVID19 patients. METHODS COVID19 patients were screened and tested at various hospitals across New Delhi, India. 114 serum samples from these patients, with and without organ morbidities were collected and annotated based on clinical presentation and treatment history. Of these, 29 samples comprising of heart, lung, kidney, gastrointestinal, liver, and neurological morbidities were considered for the discovery phase of the experiment. Proteins were isolated, quantified, trypsin digested, and the peptides were subjected to liquid chromatography assisted tandem mass spectrometry analysis. Data analysis was carried out using Proteome Discoverer software. Fold change analysis was carried out on MetaboAnalyst. KEGG, Reactome, and Wiki Pathway analysis of differentially expressed proteins were carried out using the STRING database. Potential biomarker candidates for various organ morbidities were validated using ELISA. RESULTS 254 unique proteins were identified from all the samples with a subset of 12-31 differentially expressed proteins in each of the clinical phenotypes. These proteins establish complement and coagulation cascade pathways in the pathogenesis of the organ morbidities. Validation experiments along with their diagnostic parameters confirm Secreted Protein Acidic and Rich in Cysteine, Cystatin C, and Catalase as potential biomarker candidates that can flag cardiovascular disease, renal disease, and respiratory disease, respectively. CONCLUSIONS Label free serum proteomics shows differential protein expression in COVID19 patients with morbidity as compared to those without morbidity. Identified biomarker candidates hold promise to flag organ morbidities in COVID19 for efficient patient care.
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Affiliation(s)
- Madhan Vishal Rajan
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India
| | - Vipra Sharma
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India
| | - Neelam Upadhyay
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India
| | - Ananya Murali
- Subbaiah Institute of Medical Sciences, New Delhi, Karnataka, India
| | - Sabyasachi Bandyopadhyay
- Proteomics Sub-Facility, Centralized Core Research Facility, All India Institute of Medical Sciences, New Delhi, India
| | - Gururao Hariprasad
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
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6
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Wang CH, Jiang MH, Ma JM, Yuan MC, Liao L, Duan HZ, Wang D, Duan L. Identification of independent risk factors for hypoalbuminemia in patients with CKD stages 3 and 4: the construction of a nomogram. Front Nutr 2024; 11:1453240. [PMID: 39545043 PMCID: PMC11562854 DOI: 10.3389/fnut.2024.1453240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Accepted: 10/17/2024] [Indexed: 11/17/2024] Open
Abstract
Background Hypoalbuminemia is a common complication in patients with chronic kidney disease (CKD) and is associated with various adverse clinical events. Currently, there are few studies focused on identifying risk factors and constructing models for hypoalbuminemia in patients with CKD stages 3 and 4. This study aims to identify independent risk factors for hypoalbuminemia in patients with CKD stages 3 and 4 and construct a nomogram for predicting the risk of hypoalbuminemia in these patients. Methods A total of 237 patients with CKD stages 3 and 4 treated at Anning First People's Hospital from January to December 2023 were included. Univariate and bidirectional stepwise multivariate logistic regression analyses were used to identify independent risk factors for hypoalbuminemia in these patients. Based on the results of logistic regression analyses, a nomogram was constructed. The model performance was assessed using area under the receiver operator characteristic curve, calibration curves, and decision curve analysis. Results Hemoglobin, red blood cells, serum sodium, and serum calcium were identified as independent risk factors for hypoalbuminemia in these patients. The contributions of each independent risk factor to hypoalbuminemia were visualized in a nomogram. The area under the receiver operator characteristic curve of the model was 0.819, indicating good discrimination. The calibration curves showed good agreement between predicted and observed outcomes. The decision curve analysis also verified that the model had the good clinical utility. Conclusion Hemoglobin, red blood cells, serum sodium, and serum calcium were identified as independent risk factors of hypoalbuminemia in patients with CKD stages 3 and 4. The nomogram exhibits good discrimination, calibration, and clinical utility, offering a reliable tool for the early prediction and identification of hypoalbuminemia in these patients.
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Affiliation(s)
- Chong-Hui Wang
- College of Pharmacy, Kunming Medical University, Kunming, China
- Department of Pharmacy, Anning First People’s Hospital Affiliated to Kunming University of Science and Technology, Kunming, China
| | | | - Ji-Min Ma
- College of Pharmacy, Kunming Medical University, Kunming, China
- Department of Pharmacy, Anning First People’s Hospital Affiliated to Kunming University of Science and Technology, Kunming, China
| | - Ming-Cong Yuan
- Department of Pharmacy, Anning First People’s Hospital Affiliated to Kunming University of Science and Technology, Kunming, China
- College of Pharmacy, Dali University, Dali, China
| | - Lei Liao
- College of Pharmacy, Kunming Medical University, Kunming, China
- Department of Pharmacy, Anning First People’s Hospital Affiliated to Kunming University of Science and Technology, Kunming, China
| | - Hao-Zhang Duan
- College of Pharmacy, Kunming Medical University, Kunming, China
- Department of Pharmacy, Anning First People’s Hospital Affiliated to Kunming University of Science and Technology, Kunming, China
| | - Dan Wang
- Department of Pharmacy, Anning First People’s Hospital Affiliated to Kunming University of Science and Technology, Kunming, China
| | - Lian Duan
- Department of Pharmacy, Anning First People’s Hospital Affiliated to Kunming University of Science and Technology, Kunming, China
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Tekin A, Devarajan A, Sakata KK, Qamar S, Sharma M, Valencia Morales DJ, Malinchoc M, Talaei F, Welle S, Taji J, Khosa S, Sharma N, Brown M, Lal A, Bansal V, Khan SA, La Nou AT, Sanghavi D, Cartin-Ceba R, Kashyap R, Gajic O, Domecq JP, Azadeh N. Pneumomediastinum and pneumothorax in coronavirus disease-2019: Description of a case series and a matched cohort study. Heliyon 2024; 10:e33679. [PMID: 39055836 PMCID: PMC11269848 DOI: 10.1016/j.heliyon.2024.e33679] [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: 10/05/2023] [Revised: 06/21/2024] [Accepted: 06/25/2024] [Indexed: 07/28/2024] Open
Abstract
OBJECTIVE To describe the characteristics of COVID-19 patients with pneumothorax and pneumomediastinum (PTX/PM) and their association with patient outcomes. PATIENTS AND METHODS Adults admitted to five Mayo Clinic hospitals with COVID-19 between 03/2020-01/2022 were evaluated. PTX/PM was defined by imaging. Descriptive analyses and a matched (age, sex, admission month, COVID-19 severity) cohort comparison was performed. Hospital mortality, length of stay (LOS), and predisposing factors were assessed. RESULTS Among 6663 patients, 197 had PTX/PM (3 %) (75 PM, 40 PTX, 82 both). The median age was 59, with 71 % males. Exposure to invasive and non-invasive mechanical ventilation and high-flow nasal cannula before PTX/PM were 42 %, 17 %, and 20 %, respectively. Among isolated PTX and PM/PTX patients 70 % and 53.7 % underwent an intervention, respectively, while 96 % of the PM-only group was followed conservatively.A total of 171 patients with PTX/PM were compared to 171 matched controls. PTX/PM patients had more underlying lung disease (40.9 vs. 23.4 %, p < 0.001) and lower median body mass index (BMI) (29.5 vs. 31.3 kg/m2, p = .007) than controls. Among patients with available data, PTX/PM patients had higher median positive end-expiratory and plateau pressures than controls; however, differences were not significant (10 vs. 8 cmH2O; p = 0.38 and 28 vs. 22 cmH2O; p = 0.11, respectively). PTX/PM patients had a higher odds of mortality (adjusted odds ratio [95%CI]: 3.37 [1.61-7.07]) and longer mean LOS (percent change [95%CI]: 39 [9-77]) than controls. CONCLUSION In COVID-19 patients with similar severity, PTX/PM patients had more underlying lung disease and lower BMI. They had significantly increased mortality and LOS.
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Affiliation(s)
- Aysun Tekin
- Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Anusha Devarajan
- Division of Pulmonary, Department of Medicine and Department of Critical Care Medicine, Mayo Clinic, Scottsdale, AZ, USA
| | - Kenneth K. Sakata
- Division of Pulmonary, Department of Medicine and Department of Critical Care Medicine, Mayo Clinic, Scottsdale, AZ, USA
| | - Shahraz Qamar
- Post-Baccalaureate Research Education Program, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Mayank Sharma
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
| | | | | | - Fahimeh Talaei
- Division of Pulmonary, Department of Medicine and Department of Critical Care Medicine, Mayo Clinic, Scottsdale, AZ, USA
| | - Stephanie Welle
- Division of Critical Care Medicine, Mayo Clinic Health System, Mankato, MN, USA
| | - Jamil Taji
- Division of Pulmonary Medicine, Division of Critical Care Medicine, Mayo Clinic Health Systems, Mankato, MN, USA
| | - Sandeep Khosa
- Division of Pulmonary Medicine, Division of Critical Care Medicine, Mayo Clinic Health Systems, Mankato, MN, USA
| | - Nikhil Sharma
- Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Meghan Brown
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Amos Lal
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Vikas Bansal
- Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Syed Anjum Khan
- Division of Critical Care Medicine, Mayo Clinic Health System, Mankato, MN, USA
| | - Abigail T. La Nou
- Division of Critical Care Medicine, Mayo Clinic Health System, Eau Claire, WI, USA
| | - Devang Sanghavi
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Rodrigo Cartin-Ceba
- Division of Pulmonary, Department of Medicine and Department of Critical Care Medicine, Mayo Clinic, Scottsdale, AZ, USA
| | - Rahul Kashyap
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
- Department of Research, WellSpan Health, York, PA, USA
| | - Ognjen Gajic
- Division of Critical Care Medicine, Mayo Clinic Health System, Eau Claire, WI, USA
| | - Juan P. Domecq
- Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Natalya Azadeh
- Division of Pulmonary, Department of Medicine and Department of Critical Care Medicine, Mayo Clinic, Scottsdale, AZ, USA
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Almeria M, Cejudo JC, Deus J, Krupinski J. Neurocognitive and Neuropsychiatric Sequelae in Long COVID-19 Infection. Brain Sci 2024; 14:604. [PMID: 38928604 PMCID: PMC11202095 DOI: 10.3390/brainsci14060604] [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: 05/16/2024] [Revised: 06/07/2024] [Accepted: 06/12/2024] [Indexed: 06/28/2024] Open
Abstract
Objective: To characterize the cognitive profile of long COVID-19 subjects and its possible association with clinical symptoms, emotional disturbance, biomarkers, and disease severity. Methods: We performed a single-center cross-sectional cohort study. Subjects between 20 and 60 years old with confirmed COVID-19 infection were included. The assessment was performed 6 months following hospital or ambulatory discharge. Excluded were those with prior neurocognitive impairment and severe neurological/neuropsychiatric disorders. Demographic and laboratory data were extracted from medical records. Results: Altogether, 108 participants were included, 64 were male (59.25%), and the mean age was 49.10 years. The patients were classified into four groups: non-hospitalized (NH, n = 10), hospitalized without Intensive Care Unit (ICU) or oxygen therapy (HOSPI, n = 21), hospitalized without ICU but with oxygen therapy (OXY, n = 56), and ICU (ICU, n = 21) patients. In total, 38 (35.18%) reported Subjective Cognitive Complaints (SCC). No differences were found considering illness severity between groups. Females had more persistent clinical symptoms and SCC than males. Persistent dyspnea and headache were associated with higher scores in anxiety and depression. Persistent fatigue, anxiety, and depression were associated with worse overall cognition. Conclusions: No cognitive impairment was found regarding the severity of post-COVID-19 infection. SCC was not associated with a worse cognitive performance, but with higher anxiety and depression. Persistent clinical symptoms were frequent independent of illness severity. Fatigue, anxiety, and depression were linked to poorer cognitive function. Tests for attention, processing speed, and executive function were the most sensitive in detecting cognitive changes in these patients.
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Affiliation(s)
- Marta Almeria
- Department of Neurology, Hospital Universitari MútuaTerrassa, 08221 Terrassa, Spain;
| | - Juan Carlos Cejudo
- Cognitive Impairment and Dementia Unit, Hospital Sagrat Cor, Hermanas Hospitalarias, 08760 Martorell, Spain
| | - Joan Deus
- Clinical and Health Department, Psychology Faculty, Autonomous University of Barcelona, 08193 Bellaterra, Spain
- MRI Research Unit, Department of Radiology, Hospital del Mar, 08003 Barcelona, Spain
| | - Jerzy Krupinski
- Department of Neurology, Hospital Universitari MútuaTerrassa, 08221 Terrassa, Spain;
- Faculty of Science and Engineering, Department of Life Sciences John Dalton Building, Manchester Metropolitan University, Manchester M15 6BH, UK
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Wellford SA, Moseman EA. Olfactory immunology: the missing piece in airway and CNS defence. Nat Rev Immunol 2024; 24:381-398. [PMID: 38097777 PMCID: PMC11560121 DOI: 10.1038/s41577-023-00972-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/03/2023] [Indexed: 12/23/2023]
Abstract
The olfactory mucosa is a component of the nasal airway that mediates the sense of smell. Recent studies point to an important role for the olfactory mucosa as a barrier to both respiratory pathogens and to neuroinvasive pathogens that hijack the olfactory nerve and invade the CNS. In particular, the COVID-19 pandemic has demonstrated that the olfactory mucosa is an integral part of a heterogeneous nasal mucosal barrier critical to upper airway immunity. However, our insufficient knowledge of olfactory mucosal immunity hinders attempts to protect this tissue from infection and other diseases. This Review summarizes the state of olfactory immunology by highlighting the unique immunologically relevant anatomy of the olfactory mucosa, describing what is known of olfactory immune cells, and considering the impact of common infectious diseases and inflammatory disorders at this site. We will offer our perspective on the future of the field and the many unresolved questions pertaining to olfactory immunity.
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Affiliation(s)
- Sebastian A Wellford
- Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC, USA
| | - E Ashley Moseman
- Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC, USA.
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Al-Tawfiq JA. Developments in treatment for middle east respiratory syndrome coronavirus (MERS-CoV). Expert Rev Respir Med 2024; 18:295-307. [PMID: 38881206 DOI: 10.1080/17476348.2024.2369714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Accepted: 06/14/2024] [Indexed: 06/18/2024]
Abstract
INTRODUCTION An important respiratory pathogen that has led to multiple hospital outbreaks both inside and outside of the Arabian Peninsula is the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Given the elevated case fatality rate, there exists a pressing requirement for efficacious therapeutic agents. AREAS COVERED This is an updated review of the developments in MERS treatment approaches. Using databases like PubMed, Embase, Cochrane, Scopus, and Google Scholar, a thorough search was carried out utilizing keywords like 'MERS,' 'MERS-CoV,' and 'Middle East respiratory syndrome' in conjunction with 'treatment' or 'therapy' from Jan 2012 to Feb 2024. EXPERT OPINION MERS-CoV is a highly pathogenic respiratory infection that emerged in 2012 and continues to pose a significant public health threat. Despite ongoing efforts to control the spread of MERS-CoV, there is currently no specific antiviral treatment available. While many agents have been tested both in vivo and in vitro, none of them have been thoroughly examined in extensive clinical trials. Only case reports, case series, or cohort studies have been made available as clinical studies. However, there is a limited number of randomized-controlled trials. Because cases are irregular and sporadic, conducting a large prospective randomized trials for establishing an efficacious treatment might be difficult.
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Affiliation(s)
- Jaffar A Al-Tawfiq
- Speciality Internal Medicine, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
- Infectious Disease Division, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
- Infectious Disease Division, Department of Medicine Johns Hopkins University School of Medicine, Baltimore, MD, USA
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11
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Wu S, Liao G, Mao J, Yan H, Chen J, Peng J. Factors Associated with Mortality Among Severe Omicron Patients for COVID-19. Infect Drug Resist 2024; 17:1309-1319. [PMID: 38585415 PMCID: PMC10999197 DOI: 10.2147/idr.s450504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 03/13/2024] [Indexed: 04/09/2024] Open
Abstract
Purpose The purpose of the study was to explore the potential risk factors of mortality in patients with severe pneumonia during the omicron pandemic in South China in 2022. Methods Clinical data was collected from patients hospitalized with omicron COVID-19. Then, patients were categorized into the non-survival and survival groups. A comprehensive analysis was conducted to analyze the factors associated with negative outcome in individuals suffering from severe omicron COVID-19. Results In this study, 155 severe COVID-19 patients were included, comprising 55 non-survivors and 100 survivors. Non-survivors, in comparison to survivors, exhibited elevated levels of various biomarkers including neutrophil count, hypersensitive troponin T, urea, creatinine, C-reactive protein, procalcitonin, interleukin-6, plasma D-dimer, and derived neutrophil-to-lymphocyte ratio (dNLR) (P < 0.05). They also displayed reduced lymphocyte count, platelet count, and albumin levels (P < 0.05) and were more prone to developing comorbidities, including shock, acute cardiac and renal injury, acute respiratory distress syndrome, coagulation disorders, and secondary infections. Platelet count (PLT) <100 × 10^/L, interleukin-6 (IL-6) >100 pg/mL, and dNLR >5.0 independently contributed to the risk of death in patients suffering from severe COVID-19. Conclusion PLT, IL-6, and dNRL independently contributed to the risk of mortality in patients with severe pneumonia during the 2022 omicron pandemic in South China.
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Affiliation(s)
- Shuting Wu
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Guichan Liao
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Jingchun Mao
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Haiming Yan
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Juanjuan Chen
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Jie Peng
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
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Xiao MT, Ellsworth CR, Qin X. Emerging role of complement in COVID-19 and other respiratory virus diseases. Cell Mol Life Sci 2024; 81:94. [PMID: 38368584 PMCID: PMC10874912 DOI: 10.1007/s00018-024-05157-8] [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: 09/29/2023] [Revised: 01/03/2024] [Accepted: 02/03/2024] [Indexed: 02/19/2024]
Abstract
The complement system, a key component of innate immunity, provides the first line of defense against bacterial infection; however, the COVID-19 pandemic has revealed that it may also engender severe complications in the context of viral respiratory disease. Here, we review the mechanisms of complement activation and regulation and explore their roles in both protecting against infection and exacerbating disease. We discuss emerging evidence related to complement-targeted therapeutics in COVID-19 and compare the role of the complement in other respiratory viral diseases like influenza and respiratory syncytial virus. We review recent mechanistic studies and animal models that can be used for further investigation. Novel knockout studies are proposed to better understand the nuances of the activation of the complement system in respiratory viral diseases.
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Affiliation(s)
- Mark T Xiao
- Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA, 70433, USA
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, 70112, USA
| | - Calder R Ellsworth
- Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA, 70433, USA
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, 70112, USA
| | - Xuebin Qin
- Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA, 70433, USA.
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, 70112, USA.
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Abstract
Numerous pathogens can infect the olfactory tract, yet the pandemic caused by SARS-CoV-2 has strongly emphasized the importance of the olfactory mucosa as an immune barrier. Situated in the nasal passages, the olfactory mucosa is directly exposed to the environment to sense airborne odorants; however, this also means it can serve as a direct route of entry from the outside world into the brain. As a result, olfactotropic infections can have serious consequences, including dysfunction of the olfactory system, CNS invasion, dissemination to the lower respiratory tract, and transmission between individuals. Recent research has shown that a distinctive immune response is needed to protect this neuronal and mucosal tissue. A better understanding of innate, adaptive, and structural immune barriers in the olfactory mucosa is needed to develop effective therapeutics and vaccines against olfactotropic microbes such as SARS-CoV-2. Here, we summarize the ramifications of SARS-CoV-2 infection of the olfactory mucosa, review the subsequent immune response, and discuss important areas of future research for olfactory immunity to infectious disease.
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Affiliation(s)
- Sebastian A Wellford
- Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC, USA
| | - E Ashley Moseman
- Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC, USA.
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14
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Miyazawa Y, Katsuta N, Nara T, Nojiri S, Naito T, Hiki M, Ichikawa M, Takeshita Y, Kato T, Okumura M, Tobita M. Identification of risk factors for the onset of delirium associated with COVID-19 by mining nursing records. PLoS One 2024; 19:e0296760. [PMID: 38241284 PMCID: PMC10798448 DOI: 10.1371/journal.pone.0296760] [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: 06/20/2023] [Accepted: 12/18/2023] [Indexed: 01/21/2024] Open
Abstract
COVID-19 has a range of complications, from no symptoms to severe pneumonia. It can also affect multiple organs including the nervous system. COVID-19 affects the brain, leading to neurological symptoms such as delirium. Delirium, a sudden change in consciousness, can increase the risk of death and prolong the hospital stay. However, research on delirium prediction in patients with COVID-19 is insufficient. This study aimed to identify new risk factors that could predict the onset of delirium in patients with COVID-19 using machine learning (ML) applied to nursing records. This retrospective cohort study used natural language processing and ML to develop a model for classifying the nursing records of patients with delirium. We extracted the features of each word from the model and grouped similar words. To evaluate the usefulness of word groups in predicting the occurrence of delirium in patients with COVID-19, we analyzed the temporal changes in the frequency of occurrence of these word groups before and after the onset of delirium. Moreover, the sensitivity, specificity, and odds ratios were calculated. We identified (1) elimination-related behaviors and conditions and (2) abnormal patient behavior and conditions as risk factors for delirium. Group 1 had the highest sensitivity (0.603), whereas group 2 had the highest specificity and odds ratio (0.938 and 6.903, respectively). These results suggest that these parameters may be useful in predicting delirium in these patients. The risk factors for COVID-19-associated delirium identified in this study were more specific but less sensitive than the ICDSC (Intensive Care Delirium Screening Checklist) and CAM-ICU (Confusion Assessment Method for the Intensive Care Unit). However, they are superior to the ICDSC and CAM-ICU because they can predict delirium without medical staff and at no cost.
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Affiliation(s)
- Yusuke Miyazawa
- Department of Healthcare Innovation, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Narimasa Katsuta
- Department of Psychiatry, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Tamaki Nara
- Department of Healthcare Innovation, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Medical Technology Innovation Center, Juntendo University, Tokyo, Japan
- Clinical Research and Trial Center, Juntendo University, Tokyo, Japan
| | - Shuko Nojiri
- Department of Healthcare Innovation, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Medical Technology Innovation Center, Juntendo University, Tokyo, Japan
- Clinical Research and Trial Center, Juntendo University, Tokyo, Japan
| | - Toshio Naito
- Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Makoto Hiki
- Department of Emergency and Disaster Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan
- Department of Cardiovascular Biology and Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Masako Ichikawa
- Department of Emergency and Disaster Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yoshihide Takeshita
- Department of Psychiatry, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Tadafumi Kato
- Department of Psychiatry, Juntendo University Faculty of Medicine, Tokyo, Japan
| | | | - Morikuni Tobita
- Department of Healthcare Innovation, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Medical Technology Innovation Center, Juntendo University, Tokyo, Japan
- Clinical Research and Trial Center, Juntendo University, Tokyo, Japan
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15
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Liu L, Zhou C, Jiang H, Wei H, Zhou Y, Zhou C, Ji X. Epidemiology, pathogenesis, and management of Coronavirus disease 2019-associated stroke. Front Med 2023; 17:1047-1067. [PMID: 38165535 DOI: 10.1007/s11684-023-1041-7] [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: 05/05/2023] [Accepted: 10/15/2023] [Indexed: 01/03/2024]
Abstract
The Coronavirus disease 2019 (COVID-19) epidemic has triggered a huge impact on healthcare, socioeconomics, and other aspects of the world over the past three years. An increasing number of studies have identified a complex relationship between COVID-19 and stroke, although active measures are being implemented to prevent disease transmission. Severe COVID-19 may be associated with an increased risk of stroke and increase the rates of disability and mortality, posing a serious challenge to acute stroke diagnosis, treatment, and care. This review aims to provide an update on the influence of COVID-19 itself or vaccines on stroke, including arterial stroke (ischemic stroke and hemorrhagic stroke) and venous stroke (cerebral venous thrombosis). Additionally, the neurovascular mechanisms involved in SARS-CoV-2 infection and the clinical characteristics of stroke in the COVID-19 setting are presented. Evidence on vaccinations, potential therapeutic approaches, and effective strategies for stroke management has been highlighted.
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Affiliation(s)
- Lu Liu
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100032, China
- Neurology and Intracranial Hypertension and Cerebral Venous Disease Center, National Health Commission of China, Xuanwu Hospital, Capital Medical University, Beijing, 100032, China
| | - Chenxia Zhou
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100032, China
- Neurology and Intracranial Hypertension and Cerebral Venous Disease Center, National Health Commission of China, Xuanwu Hospital, Capital Medical University, Beijing, 100032, China
| | - Huimin Jiang
- Beijing Institute of Brain Disorders, Capital Medical University, Beijing, 100069, China
| | - Huimin Wei
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China
| | - Yifan Zhou
- Beijing Institute of Brain Disorders, Capital Medical University, Beijing, 100069, China
| | - Chen Zhou
- Beijing Institute of Brain Disorders, Capital Medical University, Beijing, 100069, China.
- Department of Neurology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
| | - Xunming Ji
- Neurology and Intracranial Hypertension and Cerebral Venous Disease Center, National Health Commission of China, Xuanwu Hospital, Capital Medical University, Beijing, 100032, China.
- Beijing Institute of Brain Disorders, Capital Medical University, Beijing, 100069, China.
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 100032, China.
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16
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Bennett RP, Yoluç Y, Salter JD, Ripp A, Jessen HJ, Kaiser SM, Smith HC. Sangivamycin is preferentially incorporated into viral RNA by the SARS-CoV-2 polymerase. Antiviral Res 2023; 218:105716. [PMID: 37690700 DOI: 10.1016/j.antiviral.2023.105716] [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: 07/12/2023] [Revised: 09/05/2023] [Accepted: 09/08/2023] [Indexed: 09/12/2023]
Abstract
Sangivamycin (S) is an adenosine (A) nucleoside analog with low nanomolar antiviral activity against SARS-CoV-2 in vitro. Previously, low nanomolar antiviral efficacy was revealed when tested against multiple viral variants in several cell types. SARS-CoV-2 RNA isolated from live virus infected cells and the virions released from these cells was analyzed by mass spectrometry (MS) for S incorporation. Dose-dependent incorporation occurred up to 1.8 S per 1,000 nucleotides (49 S per genome) throughout the viral genomes isolated from both infected cells and viral particles, but this incorporation did not change the viral mutation rate. In contrast, host mRNA, affinity purified from the same infected and treated cells, contained little or no S. Sangivamycin triphosphate (STP) was synthesized to evaluate its incorporation into RNA by recombinant SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) under defined in vitro conditions. SARS-CoV-2 RdRp showed that S was not a chain terminator and S containing oligonucleotides templated as A. Though the antiviral mechanism remains to be determined, the data suggests that SARS-CoV-2 RdRp incorporates STP into SARS-CoV-2 RNA, which does not significantly impair viral RNA synthesis or the mutation rate.
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Affiliation(s)
| | - Yasemin Yoluç
- Department of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt, Germany.
| | | | - Alexander Ripp
- Institute of Organic Chemistry Albert-Ludwigs-University, Freiburg, Germany.
| | - Henning J Jessen
- Institute of Organic Chemistry Albert-Ludwigs-University, Freiburg, Germany.
| | - Stefanie M Kaiser
- Department of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt, Germany.
| | - Harold C Smith
- OyaGen, Inc., Rochester, NY, USA; Department of Biochemistry and Biophysics, Center for RNA Biology, Center for AIDS Research, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
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17
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Proust A, Queval CJ, Harvey R, Adams L, Bennett M, Wilkinson RJ. Differential effects of SARS-CoV-2 variants on central nervous system cells and blood-brain barrier functions. J Neuroinflammation 2023; 20:184. [PMID: 37537664 PMCID: PMC10398935 DOI: 10.1186/s12974-023-02861-3] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 07/25/2023] [Indexed: 08/05/2023] Open
Abstract
BACKGROUND Although mainly causing a respiratory syndrome, numerous neurological symptoms have been identified following of SARS-CoV-2 infection. However, how the virus affects the brain and how the mutations carried by the different variants modulate those neurological symptoms remain unclear. METHODS We used primary human pericytes, foetal astrocytes, endothelial cells and a microglial cell line to investigate the effect of several SARS-CoV-2 variants of concern or interest on their functional activities. Cells and a 3D blood-brain barrier model were infected with the wild-type form of SARS-CoV-2, Alpha, Beta, Delta, Eta, or Omicron (BA.1) variants at various MOI. Cells and supernatant were used to evaluate cell susceptibility to the virus using a microscopic assay as well as effects of infection on (i) cell metabolic activity using a colorimetric MTS assay; (ii) viral cytopathogenicity using the xCELLigence system; (iii) extracellular glutamate concentration by fluorometric assay; and (iv) modulation of blood-brain barrier permeability. RESULTS We demonstrate that productive infection of brain cells is SARS-CoV-2 variant dependent and that all the variants induce stress to CNS cells. The wild-type virus was cytopathic to all cell types except astrocytes, whilst Alpha and Beta variants were only cytopathic for pericytes, and the Omicron variant cytopathic for endothelial cells and pericytes. Lastly wild-type virus increases blood-brain barrier permeability and all variants, except Beta, modulate extracellular glutamate concentration, which can lead to excitotoxicity or altered neurotransmission. CONCLUSIONS These results suggest that SARS-CoV-2 is neurotropic, with deleterious consequences for the blood-brain barrier integrity and central nervous system cells, which could underlie neurological disorders following SARS-CoV-2 infection.
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Affiliation(s)
- Alizé Proust
- Tuberculosis Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
| | - Christophe J Queval
- High Throughput Screening Laboratory, The Francis Crick Institute, London, NW1 1AT, UK
| | - Ruth Harvey
- Worldwide Influenza Centre, The Francis Crick Institute, London, NW1 1AT, UK
| | - Lorin Adams
- Worldwide Influenza Centre, The Francis Crick Institute, London, NW1 1AT, UK
| | - Michael Bennett
- Worldwide Influenza Centre, The Francis Crick Institute, London, NW1 1AT, UK
| | - Robert J Wilkinson
- Tuberculosis Laboratory, The Francis Crick Institute, London, NW1 1AT, UK
- Department of Infectious Diseases, Imperial College London, London, W12 0NN, UK
- Institute of Infectious Disease and Molecular Medicine and Department of Medicine, Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory, Cape Town, 7925, Republic of South Africa
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18
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Li HWC, Ong JP, Salamat MSS, Malundo AFG, Abad CLR. Predictors and Outcomes of Hospitalized COVID-19 Patients with Liver Injury. ACTA MEDICA PHILIPPINA 2023; 57:3-10. [PMID: 39483298 PMCID: PMC11522575 DOI: 10.47895/amp.vi0.4651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/03/2024]
Abstract
OBJECTIVE To determine incidence, predictors, and impact of liver injury among hospitalized COVID-19 patients. METHODS This is a retrospective cohort study of hospitalized COVID-19 patients at the University of the Philippines-Philippine General Hospital. Liver injury (LI) was defined as ALT elevation above institutional cut-off (>50 u/L) and was classified as mild (>1x to 3x ULN), moderate (>3x to 5x ULN), or severe (>5x ULN). Significant liver injury (SLI) was defined as moderate to severe LI. Univariate analysis of SLI predictors was performed. The impact of LI on clinical outcomes was determined and adjusted for known predictors -age, sex, and comorbidities. RESULTS Of the 1,131 patients, 565 (50.04%) developed LI. SLI was associated with male sex, alcohol use, chronic liver disease, increasing COVID-19 severity, high bilirubin, AST, LDH, CRP, and low lymphocyte count and albumin. An increasing degree of LI correlated with ICU admission. Only severe LI was associated with the risk of invasive ventilation (OR: 3.54, p=0.01) and mortality (OR: 2.76, p=0.01). Severe LI, male sex, cardiovascular disease, and malignancy were associated with longer hospital stay among survivors. CONCLUSION The liver injury occurred commonly among COVID-19 patients and was associated with important clinicodemographic characteristics. Severe liver injury increases the risk of adverse outcomes among hospitalized patients.
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Affiliation(s)
- Henry Winston C. Li
- Division of Gastroenterology, Department of Medicine, Philippine General Hospital, University of the Philippines Manila
| | - Janus P. Ong
- Division of Gastroenterology, Department of Medicine, Philippine General Hospital, University of the Philippines Manila
| | - Maria Sonia S. Salamat
- Division of Infectious Diseases, Department of Medicine, Philippine General Hospital, University of the Philippines Manila
| | - Anna Flor G. Malundo
- Division of Infectious Diseases, Department of Medicine, Philippine General Hospital, University of the Philippines Manila
| | - Cybele Lara R. Abad
- Division of Infectious Diseases, Department of Medicine, Philippine General Hospital, University of the Philippines Manila
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Wang C, Hao W. Cardiac arrhythmia and immune response in COVID-19 patients. Allergol Immunopathol (Madr) 2023; 51:63-70. [PMID: 37422781 DOI: 10.15586/aei.v51i4.883] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 04/15/2023] [Indexed: 07/11/2023]
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has presented substantial challenges for providing health care due to the numerous complications on the respiratory and cardiovascular systems of people. Cardiac arrhythmia is one of the cardiac complications, and it was observed in COVID-19 patients. Moreover, arrhythmia and cardiac arrest are common in COVID-19 patients in the intensive care unit. The occurrence of cardiac arrhythmia in COVID-19 patients is associated with hypoxia, cytokine storm, myocardial ischemia and inflammatory disease such as congestive heart failure. It is necessary to know the occurrence and mechanisms of tachyarrhythmia and bradyarrhythmia in patients with COVID-19 infection for their proper management. This review provides an overview of the association between COVID-19 and arrhythmias by detailing possible pathophysiological mechanisms.
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Affiliation(s)
- Chunlian Wang
- Institute for Prevention and Control of Chronic Non-communicable Diseases, Harbin Center for Disease Control and Prevention, Harbin, China
| | - Wenqiang Hao
- The Second Ward of Internal Medicine, The Second Hospital of Heilongjiang Province, Harbin, China; ;
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20
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Binub K, Harsha P, Salim RS, Sunny S, Dabas P, Chalil S, Henry S. An Observational Study on the Utility of Lab Parameters in Evaluating the Severity of Patients in South India with Covid-19. JOURNAL OF PHARMACY AND BIOALLIED SCIENCES 2023; 15:S414-S418. [PMID: 37654375 PMCID: PMC10466675 DOI: 10.4103/jpbs.jpbs_549_22] [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: 11/06/2022] [Revised: 11/16/2022] [Accepted: 12/05/2022] [Indexed: 09/02/2023] Open
Abstract
Laboratory testing has been extremely helpful in determining the severity and determining the course of treatment for COVID-19 patients. Our aim has been to look for variables of patient's clinical and laboratory profile for two weeks and to observe their significance. Observational, Cross-sectional study. Data from the clinic and laboratory were compiled on Google form after informed consent from the patient. Statistical analysis was done using the Mann-Whitney U and unpaired t test. Population statistics included 202 patients (1st week) and 161 patients (2nd week), with the mean age of 61 ± 18 years. Most patients fell under the mild category (SPO2 >94%). High body mass index (n = 119) and hypertensive (n = 98) were the most common comorbidities observed. Diabetes, cardiovascular and respiratory diseases are the other comorbidities studied in this study. Hypoalbuminemia (n = 194) is the most deranged laboratory parameter in mild category, followed by lymphopenia (n = 109). In severe category also, hypoalbuminemia (n = 13) was deranged more. Other laboratory parameters included are CRP, D-Dimer, neutrophil and lymphocyte count. This study showed that albumin is a good predictor for estimating the severity of COVID-19 patients especially in the first week of their admission.
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Affiliation(s)
- Kanniyan Binub
- Department of Community Medicine, Malabar Medical College and Research Center, Calicut, Kerala, India
| | - P.V. Harsha
- Department of Pulmonary Medicine, Malabar Medical College and Research Center, Calicut, Kerala, India
| | - Roshni S. Salim
- Department of Community Medicine, Malabar Medical College and Research Center, Calicut, Kerala, India
| | - Sobin Sunny
- Department of Community Medicine, Malabar Medical College and Research Center, Calicut, Kerala, India
| | - Pratibha Dabas
- Department of Community Medicine, Malabar Medical College and Research Center, Calicut, Kerala, India
| | - Swathy Chalil
- Department of Community Medicine, Malabar Medical College and Research Center, Calicut, Kerala, India
| | - Sneha Henry
- Department of Biochemistry, Malabar Medical College and Research Center, Calicut, Kerala, India
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21
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Torabizadeh C, Iloonkashkooli R, Haghshenas H, Fararouei M. Prevalence of Cardiovascular Complications in Coronavirus Disease 2019 adult Patients: A Systematic Review and Meta-Analysis. IRANIAN JOURNAL OF MEDICAL SCIENCES 2023; 48:243-267. [PMID: 37791325 PMCID: PMC10542931 DOI: 10.30476/ijms.2022.93701.2504] [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: 11/27/2021] [Revised: 04/03/2022] [Accepted: 04/26/2022] [Indexed: 10/05/2023]
Abstract
Background It has been found that the new coronavirus can affect various parts of the cardiovascular system. Cardiovascular complications caused by coronavirus disease 2019 (COVID-19) are often serious and can increase the mortality rate among infected patients. This study aimed to investigate the prevalence of cardiovascular complications in COVID-19 adult patients. Methods A systematic review and meta-analysis of observational studies published in English were conducted between December 2019 and February 2021. A complete search was performed in PubMed (PubMed Central and MEDLINE), Google Scholar, Cochrane Library, Science Direct, Ovid, Embase, Scopus, CINAHL, Web of Science, and WILEY, as well as BioRXiv, MedRXiv, and gray literature. A random effect model was used to examine the prevalence of cardiovascular complications among COVID-19 patients. The I2 test was used to measure heterogeneity across the included studies. Results A total of 74 studies involving 34,379 COVID-19 patients were included for meta-analysis. The mean age of the participants was 61.30±14.75 years. The overall pooled prevalence of cardiovascular complications was 23.45%. The most prevalent complications were acute myocardial injury (AMI) (19.38%, 95% CI=13.62-26.81, test for heterogeneity I2=97.5%, P<0.001), arrhythmia (11.16%, 95% CI=8.23-14.96, test for heterogeneity I2=91.5%, P<0.001), heart failure (HF) (7.56%, 95% CI=4.50-12.45, test for heterogeneity I2=96.3%, P<0.001), and cardiomyopathy (2.78%, 95% CI=0.34-9.68). The highest pooled prevalence of cardiac enzymes was lactate dehydrogenase (61.45%), troponin (23.10%), and creatine kinase-myocardial band or creatine kinase (14.52%). Conclusion The high prevalence of serious cardiovascular complications in COVID-19 patients (AMI, arrhythmia, and HF) necessitates increased awareness by healthcare administrators.
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Affiliation(s)
- Camellia Torabizadeh
- Community Based Psychiatric Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Hajar Haghshenas
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Fararouei
- HIV/AIDs Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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22
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Sun Q, Li X, Kuang E. Subversion of autophagy machinery and organelle-specific autophagy by SARS-CoV-2 and coronaviruses. Autophagy 2023; 19:1055-1069. [PMID: 36005882 PMCID: PMC10012907 DOI: 10.1080/15548627.2022.2116677] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 08/18/2022] [Accepted: 08/19/2022] [Indexed: 12/09/2022] Open
Abstract
As a new emerging severe coronavirus, the knowledge on the SARS-CoV-2 and COVID-19 remains very limited, whereas many concepts can be learned from the homologous coronaviruses. Macroautophagy/autophagy is finely regulated by SARS-CoV-2 infection and plays important roles in SARS-CoV-2 infection and pathogenesis. This review will explore the subversion and mechanism of the autophagy-related machinery, vacuoles and organelle-specific autophagy during infection of SARS-CoV-2 and coronaviruses to provide meaningful insights into the autophagy-related therapeutic strategies for infectious diseases of SARS-CoV-2 and coronaviruses.
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Affiliation(s)
- Qinqin Sun
- Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Xiaojuan Li
- College of Clinic Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei, China
| | - Ersheng Kuang
- Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Ministry of Education, Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Guangzhou, Guangdong, China
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23
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Brainard J, Jones NR, Harrison FC, Hammer CC, Lake IR. Super-spreaders of novel coronaviruses that cause SARS, MERS and COVID-19: A systematic review. Ann Epidemiol 2023:S1047-2797(23)00058-3. [PMID: 37001627 DOI: 10.1016/j.annepidem.2023.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 01/12/2023] [Accepted: 03/26/2023] [Indexed: 03/31/2023]
Abstract
PURPOSE Most index cases with novel coronavirus infections transmit disease to just one or two other individuals, but some individuals "super-spread"-they infect many secondary cases. Understanding common factors that super-spreaders may share could inform outbreak models, and be used to guide contact tracing during outbreaks. METHODS We searched in MEDLINE, Scopus, and preprints to identify studies about people documented as transmitting pathogens that cause SARS, MERS, or COVID-19 to at least nine other people. We extracted data to describe them by age, sex, location, occupation, activities, symptom severity, any underlying conditions, disease outcome and undertook quality assessment for outbreaks published by June 2021. RESULTS The most typical super-spreader was a male age 40+. Most SARS or MERS super-spreaders were very symptomatic, the super-spreading occurred in hospital settings and frequently the individual died. In contrast, COVID-19 super-spreaders often had very mild disease and most COVID-19 super-spreading happened in community settings. CONCLUSIONS SARS and MERS super-spreaders were often symptomatic, middle- or older-age adults who had a high mortality rate. In contrast, COVID-19 super-spreaders tended to have mild disease and were any adult age. More outbreak reports should be published with anonymized but useful demographic information to improve understanding of super-spreading, super-spreaders, and the settings in which super-spreading happens.
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24
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Elkhalifa AME, Nabi SU, Shah OS, Bashir SM, Muzaffer U, Ali SI, Wani IA, Alzerwi NAN, Elderdery AY, Alanazi A, Alenazy FO, Alharbi AHA. Insight into Oncogenic Viral Pathways as Drivers of Viral Cancers: Implication for Effective Therapy. Curr Oncol 2023; 30:1924-1944. [PMID: 36826111 PMCID: PMC9955780 DOI: 10.3390/curroncol30020150] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 02/01/2023] [Accepted: 02/02/2023] [Indexed: 02/09/2023] Open
Abstract
As per a recent study conducted by the WHO, 15.4% of all cancers are caused by infectious agents of various categories, and more than 10% of them are attributed to viruses. The emergence of COVID-19 has once again diverted the scientific community's attention toward viral diseases. Some researchers have postulated that SARS-CoV-2 will add its name to the growing list of oncogenic viruses in the long run. However, owing to the complexities in carcinogenesis of viral origin, researchers across the world are struggling to identify the common thread that runs across different oncogenic viruses. Classical pathways of viral oncogenesis have identified oncogenic mediators in oncogenic viruses, but these mediators have been reported to act on diverse cellular and multiple omics pathways. In addition to viral mediators of carcinogenesis, researchers have identified various host factors responsible for viral carcinogenesis. Henceforth owing to viral and host complexities in viral carcinogenesis, a singular mechanistic pathway remains yet to be established; hence there is an urgent need to integrate concepts from system biology, cancer microenvironment, evolutionary perspective, and thermodynamics to understand the role of viruses as drivers of cancer. In the present manuscript, we provide a holistic view of the pathogenic pathways involved in viral oncogenesis with special emphasis on alteration in the tumor microenvironment, genomic alteration, biological entropy, evolutionary selection, and host determinants involved in the pathogenesis of viral tumor genesis. These concepts can provide important insight into viral cancers, which can have an important implication for developing novel, effective, and personalized therapeutic options for treating viral cancers.
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Affiliation(s)
- Ahmed M. E. Elkhalifa
- Department of Public Health, College of Health Sciences, Saudi Electronic University, Riyadh 11673, Saudi Arabia
- Department of Haematology, Faculty of Medical Laboratory Sciences, University of El Imam El Mahdi, Kosti 1158, Sudan
- Correspondence:
| | - Showkat Ul Nabi
- Large Animal Diagnostic Laboratory, Department of Clinical Veterinary Medicine, Ethics & Jurisprudence, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e-Kashmir University of Agricultural Sciences and Technology, Srinagar 190006, Jammu and Kashmir, India
| | - Ovais Shabir Shah
- Department of Sheep Husbandry Kashmir, Government of Jammu and Kashmir, Srinagar 182301, Jammu and Kashmir, India
| | - Showkeen Muzamil Bashir
- Biochemistry & Molecular Biology Lab, Division of Veterinary Biochemistry, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e-Kashmir University of Agricultural Sciences and Technology, Srinagar 190006, Jammu and Kashmir, India
| | - Umar Muzaffer
- Department of Medicine, Government Medical College and Associated Hospital, Srinagar 190010, Jammu and Kashmir, India
| | - Sofi Imtiyaz Ali
- Biochemistry & Molecular Biology Lab, Division of Veterinary Biochemistry, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e-Kashmir University of Agricultural Sciences and Technology, Srinagar 190006, Jammu and Kashmir, India
| | - Imtiyaz Ahmad Wani
- Clinical Research Laboratory, SKIMS, Srinagar 190011, Jammu and Kashmir, India
| | - Nasser A. N. Alzerwi
- Department of Surgery, College of Medicine, Majmaah University, Ministry of Education, Al Majmaah 11952, Saudi Arabia
| | - Abozer Y. Elderdery
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia
| | - Awadh Alanazi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia
| | - Fawaz O. Alenazy
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia
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25
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Abstract
The existence of coronaviruses has been known for many years. These viruses cause significant disease that primarily seems to affect agricultural species. Human coronavirus disease due to the 2002 outbreak of Severe Acute Respiratory Syndrome and the 2012 outbreak of Middle East Respiratory Syndrome made headlines; however, these outbreaks were controlled, and public concern quickly faded. This complacency ended in late 2019 when alarms were raised about a mysterious virus responsible for numerous illnesses and deaths in China. As we now know, this novel disease called Coronavirus Disease 2019 (COVID-19) was caused by Severe acute respiratory syndrome-related-coronavirus-2 (SARS-CoV-2) and rapidly became a worldwide pandemic. Luckily, decades of research into animal coronaviruses hastened our understanding of the genetics, structure, transmission, and pathogenesis of these viruses. Coronaviruses infect a wide range of wild and domestic animals, with significant economic impact in several agricultural species. Their large genome, low dependency on host cellular proteins, and frequent recombination allow coronaviruses to successfully cross species barriers and adapt to different hosts including humans. The study of the animal diseases provides an understanding of the virus biology and pathogenesis and has assisted in the rapid development of the SARS-CoV-2 vaccines. Here, we briefly review the classification, origin, etiology, transmission mechanisms, pathogenesis, clinical signs, diagnosis, treatment, and prevention strategies, including available vaccines, for coronaviruses that affect domestic, farm, laboratory, and wild animal species. We also briefly describe the coronaviruses that affect humans. Expanding our knowledge of this complex group of viruses will better prepare us to design strategies to prevent and/or minimize the impact of future coronavirus outbreaks.
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Key Words
- bcov, bovine coronavirus
- ccov, canine coronavirus
- cov(s), coronavirus(es)
- covid-19, coronavirus disease 2019
- crcov, canine respiratory coronavirus
- e, coronaviral envelope protein
- ecov, equine coronavirus
- fcov, feline coronavirus
- fipv, feline infectious peritonitis virus
- gfcov, guinea fowl coronavirus
- hcov, human coronavirus
- ibv, infectious bronchitis virus
- m, coronaviral membrane protein
- mers, middle east respiratory syndrome-coronavirus
- mhv, mouse hepatitis virus
- pedv, porcine epidemic diarrhea virus
- pdcov, porcine deltacoronavirus
- phcov, pheasant coronavirus
- phev, porcine hemagglutinating encephalomyelitis virus
- prcov, porcine respiratory coronavirus
- rt-pcr, reverse transcriptase polymerase chain reaction
- s, coronaviral spike protein
- sads-cov, swine acute diarrhea syndrome-coronavirus
- sars-cov, severe acute respiratory syndrome-coronavirus
- sars-cov-2, severe acute respiratory syndrome–coronavirus–2
- tcov, turkey coronavirus
- tgev, transmissible gastroenteritis virus
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Affiliation(s)
- Alfonso S Gozalo
- Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;,
| | - Tannia S Clark
- Office of Laboratory Animal Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
| | - David M Kurtz
- Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, North Carolina
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Almasi F, Mohammadipanah F. Neurological manifestations of SARS-CoV-2 infections: towards quantum dots based management approaches. J Drug Target 2023; 31:51-64. [PMID: 35921123 DOI: 10.1080/1061186x.2022.2110252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Developing numerous nanotechnological designed tools to monitor the existence of SARS-CoV-2, and modifying its interactions address the global needs for efficient remedies required for the management of COVID-19. Herein, through a multidisciplinary outlook encompassing different fields such as the pathophysiology of SARS-CoV-2, analysis of symptoms, and statistics of neurological complications caused by SARS-CoV-2 infection in the central and peripheral nervous systems have been testified. The anosmia (51.1%) and ageusia (45.5%) are reported the most frequent neurological manifestation. Cerebrovascular disease and encephalopathy were mainly related to severe clinical cases. In addition, we focus especially on the various concerned physiological routes, including BBB dysfunction, which transpired due to SARS-CoV-2 infection, direct and indirect effects of the virus on the brain, and also, the plausible mechanisms of viral entry to the nerve system. We also outline the characterisation, and the ongoing pharmaceutical applications of quantum dots as smart nanocarriers crossing the blood-brain barrier and their importance in neurological diseases, mainly SARS-CoV-2 related manifestations Moreover, the market status, six clinical trials recruiting quantum dots, and the challenges limiting the clinical application of QDs are highlighted.
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Affiliation(s)
- Faezeh Almasi
- Pharmaceutical Biotechnology Lab, Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran
| | - Fatemeh Mohammadipanah
- Pharmaceutical Biotechnology Lab, Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran
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27
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Neurological disorders of COVID-19: insights to applications of natural products from plants and microorganisms. Arch Pharm Res 2022; 45:909-937. [PMCID: PMC9702705 DOI: 10.1007/s12272-022-01420-3] [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: 05/04/2022] [Accepted: 11/22/2022] [Indexed: 11/29/2022]
Abstract
In addition to the typical respiratory manifestations, various disorders including involvement of the nerve system have been detected in COVID-19 ranging from 22 to 36%. Although growing records are focusing on neurological aspects of COVID-19, the pathophysiological mechanisms and related therapeutic methods remain obscure. Considering the increased concerns of SARS-CoV-2 potential for more serious neuroinvasion conditions, the present review attempts to focus on the neuroprotective effects of natural compounds as the principle source of therapeutics inhibiting multiple steps of the SARS-CoV-2 infection cycle. The great majority of the natural products with anti-SARS-CoV-2 activity mainly inhibit the attachment, entry and gene expression rather than the replication, assembly, or release. Although microbial-derived natural products comprise 38.5% of the known natural products with neuroprotective effects following viral infection, the neuroprotective potential of the majority of microorganisms is still undiscovered. Among natural products, chrysin, huperzine A, ginsenoside Rg1, pterostilbene, and terrein have shown potent in vitro neuroprotective activity and can be promising for new or repurpose drugs for neurological complications of SARS-CoV-2.
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Braunsteiner J, Jarczak D, Schmidt-Lauber C, Boenisch O, de Heer G, Burdelski C, Frings D, Sensen B, Nierhaus A, Hoxha E, Huber TB, Wichmann D, Kluge S, Fischer M, Roedl K. Outcomes of critically ill coronavirus disease 2019 patients requiring kidney replacement therapy: A retrospective cohort study. Front Med (Lausanne) 2022; 9:1027586. [PMID: 36341239 PMCID: PMC9630840 DOI: 10.3389/fmed.2022.1027586] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 10/04/2022] [Indexed: 11/25/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) has resulted in high hospitalization rates worldwide. Acute kidney injury (AKI) in patients hospitalized for COVID-19 is frequent and associated with disease severity and poor outcome. The aim of this study was to investigate the incidence of kidney replacement therapy (KRT) in critically ill patients with COVID-19 and its implication on outcome. METHODS We retrospectively analyzed all COVID-19 patients admitted to the Department of Intensive Care Medicine at the University Medical Center Hamburg-Eppendorf (Germany) between 1 March 2020 and 31 July 2021. Demographics, clinical parameters, type of organ support, length of intensive care unit (ICU) stay, mortality and severity scores were assessed. RESULTS Three-hundred critically ill patients with COVID-19 were included. The median age of the study population was 61 (IQR 51-71) years and 66% (n = 198) were male. 73% (n = 219) of patients required invasive mechanical ventilation. Overall, 68% (n = 204) of patients suffered from acute respiratory distress syndrome and 30% (n = 91) required extracorporeal membrane oxygenation (ECMO). We found that 46% (n = 139) of patients required KRT. Septic shock (OR 11.818, 95% CI: 5.941-23.506, p < 0.001), higher simplified acute physiology scores (SAPS II) (OR 1.048, 95% CI: 1.014-1.084, p = 0.006) and vasopressor therapy (OR 5.475, 95% CI: 1.127-26.589, p = 0.035) were independently associated with the initiation of KRT. 61% (n = 85) of patients with and 18% (n = 29) without KRT died in the ICU (p < 0.001). Cox regression found that KRT was independently associated with mortality (HR 2.075, 95% CI: 1.342-3.208, p = 0.001) after adjusting for confounders. CONCLUSION Critically ill patients with COVID-19 are at high risk of acute kidney injury with about half of patients requiring KRT. The initiation of KRT was associated with high mortality.
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Affiliation(s)
- Josephine Braunsteiner
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Dominik Jarczak
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Olaf Boenisch
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Geraldine de Heer
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Burdelski
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Daniel Frings
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Barbara Sensen
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Axel Nierhaus
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Elion Hoxha
- III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Tobias B. Huber
- III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Dominic Wichmann
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Kluge
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marlene Fischer
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Kevin Roedl
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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29
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Saeed U, Piracha ZZ, Uppal SR, Waheed Y, Uppal R. SARS-CoV-2 induced hepatic injuries and liver complications. Front Cell Infect Microbiol 2022; 12:726263. [PMID: 36189356 PMCID: PMC9523111 DOI: 10.3389/fcimb.2022.726263] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/23/2022] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is resilient, highly pathogenic, and rapidly transmissible. COVID-19 patients have been reported to have underlying chronic liver abnormalities linked to hepatic dysfunction. DISCUSSION Viral RNAs are detectable in fecal samples by RT-PCR even after negative respiratory samples, which suggests that SARS-CoV-2 can affect the gastrointestinal tract and the liver. The case fatality rates are higher among the elderly and those with underlying comorbidities such as hypertension, diabetes, liver abnormality, and heart disease. There is insufficient research on signaling pathways. Identification of molecular mechanisms involved in SARS-CoV-2-induced damages to hepatocytes is challenging. Herein, we demonstrated the multifactorial effects of SARS-CoV-2 on liver injury such as psychological stress, immunopathogenesis, systemic inflammation, ischemia and hypoxia, drug toxicity, antibody-dependent enhancement (ADE) of infection, and several others which can significantly damage the liver. CONCLUSION During the COVID-19 pandemic, it is necessary for clinicians across the globe to pay attention to SARS-CoV-2-mediated liver injury to manage the rising burden of hepatocellular carcinoma. To face the challenges during the resumption of clinical services for patients with pre-existing liver abnormalities and HCC, the impact of SARS-CoV-2 on hepatocytes should be investigated both in vitro and in vivo.
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Affiliation(s)
- Umar Saeed
- Department of Research and Development, Islamabad Diagnostic Center (IDC), Islamabad, Pakistan
- International Center of Medical Sciences Research(ICMSR), Islamabad, Pakistan
| | - Zahra Zahid Piracha
- Department of Research and Development, Islamabad Diagnostic Center (IDC), Islamabad, Pakistan
- International Center of Medical Sciences Research(ICMSR), Islamabad, Pakistan
| | - Sara Rizwan Uppal
- Department of Research and Development, Islamabad Diagnostic Center (IDC), Islamabad, Pakistan
| | - Yasir Waheed
- Department of ORIC, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan
| | - Rizwan Uppal
- Department of Research and Development, Islamabad Diagnostic Center (IDC), Islamabad, Pakistan
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30
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Hussaini H, Rogers S, Kataria S, Uddin K, Mohamed KH, Mohamed AS, Tariq F, Ahmad S, Awais A, Ahmed Z, Chukwurah A, Khan A. COVID-19-Induced Seizures: A Meta-Analysis of Case Series and Retrospective Cohorts. Cureus 2022; 14:e28633. [PMID: 36196331 PMCID: PMC9524720 DOI: 10.7759/cureus.28633] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2022] [Indexed: 11/30/2022] Open
Abstract
The adverse events and complications of coronavirus disease 2019 (COVID-19) continue to challenge the medical profession despite the worldwide vaccination against the severe acute respiratory coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. Other than typical respiratory manifestations, COVID-19 also presents a wide range of neurological manifestations. This article underlines the pooled incidence of COVID-19-induced seizures in patients with epilepsy and without epilepsy. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols, we conducted a bibliographical search, and an initial search revealed 1,375 articles. In total, 21 articles were included in the final analysis by following the inclusion criteria. A total of 11,526 patients from 21 published articles that met the predetermined search criteria were included. The median age of the patients was 61.9 years, of whom 51.5% were males. A total of 255 patients presented with seizures as the first manifestation of COVID-19 with a prevalence of 2.2% (95% confidence interval = 0.05-0.24, p < 0.01) (I2 = 97%), of which 71 patients had previously been diagnosed with epilepsy. Among patients with epilepsy, 49 patients had seizures as an initial presentation of SARA-CoV-2 with an incidence of 72% (0.54-0.85, p = 0.1) (I2 = 34). Although the incidence of COVID-19-induced seizures is not high compared to other neurological manifestations, seizure incidence in epileptic patients with COVID-19 is remarkably high. New-onset seizures in any patient should be considered a presentation of COVID-19 in the absence of other causative factors.
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31
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Zalpoor H, Akbari A, Nabi-Afjadi M, Forghaniesfidvajani R, Tavakol C, Barzegar Z, Iravanpour F, Hosseini M, Mousavi SR, Farrokhi MR. Hypoxia-inducible factor 1 alpha (HIF-1α) stimulated and P2X7 receptor activated by COVID-19, as a potential therapeutic target and risk factor for epilepsy. Hum Cell 2022; 35:1338-1345. [PMID: 35831562 PMCID: PMC9281298 DOI: 10.1007/s13577-022-00747-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 07/03/2022] [Indexed: 12/25/2022]
Abstract
Based on available evidence, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a neuroinvasive virus. According to the centers for disease control and prevention (CDC), coronavirus disease 2019 (COVID-19) may cause epilepsy. In this line, COVID-19 can stimulate hypoxia-inducible factor-1 alpha (HIF-1α) and activate P2X7 receptor. Both HIF-1α and P2X7 receptors are linked to epileptogenesis and seizures. Therefore, in the current study, we suggested that COVID-19 may have a role in epileptogenesis and seizure through HIF-1α stimulation and P2X7 receptor activation. Consequently, pharmacological targeting of these factors could be a promising therapeutic approach for such patients.
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Affiliation(s)
- Hamidreza Zalpoor
- Department of Neurosurgery, Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. .,Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran.
| | - Abdullatif Akbari
- Department of Neurosurgery, Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran
| | - Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran
| | - Razieh Forghaniesfidvajani
- Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran
| | - Chanour Tavakol
- Medical School, Tehran University of Medical Sciences, Tehran, Iran
| | - Zohreh Barzegar
- Department of Neurosurgery, Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farideh Iravanpour
- Department of Neurosurgery, Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahshid Hosseini
- Department of Neurosurgery, Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Reza Mousavi
- Department of Neurosurgery, Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Neurosurgery, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Majid Reza Farrokhi
- Department of Neurosurgery, Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. .,Department of Neurosurgery, Shiraz University of Medical Sciences, Shiraz, Iran.
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32
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Togha M, Hashemi SM, Yamani N, Martami F, Salami Z. A Review on Headaches Due to COVID-19 Infection. Front Neurol 2022; 13:942956. [PMID: 35911910 PMCID: PMC9327440 DOI: 10.3389/fneur.2022.942956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 06/20/2022] [Indexed: 11/13/2022] Open
Abstract
Since December 2019, the time when the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was spotted, numerous review studies have been published on COVID-19 and its neuro invasion. A growing number of studies have reported headaches as a common neurological manifestation of COVID-19. Although several hypotheses have been proposed regarding the association between headache and the coronavirus, no solid evidence has been presented for the mechanism and features of headache in COVID-19. Headache also is a common complaint with the omicron variant of the virus. COVID-19 vaccination also is a cause of new-onset headaches or aggravation of the previous headache in migraine or tension headache sufferers. In this review study, the types of headaches reported in previous studies and their possible pathogenic mechanisms are outlined. To accomplish this objective, various types of headaches are classified and their patterns are discussed according to ICHD-3 diagnostic criteria, including, headaches attributed to systemic viral infection, viral meningitis or encephalitis, non-infectious inflammatory intracranial disease, hypoxia and/or hypercapnia, cranial or cervical vascular disorder, increased cerebrospinal fluid (CSF) pressure, refractive error, external-compression headache, and cough headache. Then, their pathogeneses are categorized into three main categories, direct trigeminal involvement, vascular invasion, and inflammatory mediators. Furthermore, persistent headache after recovery and the predictors of intensity is further investigated. Post-vaccination headache is also discussed in this review.
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Affiliation(s)
- Mansoureh Togha
- Headache Department, Iranian Center of Neurological Researches, Institute of Neuroscience, Tehran University of Medical Sciences, Tehran, Iran
- Headache Department, Neurology Ward, Sina Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyedeh Melika Hashemi
- Headache Department, Iranian Center of Neurological Researches, Institute of Neuroscience, Tehran University of Medical Sciences, Tehran, Iran
| | - Nooshin Yamani
- Neurology Department, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Fahimeh Martami
- Headache Department, Iranian Center of Neurological Researches, Institute of Neuroscience, Tehran University of Medical Sciences, Tehran, Iran
| | - Zhale Salami
- Headache Department, Iranian Center of Neurological Researches, Institute of Neuroscience, Tehran University of Medical Sciences, Tehran, Iran
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Channappanavar R, Selvaraj M, More S, Perlman S. Alveolar macrophages protect mice from MERS-CoV-induced pneumonia and severe disease. Vet Pathol 2022; 59:627-638. [PMID: 35499307 PMCID: PMC11992969 DOI: 10.1177/03009858221095270] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/13/2024]
Abstract
Emerging and re-emerging human coronaviruses (hCoVs) cause severe respiratory illness in humans, but the basis for lethal pneumonia in these diseases is not well understood. Alveolar macrophages (AMs) are key orchestrators of host antiviral defense and tissue tolerance during a variety of respiratory infections, and AM dysfunction is associated with severe COVID-19. In this study, using a mouse model of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we examined the role of AMs in MERS pathogenesis. Our results show that depletion of AMs using clodronate (CL) liposomes significantly increased morbidity and mortality in human dipeptidyl peptidase 4 knock-in (hDPP4-KI) mice. Detailed examination of control and AM-depleted lungs at different days postinfection revealed increased neutrophil activity but a significantly reduced MERS-CoV-specific CD4 T-cell response in AM-deficient lungs during later stages of infection. Furthermore, enhanced MERS severity in AM-depleted mice correlated with lung inflammation and lesions. Collectively, these data demonstrate that AMs are critical for the development of an optimal virus-specific T-cell response and controlling excessive inflammation during MERS-CoV infection.
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Affiliation(s)
- Rudragouda Channappanavar
- Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University. Stillwater, OK, 74078
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, 74084
| | - Muneeswaran Selvaraj
- Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University. Stillwater, OK, 74078
| | - Sunil More
- Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University. Stillwater, OK, 74078
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, 74084
| | - Stanley Perlman
- Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa. Iowa City, IA 52242
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Ning T, Liu S, Xu J, Yang Y, Zhang N, Xie S, Min L, Zhang S, Zhu S, Wang Y. Potential intestinal infection and faecal-oral transmission of human coronaviruses. Rev Med Virol 2022; 32:e2363. [PMID: 35584273 PMCID: PMC9348496 DOI: 10.1002/rmv.2363] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 02/25/2022] [Accepted: 05/06/2022] [Indexed: 01/08/2023]
Abstract
Human coronaviruses (HCoVs) were first described in 1960s for patients experiencing common cold. Since then, increasing number of HCoVs have been discovered, including those causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the circulating coronavirus disease 2019 (COVID‐19), which can cause fatal respiratory disease in humans on infection. HCoVs are believed to spread mainly through respiratory droplets and close contact. However, studies have shown that a large proportion of patients with HCoV infection develop gastrointestinal (GI) symptoms, and many patients with confirmed HCoV infection have shown detectable viral RNA in their faecal samples. Furthermore, multiple in vitro and in vivo animal studies have provided direct evidence of intestinal HCoV infection. These data highlight the nature of HCoV GI infection and its potential faecal‐oral transmission. Here, we summarise the current findings on GI manifestations of HCoVs. We also discuss how HCoV GI infection might occur and the current evidence to establish the occurrence of faecal‐oral transmission.
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Affiliation(s)
- Tingting Ning
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Si Liu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Junxuan Xu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Yi Yang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Nan Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Sian Xie
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Li Min
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Shengtao Zhu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Youchun Wang
- Division of HIV/AIDS and Sexually Transmitted Virus Vaccines, National Institutes for Food and Drug Control (NIFDC), Beijing, China
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Elnaggar M, Abomhya A, Elkhattib I, Dawoud N, Doshi R. COVID-19 and liver diseases, what we know so far. World J Clin Cases 2022; 10:3969-3980. [PMID: 35665122 PMCID: PMC9131221 DOI: 10.12998/wjcc.v10.i13.3969] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 10/15/2021] [Accepted: 03/26/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) pneumonia outbreak started in December 2019. On March 12, 2020, the World Health Organization (WHO) declared that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a pandemic, and as of May 2021, SARS-CoV-2 has infected over 167.3 million patients, including 3.4 million deaths, reported to WHO. In this review, we will focus on the relationship between SARS-CoV-2 infection and the liver. We will discuss how chronic liver diseases affect the COVID-19 disease course and outcomes. We will also discuss the SARS-CoV-2 effects on the liver, mechanisms of acute liver injury, and potential management plans.
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Affiliation(s)
- Mohamed Elnaggar
- Department of Internal Medicine, University of Nevada Reno School of Medicine, Reno, NV 89052, United States
| | - Ahmed Abomhya
- Department of Internal Medicine, The Brooklyn Hospital Center, Brooklyn, NY 11200, United States
| | - Ismail Elkhattib
- Department of Internal Medicine, University of Connecticut, Farmington, CT 06030, United States
| | - Nabila Dawoud
- Department of Internal Medicine, University of Kentucky, Lexington, KY 40508, United States
| | - Rajkumar Doshi
- Department of Cardiology, St Joseph's University Medical Center, Paterson, NJ 07503, United States
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Pergolizzi JV, Raffa RB, Varrassi G, Magnusson P, LeQuang JA, Paladini A, Taylor R, Wollmuth C, Breve F, Chopra M, Nalamasu R, Christo PJ. Potential neurological manifestations of COVID-19: a narrative review. Postgrad Med 2022; 134:395-405. [PMID: 33089707 PMCID: PMC7799377 DOI: 10.1080/00325481.2020.1837503] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 10/13/2020] [Indexed: 01/08/2023]
Abstract
Neurological manifestations are increasingly reported in a subset of COVID-19 patients. Previous infections related to coronaviruses, namely Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS) also appeared to have neurological effects on some patients. The viruses associated with COVID-19 like that of SARS enters the body via the ACE-2 receptors in the central nervous system, which causes the body to balance an immune response against potential damage to nonrenewable cells. A few rare cases of neurological sequelae of SARS and MERS have been reported. A growing body of evidence is accumulating that COVID-19, particularly in severe cases, may have neurological consequences although respiratory symptoms nearly always develop prior to neurological ones. Patients with preexisting neurological conditions may be at elevated risk for COVID-19-associated neurological symptoms. Neurological reports in COVID-19 patients have described encephalopathy, Guillain-Barré syndrome, myopathy, neuromuscular disorders, encephalitis, cephalgia, delirium, critical illness polyneuropathy, and others. Treating neurological symptoms can pose clinical challenges as drugs that suppress immune response may be contraindicated in COVID-19 patients. It is possible that in some COVID-19 patients, neurological symptoms are being overlooked or misinterpreted. To date, neurological manifestations of COVID-19 have been described largely within the disease trajectory and the long-term effects of such manifestations remain unknown.
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Affiliation(s)
| | - Robert B. Raffa
- Temple University School of Pharmacy, Temple University, Philadelphia, PA, USA
- University of Arizona College of Pharmacy, Tucson, AZ, USA
| | | | - Peter Magnusson
- Centre for Research and Development, Region Gävleborg/Uppsala University, Gävle, Sweden
- Department of Medicine, Cardiology Research Unit, Karolinska Institutet, Stockholm, Sweden
| | | | | | | | | | - Frank Breve
- NEMA Research, Inc., Naples, FL, USA
- Department of Pharmacy Practice, Temple University School of Pharmacy, Philadelphia, PA, USA
| | | | - Rohit Nalamasu
- Department of Physical Medicine and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA
| | - Paul J. Christo
- Division of Pain Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Do Mechanically Ventilated COVID-19 Patients Present a Higher Case-Fatality Rate Compared With Other Infectious Respiratory Pandemics? A Systematic Review and Meta-Analysis. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2022. [DOI: 10.1097/ipc.0000000000001134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Aloufi BH, Snoussi M, Sulieman AME. Antiviral Efficacy of Selected Natural Phytochemicals against SARS-CoV-2 Spike Glycoprotein Using Structure-Based Drug Designing. Molecules 2022; 27:2401. [PMID: 35458599 PMCID: PMC9025634 DOI: 10.3390/molecules27082401] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 03/30/2022] [Accepted: 04/06/2022] [Indexed: 11/17/2022] Open
Abstract
SARS-CoV-2 is a highly virulent coronavirus that first surfaced in late 2019 and has since created a pandemic of the acute respiratory sickness known as "coronavirus disease 2019" (COVID-19), posing a threat to human health and public safety. S-RBD is a coronaviral protein that is essential for a coronavirus (CoV) to bind and penetrate into host cells. As a result, it has become a popular pharmacological target. The goal of this study was to find potential candidates for anti-coronavirus disease 2019 (COVID-19) drugs by targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-RBD with novel bioactive compounds and molecular interaction studies of 15,000 phytochemicals belonging to different flavonoid subgroups. A spike protein crystal structure attached to the ACE2 structure was obtained from the PDB database. A library of 15,000 phytochemicals was made by collecting compounds from different databases, such as the Zinc-database, PubChem-database, and MPD3-database. This library was docked against a receptor binding domain of a spike glycoprotein through the Molecular Operating Environment (MOE). The top drug candidates Phylloflavan, Milk thistle, Ilexin B and Isosilybin B, after virtual screening, were selected on the basis of the least binding score. Phylloflavan ranked as the top compound because of its least binding affinity score of -14.09 kcal/mol. In silico studies showed that all those compounds showed good activity and could be used as an immunological response with no bioavailability issues. Absorption, distribution, metabolism, excretion and a toxicological analysis were conducted through SwissADME. Stability and effectiveness of the docked complexes were elucidated by performing the 100 ns molecular dynamic simulation through the Desmond package.
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Affiliation(s)
- Bandar Hamad Aloufi
- Department of Biology, College of Science, University of Hail, P.O. Box 2440, Ha’il 2440, Saudi Arabia; (B.H.A.); (A.M.E.S.)
| | - Mejdi Snoussi
- Department of Biology, College of Science, University of Hail, P.O. Box 2440, Ha’il 2440, Saudi Arabia; (B.H.A.); (A.M.E.S.)
- Laboratory of Genetics, Biodiversity and Valorisation of Bioressources, High Institute of Biotechnology, University of Monastir, Monastir 5000, Tunisia
| | - Abdel Moneim E. Sulieman
- Department of Biology, College of Science, University of Hail, P.O. Box 2440, Ha’il 2440, Saudi Arabia; (B.H.A.); (A.M.E.S.)
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Kariyawasam JC, Jayarajah U, Abeysuriya V, Riza R, Seneviratne SL. Involvement of the Liver in COVID-19: A Systematic Review. Am J Trop Med Hyg 2022; 106:1026-1041. [PMID: 35203056 PMCID: PMC8991364 DOI: 10.4269/ajtmh.21-1240] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 01/16/2022] [Indexed: 01/11/2023] Open
Abstract
COVID-19, a respiratory viral infection, has affected 388 million individuals worldwide as of the February 4, 2022. In this review, we have outlined the important liver manifestations of COVID-19 and discussed the possible underlying pathophysiological mechanisms and their diagnosis and management. Factors that may contribute to hepatic involvement in COVID-19 include direct viral cytopathic effects, exaggerated immune responses/systemic inflammatory response syndrome, hypoxia-induced changes, vascular changes due to coagulopathy, endothelitis, cardiac congestion from right heart failure, and drug-induced liver injury. The majority of COVID-19-associated liver symptoms are mild and self-limiting. Thus management is generally supportive. Liver function tests and abdominal imaging are the primary investigations done in relation to liver involvement in COVID-19 patients. However, imaging findings are nonspecific. Severe acute respiratory syndrome coronavirus 2 RNA has been found in liver biopsies. However, there is limited place for liver biopsy in the clinical context, as it does not influence management. Although, the management is supportive in the majority of patients without previous liver disease, special emphasis is needed in those with nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, hepatitis B and C infections, and alcoholic liver disease, and in liver transplant recipients.
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Affiliation(s)
| | - Umesh Jayarajah
- Postgraduate Institute of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Visula Abeysuriya
- Nawaloka Hospital Research and Education Foundation, Nawaloka Hospitals, Colombo, Sri Lanka
| | - Rishdha Riza
- Colombo South Teaching Hospital, Colombo, Sri Lanka
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Casoli T. SARS-CoV-2 Morbidity in the CNS and the Aged Brain Specific Vulnerability. Int J Mol Sci 2022; 23:3782. [PMID: 35409141 PMCID: PMC8998499 DOI: 10.3390/ijms23073782] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 03/26/2022] [Accepted: 03/28/2022] [Indexed: 01/27/2023] Open
Abstract
The infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be the cause of a fatal disease known as coronavirus disease 2019 (COVID-19) affecting the lungs and other organs. Particular attention has been given to the effects of the infection on the brain due to recurring neurological symptoms associated with COVID-19, such as ischemic or hemorrhagic stroke, encephalitis and myelitis, which are far more severe in the elderly compared to younger patients. The specific vulnerability of the aged brain could derive from the impaired immune defenses, from any of the altered homeostatic mechanisms that contribute to the aging phenotype, and from particular changes in the aged brain involving neurons and glia. While neuronal modifications could contribute indirectly to the damage induced by SARS-CoV-2, glia alterations could play a more direct role, as they are involved in the immune response to viral infections. In aged patients, changes regarding glia include the accumulation of dystrophic forms, reduction of waste removal, activation of microglia and astrocytes, and immunosenescence. It is plausible to hypothesize that SARS-CoV-2 infection in the elderly may determine severe brain damage because of the frail phenotype concerning glial cells.
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Affiliation(s)
- Tiziana Casoli
- Center for Neurobiology of Aging, Scientific Technological Area, IRCCS INRCA, Via Birarelli 8, 60121 Ancona, Italy
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Irani S. Immune Responses in SARS-CoV-2, SARS-CoV, and MERS-CoV Infections: A Comparative Review. Int J Prev Med 2022; 13:45. [PMID: 35529506 PMCID: PMC9069147 DOI: 10.4103/ijpvm.ijpvm_429_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 09/21/2021] [Indexed: 12/04/2022] Open
Abstract
Coronavirus, discovered in the 1960s, is able to infect human hosts and causes mild to serious respiratory problems. In the last two decades, the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recognized. It has long been demonstrated that MERS-CoV binds to dipeptidyl peptidase 4 and SARS-CoV binds to angiotensin-converting enzyme 2. A "cytokine storm" is the main pathophysiology of aforementioned viruses. Infiltration of neutrophils at the site of the infection is a risk factor for the development of acute respiratory distress syndrome and death. The new coronavirus, SARS-CoV-2, has infected more people than SARS-Cov and MERS-CoV as it can easily be transmitted from person to person. Epidemiological studies indicate that majority of individuals are asymptomatic; therefore, an effective and an efficient tool is required for rapid testing. Identification of various cytokine and inflammatory factor expression levels can help in outcome prediction. In this study we reviewed immune responses in SARS-CoV, Mers-CoV, and SARS-COV-2 infections and the role of inflammatory cells.
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Affiliation(s)
- Soussan Irani
- Dental Research Centre, Oral Pathology Department, Dental Faculty, Hamadan University of Medical Sciences, Hamadan, Iran
- Pathology Department of Faculty of Medicine, Griffith University, Gold Coast, Australia
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Saceleanu V, Moreanu MS, Covache-Busuioc RA, Mohan AG, Ciurea AV. SARS-COV-2 - the pandemic of the XXI century, clinical manifestations - neurological implications. J Med Life 2022; 15:319-327. [PMID: 35450003 PMCID: PMC9015186 DOI: 10.25122/jml-2020-0151] [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: 09/16/2020] [Accepted: 03/02/2022] [Indexed: 11/21/2022] Open
Abstract
In December 2019, in Wuhan, China, the first cases of infection with SARS-CoV 2 responsible for COVID-19 disease were identified. SARS-CoV 2 was declared a pandemic on March 11, 2020, and since then has attracted the medical world's attention. The threat to humans' health that this emerging pandemic could leave raises awareness on the importance of understanding the mechanisms that underlie the developing conditions. The epidemiology, clinical picture, and pathogenesis of COVID-19 show that this virus presents new strategies to overcome the past defensive medicine. While all the current data has focused on the pulmonary and cardiovascular manifestations, little has been written about the neurological implications of the disease. This review updates new clinical aspects that SARS-CoV 2 expresses in humans by focusing primarily on neurological manifestations. The damage to the nervous system became more apparent - anosmia, ageusia, polyneuritis, meningitis, meningoencephalitis, stroke, acute necrotizing encephalopathy. Oxygen therapy is vital for those in critical health situations. Finally, prevention is the most important element in breaking the epidemiological chain.
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Affiliation(s)
- Vicentiu Saceleanu
- Department of Neurosurgery, Faculty of Medicine, Lucian Blaga University, Sibiu, Romania
- Department of Neurosurgery, County Emergency Hospital, Sibiu, Romania
| | - Mihai-Stelian Moreanu
- Department of Neurosurgery, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | | | - Aurel George Mohan
- Department of Neurosurgery, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
- Department of Neurosurgery, County Emergency Hospital, Oradea, Romania
| | - Alexandru-Vlad Ciurea
- Department of Neurosurgery, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Neurosurgery, Sanador Clinical Hospital, Bucharest, Romania
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Hamady A, Lee J, Loboda ZA. Waning antibody responses in COVID-19: what can we learn from the analysis of other coronaviruses? Infection 2022; 50:11-25. [PMID: 34324165 PMCID: PMC8319587 DOI: 10.1007/s15010-021-01664-z] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 07/08/2021] [Indexed: 12/16/2022]
Abstract
OBJECTIVES The coronavirus disease 2019 (COVID-19), caused by the novel betacoronavirus severe acute respiratory syndrome 2 (SARS-CoV-2), was declared a pandemic in March 2020. Due to the continuing surge in incidence and mortality globally, determining whether protective, long-term immunity develops after initial infection or vaccination has become critical. METHODS/RESULTS In this narrative review, we evaluate the latest understanding of antibody-mediated immunity to SARS-CoV-2 and to other coronaviruses (SARS-CoV, Middle East respiratory syndrome coronavirus and the four endemic human coronaviruses) in order to predict the consequences of antibody waning on long-term immunity against SARS-CoV-2. We summarise their antibody dynamics, including the potential effects of cross-reactivity and antibody waning on vaccination and other public health strategies. At present, based on our comparison with other coronaviruses we estimate that natural antibody-mediated protection for SARS-CoV-2 is likely to last for 1-2 years and therefore, if vaccine-induced antibodies follow a similar course, booster doses may be required. However, other factors such as memory B- and T-cells and new viral strains will also affect the duration of both natural and vaccine-mediated immunity. CONCLUSION Overall, antibody titres required for protection are yet to be established and inaccuracies of serological methods may be affecting this. We expect that with standardisation of serological testing and studies with longer follow-up, the implications of antibody waning will become clearer.
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Affiliation(s)
- Ali Hamady
- Department of Immunology and Inflammation, Imperial College London, London, UK
| | - JinJu Lee
- Department of Immunology and Inflammation, Imperial College London, London, UK
| | - Zuzanna A Loboda
- Department of Immunology and Inflammation, Imperial College London, London, UK.
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Pellinen J, Holmes MG. Evaluation and Treatment of Seizures and Epilepsy During the COVID-19 Pandemic. Curr Neurol Neurosci Rep 2022; 22:11-17. [PMID: 35080752 PMCID: PMC8790547 DOI: 10.1007/s11910-022-01174-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/30/2021] [Indexed: 12/13/2022]
Abstract
Purpose of Review Seizures, including status epilepticus, have been reported in association with acute COVID-19 infection. People with epilepsy (PWE) have suffered from seizure exacerbations during the pandemic. This article reviews the data for clinical and electrographic seizures associated with COVID-19, technical EEG considerations for reducing risk of transmission, and factors contributing to seizure exacerbations in PWE as well as strategies to address this issue. Recent Findings An increasing number of studies of larger cohorts, accounting for a variety of variables and often utilizing EEG with standardized terminology, are assessing the prevalence of seizures in hospitalized patients with acute COVID-19 infections, and gaining insight into the prevalence of seizures and their effect on outcomes. Additionally, recent studies are evaluating the effect of the pandemic on PWE, barriers faced, and the usefulness of telehealth. Summary Although there is still much to learn regarding COVID-19, current studies help in assessing the risk of seizures, guiding EEG utilization, and optimizing the use of telehealth during the pandemic.
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Affiliation(s)
- Jacob Pellinen
- Department of Neurology, School of Medicine, University of Colorado, Aurora, CO USA
| | - Manisha Gupte Holmes
- Comprehensive Epilepsy Center, School of Medicine, New York University, New York, NY USA
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Batta Y, King C, Johnson J, Haddad N, Boueri M, Haddad G. Sequelae and Comorbidities of COVID-19 Manifestations on the Cardiac and the Vascular Systems. Front Physiol 2022; 12:748972. [PMID: 35095546 PMCID: PMC8795698 DOI: 10.3389/fphys.2021.748972] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 10/28/2021] [Indexed: 01/08/2023] Open
Abstract
COVID-19 patients with pre-existing cardiovascular conditions are at greater risk of severe illness due to the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus. This review evaluates the highest risk factors for these patients, not limited to pre-existing hypertension, cardiac arrhythmias, hypercoagulation, ischemic heart disease, and a history of underlying heart conditions. SARS-CoV-2 may also precipitate de novo cardiac complications. The interplay between existing cardiac conditions and de novo cardiac complications is the focus of this review. In particular, SARS-CoV-2 patients present with hypercoagulation conditions, cardiac arrhythmias, as significant complications. Also, cardiac arrhythmias are another well-known cardiovascular-related complication seen in COVID-19 infections and merit discussion in this review. Amid the pandemic, myocardial infarction (MI) has been reported to a high degree in SARS-CoV-2 patients. Currently, the specific causative mechanism of the increased incidence of MI is unclear. However, studies suggest several links to high angiotensin-converting enzyme 2 (ACE2) expression in myocardial and endothelial cells, systemic hyper-inflammation, an imbalance between myocardial oxygen supply and demand, and loss of ACE2-mediated cardio-protection. Furthermore, hypertension and SARS-CoV-2 infection patients' prognosis has shown mixed results across current studies. For this reason, an in-depth analysis of the interactions between SARS-CoV2 and the ACE2 cardio-protective mechanism is warranted. Similarly, ACE2 receptors are also expressed in the cerebral cortex tissue, both in neurons and glia. Therefore, it seems very possible for both cardiovascular and cerebrovascular systems to be damaged leading to further dysregulation and increased risk of mortality risk. This review aims to discuss the current literature related to potential complications of COVID-19 infection with hypertension and the vasculature, including the cervical one. Finally, age is a significant prognostic indicator among COVID-19 patients. For a mean age group of 70 years, the main presenting symptoms include fever, shortness of breath, and a persistent cough. Elderly patients with cardiovascular comorbidities, particularly hypertension and diabetes, represent a significant group of critical cases with increased case fatality rates. With the current understanding of COVID-19, it is essential to explore the mechanisms by which SARS-CoV-2 operates to improve clinical outcomes for patients suffering from underlying cardiovascular diseases and reduce the risk of such conditions de novo.
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Affiliation(s)
- Yashvardhan Batta
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
| | - Cody King
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
| | - John Johnson
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
| | - Natasha Haddad
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
| | | | - Georges Haddad
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
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Hornick MG, Olson ME, Jadhav AL. SARS-CoV-2 Psychiatric Sequelae: A Review of Neuroendocrine Mechanisms and Therapeutic Strategies. Int J Neuropsychopharmacol 2022; 25:1-12. [PMID: 34648616 PMCID: PMC8524640 DOI: 10.1093/ijnp/pyab069] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 09/07/2021] [Accepted: 10/12/2021] [Indexed: 12/15/2022] Open
Abstract
From the earliest days of the coronavirus disease 2019 (COVID-19) pandemic, there have been reports of significant neurological and psychological symptoms following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This narrative review is designed to examine the potential psychoneuroendocrine pathogenic mechanisms by which SARS-CoV-2 elicits psychiatric sequelae as well as to posit potential pharmacologic strategies to address and reverse these pathologies. Following a brief overview of neurological and psychological sequelae from previous viral pandemics, we address mechanisms by which SARS-CoV-2 could enter or otherwise elicit changes in the CNS. We then examine the hypothesis that COVID-19-induced psychiatric disorders result from challenges to the neuroendocrine system, in particular the hypothalamic-pituitary-adrenal stress axis and monoamine synthesis, physiological mechanisms that are only further enhanced by the pandemic-induced social environment of fear, isolation, and socioeconomic pressure. Finally, we evaluate several FDA-approved therapeutics in the context of COVID-19-induced psychoneuroendocrine disorders.
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Affiliation(s)
- Mary G Hornick
- Roosevelt University, College of Science, Health and Pharmacy, Schaumburg, Illinois, USA
| | - Margaret E Olson
- Roosevelt University, College of Science, Health and Pharmacy, Schaumburg, Illinois, USA
| | - Arun L Jadhav
- Roosevelt University, College of Science, Health and Pharmacy, Schaumburg, Illinois, USA
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Sonkar G, Singh S, Sonkar S. A systematic review approach in understanding the COVID-19 mechanism in diabetes and its progression to diabetic microvascular complications. JOURNAL OF DIABETOLOGY 2022. [DOI: 10.4103/jod.jod_87_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Cavallieri F, Sellner J, Zedde M, Moro E. Neurologic complications of coronavirus and other respiratory viral infections. HANDBOOK OF CLINICAL NEUROLOGY 2022; 189:331-358. [PMID: 36031313 PMCID: PMC9418023 DOI: 10.1016/b978-0-323-91532-8.00004-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
In humans, several respiratory viruses can have neurologic implications affecting both central and peripheral nervous system. Neurologic manifestations can be linked to viral neurotropism and/or indirect effects of the infection due to endothelitis with vascular damage and ischemia, hypercoagulation state with thrombosis and hemorrhages, systemic inflammatory response, autoimmune reactions, and other damages. Among these respiratory viruses, recent and huge attention has been given to the coronaviruses, especially the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic started in 2020. Besides the common respiratory symptoms and the lung tropism of SARS-CoV-2 (COVID-19), neurologic manifestations are not rare and often present in the severe forms of the infection. The most common acute and subacute symptoms and signs include headache, fatigue, myalgia, anosmia, ageusia, sleep disturbances, whereas clinical syndromes include mainly encephalopathy, ischemic stroke, seizures, and autoimmune peripheral neuropathies. Although the pathogenetic mechanisms of COVID-19 in the various acute neurologic manifestations are partially understood, little is known about long-term consequences of the infection. These consequences concern both the so-called long-COVID (characterized by the persistence of neurological manifestations after the resolution of the acute viral phase), and the onset of new neurological symptoms that may be linked to the previous infection.
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Affiliation(s)
- Francesco Cavallieri
- Neurology Unit, Neuromotor and Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy,Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Johann Sellner
- Department of Neurology, Landesklinikum Mistelbach-Gänserndorf, Mistelbach, Austria,Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, Salzburg, Austria
| | - Marialuisa Zedde
- Neurology Unit, Neuromotor and Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Elena Moro
- Division of Neurology, CHU of Grenoble, Grenoble Alpes University, Grenoble Institute of Neurosciences, Grenoble, France,Correspondence to: Elena Moro, Service de neurologie, CHU de Grenoble (Hôpital Nord), Boulevard de la Chantourne, 38043 La Tronche, France. Tel: + 33-4-76-76-94-52, Fax: +33-4-76-76-56-31
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Xie J, Shi D, Bao M, Hu X, Wu W, Sheng J, Xu K, Wang Q, Wu J, Wang K, Fang D, Li Y, Li L. A Predictive Nomogram for Predicting Improved Clinical Outcome Probability in Patients with COVID-19 in Zhejiang Province, China. ENGINEERING (BEIJING, CHINA) 2022; 8:122-129. [PMID: 32837744 PMCID: PMC7274972 DOI: 10.1016/j.eng.2020.05.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 04/14/2020] [Accepted: 05/03/2020] [Indexed: 05/08/2023]
Abstract
The aim of this research was to develop a quantitative method for clinicians to predict the probability of improved prognosis in patients with coronavirus disease 2019 (COVID-19). Data on 104 patients admitted to hospital with laboratory-confirmed COVID-19 infection from 10 January 2020 to 26 February 2020 were collected. Clinical information and laboratory findings were collected and compared between the outcomes of improved patients and non-improved patients. The least absolute shrinkage and selection operator (LASSO) logistics regression model and two-way stepwise strategy in the multivariate logistics regression model were used to select prognostic factors for predicting clinical outcomes in COVID-19 patients. The concordance index (C-index) was used to assess the discrimination of the model, and internal validation was performed through bootstrap resampling. A novel predictive nomogram was constructed by incorporating these features. Of the 104 patients included in the study (median age 55 years), 75 (72.1%) had improved short-term outcomes, while 29 (27.9%) showed no signs of improvement. There were numerous differences in clinical characteristics and laboratory findings between patients with improved outcomes and patients without improved outcomes. After a multi-step screening process, prognostic factors were selected and incorporated into the nomogram construction, including immunoglobulin A (IgA), C-reactive protein (CRP), creatine kinase (CK), acute physiology and chronic health evaluation II (APACHE II), and interaction between CK and APACHE II. The C-index of our model was 0.962 (95% confidence interval (CI), 0.931-0.993) and still reached a high value of 0.948 through bootstrapping validation. A predictive nomogram we further established showed close performance compared with the ideal model on the calibration plot and was clinically practical according to the decision curve and clinical impact curve. The nomogram we constructed is useful for clinicians to predict improved clinical outcome probability for each COVID-19 patient, which may facilitate personalized counselling and treatment.
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Affiliation(s)
- Jiaojiao Xie
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Ding Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Mingyang Bao
- State Key Laboratory of Genetic Engineering, Institute of Biostatistics, School of Life Sciences, Fudan University, Shanghai 200433, China
| | - Xiaoyi Hu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Key Lab of Combined Multi-organ Transplantation of the Ministry of Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Wenrui Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jifang Sheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Kaijin Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Qing Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jingjing Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Kaicen Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Daiqiong Fang
- Division of of Endocrinology and Metabolism, Department of Internal Medicine System, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Yating Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
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Pustake M, Tambolkar I, Giri P, Gandhi C. SARS, MERS and CoVID-19: An overview and comparison of clinical, laboratory and radiological features. J Family Med Prim Care 2022; 11:10-17. [PMID: 35309670 PMCID: PMC8930171 DOI: 10.4103/jfmpc.jfmpc_839_21] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 06/30/2021] [Accepted: 07/04/2021] [Indexed: 11/04/2022] Open
Abstract
In the 21st century, we have seen a total of three outbreaks by members of the coronavirus family. Although the first two outbreaks did not result in a pandemic, the third and the latest outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) culminated in a pandemic. This pandemic has been extremely significant on a social and international level. As these viruses belong to the same family, they are closely related. Despite their numerous similarities, they have slight distinctions that render them distinct from one another. The Severe Acute Respiratory Distress Syndrome and Middle East Respiratory Syndrome (MERS) cases were reported to have a very high case fatality rate of 9.5 and 34.4% respectively. In contrast, the CoVID-19 has a case fatality rate of 2.13%. Also, there are no clear medical countermeasures for these coronaviruses yet. We can cross information gaps, including cultural weapons for fighting and controlling the spread of MERS-CoV and SARS-CoV-2, and plan efficient and comprehensive defensive lines against coronaviruses that might arise or reemerge in the future by gaining a deeper understanding of these coronaviruses and the illnesses caused by them. The review thoroughly summarises the state-of-the-art information and compares the biochemical properties of these deadly coronaviruses with the clinical characteristics, laboratory features and radiological manifestations of illnesses induced by them, with an emphasis on comparing and contrasting their similarities and differences.
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Affiliation(s)
- Manas Pustake
- Department of Internal Medicine, Grant Government Medical College and Sir JJ Group of Hospitals, Mumbai, India
| | - Isha Tambolkar
- Department of Internal Medicine, BJ Government Medical College and Sassoon Hospital, Pune, India
| | - Purushottam Giri
- Department of Community Medicine, IIMSR Medical College, Badnapur, District. Jalna, Maharashtra, India
| | - Charmi Gandhi
- Department of Internal Medicine, Grant Government Medical College and Sir JJ Group of Hospitals, Mumbai, India
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