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Shrwani KJ, Mahallawi WH, Mohana AI, Algaissi A, Dhayhi N, Sharwani NJ, Gadour E, Aldossari SM, Asiri H, Kameli N, Asiri AY, Asiri AM, Sherwani AJ, Cunliffe N, Zhang Q. Mucosal immunity in upper and lower respiratory tract to MERS-CoV. Front Immunol 2024; 15:1358885. [PMID: 39281686 PMCID: PMC11392799 DOI: 10.3389/fimmu.2024.1358885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 07/15/2024] [Indexed: 09/18/2024] Open
Abstract
INTRODUCTION Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged as a deadly pathogen with a mortality rate of up to 36.2%. MERS-CoV can cause severe respiratory tract disease and multiorgan failure. Therefore, therapeutic vaccines are urgently needed. This intensive review explores the human immune responses and their immunological mechanisms during MERS-CoV infection in the mucosa of the upper and lower respiratory tracts (URT and LRT, respectively). OBJECTIVE The aim of this study is to provide a valuable, informative, and critical summary of the protective immune mechanisms against MERS-CoV infection in the URT/LRT for the purpose of preventing and controlling MERS-CoV disease and designing effective therapeutic vaccines. METHODS In this review, we focus on the immune potential of the respiratory tract following MERS-CoV infection. We searched PubMed, Embase, Web of Science, Cochrane, Scopus, and Google Scholar using the following terms: "MERS-CoV", "B cells", "T cells", "cytokines", "chemokines", "cytotoxic", and "upper and lower respiratory tracts". RESULTS We found and included 152 studies in this review. We report that the cellular innate immune response, including macrophages, dendritic cells, and natural killer cells, produces antiviral substances such as interferons and interleukins to prevent the virus from spreading. In the adaptive and humoral immune responses, CD4+ helper T cells, CD8+ cytotoxic T cells, B cells, and plasma cells protect against MERS-CoV infection in URT and LRT. CONCLUSION The human nasopharynx-associated lymphoid tissue (NALT) and bronchus-associated lymphoid tissue (BALT) could successfully limit the spread of several respiratory pathogens. However, in the case of MERS-CoV infection, limited research has been conducted in humans with regard to immunopathogenesis and mucosal immune responses due to the lack of relevant tissues. A better understanding of the immune mechanisms of the URT and LRT is vital for the design and development of effective MERS-CoV vaccines.
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Affiliation(s)
- Khalid J. Shrwani
- Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
- Public Health Authority, Saudi Center for Disease Prevention and Control (SCDC), Jazan, Saudi Arabia
| | - Waleed H. Mahallawi
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Taibah University, Madinah, Saudi Arabia
| | - Abdulrhman I. Mohana
- Department of Antimicrobial Resistance, Public Health Authority, Riyadh, Saudi Arabia
| | - Abdullah Algaissi
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
- Emerging and Endemic Infectious Diseases Research Unit, Health Sciences Research Center, Jazan University, Jazan, Saudi Arabia
| | - Nabil Dhayhi
- Department of Pediatrics, King Fahad Central Hospital, Ministry of Health, Gizan, Saudi Arabia
| | - Nouf J. Sharwani
- Department of Surgery, Mohammed bin Nasser Hospital, Ministry of Health, Gizan, Saudi Arabia
| | - Eyad Gadour
- Department of Gastroenterology and Hepatology, King Abdulaziz National Guard Hospital, Ahsa, Saudi Arabia
- Department of Medicine, Faculty of Medicine, Zamzam University College, Khartoum, Sudan
| | - Saeed M. Aldossari
- Medical Laboratory Technology Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Hasan Asiri
- Medical Laboratory Department, Prince Mohammed bin Abdulaziz Hospital, Riyadh, Saudi Arabia
| | - Nader Kameli
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Ayad Y. Asiri
- Intensive Care Unit Department, Al Inma Medical Group, Al Hayat National Hospital, Ministry of Health, Riyadh, Saudi Arabia
| | - Abdullah M. Asiri
- Preventive Medicine Assistant Deputyship, Ministry of Health, Riyadh, Saudi Arabia
| | - Alaa J. Sherwani
- Department of Pediatrics, Abu-Arish General Hospital, Ministry of Health, Gizan, Saudi Arabia
| | - Nigel Cunliffe
- Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Qibo Zhang
- Academic and Research Departments, Section of Immunology, School of Biosciences, University of Surrey, Surrey, United Kingdom
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Kim C, Seok H, Kim J, Park DW, van Assen M, De Cecco CN, Choi H, Kim C, Hwang SH, Yong HS, Oh YW, Choi WS. COVID-19's Radiologic, Functional, and Serologic Consequences at 6-Month and 18-Month Follow-up: A Prospective Cohort Study. J Korean Med Sci 2024; 39:e228. [PMID: 39164053 PMCID: PMC11333807 DOI: 10.3346/jkms.2024.39.e228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 06/27/2024] [Indexed: 08/22/2024] Open
Abstract
BACKGROUND We evaluated the radiologic, pulmonary functional, and antibody statuses of coronavirus disease 2019 (COVID-19) patients 6 and 18 months after discharge, comparing changes in status and focusing on risk factors for residual computed tomography (CT) abnormalities. METHODS This prospective cohort study was conducted on COVID-19 patients discharged between April 2020 and January 2021. Chest CT, pulmonary function testing (PFT), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) measurements were performed 6 and 18 months after discharge. We evaluated factors associated with residual CT abnormalities and the correlation between lesion volume in CT (lesionvolume), PFT, and IgG levels. RESULTS This study included 68 and 42 participants evaluated 6 and 18 months, respectively, after hospitalizations for COVID-19. CT abnormalities were noted in 22 participants (32.4%) at 6 months and 13 participants (31.0%) at 18 months. Lesionvolume was significantly lower at 18 months than 6 months (P < 0.001). Patients with CT abnormalities at 6 months showed lower forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC), and patients with CT abnormalities at 18 months exhibited lower FVC. FVC significantly improved between 6 and 18 months of follow-up (all P < 0.0001). SARS-CoV-2 IgG levels were significantly higher in patients with CT abnormalities at 6 and 18 months (P < 0.001). At 18-month follow-up assessments, age was associated with CT abnormalities (odds ratio, 1.17; 95% confidence interval, 1.03-1.32; P = 0.01), and lesionvolume showed a positive correlation with IgG level (r = 0.643, P < 0.001). CONCLUSION At 18-month follow-up assessments, 31.0% of participants exhibited residual CT abnormalities. Age and higher SARS-CoV-2 IgG levels were significant predictors, and FVC was related to abnormal CT findings at 18 months. Lesionvolume and FVC improved between 6 and 18 months. TRIAL REGISTRATION Clinical Research Information Service Identifier: KCT0008573.
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Affiliation(s)
- Cherry Kim
- Department of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Hyeri Seok
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Jooyun Kim
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Dae Won Park
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Marly van Assen
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
- Translational Laboratory for Cardiothoracic Imaging and Artificial Intelligence, Emory University School of Medicine, Atlanta, GA, USA
| | - Carlo N De Cecco
- Translational Laboratory for Cardiothoracic Imaging and Artificial Intelligence, Emory University School of Medicine, Atlanta, GA, USA
- Division of Cardiothoracic Imaging, Department of Radiology, Emory University, Atlanta, GA, USA
| | - Hangseok Choi
- Medical Science Research Center, Korea University College of Medicine, Seoul, Korea
| | - Chohee Kim
- Department of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Sung Ho Hwang
- Department of Radiology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Hwan Seok Yong
- Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Yu-Whan Oh
- Department of Radiology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Won Suk Choi
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
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McKendry R, Lemm NM, Papargyris L, Chiu C. Human Challenge Studies with Coronaviruses Old and New. Curr Top Microbiol Immunol 2024; 445:69-108. [PMID: 35181805 DOI: 10.1007/82_2021_247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Coronavirus infections have been known to cause disease in animals since as early as the 1920s. However, only seven coronaviruses capable of causing human disease have been identified thus far. These Human Coronaviruses (HCoVs) include the causes of the common cold, but more recent coronaviruses that have emerged (i.e. SARS-CoV, MERS-CoV and SARS-CoV-2) are associated with much greater morbidity and mortality. HCoVs have been relatively under-studied compared to other common respiratory infections, as historically they have presented with mild symptoms. This has led to a relatively limited understanding of their animal reservoirs, transmission and determinants of immune protection. To address this, human infection challenge studies with HCoVs have been performed that enable a detailed clinical and immunological analysis of the host response at specific time points under controlled conditions with standardised viral inocula. Until recently, all such human challenge studies were conducted with common cold HCoVs, with the study of SARS-CoV and MERS-CoV unacceptable due to their greater pathogenicity. However, with the emergence of SARS-CoV-2 and the COVID-19 pandemic during which severe outcomes in young healthy adults have been rare, human challenge studies with SARS-CoV-2 are now being developed. Two SARS-CoV-2 human challenge studies in the UK studying individuals with and without pre-existing immunity are underway. As well as providing a platform for testing of antivirals and vaccines, such studies will be critical for understanding the factors associated with susceptibility to SARS-CoV-2 infection and thus developing improved strategies to tackle the current as well as future HCoV pandemics. Here, we summarise the major questions about protection and pathogenesis in HCoV infection that human infection challenge studies have attempted to answer historically, as well as the knowledge gaps that aim to be addressed with contemporary models.
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Affiliation(s)
- Richard McKendry
- Department of Infectious Disease, Imperial College London, London, UK
| | - Nana-Marie Lemm
- Department of Infectious Disease, Imperial College London, London, UK
| | - Loukas Papargyris
- Department of Infectious Disease, Imperial College London, London, UK
| | - Christopher Chiu
- Department of Infectious Disease, Imperial College London, London, UK.
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Handel A, Miller JC, Ge Y, Fung ICH. If Long-Term Suppression is not Possible, how do we Minimize Mortality for Infectious Disease Outbreaks? Disaster Med Public Health Prep 2023; 17:e547. [PMID: 38037811 DOI: 10.1017/dmp.2023.203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2023]
Abstract
OBJECTIVE For any emerging pathogen, the preferred approach is to drive it to extinction with non-pharmaceutical interventions (NPI) or suppress its spread until effective drugs or vaccines are available. However, this might not always be possible. If containment is infeasible, the best people can hope for is pathogen transmission until population level immunity is achieved, with as little morbidity and mortality as possible. METHODS A simple computational model was used to explore how people should choose NPI in a non-containment scenario to minimize mortality if mortality risk differs by age. RESULTS Results show that strong NPI might be worse overall if they cannot be sustained compared to weaker NPI of the same duration. It was also shown that targeting NPI at different age groups can lead to similar reductions in the total number of infected, but can have strong differences regarding the reduction in mortality. CONCLUSIONS Strong NPI that can be sustained until drugs or vaccines become available are always preferred for preventing infection and mortality. However, if people encounter a worst-case scenario where interventions cannot be sustained, allowing some infections to occur in lower-risk groups might lead to an overall greater reduction in mortality than trying to protect everyone equally.
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Affiliation(s)
- Andreas Handel
- Department of Epidemiology and Biostatistics, The University of Georgia, Athens, GA, USA
| | - Joel C Miller
- School of Computing, Engineering and Mathematical Sciences, La Trobe University, Bundoora, VIC, Australia
| | - Yang Ge
- School of Health Professions, The University of Southern Mississippi, Hattiesburg, MS, USA
| | - Isaac Chun-Hai Fung
- Department of Biostatistics, Epidemiology, and Environmental Health Sciences, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA, USA
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Peterhoff D, Wiegrebe S, Einhauser S, Patt AJ, Beileke S, Günther F, Steininger P, Niller HH, Burkhardt R, Küchenhoff H, Gefeller O, Überla K, Heid IM, Wagner R. Population-based study of the durability of humoral immunity after SARS-CoV-2 infection. Front Immunol 2023; 14:1242536. [PMID: 37868969 PMCID: PMC10585261 DOI: 10.3389/fimmu.2023.1242536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 09/19/2023] [Indexed: 10/24/2023] Open
Abstract
SARS-CoV-2 antibody quantity and quality are key markers of humoral immunity. However, there is substantial uncertainty about their durability. We investigated levels and temporal change of SARS-CoV-2 antibody quantity and quality. We analyzed sera (8 binding, 4 avidity assays for spike-(S-)protein and nucleocapsid-(N-)protein; neutralization) from 211 seropositive unvaccinated participants, from the population-based longitudinal TiKoCo study, at three time points within one year after infection with the ancestral SARS-CoV-2 virus. We found a significant decline of neutralization titers and binding antibody levels in most assays (linear mixed regression model, p<0.01). S-specific serum avidity increased markedly over time, in contrast to N-specific. Binding antibody levels were higher in older versus younger participants - a difference that disappeared for the asymptomatic-infected. We found stronger antibody decline in men versus women and lower binding and avidity levels in current versus never-smokers. Our comprehensive longitudinal analyses across 13 antibody assays suggest decreased neutralization-based protection and prolonged affinity maturation within one year after infection.
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Affiliation(s)
- David Peterhoff
- Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, Regensburg, Germany
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany
| | - Simon Wiegrebe
- Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
- Statistical Consulting Unit StaBLab, Department of Statistics, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
| | - Sebastian Einhauser
- Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, Regensburg, Germany
| | - Arisha J. Patt
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany
| | - Stephanie Beileke
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Felix Günther
- Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
- Statistical Consulting Unit StaBLab, Department of Statistics, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
| | - Philipp Steininger
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Hans H. Niller
- Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, Regensburg, Germany
| | - Ralph Burkhardt
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany
| | - Helmut Küchenhoff
- Statistical Consulting Unit StaBLab, Department of Statistics, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
| | - Olaf Gefeller
- Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Klaus Überla
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Iris M. Heid
- Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
| | - Ralf Wagner
- Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, Regensburg, Germany
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany
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Stoian M, Roman A, Boeriu A, Onișor D, Bandila SR, Babă DF, Cocuz I, Niculescu R, Costan A, Laszlo SȘ, Corău D, Stoian A. Long-Term Radiological Pulmonary Changes in Mechanically Ventilated Patients with Respiratory Failure due to SARS-CoV-2 Infection. Biomedicines 2023; 11:2637. [PMID: 37893011 PMCID: PMC10604756 DOI: 10.3390/biomedicines11102637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/18/2023] [Accepted: 09/24/2023] [Indexed: 10/29/2023] Open
Abstract
From the first reports of SARS-CoV-2, at the end of 2019 to the present, the global mortality associated with COVID-19 has reached 6,952,522 deaths as reported by the World Health Organization (WHO). Early intubation and mechanical ventilation can increase the survival rate of critically ill patients. This prospective study was carried out on 885 patients in the ICU of Mureș County Clinical Hospital, Romania. After applying inclusion and exclusion criteria, a total of 54 patients were included. Patients were monitored during hospitalization and at 6-month follow-up. We analyzed the relationship between invasive mechanical ventilation (IMV) and non-invasive mechanical ventilation (NIMV) and radiological changes on thoracic CT scans performed at 6-month follow-up and found no significant association. Regarding paraclinical analysis, there was a statistically significant association between patients grouped by IMV and ferritin level on day 1 of admission (p = 0.034), and between patients grouped by PaO2/FiO2 ratio with metabolic syndrome (p = 0.03) and the level of procalcitonin (p = 0.01). A significant proportion of patients with COVID-19 admitted to the ICU developed pulmonary fibrosis as observed at a 6-month evaluation. Patients with oxygen supplementation or mechanical ventilation require dynamic monitoring and radiological investigations, as there is a possibility of long-term pulmonary fibrosis that requires pharmacological interventions and finding new therapeutic alternatives.
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Affiliation(s)
- Mircea Stoian
- Department of Anesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, 540139 Targu Mures, Romania;
| | - Adina Roman
- Gastroenterology Department, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, 540142 Targu Mures, Romania; (A.B.); (D.O.)
| | - Alina Boeriu
- Gastroenterology Department, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, 540142 Targu Mures, Romania; (A.B.); (D.O.)
| | - Danusia Onișor
- Gastroenterology Department, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, 540142 Targu Mures, Romania; (A.B.); (D.O.)
| | - Sergio Rareș Bandila
- Orthopedic Surgery and Traumatology Service, Marina Baixa Hospital, Av. Alcade En Jaume Botella Mayor, 03570 Villajoyosa, Spain;
| | - Dragoș Florin Babă
- Department of Cell and Molecular Biology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, 540142 Targu Mures, Romania;
| | - Iuliu Cocuz
- Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, 540136 Targu Mures, Romania; (I.C.); (R.N.); (A.S.)
| | - Raluca Niculescu
- Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, 540136 Targu Mures, Romania; (I.C.); (R.N.); (A.S.)
| | - Anamaria Costan
- Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, 540142 Targu Mures, Romania;
| | - Sergiu Ștefan Laszlo
- Intensive Care Unit, Mureș County Hospital, Street Gheorghe Marinescu no 1, 540136 Targu Mures, Romania;
| | - Dragoș Corău
- Intensive Care Unit, Mureș County Hospital, Street Gheorghe Marinescu no 1, 540136 Targu Mures, Romania;
| | - Adina Stoian
- Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, 540136 Targu Mures, Romania; (I.C.); (R.N.); (A.S.)
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De Thoisy A, Woudenberg T, Pelleau S, Donnadieu F, Garcia L, Pinaud L, Tondeur L, Meola A, Arowas L, Clement N, Backovic M, Ungeheuer MN, Fontanet A, White M. Seroepidemiology of the Seasonal Human Coronaviruses NL63, 229E, OC43 and HKU1 in France. Open Forum Infect Dis 2023; 10:ofad340. [PMID: 37496603 PMCID: PMC10368309 DOI: 10.1093/ofid/ofad340] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 06/30/2023] [Indexed: 07/28/2023] Open
Abstract
Background The seasonal human coronaviruses (HCoV) NL63, 229E, OC43, and HKU1 are globally endemic, yet the majority of HCoV infections remain undiagnosed. Methods In a cross-sectional study, 2389 serum samples were collected from children and adults in France in 2020. In a longitudinal cohort study, 2520 samples were collected from 898 French individuals followed up between 2020 and 2021. Antibodies to HCoVs were measured using a bead-based multiplex assay. Results The rate of waning of anti-HCoV spike immunoglobulin G antibodies was estimated as 0.22-0.47 year-1 for children, and 0.13-0.27 year-1 for adults. Seroreversion was estimated as 0.31-1.37 year-1 in children and 0.19-0.72 year-1 in adults. The estimated seroconversion rate in children was consistent with 20%-39% of children being infected every year with each HCoV. Conclusions The high force of infection in children indicates that HCoVs may be responsible for a substantial proportion of fever episodes experienced by children.
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Affiliation(s)
- Alix De Thoisy
- Infectious Disease Epidemiology and Analytics G5 Unit, Department of Global Health, Institut Pasteur, Université Paris Cité, Paris, France
| | - Tom Woudenberg
- Infectious Disease Epidemiology and Analytics G5 Unit, Department of Global Health, Institut Pasteur, Université Paris Cité, Paris, France
| | - Stéphane Pelleau
- Correspondence: Michael White, PhD, Infectious Disease Epidemiology and Analytics G5 Unit, Department of Global Health, Institut Pasteur, Rue du Docteur Roux, Paris 75015, France (); Stéphane Pelleau, PhD, Infectious Disease Epidemiology and Analytics G5 Unit, Department of Global Health, Institut Pasteur, Rue du Docteur Roux, Paris 75015, France ()
| | - Françoise Donnadieu
- Infectious Disease Epidemiology and Analytics G5 Unit, Department of Global Health, Institut Pasteur, Université Paris Cité, Paris, France
| | - Laura Garcia
- Infectious Disease Epidemiology and Analytics G5 Unit, Department of Global Health, Institut Pasteur, Université Paris Cité, Paris, France
| | - Laurie Pinaud
- Epidemiology of Emerging Diseases Unit, Department of Global Health, Institut Pasteur, Université Paris Cité, Paris, France
| | - Laura Tondeur
- Epidemiology of Emerging Diseases Unit, Department of Global Health, Institut Pasteur, Université Paris Cité, Paris, France
| | - Annalisa Meola
- Structural Virology Unit, Department of Virology and CNRS UMR 3569, Institut Pasteur, Université Paris Cité, Paris, France
| | - Laurence Arowas
- Investigation Clinique et Accès aux Ressources Biologiques (ICAReB), Center for Translational Research, Institut Pasteur, Paris, France
| | - Nathalie Clement
- Coordination Clinique du CRT, Center for Translational Research, Institut Pasteur, Paris, France
| | - Marija Backovic
- Structural Virology Unit, Department of Virology and CNRS UMR 3569, Institut Pasteur, Université Paris Cité, Paris, France
| | - Marie-Noëlle Ungeheuer
- Investigation Clinique et Accès aux Ressources Biologiques (ICAReB), Center for Translational Research, Institut Pasteur, Paris, France
| | - Arnaud Fontanet
- Epidemiology of Emerging Diseases Unit, Department of Global Health, Institut Pasteur, Université Paris Cité, Paris, France
- PACRI Unit, Conservatoire National des Arts et Métiers, Paris, France
| | - Michael White
- Correspondence: Michael White, PhD, Infectious Disease Epidemiology and Analytics G5 Unit, Department of Global Health, Institut Pasteur, Rue du Docteur Roux, Paris 75015, France (); Stéphane Pelleau, PhD, Infectious Disease Epidemiology and Analytics G5 Unit, Department of Global Health, Institut Pasteur, Rue du Docteur Roux, Paris 75015, France ()
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Facciuolo A, Van Kessel J, Kroeker A, Liao M, Lew JM, Falzarano D, Kelvin AA, Gerdts V, Napper S. Longitudinal analysis of SARS-CoV-2 reinfection reveals distinct kinetics and emergence of cross-neutralizing antibodies to variants of concern. Front Microbiol 2023; 14:1148255. [PMID: 37065160 PMCID: PMC10090301 DOI: 10.3389/fmicb.2023.1148255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023] Open
Abstract
The ongoing evolution of SARS-CoV-2 continues to raise new questions regarding the duration of immunity to reinfection with emerging variants. To address these knowledge gaps, controlled investigations in established animal models are needed to assess duration of immunity induced by each SARS-CoV-2 lineage and precisely evaluate the extent of cross-reactivity and cross-protection afforded. Using the Syrian hamster model, we specifically investigated duration of infection acquired immunity to SARS-CoV-2 ancestral Wuhan strain over 12 months. Plasma spike- and RBD-specific IgG titers against ancestral SARS-CoV-2 peaked at 4 months post-infection and showed a modest decline by 12 months. Similar kinetics were observed with plasma virus neutralizing antibody titers which peaked at 2 months post-infection and showed a modest decline by 12 months. Reinfection with ancestral SARS-CoV-2 at regular intervals demonstrated that prior infection provides long-lasting immunity as hamsters were protected against severe disease when rechallenged at 2, 4, 6, and 12 months after primary infection, and this coincided with the induction of high virus neutralizing antibody titers. Cross-neutralizing antibody titers against the B.1.617.2 variant (Delta) progressively waned in blood over 12 months, however, re-infection boosted these titers to levels equivalent to ancestral SARS-CoV-2. Conversely, cross-neutralizing antibodies to the BA.1 variant (Omicron) were virtually undetectable at all time-points after primary infection and were only detected following reinfection at 6 and 12 months. Collectively, these data demonstrate that infection with ancestral SARS-CoV-2 strains generates antibody responses that continue to evolve long after resolution of infection with distinct kinetics and emergence of cross-reactive and cross-neutralizing antibodies to Delta and Omicron variants and their specific spike antigens.
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Affiliation(s)
- Antonio Facciuolo
- Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada
- Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada
- *Correspondence: Antonio Facciuolo,
| | - Jill Van Kessel
- Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada
| | - Andrea Kroeker
- Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada
| | - Mingmin Liao
- Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada
| | - Jocelyne M. Lew
- Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada
| | - Darryl Falzarano
- Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada
- Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada
| | - Alyson A. Kelvin
- Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada
- Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada
| | - Volker Gerdts
- Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada
- Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada
| | - Scott Napper
- Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada
- Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada
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9
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Liontos A, Asimakopoulos AG, Markopoulos GS, Biros D, Athanasiou L, Tsourlos S, Dova L, Rapti IC, Tsiakas I, Ntzani E, Evangelou E, Tzoulaki I, Tsilidis K, Vartholomatos G, Dounousi E, Milionis H, Christaki E. Correlation of Lymphocyte Subpopulations, Clinical Features and Inflammatory Markers during Severe COVID-19 Onset. Pathogens 2023; 12:pathogens12030414. [PMID: 36986336 PMCID: PMC10057940 DOI: 10.3390/pathogens12030414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/26/2023] [Accepted: 03/01/2023] [Indexed: 03/08/2023] Open
Abstract
Background: Dysregulation of the immune response in the course of COVID-19 has been implicated in critical outcomes. Lymphopenia is evident in severe cases and has been associated with worse outcomes since the early phases of the pandemic. In addition, cytokine storm has been associated with excessive lung injury and concomitant respiratory failure. However, it has also been hypothesized that specific lymphocyte subpopulations (CD4 and CD8 T cells, B cells, and NK cells) may serve as prognostic markers for disease severity. The aim of this study was to investigate possible associations of lymphocyte subpopulations alterations with markers of disease severity and outcomes in patients hospitalized with COVID-19. Materials/Methods: A total of 42 adult hospitalized patients were included in this study, from June to July 2021. Flow-cytometry was used to calculate specific lymphocyte subpopulations on day 1 (admission) and on day 5 of hospitalization (CD45, CD3, CD3CD8, CD3CD4, CD3CD4CD8, CD19, CD16CD56, CD34RA, CD45RO). Markers of disease severity and outcomes included: burden of disease on CT (% of affected lung parenchyma injury), C-reactive protein and interleukin-6 levels. PO2/FiO2 ratio and differences in lymphocytes subsets between two timepoints were also calculated. Logistic and linear regressions were used for the analyses. All analyses were performed using Stata (version 13.1; Stata Corp, College Station, TX, USA). Results: Higher levels of CD16CD56 cells (Natural Killer cells) were associated with higher risk of lung injury (>50% of lung parenchyma). An increase in CD3CD4 and CD4RO cell count difference between day 5 and day 1 resulted in a decrease of CRP difference between these timepoints. On the other hand, CD45RARO difference was associated with an increase in the difference of CRP levels between the two timepoints. No other significant differences were found in the rest of the lymphocyte subpopulations. Conclusions: Despite a low patient number, this study showed that alterations in lymphocyte subpopulations are associated with COVID-19 severity markers. It was observed that an increase in lymphocytes (CD4 and transiently CD45RARO) resulted in lower CRP levels, perhaps leading to COVID-19 recovery and immune response homeostasis. However, these findings need further evaluation in larger scale trials.
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Affiliation(s)
- Angelos Liontos
- 1st Division of Internal Medicine & Infectious Diseases Unit, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Alexandros-George Asimakopoulos
- Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Georgios S. Markopoulos
- Haematology Laboratory, Unit of Molecular Biology and Translational Flow Cytometry, University Hospital of Ioannina, 45110 Ioannina, Greece
| | - Dimitrios Biros
- 1st Division of Internal Medicine & Infectious Diseases Unit, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Lazaros Athanasiou
- 1st Division of Internal Medicine & Infectious Diseases Unit, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Stavros Tsourlos
- 1st Division of Internal Medicine & Infectious Diseases Unit, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Leukothea Dova
- Haematology Laboratory, Unit of Molecular Biology and Translational Flow Cytometry, University Hospital of Ioannina, 45110 Ioannina, Greece
| | - Iro-Chrisavgi Rapti
- 1st Division of Internal Medicine & Infectious Diseases Unit, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Ilias Tsiakas
- 1st Division of Internal Medicine & Infectious Diseases Unit, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Evangelia Ntzani
- Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Evangelos Evangelou
- Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Ioanna Tzoulaki
- Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Konstantinos Tsilidis
- Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - George Vartholomatos
- Haematology Laboratory, Unit of Molecular Biology and Translational Flow Cytometry, University Hospital of Ioannina, 45110 Ioannina, Greece
| | - Evangelia Dounousi
- Department of Nephrology, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Haralampos Milionis
- 1st Division of Internal Medicine & Infectious Diseases Unit, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Eirini Christaki
- 1st Division of Internal Medicine & Infectious Diseases Unit, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece
- Correspondence: ; Tel.: +30-26-5109-9640
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10
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Impact of MERS-CoV and SARS-CoV-2 Viral Infection on Immunoglobulin-IgG Cross-Reactivity. Vaccines (Basel) 2023; 11:vaccines11030552. [PMID: 36992136 DOI: 10.3390/vaccines11030552] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 02/15/2023] [Accepted: 02/23/2023] [Indexed: 03/03/2023] Open
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has posed a considerable threat to public health and global economies. SARS-CoV-2 has largely affected a vast world population and was declared a COVID-19 pandemic outbreak, with a substantial surge of SARS-CoV-2 infection affecting all aspects of the virus’ natural course of infection and immunity. The cross-reactivity between the different coronaviruses is still a knowledge gap in the understanding of the SARS-CoV-2 virus. This study aimed to investigate the impact of MERS-CoV and SARS-CoV-2 viral infections on immunoglobulin-IgG cross-reactivity. Our retrospective cohort study hypothesized the possible reactivation of immunity in individuals with a history of infection to Middle East Respiratory Syndrome coronavirus (MERS-CoV) when infected with SARS-CoV-2. The total number of participants included was 34; among them, 22 (64.7%) were males, and 12 (35.29%) were females. The mean age of the participants was 40.3 ± 12.9 years. This study compared immunoglobulin (IgG) levels against SARS-CoV-2 and MERS-CoV across various groups with various histories of infection. The results showed that a reactive borderline IgG against both MERS-CoV and SARS-CoV-2 in participants with past infection to both viruses was 40% compared with 37.5% among those with past infection with MERS-CoV alone. Our study results establish that individuals infected with both SARS-CoV-2 and MERS-CoV showed higher MERS-CoV IgG levels compared with those of individuals infected previously with MERS-CoV alone and compared with those of individuals in the control. The results further highlight cross-adaptive immunity between MERS-CoV and SARS-CoV. Our study concludes that individuals with previous infections with both MERS-CoV and SARS-CoV-2 showed significantly higher MERS-CoV IgG levels compared with those of individuals infected only with MERS-CoV and compared with those of individuals in the control, suggesting cross-adaptive immunity between MERS-CoV and SARS-CoV.
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11
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Alibolandi Z, Ostadian A, Sayyah S, Haddad Kashani H, Ehteram H, Banafshe HR, Hajijafari M, Sepehrnejad M, Riahi Kashani N, Azadchehr MJ, Nikzad H, Seyed Hosseini E. The correlation between IgM and IgG antibodies with blood profile in patients infected with severe acute respiratory syndrome coronavirus. Clin Mol Allergy 2022; 20:15. [PMID: 36550478 PMCID: PMC9774079 DOI: 10.1186/s12948-022-00180-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 10/07/2022] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVES This study aimed to determine the levels of IgM and IgG antibody response to the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 in coronavirus disease 2019 (COVID-19) patients with different disease severity. METHODS IgM and IgG antibody levels were evaluated via enzyme-linked immunosorbent assay (ELISA). In total, 100 patients with confirmed SARS-CoV-2 infection were enrolled in this study and viral RNA was detected by using Real-time PCR technique. Clinical and laboratory data were collected and analyzed after hospital admission for COVID-19 and two months post-admission. RESULTS The level of anti-SARS-CoV-2 antibody IgG was significantly higher in the severe patients than those in moderate and mild groups, 2 months after admission. Also, level of IgG was positively associated with increased WBC, NUT and LYM counts in sever than mild or moderate groups after admission to hospital. CONCLUSION Our findings suggested that patients with severe illness might experience longer virus exposure times and have a stronger antibody response against viral infection. Thus, they have longer time immunity compared with other groups.
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Affiliation(s)
- Zahra Alibolandi
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Gametogenesis Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Amirreza Ostadian
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Gametogenesis Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Saeed Sayyah
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Gametogenesis Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Haddad Kashani
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
- Gametogenesis Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
| | - Hassan Ehteram
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Department of Pathology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamid Reza Banafshe
- Department of Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Hajijafari
- Department of Anesthesiology, Beheshti Hospital, Kashan University of Medical Sciences, Kashan, Iran
| | - Mahdi Sepehrnejad
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Gametogenesis Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Narjes Riahi Kashani
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Gametogenesis Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammd-Javad Azadchehr
- Department of Biostatistics, Infectious Disease Research Center, Kashan University of Medical Sciences, Kashan, Iran
| | - Hossein Nikzad
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Gametogenesis Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Elahe Seyed Hosseini
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
- Gametogenesis Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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12
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Liang D, Zhang G, Huang M, Wang L, Hong W, Li A, Liang Y, Wang T, Lu J, Ou M, Ren Z, Lu H, Zheng R, Cai X, Pan X, Xia J, Ke C. Progress of the COVID-19: Persistence, Effectiveness, and Immune Escape of the Neutralizing Antibody in Convalescent Serum. Pathogens 2022; 11:pathogens11121531. [PMID: 36558864 PMCID: PMC9782332 DOI: 10.3390/pathogens11121531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 12/06/2022] [Accepted: 12/08/2022] [Indexed: 12/15/2022] Open
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a new coronavirus causing Coronavirus Disease 2019 (COVID-19), is a major topic of global human health concern. The Delta and Omicron variants have caused alarming responses worldwide due to their high transmission rates and a number of mutations. During a one-year follow-up (from June 2020 to June 2021), we included 114 patients with SARS-CoV-2 infection to study the long-term dynamics and the correlative factors of neutralizing antibodies (NAbs) in convalescent patients. The blood samples were collected at two detection time points (at 6 and 12 months after discharge). We evaluated the NAbs response of discharged patients by performing a micro-neutralization assay using a SARS-CoV-2 wild type. In addition, a total of 62 serum samples from discharged COVID-19 patients with Alpha, Beta, Delta, and Omicron variants of infection were enrolled to perform cross-neutralization tests using the original SARS-CoV-2 strain and VOCs variants (including Alpha, Beta, Gamma, Delta, and Omicron variants) and to assess the ability of NAbs against the SARS-CoV-2 variants. NAbs seroconversion occurred in 91.46% of patients (n = 82) in the first timepoint and in 89.29% of patients (n = 84) in the second detection point, and three kinds of NAbs kinetics curves were perceived. The NAbs levels in young patients had higher values than those in elder patients. The kinetics of disease duration was accompanied by an opposite trend in NAbs levels. Despite a declining NAbs response, NAbs activity was still detectable in a substantial proportion of recovered patients one year after discharge. Compared to the wild strain, the Omicron strain could lead to a 23.44-, 3.42-, 8.03-, and 2.57-fold reduction in neutralization capacity in "SAlpha", "SBeta", "SDelta", and "SOmicron", respectively, and the NAbs levels against the Omicron strain were significantly lower than those of the Beta and Delta variants. Remarkably, the NAbs activity of convalescent serum with Omicron strain infection was most obviously detectable against six SARS-CoV-2 strains in our study. The role of the vaccination history in NAbs levels further confirmed the previous study that reported vaccine-induced NAbs as the convincing protection mechanism against SARS-CoV-2. In conclusion, our findings highlighted the dynamics of the long-term immune responses after the disappearance of symptoms and revealed that NAbs levels varied among all types of convalescent patients with COVID-19 and that NAbs remained detectable for one year, which is reassuring in terms of protection against reinfection. Moreover, a moderate correlation between the duration of disease and Nabs titers was observed, whereas age was negatively correlated with Nabs titers. On the other hand, compared with other VOCs, the Omicron variant was able to escape the defenses of the immune system more significantly, and the convalescent serum infected with the Omicron variant played a critical part in protection against different SARS-CoV-2 variants. Recovery serum from individuals vaccinated with inactivated vaccine preceding infection with the Omicron strain had a high efficacy against the original strain and the VOCs variants, whereas the convalescent serum of persons vaccinated by inactivated vaccine prior to infection with the Delta variant was only potent against the wild-type strain.
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Affiliation(s)
- Dan Liang
- Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, China
- Emergency Key Team, Guangzhou National Laboratory, Guangzhou 510700, China
- Guangdong Provincial Center for Disease Control and Prevention, Guangdong Workstation for Emerging Infectious Disease Control and Prevention, Guangzhou 511430, China
| | - Guanting Zhang
- Guangdong Provincial Center for Disease Control and Prevention, Guangdong Workstation for Emerging Infectious Disease Control and Prevention, Guangzhou 511430, China
| | - Mingxing Huang
- The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China
| | - Li Wang
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Wenshan Hong
- MPH Education Center, Shantou University Medical College, Shantou 515041, China
| | - An’an Li
- School of Public Health, Southern Medical University, Guangzhou 510515, China
| | - Yufeng Liang
- School of Public Health, Southern Medical University, Guangzhou 510515, China
| | - Tao Wang
- MPH Education Center, Shantou University Medical College, Shantou 515041, China
| | - Jiahui Lu
- The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China
| | - Mengdang Ou
- The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China
| | - Zhongqiang Ren
- Second People’s Hospital of Zhongshan, Zhongshan 528447, China
| | - Huiyi Lu
- Second People’s Hospital of Zhongshan, Zhongshan 528447, China
| | - Rutian Zheng
- Huizhou Central People’s Hospital, Huizhou 516001, China
| | - Xionghui Cai
- Huizhou Central People’s Hospital, Huizhou 516001, China
| | - Xingfei Pan
- Department of Infectious Diseases, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
| | - Jinyu Xia
- The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China
| | - Changwen Ke
- Emergency Key Team, Guangzhou National Laboratory, Guangzhou 510700, China
- Guangdong Provincial Center for Disease Control and Prevention, Guangdong Workstation for Emerging Infectious Disease Control and Prevention, Guangzhou 511430, China
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
- MPH Education Center, Shantou University Medical College, Shantou 515041, China
- School of Public Health, Southern Medical University, Guangzhou 510515, China
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13
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Odendahl M, Endler I, Haubold B, Rodionov RN, Bornstein SR, Tonn T. SARS-CoV-2-specicific humoral immunity in convalescent patients with mild COVID-19 is supported by CD4 + T-cell help and negatively correlated with Alphacoronavirus-specific antibody titer. Immunol Lett 2022; 251-252:38-46. [PMID: 36174771 PMCID: PMC9512529 DOI: 10.1016/j.imlet.2022.09.007] [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: 05/06/2022] [Revised: 07/29/2022] [Accepted: 09/26/2022] [Indexed: 01/31/2023]
Abstract
This study aimed at investigating the nature of SARS-CoV-2-specific immunity in patients with mild COVID-19 and sought to identify parameters most relevant for the generation of neutralizing antibody responses in convalescent COVID-19 patients. In the majority of the examined patients a cellular as well as humoral immune response directed to SARS-CoV-2 was detected. The finding of an anti-SARS-CoV-2-reactive cellular immune response in healthy individuals suggests a pre-existing immunity to various common cold HCoVs which share close homology with SARS-CoV-2. The humoral immunity to the S protein of SARS-CoV-2 detected in convalescent COVID-19 patients correlates with the presence of SARS-CoV-2-reactive CD4+ T cells expressing Th1 cytokines. Remarkably, an inverse correlation of SARS-CoV-2 S protein-specific IgGs with HCoV-NL63 and HCoV-229E S1 protein-specific IgGs suggests that pre-existing immunity to Alphacoronaviruses might have had an inhibitory imprint on the immune response to SARS-CoV-2-infection in the examined patients with mild COVID-19.
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Affiliation(s)
- Marcus Odendahl
- Experimental Transfusion Medicine, Medical Faculty Carl Gustav Carus, Technical University Dresden, Germany,Institute for Transfusion Medicine Dresden, German Red Cross Blood Donation Service North-East, Dresden, Germany,Corresponding author at: Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East gGmbH, Blasewitzerstr. 68-70, 01309 Dresden, Germany
| | - Iris Endler
- Experimental Transfusion Medicine, Medical Faculty Carl Gustav Carus, Technical University Dresden, Germany,Institute for Transfusion Medicine Dresden, German Red Cross Blood Donation Service North-East, Dresden, Germany
| | - Beate Haubold
- Institute for Transfusion Medicine Dresden, German Red Cross Blood Donation Service North-East, Dresden, Germany
| | - Roman N. Rodionov
- Department of Medicine III, University Hospital Carl-Gustav, Dresden, Germany
| | - Stefan R. Bornstein
- Department of Medicine III, University Hospital Carl-Gustav, Dresden, Germany,Department of Diabetes, School of Life Course Science and Medicine, King's College London, London, United Kingdom
| | - Torsten Tonn
- Experimental Transfusion Medicine, Medical Faculty Carl Gustav Carus, Technical University Dresden, Germany,Institute for Transfusion Medicine Dresden, German Red Cross Blood Donation Service North-East, Dresden, Germany,Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany
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14
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Cheng ZJ, Huang H, Liu Q, Zhong R, Liang Z, Xue M, Liu M, Li S, Wang H, Zheng P, Zheng C, Sun B. Immunoassay and mass cytometry revealed immunological profiles induced by inactivated BBIBP COVID-19 vaccine. J Med Virol 2022; 94:5206-5216. [PMID: 35801663 PMCID: PMC9350407 DOI: 10.1002/jmv.27983] [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: 06/17/2022] [Accepted: 06/29/2022] [Indexed: 12/15/2022]
Abstract
With the global prevalence of COVID-19 and the constant emergence of viral variants, boosters for COVID-19 vaccines to enhance antibody titers in human bodies will become an inevitable trend. However, there is a lack of data on antibody levels and the protective effects of booster injections. This study monitored and analyzed the antibody potency and the antibody responses induced by the booster injection in the subjects who received three vaccine doses. The study was conducted in a multicenter collaboration and recruited 360 healthy adults aged 20-74. Participants received the first, second, and booster doses of inactivated Sinopharm/BBIBP COVID-19 vaccine at 0, 1, and 7 months. Vaccine-induced virus-specific antibody levels (SARS-COV-2-IgA/IgM/IgG) were monitored at multiple time points, surrogate virus neutralization test (sVNT), and the spatial distribution and proportion of immune cells and markers were analyzed using the CyTOF method before vaccination and a month after the second dose. The titers of SARS-CoV-2-IgA/IgM/IgG and neutralizing antibodies increased to a high level in the first month after receiving the second dose of vaccine and declined slowly after that. The antibody levels of SARS-CoV-2-IgG and sVNT were significantly increased at 0.5 months after the induction of the booster (p < 0.05). Despite a downward trend, the antibody levels were still high in the following 6 months. The B cell concentration (in humoral sample) a month after the second injection was significantly reduced compared to that before the vaccine injection (p < 0.05). The proportion of the C01 cell cluster was significantly decreased compared with that before vaccine injection (p < 0.05). Individual cell surface markers showed distinctions in spatial distribution but were not significantly different. This study has shown that serum antibody titer levels will decrease with time by monitoring and analyzing the antibody efficacy and the antibody reaction caused by the booster injection of healthy people who received the whole vaccination (completed three injections). Still, the significant peak of the antibody titer levels after booster highlights the recall immune response. It can maintain a high concentration of antibody levels for a long time, which signifies that the protection ability has been enhanced following the injection of booster immunization. Additionally, CyTOF data shows the active production of antibodies and the change in the immunity environment.
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Affiliation(s)
- Zhangkai J. Cheng
- Department of Allergy and Clinical Immunology, Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory DiseaseGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina,Medical CollegeInner Mongolia Minzu UniversityTongliaoChina,Guangzhou LaboratoryGuangzhouChina
| | - Huimin Huang
- Department of Allergy and Clinical Immunology, Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory DiseaseGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
| | - Qiwen Liu
- Department of Allergy and Clinical Immunology, Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory DiseaseGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina,Nanshan SchoolGuangzhou Medical UniversityGuangzhouChina
| | | | - Zhiman Liang
- Department of Allergy and Clinical Immunology, Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory DiseaseGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
| | - Mingshan Xue
- Department of Allergy and Clinical Immunology, Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory DiseaseGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina,Guangzhou LaboratoryGuangzhouChina
| | - Mingtao Liu
- Department of Allergy and Clinical Immunology, Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory DiseaseGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
| | - Siping Li
- Dongguan Eighth People's HospitalDongguanChina
| | - Hongman Wang
- Fifth Affiliated Hospital of Zunyi Medical UniversityZhuhaiChina
| | - Peiyan Zheng
- Department of Allergy and Clinical Immunology, Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory DiseaseGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
| | - Chunfu Zheng
- Medical CollegeInner Mongolia Minzu UniversityTongliaoChina,Key Laboratory of Zoonose Prevention and ControlUniversities of Inner Mongolia Autonomous RegionTongliaoChina,Department of Microbiology, Immunology and Infectious DiseasesUniversity of CalgaryCalgaryAlbertaCanada
| | - Baoqing Sun
- Department of Allergy and Clinical Immunology, Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory DiseaseGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina,Guangzhou LaboratoryGuangzhouChina
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15
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Collins E, Galipeau Y, Arnold C, Bosveld C, Heiskanen A, Keeshan A, Nakka K, Shir-Mohammadi K, St-Denis-Bissonnette F, Tamblyn L, Vranjkovic A, Wood LC, Booth R, Buchan CA, Crawley AM, Little J, McGuinty M, Saginur R, Langlois MA, Cooper CL. Cohort profile: Stop the Spread Ottawa (SSO) -a community-based prospective cohort study on antibody responses, antibody neutralisation efficiency and cellular immunity to SARS-CoV-2 infection and vaccination. BMJ Open 2022; 12:e062187. [PMID: 36691221 PMCID: PMC9461086 DOI: 10.1136/bmjopen-2022-062187] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 08/16/2022] [Indexed: 01/27/2023] Open
Abstract
PURPOSE To investigate the robustness and longevity of SARS-CoV-2 immune responses conferred by natural infection and vaccination among priority populations such as immunocompromised individuals and people with post-acute sequelae of COVID-19 in a prospective cohort study (Stop the Spread Ottawa-SSO) in adults living in the Ottawa region. In this paper, we describe the study design, ongoing data collection and baseline characteristics of participants. PARTICIPANTS Since October 2020, participants who tested positive for COVID-19 (convalescents) or at high risk of exposure to the virus (under surveillance) have provided monthly blood and saliva samples over a 10-month period. As of 2 November 2021, 1026 adults had completed the baseline survey and 976 had attended baseline bloodwork. 300 participants will continue to provide bimonthly blood samples for 24 additional months (ie, total follow-up of 34 months). FINDINGS TO DATE The median age of the baseline sample was 44 (IQR 23, range: 18-79) and just over two-thirds (n=688; 67.1%) were female. 255 participants (24.9%) had a history of COVID-19 infection confirmed by PCR and/or serology. Over 600 participants (60.0%) work in high-risk occupations (eg, healthcare, teaching and transportation). 108 participants (10.5%) reported immunocompromising conditions or treatments at baseline (eg, cancer, HIV, other immune deficiency, and/or use of immunosuppressants). FUTURE PLANS SSO continues to yield rich research potential, given the collection of pre-vaccine baseline data and samples from the majority of participants, recruitment of diverse subgroups of interest, and a high level of participant retention and compliance with monthly sampling. The 24-month study extension will maximise opportunities to track SARS-CoV-2 immunity and vaccine efficacy, detect and characterise emerging variants, and compare subgroup humoral and cellular response robustness and persistence.
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Affiliation(s)
- Erin Collins
- School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Yannick Galipeau
- Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada
| | - Corey Arnold
- Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada
| | - Cameron Bosveld
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Aliisa Heiskanen
- School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Alexa Keeshan
- School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Kiran Nakka
- Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada
- Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Khatereh Shir-Mohammadi
- Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada
| | | | - Laura Tamblyn
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Agatha Vranjkovic
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Leah C Wood
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Ronald Booth
- Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Immunology Section, Eastern Ontario Regional Laboratory Association (EORLA), Ottawa, Ontario, Canada
| | - C Arianne Buchan
- Division of Infectious Diseases, Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Angela M Crawley
- Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- Coronavirus Variants Rapid Response Network (CoVaRR-Net), Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Centre for Infection, Immunity and Inflammation (CI3), University of Ottawa, Ottawa, Ontario, Canada
| | - Julian Little
- School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- Coronavirus Variants Rapid Response Network (CoVaRR-Net), Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- The Knowledge Synthesis and Application Unit (KSAU), University of Ottawa, Ottawa, Ontario, Canada
| | - Michaeline McGuinty
- Division of Infectious Diseases, Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Raphael Saginur
- Division of Infectious Diseases, Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Ottawa Health Science Network Research Ethics Board (OHSN-REB), Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Marc-André Langlois
- Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada
- Coronavirus Variants Rapid Response Network (CoVaRR-Net), Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Centre for Infection, Immunity and Inflammation (CI3), University of Ottawa, Ottawa, Ontario, Canada
| | - Curtis L Cooper
- Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- Division of Infectious Diseases, Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Coronavirus Variants Rapid Response Network (CoVaRR-Net), Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Centre for Infection, Immunity and Inflammation (CI3), University of Ottawa, Ottawa, Ontario, Canada
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16
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SARS-CoV-2 infection: Pathogenesis, Immune Responses, Diagnosis. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2022. [DOI: 10.22207/jpam.16.3.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
COVID-19 has emerged as the most alarming infection of the present time instigated by the virus SARS-CoV-2. In spite of advanced research technologies, the exact pathophysiology and treatment of the condition still need to be explored. However, SARS-CoV-2 has several structural and functional similarities that resemble SARS-CoV and MERS-CoV which may be beneficial in exploring the possible treatment and diagnostic strategies for SARS-CoV-2. This review discusses the pathogen phenotype, genotype, replication, pathophysiology, elicited immune response and emerging variants of SARS-CoV-2 and their similarities with other similar viruses. SARS-CoV-2 infection is detected by a number of diagnostics techniques, their advantages and limitations are also discussed in detail. The review also focuses on nanotechnology-based easy and fast detection of SARS-CoV-2 infection. Various pathways which might play a vital role during SARS-CoV-2 infection have been elaborately discussed since immune response plays a major role during viral infections.
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17
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Nguyen DC, Lamothe PA, Woodruff MC, Saini AS, Faliti CE, Sanz I, Lee FE. COVID-19 and plasma cells: Is there long-lived protection? Immunol Rev 2022; 309:40-63. [PMID: 35801537 PMCID: PMC9350162 DOI: 10.1111/imr.13115] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Infection with SARS-CoV-2, the etiology of the ongoing COVID-19 pandemic, has resulted in over 450 million cases with more than 6 million deaths worldwide, causing global disruptions since early 2020. Memory B cells and durable antibody protection from long-lived plasma cells (LLPC) are the mainstay of most effective vaccines. However, ending the pandemic has been hampered by the lack of long-lived immunity after infection or vaccination. Although immunizations offer protection from severe disease and hospitalization, breakthrough infections still occur, most likely due to new mutant viruses and the overall decline of neutralizing antibodies after 6 months. Here, we review the current knowledge of B cells, from extrafollicular to memory populations, with a focus on distinct plasma cell subsets, such as early-minted blood antibody-secreting cells and the bone marrow LLPC, and how these humoral compartments contribute to protection after SARS-CoV-2 infection and immunization.
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Affiliation(s)
- Doan C. Nguyen
- Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of MedicineEmory UniversityAtlantaGeorgiaUSA
| | - Pedro A. Lamothe
- Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of MedicineEmory UniversityAtlantaGeorgiaUSA
| | - Matthew C. Woodruff
- Division of Rheumatology, Department of MedicineEmory UniversityAtlantaGeorgiaUSA
- Emory Autoimmunity Center of ExcellenceEmory UniversityAtlantaGeorgiaUSA
- Lowance Center for Human ImmunologyEmory UniversityAtlantaGeorgiaUSA
| | - Ankur S. Saini
- Division of Rheumatology, Department of MedicineEmory UniversityAtlantaGeorgiaUSA
- Emory Autoimmunity Center of ExcellenceEmory UniversityAtlantaGeorgiaUSA
- Lowance Center for Human ImmunologyEmory UniversityAtlantaGeorgiaUSA
| | - Caterina E. Faliti
- Division of Rheumatology, Department of MedicineEmory UniversityAtlantaGeorgiaUSA
- Lowance Center for Human ImmunologyEmory UniversityAtlantaGeorgiaUSA
| | - Ignacio Sanz
- Division of Rheumatology, Department of MedicineEmory UniversityAtlantaGeorgiaUSA
- Emory Autoimmunity Center of ExcellenceEmory UniversityAtlantaGeorgiaUSA
- Lowance Center for Human ImmunologyEmory UniversityAtlantaGeorgiaUSA
| | - Frances Eun‐Hyung Lee
- Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of MedicineEmory UniversityAtlantaGeorgiaUSA
- Lowance Center for Human ImmunologyEmory UniversityAtlantaGeorgiaUSA
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18
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Muslim Dawood S, Khudhur Al Joofy I. Evaluation of IgM and IgG in COVID-19 Recovered Patients in Iraq. ARCHIVES OF RAZI INSTITUTE 2022; 77:1191-1197. [PMID: 36618307 PMCID: PMC9759244 DOI: 10.22092/ari.2022.357515.2054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 04/01/2022] [Indexed: 01/10/2023]
Abstract
Severe acute respiratory syndrome coronavirus-2 is a major threat to health care worldwide with high morbidity and mortality. Therefore, understanding the role of immune mechanisms and humoral response is vital in this disease. The present study aimed to investigate the relationship between Immunoglobulins (IgM, IgG) in COVID-19 recovered patients with age, gender, and severity of the disease. The duration of effect of antibody levels and protection against re-infection has also been evaluated in the patients. Three groups participated in this study; group 1: 0-14 days after recovery, group 2: 2 months after recovery, group 3: 3 months after recovery, group 4: 4-6 months after recovery, group 5: more than 6 months. The nasopharyngeal swab was used to confirm recovery by Real-Time Polymerase Chain Reaction (RT-PCR) technique. IgM and IgG antibody levels were evaluated using Enzyme-Linked Immuno Fluorescent Assay (ELIFA) technique. The results indicated that the IgM levels increased for one month during the seven days after infection and then decreased in most patients (P≤0.05). The mean of IgG in group 1 increased compared to those of other studied groups. A significant decrease was observed in group 2 compared to group 1, as well as in group 3 compared to groups 1, and 2. Also, a significant difference existed between group 4 compared to groups 1, 2, and 3. Finally, significant differences were noticed between group 5 compared to groups 1, 2, 3, and 4 (P≤0.05). No significant differences were observed in antibodies level between male, and female COVID-19 recovered patients in groups 1, 2, 3, 4, and 5 (P≤0.05). Finally, highly significant differences in IgG levels between mild, moderate, and severe subgroups in groups 1 and 2. The present study demonstrated that IgM and IgG against SARS-CoV-2 appeared in the early stages of the disease and decreased after 1 month and failed to maintain high levels during the 6-month observation.
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Affiliation(s)
- S Muslim Dawood
- Educational Laboratories, Unit of Clinical Immunology, Baghdad Medical City, Baghdad, Iraq
| | - I Khudhur Al Joofy
- Department of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq
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19
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The Duration and Determinants of Anti-SARS-CoV-2 Immunoglobulin G in Cancer Patients with SARS-CoV-2 Infection: A Longitudinal Study. Curr Microbiol 2022; 79:237. [PMID: 35767154 PMCID: PMC9242909 DOI: 10.1007/s00284-022-02933-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 06/10/2022] [Indexed: 11/15/2022]
Abstract
Patients with cancer have an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a high case-fatality rate. The duration of anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies in cancer patients following SARS-CoV-2 infection has not been reported previously. We conducted a longitudinal study at a cancer center in Wuhan, China to determine the duration of the humoral immune response following SARS-CoV-2 infection in cancer patients and to determine factors associated with a short duration (< 6 months) of anti-SARS-CoV-2 immunoglobulin G (IgG). Of 2139 cancer patients screened, 78 with confirmed SARS-CoV-2 infection were included in this study. SARS-CoV-2 IgG antibodies were present for < 6 months in 39.7% of these patients. In addition, patients who received chemotherapy were more likely to have a short duration of anti-SARS-CoV-2 IgG (odds ratio 5.31, 95% confidence interval 1.09–26.02, P < 0.05). Our study suggests that cancer patients, especially those who were receiving chemotherapy, have a shorter anti-SARS-CoV-2 IgG duration following infection and therefore, should be prioritized for vaccination.
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20
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Hancock TJ, Hickman P, Kazerooni N, Kennedy M, Kania SA, Dennis M, Szafranski N, Gerhold R, Su C, Masi T, Smith S, Sparer TE. Possible Cross-Reactivity of Feline and White-Tailed Deer Antibodies against the SARS-CoV-2 Receptor Binding Domain. J Virol 2022; 96:e0025022. [PMID: 35352999 PMCID: PMC9044950 DOI: 10.1128/jvi.00250-22] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 02/17/2022] [Indexed: 02/07/2023] Open
Abstract
In late 2019, a novel coronavirus began circulating within humans in central China. It was designated SARS-CoV-2 because of its genetic similarities to the 2003 SARS coronavirus (SARS-CoV). Now that SARS-CoV-2 has spread worldwide, there is a risk of it establishing new animal reservoirs and recombination with native circulating coronaviruses. To screen local animal populations in the United States for exposure to SARS-like coronaviruses, we developed a serological assay using the receptor binding domain (RBD) from SARS-CoV-2. SARS-CoV-2's RBD is antigenically distinct from common human and animal coronaviruses, allowing us to identify animals previously infected with SARS-CoV or SARS-CoV-2. Using an indirect enzyme-linked immunosorbent assay (ELISA) for SARS-CoV-2's RBD, we screened serum from wild and domestic animals for the presence of antibodies against SARS-CoV-2's RBD. Surprisingly prepandemic feline serum samples submitted to the University of Tennessee Veterinary Hospital were ∼50% positive for anti-SARS RBD antibodies. Some of these samples were serologically negative for feline coronavirus (FCoV), raising the question of the etiological agent generating anti-SARS-CoV-2 RBD cross-reactivity. We also identified several white-tailed deer from South Carolina with anti-SARS-CoV-2 antibodies. These results are intriguing, as cross-reactive antibodies toward SARS-CoV-2 RBD have not been reported to date. The etiological agent responsible for seropositivity was not readily apparent, but finding seropositive cats prior to the current SARS-CoV-2 pandemic highlights our lack of information about circulating coronaviruses in other species. IMPORTANCE We report cross-reactive antibodies from prepandemic cats and postpandemic South Carolina white-tailed deer that are specific for that SARS-CoV RBD. There are several potential explanations for this cross-reactivity, each with important implications to coronavirus disease surveillance. Perhaps the most intriguing possibility is the existence and transmission of an etiological agent (such as another coronavirus) with similarity to SARS-CoV-2's RBD region. However, we lack conclusive evidence of prepandemic transmission of a SARS-like virus. Our findings provide impetus for the adoption of a One Health Initiative focusing on infectious disease surveillance of multiple animal species to predict the next zoonotic transmission to humans and future pandemics.
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Affiliation(s)
- Trevor J. Hancock
- Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA
| | - Peyton Hickman
- Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA
| | - Niloo Kazerooni
- Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, Tennessee, USA
| | - Melissa Kennedy
- Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, Tennessee, USA
| | - Stephen A. Kania
- Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, Tennessee, USA
| | - Michelle Dennis
- Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, Tennessee, USA
| | - Nicole Szafranski
- Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, Tennessee, USA
| | - Richard Gerhold
- Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, Tennessee, USA
| | - Chunlei Su
- Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA
| | - Tom Masi
- Graduate School of Medicine, University of Tennessee Medical Center, Knoxville, Tennessee, USA
| | - Stephen Smith
- MEDIC Regional Blood Center, Knoxville, Tennessee, USA
| | - Tim E. Sparer
- Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA
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21
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Rando HM, Brueffer C, Lordan R, Dattoli AA, Manheim D, Meyer JG, Mundo AI, Perrin D, Mai D, Wellhausen N, Gitter A, Greene CS. Molecular and Serologic Diagnostic Technologies for SARS-CoV-2. ARXIV 2022:arXiv:2204.12598v2. [PMID: 35547240 PMCID: PMC9094103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Revised: 04/28/2022] [Indexed: 01/09/2023]
Abstract
The COVID-19 pandemic has presented many challenges that have spurred biotechnological research to address specific problems. Diagnostics is one area where biotechnology has been critical. Diagnostic tests play a vital role in managing a viral threat by facilitating the detection of infected and/or recovered individuals. From the perspective of what information is provided, these tests fall into two major categories, molecular and serological. Molecular diagnostic techniques assay whether a virus is present in a biological sample, thus making it possible to identify individuals who are currently infected. Additionally, when the immune system is exposed to a virus, it responds by producing antibodies specific to the virus. Serological tests make it possible to identify individuals who have mounted an immune response to a virus of interest and therefore facilitate the identification of individuals who have previously encountered the virus. These two categories of tests provide different perspectives valuable to understanding the spread of SARS-CoV-2. Within these categories, different biotechnological approaches offer specific advantages and disadvantages. Here we review the categories of tests developed for the detection of the SARS-CoV-2 virus or antibodies against SARS-CoV-2 and discuss the role of diagnostics in the COVID-19 pandemic.
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Affiliation(s)
- Halie M Rando
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, United States of America; Center for Health AI, University of Colorado School of Medicine, Aurora, Colorado, United States of America · Funded by the Gordon and Betty Moore Foundation (GBMF 4552); the National Human Genome Research Institute (R01 HG010067)
| | | | - Ronan Lordan
- Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-5158, USA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA
| | - Anna Ada Dattoli
- Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - David Manheim
- 1DaySooner, Delaware, United States of America; Risk and Health Communication Research Center, School of Public Health, University of Haifa, Haifa, Israel; Technion, Israel Institute of Technology, Haifa, Israel · Funded by Center for Effective Altruism, Long Term Future Fund
| | - Jesse G Meyer
- Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America · Funded by National Institute of General Medical Sciences (R35 GM142502)
| | - Ariel I Mundo
- Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas, USA
| | - Dimitri Perrin
- School of Computer Science, Queensland University of Technology, Brisbane, Australia; Centre for Data Science, Queensland University of Technology, Brisbane, Australia
| | - David Mai
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, and Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA
| | - Nils Wellhausen
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Anthony Gitter
- Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America; Morgridge Institute for Research, Madison, Wisconsin, United States of America · Funded by John W. and Jeanne M. Rowe Center for Research in Virology
| | - Casey S Greene
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Childhood Cancer Data Lab, Alex's Lemonade Stand Foundation, Philadelphia, Pennsylvania, United States of America; Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, United States of America; Center for Health AI, University of Colorado School of Medicine, Aurora, Colorado, United States of America · Funded by the Gordon and Betty Moore Foundation (GBMF 4552); the National Human Genome Research Institute (R01 HG010067)
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22
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Bartlett ML, Suwanmanee S, Peart Akindele N, Ghimire S, Chan AK, Guo C, Gould SJ, Cox AL, Griffin DE. Continued Virus-Specific Antibody-Secreting Cell Production, Avidity Maturation and B Cell Evolution in Patients Hospitalized with COVID-19. Viral Immunol 2022; 35:259-272. [PMID: 35285743 PMCID: PMC9063170 DOI: 10.1089/vim.2021.0191] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Understanding the development and sustainability of the virus-specific protective immune response to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains incomplete with respect to the appearance and disappearance of virus-specific antibody-secreting cells (ASCs) in circulation. Therefore, we performed cross-sectional and longitudinal analyses of peripheral blood mononuclear cells and plasma collected from 55 hospitalized patients up to 4 months after onset of COVID-19 symptoms. Spike (S)- and nucleocapsid (N)-specific IgM and IgG ASCs appeared within 2 weeks accompanied by flow cytometry increases in double negative plasmablasts consistent with a rapid extrafollicular B cell response. Total and virus-specific IgM and IgG ASCs peaked at 3-4 weeks and were still being produced at 3-4 months accompanied by increasing antibody avidity consistent with a slower germinal center B cell response. N-specific ASCs were produced for longer than S-specific ASCs and avidity maturation was greater for antibody to N than S. Patients with more severe disease produced more S-specific IgM and IgG ASCs than those with mild disease and had higher levels of N- and S-specific antibody. Women had more B cells in circulation than men and produced more S-specific IgA and IgG and N-specific IgG ASCs. Flow cytometry analysis of B cell phenotypes showed an increase in circulating B cells at 4-6 weeks with decreased percentages of switched and unswitched memory B cells. These data indicate ongoing antigen-specific stimulation, maturation, and production of ASCs for several months after onset of symptoms in patients hospitalized with COVID-19.
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Affiliation(s)
- Maggie L. Bartlett
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - San Suwanmanee
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Nadine Peart Akindele
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Shristi Ghimire
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Andy K.P. Chan
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Chenxu Guo
- Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Stephen J. Gould
- Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Andrea L. Cox
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Diane E. Griffin
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
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23
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Yan LN, Liu PP, Li XG, Zhou SJ, Li H, Wang ZY, Shen F, Lu BC, Long Y, Xiao X, Wang ZD, Li D, Han HJ, Yu H, Zhou SH, Lv WL, Yu XJ. Neutralizing Antibodies and Cellular Immune Responses Against SARS-CoV-2 Sustained One and a Half Years After Natural Infection. Front Microbiol 2022; 12:803031. [PMID: 35310397 PMCID: PMC8928406 DOI: 10.3389/fmicb.2021.803031] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 12/20/2021] [Indexed: 12/23/2022] Open
Abstract
Background COVID-19 has caused more than 2.6 billion infections and several million deaths since its outbreak 2 years ago. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population. Methods We collected blood samples from individuals who were from the first wave of the COVID-19 epidemic in Wuhan between December 30, 2019, and February 24, 2020. We analyzed NAbs to SARS-CoV-2 using pseudoviruses and IgG antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) protein using enzyme-linked immunosorbent assay in patients’ sera and determined SARS-CoV-2-specific T-cell responses of patients with ELISpot assays. Results We found that 91.9% (57/62) and 88.9% (40/45) of COVID-19 patients had NAbs against SARS-CoV-2 in a year (10–11 months) and one and a half years (17–18 months), respectively, after the onset of illness, indicating that NAbs against SARS-CoV-2 waned slowly and possibly persisted over a long period time. Over 80% of patients had IgG antibodies to SARS-CoV-2 S and N protein one and a half years after illness onset. Most patients also had robust memory T-cell responses against SARS-CoV-2 one and a half years after the illness. Among the patients, 95.6% (43/45) had an IFN-γ-secreting T-cell response and 93.8% (15/16) had an IL-2-secreting T-cell response. The T-cell responses to SARS-CoV-2 were positively correlated with antibodies (including neutralizing antibodies and IgG antibodies to S and N protein) in COVID-19 patients. Eighty percent (4/5) of neutralizing antibody-negative patients also had SARS-CoV-2-specific T-cell response. After long-term infection, protective immunity was independent of disease severity, sex, and age. Conclusions We concluded that SARS-CoV-2 infection elicited a robust and persistent neutralizing antibody and memory T-cell response in COVID-19 patients, indicating that these sustained immune responses, among most SARS-CoV-2-infected people, may play a crucial role in protection against reinfection.
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Affiliation(s)
- Li-Na Yan
- State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan, China
| | - Pan-Pan Liu
- State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan, China
| | - Xu-Gui Li
- The Department of Clinical Laboratory Medicine, Hubei 672 Orthopaedics Hospital, Wuhan, China
| | - Shi-Jing Zhou
- The Department of Clinical Laboratory Medicine, Hubei 672 Orthopaedics Hospital, Wuhan, China
| | - Hao Li
- The First School of Clinical Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Zhi-Yin Wang
- Department of Clinical Laboratory Medicine, Hubei University of Chinese Medicine Huangjiahu Hospital, Wuhan, China
| | - Feng Shen
- College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, China
| | - Bi-Chao Lu
- Clinical College, Hubei University of Chinese Medicine, Wuhan, China
| | - Yu Long
- Clinical College, Hubei University of Chinese Medicine, Wuhan, China
| | - Xiao Xiao
- State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan, China
| | - Zhen-Dong Wang
- School of Public Health, Xi'an Medical University, Xi'an, China
| | - Dan Li
- State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan, China
| | - Hui-Ju Han
- State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan, China
| | - Hao Yu
- Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch, Galveston, TX, United States
| | - Shu-Han Zhou
- Clinical College, Hubei University of Chinese Medicine, Wuhan, China
| | - Wen-Liang Lv
- Clinical College, Hubei University of Chinese Medicine, Wuhan, China
| | - Xue-Jie Yu
- State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan, China
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Abstract
Severe acute respiratory syndrome coronavirus 2 (COVID)-19 has emerged as the greatest global health threat in generations. An unprecedented mobilization of researchers has generated a wealth of data on humoral responses to SARS-CoV-2 within a year of the pandemic's beginning. The rapidly developed understanding of acute-phase antibody induction and medium-term antibody durability in COVID-19 is important at an individual level to inform patient care and a population level to help predict transmission dynamics. In this brief review, we will describe the development and maintenance of antibody responses to immunization and infections generally and the specific antibody dynamics observed for COVID-19. These crucial features of the humoral response have implications for the use of antibody therapeutics against the virus and can inform the likelihood of reinfection of individuals by the virus.
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Affiliation(s)
- Adam Zuiani
- Department of Medicine, Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA,Department of Medicine, Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA,BioNTech, Cambridge, MA 02139, USA
| | - Duane R. Wesemann
- Department of Medicine, Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA,Department of Medicine, Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA,Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA,Corresponding author. Department of Medicine, Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139
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Slabakova Y, Gerenska D, Ivanov N, Velikova T. Immune titers of protection against severe acute respiratory syndrome coronavirus 2: are we there yet? EXPLORATION OF IMMUNOLOGY 2022:9-24. [DOI: 10.37349/ei.2022.00033] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 01/04/2022] [Indexed: 11/30/2024]
Abstract
A few pieces of research exist about the protective titer against severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2; SARS-CoV-2) in monkeys and humans in which the protection could be shown as dose-dependent. Early studies supposed that higher levels of pre-existing neutralizing antibodies (Nabs) against SARS-CoV-2 can potentially correlate with the protection to consequent infection. The data so far showed that cellular immunity is as essential as the humoral one. If needed, its presence can be beneficial if the titer of immunoglobulins is not optimal. It is also known that the immune response to the vaccine is similar to the one after natural infection with a production of very high naturalization titers antibodies. However, medical community is still unaware of the immunoglobulin titer needed for protection against the virus. The answers to the questions regarding correlates of protection are yet to be discovered. Still, no studies indicate a specific virus-Nab titer, so one can assume a patient is protected from being infected in the future. The evoked immunological response is indeed encouraging, but a future investigation is needed. Nonetheless, it remains a mystery how long the immunity lasts and whether it will be enough to shield the patients in the long run. Therefore, identifying immune protection correlations, including neutralization titer of antibodies and T cell immune response against SARS-CoV-2, could give a clue. Unfortunately, recent studies in the field have been more controversial than concise, and the data available is far from consensus.
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Affiliation(s)
- Yoanna Slabakova
- Medical University-Sofia; Blvd. “Akademik Ivan Evstratiev Geshov” 15, 1431 Sofia, Bulgaria
| | - Dilyana Gerenska
- Department of Pharmacovigilance, Blvd. “Tsarigradsko shoes” 115G, 1784 Sofia, Bulgaria
| | - Nedelcho Ivanov
- Department of Clinical Immunology, University Hospital Alexandrovska, Sveti Georgi Sofiyski 1, 1431 Sofia, Bulgaria; Medical University-Sofia, Sofia, Bulgaria
| | - Tsvetelina Velikova
- Department of Clinical Immunology, University Hospital Lozenetz, Kozyak 1 str, 1407 Sofia, Bulgaria; Sofia University St. Kliment Ohridski, Sofia, Bulgaria
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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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Canto e Castro L, Gomes A, Serrano M, Pereira AHG, Ribeiro R, Napoleão P, Domingues I, Silva C, Fanczal J, Afonso Â, Lopes A, Toader I, de Sousa MJR, de Sousa JGR, de Sousa G, Mota MM, Silva‐Santos B, Veldhoen M, Ribeiro RM. Longitudinal SARS-CoV-2 seroprevalence in Portugal and antibody maintenance 12 months after infection. Eur J Immunol 2022; 52:149-160. [PMID: 34695227 PMCID: PMC8646574 DOI: 10.1002/eji.202149619] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/01/2021] [Accepted: 10/22/2021] [Indexed: 11/10/2022]
Abstract
During the COVID-19 pandemic, Portugal has experienced three distinct SARS-CoV-2 infection waves. We previously documented the prevalence of SARS-CoV-2 immunity, measured by specific antibodies, in September 2020, 6 months after the initial moderate wave. Here, we show the seroprevalence changes 6 months later, up to the second week of March 2021, shortly following the third wave, which was one of the most severe in the world, and 2 months following the start of the vaccination campaign. A longitudinal epidemiological study was conducted, with a stratified quota sample of the Portuguese population. Serological testing was performed, including ELISA determination of antibody class and titers. The proportion of seropositives, which was 2.2% in September 2020, rose sharply to 17.3% (95% CI: 15.8-18.8%) in March 2021. Importantly, circulating IgG and IgA antibody levels were very stable 6 months after the initial determination and up to a year after initial infection, indicating long-lasting infection immunity against SARS-CoV-2. Moreover, vaccinated people had higher IgG levels from 3 weeks post-vaccination when compared with previously infected people at the same time post-infection.
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Affiliation(s)
- Luísa Canto e Castro
- Faculdade de Ciências, Centro de Estatística e Aplicações e Fundação Francisco Manuel dos SantosUniversidade de LisboaLisbonPortugal
| | - Andreia Gomes
- Instituto de Medicina MolecularFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
| | - Marta Serrano
- Instituto de Medicina MolecularFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
| | | | - Rita Ribeiro
- Centro de Medicina Laboratorial Germano de SousaLisbonPortugal
| | - Patrícia Napoleão
- Instituto de Medicina MolecularFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
| | - Inês Domingues
- Instituto de Medicina MolecularFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
| | - Cláudia Silva
- Instituto de Medicina MolecularFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
| | - Júlia Fanczal
- Instituto de Medicina MolecularFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
| | - Ângela Afonso
- Instituto de Medicina MolecularFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
| | - Andreia Lopes
- Instituto de Medicina MolecularFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
| | - Ionela Toader
- Instituto de Medicina MolecularFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
| | | | | | | | - Maria M. Mota
- Instituto de Medicina MolecularFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
| | - Bruno Silva‐Santos
- Instituto de Medicina MolecularFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
| | - Marc Veldhoen
- Instituto de Medicina MolecularFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
| | - Ruy M. Ribeiro
- Instituto de Medicina MolecularFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
- Laboratório de Biomatemática, Instituto de Saúde AmbientalFaculdade de MedicinaUniversidade de LisboaLisbonPortugal
- Theoretical Biology and BiophysicsLos Alamos National LaboratoryNew MexicoUSA
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Peart Akindele N, Pieterse L, Suwanmanee S, Griffin DE. OUP accepted manuscript. J Infect Dis 2022; 226:822-832. [PMID: 35436340 PMCID: PMC9047220 DOI: 10.1093/infdis/jiac119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 04/15/2022] [Indexed: 11/23/2022] Open
Abstract
Multisystem inflammatory syndrome in children (MIS-C) can complicate infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but differences in the immune responses during MIS-C compared to coronavirus disease 2019 (COVID-19) are poorly understood. We longitudinally compared the amounts and avidity of plasma anti-nucleocapsid (N) and spike (S) antibodies, phenotypes of B cells, and numbers of virus-specific antibody-secreting cells in circulation of children hospitalized with COVID-19 (n = 10) and with MIS-C (n = 12). N-specific immunoglobulin G (IgG) was higher early after presentation for MIS-C than COVID-19 patients and avidity of N- and S-specific IgG at presentation did not mature further during follow-up as it did for COVID-19. Both groups had waning proportions of B cells in circulation and decreasing but sustained production of virus-specific antibody-secreting cells for months. Overall, B-cell responses were similar, but those with MIS-C demonstrated a more mature antibody response at presentation compared to COVID-19, suggesting a postinfectious entity.
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Affiliation(s)
- Nadine Peart Akindele
- Present affiliations: United States Food and Drug Administration, Silver Spring, Maryland, USA
| | - Lisa Pieterse
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | | | - Diane E Griffin
- Correspondence: Diane E. Griffin, MD, PhD, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Rm E5636, Baltimore, MD 21205, USA ()
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Alefishat E, Jelinek HF, Mousa M, Tay GK, Alsafar HS. Immune response to SARS-CoV-2 Variants: A focus on severity, susceptibility, and preexisting immunity. J Infect Public Health 2022; 15:277-288. [PMID: 35074728 PMCID: PMC8757655 DOI: 10.1016/j.jiph.2022.01.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 11/16/2021] [Accepted: 01/09/2022] [Indexed: 01/08/2023] Open
Abstract
The heterogeneous phenotypes among patients with coronavirus disease 2019 (COVID-19) has drawn worldwide attention, especially those with severe symptoms without comorbid conditions. Immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative virus of COVID-19, occur mainly by the innate immune response via the interferon (IFN)-mediated pathways, and the adaptive immunity via the T lymphocyte and the antibody mediated pathways. The ability of the original Wuhan SARS-CoV-2 strain, and possibly more so with new emerging variants, to antagonize IFN-mediated antiviral responses can be behind the higher early viral load, higher transmissibility, and milder symptoms compared to SARS-CoV and are part of the continued clinical evolution of COVID-19. Since it first emerged, several variants of SARS-CoV-2 have been circulating worldwide. Variants that have the potential to elude natural or vaccine-mediated immunity are variants of concern. This review focuses on the main host factors that may explain the immune responses to SARS-CoV-2 and its variants in the context of susceptibility, severity, and preexisting immunity.
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Affiliation(s)
- Eman Alefishat
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; Department of Pharmacology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan
| | - Herbert F Jelinek
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; Department of Biomedical Engineering, College of Engineering, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; Center of Heath Engineering Innovation, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Mira Mousa
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; Nuffield Department of Women's and Reproduction Health, Oxford University, Oxford, United Kingdom
| | - Guan K Tay
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; Discipline of Psychiatry, Medical School, the University of Western Australia, Perth WA, Australia; School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
| | - Habiba S Alsafar
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; Department of Biomedical Engineering, College of Engineering, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; Department of Genetics and Molecular Biology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; Emirates Bio-Research Center, Ministry of Interior, Abu Dhabi, United Arab Emirates.
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Veenhuis RT, Zeiss CJ. Animal Models of COVID-19 II. Comparative Immunology. ILAR J 2021; 62:17-34. [PMID: 33914873 PMCID: PMC8135340 DOI: 10.1093/ilar/ilab010] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 12/03/2020] [Accepted: 12/20/2020] [Indexed: 12/22/2022] Open
Abstract
Developing strong animal models is essential for furthering our understanding of how the immune system functions in response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The alarming speed at which SARS-CoV-2 has spread, and the high mortality rate of severe Coronavirus Disease 2019 (COVID-19), has required both basic science and clinical research to move at an unprecedented pace. Models previously developed to study the immune response against SARS-CoV have been rapidly deployed to now study SARS-CoV-2. To date, both small and large animal models are remarkably consistent when infected with SARS-CoV-2; however, certain models have proven more useful when answering specific immunological questions than others. Small animal models, such as Syrian hamsters, ferrets, and mice carrying the hACE2 transgene, appear to reliably recapitulate the initial cytokine surge seen in COVID-19 as well as show significant innate and adaptive cell infiltration in to the lung early in infection. Additionally, these models develop strong antibody responses to the virus, are protected from reinfection, and genetically modified versions exist that can be used to ask specific immunological questions. Large animal models such as rhesus and cynomologus macaques and African green monkeys are critical to understanding how the immune system responds to SARS-CoV-2 infection because they are considered to be the most similar to humans. These models are considered the gold standard for assessing vaccine efficacy and protection, and recapitulate the initial cytokine surge, immune cell infiltration into the lung, certain aspects of thrombosis, and the antibody and T-cell response to the virus. In this review, we discuss both small and large animal model studies previously used in SARS-CoV-2 research that may be useful in elucidating the immunological contributions to hallmark syndromes observed with COVID-19.
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Affiliation(s)
- Rebecca T Veenhuis
- Department of Molecular and Comparative Pathobiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Caroline J Zeiss
- Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
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31
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SARS-CoV-2 and Variant Diagnostic Testing Approaches in the United States. Viruses 2021; 13:v13122492. [PMID: 34960762 PMCID: PMC8703625 DOI: 10.3390/v13122492] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 11/29/2021] [Accepted: 12/08/2021] [Indexed: 12/23/2022] Open
Abstract
Purpose of Review Given the rapid development of diagnostic approaches to test for and diagnose infection with SARS-CoV-2 and its associated variants including Omicron (B.1.1.529), many options are available to diagnose infection. Multiple established diagnostic companies are now providing testing platforms whereas initially, testing was being performed with simple PCR-based tests using standard laboratory reagents. Recent Findings Additional testing platforms continue to be developed, including those to detect specific variants, but challenges with testing, including obtaining testing reagents and other related supplies, are frequently encountered. With time, the testing supply chain has improved, and more established companies are providing materials to support these testing efforts. In the United States (U.S.), the need for rapid assay development and subsequent approval through the attainment of emergency use authorization (EUA) has superseded the traditional arduous diagnostic testing approval workflow mandated by the FDA. Through these efforts, the U.S. has been able to continue to significantly increase its testing capabilities to address this pandemic; however, challenges still remain due to the diversity of the performance characteristics of tests being utilized and newly discovered viral variants. Summary This review provides an overview of the current diagnostic testing landscape, with pertinent information related to SARS-CoV-2 virology, variants and antibody responses that are available to diagnose infection in the U.S.
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Zhou F, Tao M, Shang L, Liu Y, Pan G, Jin Y, Wang L, Hu S, Li J, Zhang M, Fu Y, Yang S. Assessment of Sequelae of COVID-19 Nearly 1 Year After Diagnosis. Front Med (Lausanne) 2021; 8:717194. [PMID: 34888318 PMCID: PMC8649686 DOI: 10.3389/fmed.2021.717194] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 10/25/2021] [Indexed: 12/12/2022] Open
Abstract
Background: A previous study has shown that 81% of the COVID-19 patients had mild or moderate symptoms. However, most studies on the sequelae in COVID-19 patients focused on severe cases and the long-term follow-up studies on the health consequences in non-severe cases are limited. The current study aimed to assess the sequelae of COVID-19 in patients nearly 1 year after diagnosis with a particular focus on the recovery of patients with non-severe COVID-19. Methods: We enrolled 120 patients infected with SARS-CoV-2 discharged from Wuhan Union hospital west district (designated hospital for COVID-19) and Fangcang shelter hospitals between January 29, 2020 and April 1, 2020. All participants were asked to complete a series of questionnaires to assess their symptoms and quality of life and for psychological evaluation. Also, pulmonary function test, chest CT, 6-min walking test (6MWT), routine blood test, liver and kidney function tests, fasting blood glucose test, lipid test, and immunoglobulin G antibody test were performed to evaluate their health. Results: The mean age of the study population was 51.6 ± 10.8 years. Of the 120 patients, 104 (86.7%) were cases of non-severe COVID-19. The follow-up study was performed between November 23, 2020 and January 11, 2021, and the median time between the diagnosis and the follow-up was 314.5 (IQR, 296–338) days. Sleep difficulties, shortness of breath, fatigue, and joint pain were common symptoms observed during follow-up and nearly one-third of the non-severe cases had these symptoms. A total of 50 (41.7%) and 45 (37.5%) patients reported anxiety and depression, respectively. And 18.3% of the patients showed negative results in the IgG test at the follow-up, which correlated with the severity of the infection (R = 0.203, p = 0.026), and the proportion of IgG negative cases in non-severe COVID-19 patients was higher than that in the severe cases (20.2 vs. 6.3%). Pulmonary diffusion impairment was reported in 30 (26.1%) out of 115 patients, and 24 (24.2%) out of the 99 non-severe cases. The values of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FVC/FEV1, vital capacity (VC), total lung capacity (TLC), and residual volume (RV) were less than the normal range in 1.7, 8.6, 0.9, 11.2, 7.0, and 0.9% of the patients, respectively. A total of 55 (56.7%) out of the 97 patients showed abnormal CT findings, including ground-glass opacities (GGO), bronchiectasis, nodules, lines and bands, and fibrosis. Furthermore, there was a correlation between all the SF-36-domain scores and the duration of hospitalization, pulmonary function, and a 6MWT. Conclusions: At the nearly 1-year follow-up, COVID-19 survivors still had multi-system issues, including those in the respiratory functioning, radiography, quality of life, and anxiety and depression. Moreover, non-severe cases also showed some sequelae and the proportion of IgG negative cases in the non-severe patients was higher than that in severe cases. Therefore, conducting follow-ups and preventing the reinfection of SARS-CoV-2 in this group is necessary.
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Affiliation(s)
- Fangyuan Zhou
- Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Meihui Tao
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Luorui Shang
- Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuhan Liu
- Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Guangtao Pan
- Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yan Jin
- Department of Emergency, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Wang
- Department of Emergency, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shaoke Hu
- Department of Medical Engineering, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jinxiao Li
- Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mengqi Zhang
- Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu Fu
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shenglan Yang
- Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Anderson RM, Vegvari C, Hollingsworth TD, Pi L, Maddren R, Ng CW, Baggaley RF. The SARS-CoV-2 pandemic: remaining uncertainties in our understanding of the epidemiology and transmission dynamics of the virus, and challenges to be overcome. Interface Focus 2021; 11:20210008. [PMID: 34956588 PMCID: PMC8504893 DOI: 10.1098/rsfs.2021.0008] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/14/2021] [Indexed: 12/11/2022] Open
Abstract
Great progress has been made over the past 18 months in scientific understanding of the biology, epidemiology and pathogenesis of SARS-CoV-2. Extraordinary advances have been made in vaccine development and the execution of clinical trials of possible therapies. However, uncertainties remain, and this review assesses these in the context of virus transmission, epidemiology, control by social distancing measures and mass vaccination and the effect on all of these on emerging variants. We briefly review the current state of the global pandemic, focussing on what is, and what is not, well understood about the parameters that control viral transmission and make up the constituent parts of the basic reproductive number R 0. Major areas of uncertainty include factors predisposing to asymptomatic infection, the population fraction that is asymptomatic, the infectiousness of asymptomatic compared to symptomatic individuals, the contribution of viral transmission of such individuals and what variables influence this. The duration of immunity post infection and post vaccination is also currently unknown, as is the phenotypic consequences of continual viral evolution and the emergence of many viral variants not just in one location, but globally, given the high connectivity between populations in the modern world. The pattern of spread of new variants is also examined. We review what can be learnt from contact tracing, household studies and whole-genome sequencing, regarding where people acquire infection, and how households are seeded with infection since they constitute a major location for viral transmission. We conclude by discussing the challenges to attaining herd immunity, given the uncertainty in the duration of vaccine-mediated immunity, the threat of continued evolution of the virus as demonstrated by the emergence and rapid spread of the Delta variant, and the logistics of vaccine manufacturing and delivery to achieve universal coverage worldwide. Significantly more support from higher income countries (HIC) is required in low- and middle-income countries over the coming year to ensure the creation of community-wide protection by mass vaccination is a global target, not one just for HIC. Unvaccinated populations create opportunities for viral evolution since the net rate of evolution is directly proportional to the number of cases occurring per unit of time. The unit for assessing success in achieving herd immunity is not any individual country, but the world.
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Affiliation(s)
- Roy M. Anderson
- Department of Infectious Disease Epidemiology, Imperial College London, London, UK
| | - Carolin Vegvari
- Department of Infectious Disease Epidemiology, Imperial College London, London, UK
| | - T. Déirdre Hollingsworth
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
- Joint Universities Pandemic and Epidemiological Research (JUNIPER) consortium, University of Leicester, Leicester, UK
| | - Li Pi
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
- Joint Universities Pandemic and Epidemiological Research (JUNIPER) consortium, University of Leicester, Leicester, UK
| | - Rosie Maddren
- Department of Infectious Disease Epidemiology, Imperial College London, London, UK
| | - Chi Wai Ng
- Department of Infectious Disease Epidemiology, Imperial College London, London, UK
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Nimavat J, Mootapally C, Nathani NM, Dave D, Kher MN, Mahajan MS, Joshi CG, Bhatt VD. Evolutionary and Antigenic Profiling of the Tendentious D614G Mutation of SARS-CoV-2 in Gujarat, India. Front Genet 2021; 12:764927. [PMID: 34858480 PMCID: PMC8632030 DOI: 10.3389/fgene.2021.764927] [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: 08/26/2021] [Accepted: 10/18/2021] [Indexed: 11/24/2022] Open
Abstract
Humankind has suffered many pandemics in history including measles, SARS, MERS, Ebola, and recently the novel Coronavirus disease caused by SARS-CoV-2. As of September 2021, it has affected over 200 million people and caused over 4 million deaths. India is the second most affected country in the world. Up to this date, more than 38 Lakh viral genomes have been submitted to public repositories like GISAID and NCBI to analyze the virus phylogeny and mutations. Here, we analyzed 2349 genome sequences of SARS-CoV-2 submitted in GISAID by a single institute pertaining to infections from the Gujarat state to know their variants and phylogenetic distributions with a major focus on the spike protein. More than 93% of the genomes had one or more mutations in the spike glycoprotein. The D614G variant in spike protein is reported to have a very high frequency of >95% globally followed by the L452R and P681R, thus getting significant attention. The antigenic propensity of a small peptide of 29 residues from 597 to 625 of the spike protein variants having D614 and G614 showed that G614 has a little higher antigenic propensity. Thus, the D614G is the cause for higher viral antigenicity, however, it has not been reported to be effective to be causing more deaths.
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Affiliation(s)
- Jay Nimavat
- Department of Pharmaceutical Sciences, Saurashtra University, Rajkot, India
| | - Chandrashekar Mootapally
- School of Applied Sciences and Technology (GTU-SAST), Gujarat Technological University, Ahmedabad, India
| | - Neelam M Nathani
- School of Applied Sciences and Technology (GTU-SAST), Gujarat Technological University, Ahmedabad, India
| | - Devyani Dave
- Department of Pharmaceutical Sciences, Saurashtra University, Rajkot, India
| | | | - Mayur S Mahajan
- Atal Incubation Centre, Gujarat Technological University, Ahmedabad, India
| | - Chaitanya G Joshi
- Gujarat Biotechnology Research Centre, Department of Science and Technology, Gandhinagar, India
| | - Vaibhav D Bhatt
- School of Applied Sciences and Technology (GTU-SAST), Gujarat Technological University, Ahmedabad, India.,Atal Incubation Centre, Gujarat Technological University, Ahmedabad, India
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35
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Gaudreault NN, Carossino M, Morozov I, Trujillo JD, Meekins DA, Madden DW, Cool K, Artiaga BL, McDowell C, Bold D, Balaraman V, Kwon T, Ma W, Henningson J, Wilson DW, Wilson WC, Balasuriya UBR, García-Sastre A, Richt JA. Experimental re-infected cats do not transmit SARS-CoV-2. Emerg Microbes Infect 2021; 10:638-650. [PMID: 33704016 PMCID: PMC8023599 DOI: 10.1080/22221751.2021.1902753] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/09/2021] [Accepted: 03/10/2021] [Indexed: 12/12/2022]
Abstract
SARS-CoV-2 is the causative agent of COVID-19 and responsible for the current global pandemic. We and others have previously demonstrated that cats are susceptible to SARS-CoV-2 infection and can efficiently transmit the virus to naïve cats. Here, we address whether cats previously exposed to SARS-CoV-2 can be re-infected with SARS-CoV-2. In two independent studies, SARS-CoV-2-infected cats were re-challenged with SARS-CoV-2 at 21 days post primary challenge (DPC) and necropsies performed at 4, 7 and 14 days post-secondary challenge (DP2C). Sentinels were co-mingled with the re-challenged cats at 1 DP2C. Clinical signs were recorded, and nasal, oropharyngeal, and rectal swabs, blood, and serum were collected and tissues examined for histologic lesions. Viral RNA was transiently shed via the nasal, oropharyngeal and rectal cavities of the re-challenged cats. Viral RNA was detected in various tissues of re-challenged cats euthanized at 4 DP2C, mainly in the upper respiratory tract and lymphoid tissues, but less frequently and at lower levels in the lower respiratory tract when compared to primary SARS-CoV-2 challenged cats at 4 DPC. Viral RNA and antigen detected in the respiratory tract of the primary SARS-CoV-2 infected cats at early DPCs were absent in the re-challenged cats. Naïve sentinels co-housed with the re-challenged cats did not shed virus or seroconvert. Together, our results indicate that cats previously infected with SARS-CoV-2 can be experimentally re-infected with SARS-CoV-2; however, the levels of virus shed was insufficient for transmission to co-housed naïve sentinels. We conclude that SARS-CoV-2 infection in cats induces immune responses that provide partial, non-sterilizing immune protection against re-infection.
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Affiliation(s)
- Natasha N. Gaudreault
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Mariano Carossino
- Louisiana Animal Disease Diagnostic Laboratory and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA
| | - Igor Morozov
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Jessie D. Trujillo
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - David A. Meekins
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Daniel W. Madden
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Konner Cool
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Bianca Libanori Artiaga
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Chester McDowell
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Dashzeveg Bold
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Velmurugan Balaraman
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Taeyong Kwon
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Wenjun Ma
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
- Department of Veterinary Pathobiology and Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, USA
| | - Jamie Henningson
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Dennis W. Wilson
- Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA
| | - William C. Wilson
- Arthropod Borne Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Manhattan, KS, USA
| | - Udeni B. R. Balasuriya
- Louisiana Animal Disease Diagnostic Laboratory and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA
| | - Adolfo García-Sastre
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Juergen A. Richt
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
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36
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Bontzos G, Gkiala A, Karakosta C, Maliotis N, Detorakis ET. COVID-19 in Ophthalmology. Current Disease Status and Challenges during Clinical Practice. MAEDICA 2021; 16:668-680. [PMID: 35261670 PMCID: PMC8897783 DOI: 10.26574/maedica.2020.16.4.668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Purpose: The novel coronavirus disease 2019 (COVID-19) has raised a global public health concern. The purpose of this review is to summarize the evidence currently available on COVID-19 for its ocular implications and manifestations from both pathogenetic and clinical standpoints. Methods: For this narrative review, more than 100 relevant scientific articles were considered from various databases (PubMed, Google Scholar, and Science Direct) using keywords such as coronavirus outbreak, COVID-19, ophthalmology, ocular symptoms. Results:Daily healthcare both from patient and physician perspective, as well as on some guidelines regarding prevention and management have dramatically changed over the last few months. Although COVID-19 infection mainly affects the respiratory system as well as the gastrointestinal, cardiovascular, and urinary systems, it may cause a wide spectrum of ocular manifestations. Various challenges have to be faced to minimize exposure for both patients and physicians. Conclusion:The risk of COVID-19 infection should be considered and medical care should be prioritized for urgent cases. Appropriate management for patients with chronic cases that may result in adverse outcomes should not be neglected, while patients that can be monitored remotely should be identified.
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Affiliation(s)
- Georgios Bontzos
- Department of Ophthalmology, 'Korgialenio-Benakio' General Hospital, 11526 Athens, Greece
| | - Anastasia Gkiala
- Department of Ophthalmology, 'Korgialenio-Benakio' General Hospital, 11526 Athens, Greece
| | - Christina Karakosta
- Department of Ophthalmology, 'Korgialenio-Benakio' General Hospital, 11526 Athens, Greece
| | - Neofytos Maliotis
- Department of Ophthalmology, General Hospital of Nikaia "Agios Panteleimon", 18454 Athens, Greece
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Li H, Zhang Y, Li D, Deng YQ, Xu H, Zhao C, Liu J, Wen D, Zhao J, Li Y, Wu Y, Liu S, Liu J, Hao J, Yuan F, Duo S, Qin CF, Zheng A. Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein. Signal Transduct Target Ther 2021; 6:389. [PMID: 34759261 PMCID: PMC8578532 DOI: 10.1038/s41392-021-00797-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 10/09/2021] [Accepted: 10/18/2021] [Indexed: 12/14/2022] Open
Abstract
SARS-CoV-2 and SARS-CoV are genetically related coronavirus and share the same cellular receptor ACE2. By replacing the VSV glycoprotein with the spikes (S) of SARS-CoV-2 and SARS-CoV, we generated two replication-competent recombinant viruses, rVSV-SARS-CoV-2 and rVSV-SARS-CoV. Using wild-type and human ACE2 (hACE2) knock-in mouse models, we found a single dose of rVSV-SARS-CoV could elicit strong humoral immune response via both intranasal (i.n.) and intramuscular (i.m.) routes. Despite the high genetic similarity between SARS-CoV-2 and SARS-CoV, no obvious cross-neutralizing activity was observed in the immunized mice sera. In macaques, neutralizing antibody (NAb) titers induced by one i.n. dose of rVSV-SARS-CoV-2 were eight-fold higher than those by a single i.m. dose. Thus, our data indicates that rVSV-SARS-CoV-2 might be suitable for i.n. administration instead of the traditional i.m. immunization in human. Because rVSV-SARS-CoV elicited significantly stronger NAb responses than rVSV-SARS-CoV-2 in a route-independent manner, we generated a chimeric antigen by replacing the receptor binding domain (RBD) of SARS-CoV S with that from the SARS-CoV-2. rVSV expressing the chimera (rVSV-SARS-CoV/2-RBD) induced significantly increased NAbs against SARS-CoV-2 in mice and macaques than rVSV-SARS-CoV-2, with a safe Th1-biased response. Serum immunized with rVSV-SARS-CoV/2-RBD showed no cross-reactivity with SARS-CoV. hACE2 mice receiving a single i.m. dose of either rVSV-SARS-CoV-2 or rVSV-SARS-CoV/2-RBD were fully protected against SARS-CoV-2 challenge without obvious lesions in the lungs. Our results suggest that transplantation of SARS-CoV-2 RBD into the S protein of SARS-CoV might be a promising antigen design for COVID-19 vaccines.
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Affiliation(s)
- Hongyue Li
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
- CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, 100101, Beijing, China
| | - Yuhang Zhang
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
- CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, 100101, Beijing, China
| | - Dong Li
- Shenzhen Kangtai, Biotechnology Co., Ltd, 518106, Shenzhen, Guangdong, China
| | - Yong-Qiang Deng
- State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, 100071, Beijing, China
| | - Hongde Xu
- School of Pharmaceutical Sciences, Zhengzhou University, 450001, Zhengzhou, Henan, China
| | - Chaoyue Zhao
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
- CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, 100101, Beijing, China
| | - Jiandong Liu
- Shenzhen Kangtai, Biotechnology Co., Ltd, 518106, Shenzhen, Guangdong, China
| | - Dan Wen
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
- CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, 100101, Beijing, China
| | - Jianguo Zhao
- State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
| | - Yongchun Li
- School of Pharmaceutical Sciences, Zhengzhou University, 450001, Zhengzhou, Henan, China
| | - Yong Wu
- Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, 102629, Beijing, China
| | - Shujun Liu
- Laboratory Animal Center, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
| | - Jiankai Liu
- Shenzhen Kangtai, Biotechnology Co., Ltd, 518106, Shenzhen, Guangdong, China
| | - Junfeng Hao
- Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China
| | - Fei Yuan
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
| | - Shuguang Duo
- Laboratory Animal Center, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
| | - Cheng-Feng Qin
- State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, 100071, Beijing, China.
| | - Aihua Zheng
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
- CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, 100101, Beijing, China.
- College of Life Science, Henan Normal University, 453007, Xinxiang, China.
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38
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Thomas E, Delabat S, Andrews DM. Diagnostic Testing for SARS-CoV-2 Infection. CURRENT HEPATOLOGY REPORTS 2021; 20:166-174. [PMID: 34725630 PMCID: PMC8550867 DOI: 10.1007/s11901-021-00567-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 08/14/2021] [Indexed: 12/22/2022]
Abstract
PURPOSE OF REVIEW Given the rapid development of diagnostic approaches to test for and diagnose infection with SARS-CoV-2, many options are available to assess infection. Multiple established diagnostic companies are now providing testing platforms whereas initially, testing was being performed with simple PCR-based tests using standard laboratory reagents. RECENT FINDINGS Additional testing platforms continue to be developed but challenges with testing, including obtaining testing reagents and other related supplies, are frequently encountered. With time, the testing supply chain will improve and more companies will be providing materials to support these testing efforts. In the USA, the need for rapid assay development and subsequent approval through attainment of emergency use authorization (EUA) has superseded the traditional arduous diagnostic testing approval workflow mandated by the FDA. It is anticipated that the USA will be able to continue to significantly increase its testing capabilities to address this pandemic; however, challenges remain due to the diversity of the performance characteristics of tests being utilized. SUMMARY This review provides an overview of the current diagnostic testing landscape, with pertinent information related to SARS-CoV-2 virology and antibody responses, that is available to diagnose infection.
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Affiliation(s)
- Emmanuel Thomas
- Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL USA
- Schiff Center for Liver Disease, University of Miami Miller School of Medicine, 1550 NW 10th Ave., Papanicolaou Bldg., RM PAP 514, Miami, FL 33136 USA
| | - Stephanie Delabat
- Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL USA
| | - David M. Andrews
- Department of Pathology, University of Miami Miller School of Medicine, Miami, FL USA
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39
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Hagihara M, Ohara S, Uchida T, Inoue M. Practical management of patients with hematological diseases during the COVID-19 pandemic in Japan. Int J Hematol 2021; 114:709-718. [PMID: 34669154 PMCID: PMC8527309 DOI: 10.1007/s12185-021-03175-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 06/09/2021] [Indexed: 12/15/2022]
Abstract
Polymerase chain reaction (PCR) tests cannot always detect the SARS-CoV-2 virus, possibly due to differences in sensitivity between sample types. Under these circumstances, immunochromatography may serve as an alternative method to detect anti-SARS-CoV-2 IgG antibodies that indicate a history of infection. In our analysis of patients with severe COVID-19 infection, we found that 14 of 19 serum samples were positive for IgG antibodies, whereas 6 of 10 samples from patients with asymptomatic or mild cases were negative. Two patients with immune thrombocytopenia who were treated with prednisolone experienced aggressive COVID-19-related respiratory failure and eventually died. Patients not in remission and those who received steroid-based chemotherapy had a higher risk of death, and patients with lymphoid malignancies including lymphoma and myeloma died in larger numbers than those with myeloid malignancies. A stricter cohorting strategy based on repeat PCR tests or isolation to a private room should be adopted in routine care in hematology departments to prevent viral spread to the environment.
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40
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Durand GA, de Laval F, de Bonet d'Oléon A, Le Flem FX, Morin Y, Badaut C, Grard G, Brossier C, Fossier M, Dia A, Letois F, Geulen M, Piorkowski G, Meynard JB, Peduzzi F, Leparc-Goffart I, Pommier de Santi V. COVID-19 outbreak among French firefighters, Marseille, France, 2020. ACTA ACUST UNITED AC 2021; 26. [PMID: 34651571 PMCID: PMC8518307 DOI: 10.2807/1560-7917.es.2021.26.41.2001676] [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] [Indexed: 01/19/2023]
Abstract
We investigated a COVID-19 outbreak at a fire station in Marseille, France. Confirmed cases were defined as individuals with positive SARS-CoV-2 reverse transcription (RT)-PCR and/or neutralising antibodies. All 85 firefighters at work during the outbreak period were included after questioning and sampled for RT-PCR and viral neutralisation assay. Twenty-three firefighters were confirmed positive, 19 of them were symptomatic, and four asymptomatic cases were confirmed by virus neutralisation. A total of 22 firefighters had specific neutralising antibodies against SARS-CoV-2. Neutralising antibodies were found in four asymptomatic and 18 symptomatic cases. Eleven symptomatic cases had high titres (≥ 1:80). The earliest detection of neutralising antibodies was 7 days after symptom onset, and 80% had neutralising antibodies 15 days after onset. One viral culture was positive 13 days after onset. The attack rate was 27%. We identified two introductions of the virus in this outbreak, through a presymptomatic and a paucisymptomatic case. Asymptomatic cases were not the source of a third generation of cases, although they worked without wearing a mask, indicating that asymptomatic cases did not play a significant role in this outbreak. Management and strategy based on early research of clinical signs associated with self-quarantine was effective.
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Affiliation(s)
- Guillaume André Durand
- French Armed Forces Biomedical Research Institute, National Reference Laboratory for Arboviruses, Marseille, France.,Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207), Marseille, France
| | - Franck de Laval
- French Military Health Service, French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France.,Aix-Marseille University, INSERM, IRD, SESSTIM (Economic and Social Sciences, Health Systems, and Medical Informatics), Marseille, France
| | - Albane de Bonet d'Oléon
- French Military Health Service, French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France
| | - François Xavier Le Flem
- Marseille Battalion of Navy Firefighters, 9 boulevard de Strasbourg, 13233 Marseille Cedex 20, France
| | - Yann Morin
- French Military Health Service, French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France
| | - Cyril Badaut
- Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207), Marseille, France.,Microbiology and Infectious Diseases Department, Institut de Recherche Biomédicale des Armées (IRBA), Brétigny-sur-Orge Cedex, France
| | - Gilda Grard
- French Armed Forces Biomedical Research Institute, National Reference Laboratory for Arboviruses, Marseille, France.,Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207), Marseille, France
| | - Constance Brossier
- French Military Health Service, French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France
| | - Marion Fossier
- French Military Health Service, French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France
| | - Aissata Dia
- French Military Health Service, French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France
| | - Flavie Letois
- French Military Health Service, French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France
| | - Manon Geulen
- French Armed Forces Biomedical Research Institute, National Reference Laboratory for Arboviruses, Marseille, France.,Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207), Marseille, France
| | - Géraldine Piorkowski
- Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207), Marseille, France
| | - Jean-Baptiste Meynard
- French Military Health Service, French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France
| | - Frank Peduzzi
- Marseille Battalion of Navy Firefighters, 9 boulevard de Strasbourg, 13233 Marseille Cedex 20, France
| | - Isabelle Leparc-Goffart
- French Armed Forces Biomedical Research Institute, National Reference Laboratory for Arboviruses, Marseille, France.,Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207), Marseille, France
| | - Vincent Pommier de Santi
- French Military Health Service, French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France.,University Hospital Institute Méditerranée Infection, Marseille, France.,Aix-Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France
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41
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Hristov DR, Gomez-Marquez J, Wade D, Hamad-Schifferli K. SARS-CoV-2 and approaches for a testing and diagnostic strategy. J Mater Chem B 2021; 9:8157-8173. [PMID: 34494642 DOI: 10.1039/d1tb00674f] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The COVID-19 pandemic has led to an unprecedented global health challenge, creating sudden, massive demands for diagnostic testing, treatment, therapies, and vaccines. In particular, the development of diagnostic assays for SARS-CoV-2 has been pursued as they are needed for quarantine, disease surveillance, and patient treatment. One of the major lessons the pandemic highlighted was the need for fast, cheap, scalable and reliable diagnostic methods, such as paper-based assays. Furthermore, it has previously been suggested that paper-based tests may be more suitable for settings with lower resource availability and may help alleviate some supply chain challenges which arose during the COVID-19 pandemic. Therefore, we explore how such devices may fit in a comprehensive diagnostic strategy and how some of the challenges to the technology, e.g. low sensitivity, may be addressed. We discuss the properties of the SARS-CoV-2 virus itself, the COVID-19 disease pathway, and the immune response. We then describe the different diagnostic strategies that have been pursued, focusing on molecular strategies for viral genetic material, antigen tests, and serological assays, and innovations for improving the diagnostic sensitivity and capabilities. Finally, we discuss pressing issues for the future, and what needs to be addressed for the ongoing pandemic and future outbreaks.
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Affiliation(s)
- Delyan R Hristov
- Department of Engineering, University of Massachusetts Boston, Boston, MA, USA.
| | - Jose Gomez-Marquez
- Little Devices Lab, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Djibril Wade
- iLEAD (Innovation in Laboratory Engineered Accelerated Diagnostics), Institut de Recherche en Santé, de Surveillance Epidémiologique et de Formations (IRESSEF), Dakar, Senegal
| | - Kimberly Hamad-Schifferli
- Department of Engineering, University of Massachusetts Boston, Boston, MA, USA. .,School for the Environment, University of Massachusetts Boston, Boston, MA, USA
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42
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Hamelin DJ, Fournelle D, Grenier JC, Schockaert J, Kovalchik KA, Kubiniok P, Mostefai F, Duquette JD, Saab F, Sirois I, Smith MA, Pattijn S, Soudeyns H, Decaluwe H, Hussin J, Caron E. The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA-supertype-dependent manner. Cell Syst 2021; 13:143-157.e3. [PMID: 34637888 PMCID: PMC8492600 DOI: 10.1016/j.cels.2021.09.013] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 06/03/2021] [Accepted: 09/23/2021] [Indexed: 02/09/2023]
Abstract
The rapid, global dispersion of SARS-CoV-2 has led to the emergence of a diverse range of variants. Here, we describe how the mutational landscape of SARS-CoV-2 has shaped HLA-restricted T cell immunity at the population level during the first year of the pandemic. We analyzed a total of 330,246 high-quality SARS-CoV-2 genome assemblies, sampled across 143 countries and all major continents from December 2019 to December 2020 before mass vaccination or the rise of the Delta variant. We observed that proline residues are preferentially removed from the proteome of prevalent mutants, leading to a predicted global loss of SARS-CoV-2 T cell epitopes in individuals expressing HLA-B alleles of the B7 supertype family; this is largely driven by a dominant C-to-U mutation type at the RNA level. These results indicate that B7-supertype-associated epitopes, including the most immunodominant ones, were more likely to escape CD8+ T cell immunosurveillance during the first year of the pandemic.
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Affiliation(s)
| | - Dominique Fournelle
- Montreal Heart Institute, Department of Medicine, Université de Montréal, Montréal, QC, Canada
| | - Jean-Christophe Grenier
- Montreal Heart Institute, Department of Medicine, Université de Montréal, Montréal, QC, Canada
| | - Jana Schockaert
- ImmunXperts, a Nexelis Group Company, 6041 Gosselies, Belgium
| | | | - Peter Kubiniok
- CHU Sainte-Justine Research Center, Montréal, QC, Canada
| | - Fatima Mostefai
- Montreal Heart Institute, Department of Medicine, Université de Montréal, Montréal, QC, Canada
| | | | - Frederic Saab
- CHU Sainte-Justine Research Center, Montréal, QC, Canada
| | | | - Martin A Smith
- CHU Sainte-Justine Research Center, Montréal, QC, Canada; Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada
| | - Sofie Pattijn
- ImmunXperts, a Nexelis Group Company, 6041 Gosselies, Belgium
| | - Hugo Soudeyns
- CHU Sainte-Justine Research Center, Montréal, QC, Canada; Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada; Department of Pediatrics, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada
| | - Hélène Decaluwe
- CHU Sainte-Justine Research Center, Montréal, QC, Canada; Department of Pediatrics, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada
| | - Julie Hussin
- Montreal Heart Institute, Department of Medicine, Université de Montréal, Montréal, QC, Canada; Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
| | - Etienne Caron
- CHU Sainte-Justine Research Center, Montréal, QC, Canada; Department of Pathology and Cellular Biology, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
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43
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IgG Antibodies Develop to Spike but Not to the Nucleocapsid Viral Protein in Many Asymptomatic and Light COVID-19 Cases. Viruses 2021; 13:v13101945. [PMID: 34696374 PMCID: PMC8539461 DOI: 10.3390/v13101945] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 09/26/2021] [Accepted: 09/26/2021] [Indexed: 12/29/2022] Open
Abstract
Since SARS-CoV-2 appeared in late 2019, many studies on the immune response to COVID-19 have been conducted, but the asymptomatic or light symptom cases were somewhat understudied as respective individuals often did not seek medical help. Here, we analyze the production of the IgG antibodies to viral nucleocapsid (N) protein and receptor-binding domain (RBD) of the spike protein and assess the serum neutralization capabilities in a cohort of patients with different levels of disease severity. In half of light or asymptomatic cases the antibodies to the nucleocapsid protein, which serve as the main target in many modern test systems, were not detected. They were detected in all cases of moderate or severe symptoms, and severe lung lesions correlated with respective higher signals. Antibodies to RBD were present in the absolute majority of samples, with levels being sometimes higher in light symptom cases. We thus suggest that the anti-RBD/anti-N antibody ratio may serve as an indicator of the disease severity. Anti-RBD IgG remained detectable after a year or more since the infection, even with a slight tendency to raise over time, and the respective signal correlated with the serum capacity to inhibit the RBD interaction with the ACE-2 receptor.
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44
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Khan AA, Alahmari AA, Almuzaini Y, Alamri F, Alsofayan YM, Aburas A, Al-Muhsen S, Van Kerkhove M, Yezli S, Ciottone GR, Assiri AM, Jokhdar HA. Potential Cross-Reactive Immunity to COVID-19 Infection in Individuals With Laboratory-Confirmed MERS-CoV Infection: A National Retrospective Cohort Study From Saudi Arabia. Front Immunol 2021; 12:727989. [PMID: 34603300 PMCID: PMC8484965 DOI: 10.3389/fimmu.2021.727989] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Accepted: 08/17/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND A growing number of experiments have suggested potential cross-reactive immunity between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and previous human coronaviruses. We conducted the present retrospective cohort study to investigate the relationship between previous Middle East respiratory syndrome-coronavirus (MERS-CoV) infection and the risk of SARS-CoV-2 infection as well as the relationship between previous MERS-CoV and COVID-19-related hospitalization and mortality. METHODS Starting in March 2020, we prospectively followed two groups of individuals who tested negative for COVID-19 infection. The first group had a previously confirmed MERS-CoV infection, which was compared to a control group of MERS-negative individuals. The studied cohort was then followed until November 2020 to track evidence of contracting COVID-19 infection. FINDINGS A total of 82 (24%) MERS-positive and 260 (31%) MERS-negative individuals had COVID-19 infection. Patients in the MERS-positive group had a lower risk of COVID-19 infection than those in the MERS-negative group (Risk ratio [RR] 0.696, 95% confidence interval [CI] 0.522-0.929; p =0.014). The risk of COVID-19-related hospitalization in the MERS-positive group was significantly higher (RR 4.036, 95% CI 1.705-9.555; p =0.002). The case fatality rate (CFR) from COVID-19 was 4.9% in the MERS-positive group and 1.2% in the MERS-negative group (p =0.038). The MERS-positive group had a higher risk of death than the MERS-negative group (RR 6.222, 95% CI 1.342-28.839; p =0.019). However, the risk of mortality was similar between the two groups when death was adjusted for age (p =0.068) and age and sex (p =0.057). After controlling for all the independent variables, only healthcare worker occupation and >1 comorbidity were independent predictors of SARS-CoV-2 infection. INTERPRETATION Individuals with previous MERS-CoV infection can exhibit a cross-reactive immune response to SARS-CoV-2 infection. Our study demonstrated that patients with MERS-CoV infection had higher risks of COVID-19-related hospitalization and death than MERS-negative individuals.
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Affiliation(s)
- Anas A. Khan
- Department of Emergency Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Global Center of Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia
| | - Ahmed A. Alahmari
- Global Center of Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia
| | - Yasir Almuzaini
- Global Center of Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia
| | - Fahad Alamri
- Global Center of Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia
| | | | - Alhanouf Aburas
- Global Center of Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia
| | - Saleh Al-Muhsen
- Immunology Research Laboratory, Department of Pediatrics, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Maria Van Kerkhove
- Infectious Hazards Management, Health Emergencies Programme, World Health Organization, Geneva, Switzerland
| | - Saber Yezli
- Global Center of Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia
| | - Gregory R. Ciottone
- Department of Emergency Medicine, Harvard Medical School, Boston, MA, United States
| | | | - Hani A. Jokhdar
- Deputyship of Public Health, Ministry of Health, Riyadh, Saudi Arabia
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45
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Bonfante F, Costenaro P, Cantarutti A, Di Chiara C, Bortolami A, Petrara MR, Carmona F, Pagliari M, Cosma C, Cozzani S, Mazzetto E, Di Salvo G, Da Dalt L, Palma P, Barzon L, Corrao G, Terregino C, Padoan A, Plebani M, De Rossi A, Donà D, Giaquinto C. Mild SARS-CoV-2 Infections and Neutralizing Antibody Titers. Pediatrics 2021; 148:peds.2021-052173. [PMID: 34158312 DOI: 10.1542/peds.2021-052173] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/14/2021] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Recent evidence suggests that neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 may persist over time; however, knowledge regarding pediatric subjects is limited. METHODS A single-center, prospective observational study was conducted on 57 family clusters of coronavirus disease 2019, including children of neonatal and pediatric age attending the University Hospital of Padua (Italy). For each patient, blood samples were collected for both the quantification of nAbs through a plaque reduction neutralizing test and the detection of antinucleocapsid-spike protein immunoglobulin G and/or immunoglobulin M. RESULTS We analyzed 283 blood samples collected from 152 confirmed coronavirus disease 2019 cases (82 parents and 70 children or older siblings of median age of 8 years, interquartile range: 4-13), presenting asymptomatic or with mildly symptomatic disease. Despite the decrease of immunoglobulin G over time, nAbs were found to persist up to 7 to 8 months in children, whereas adults recorded a modest declining trend. Interestingly, children aged <6 years, and, in particular, those aged <3 years, developed higher long-lasting levels of nAbs compared with older siblings and/or adults. CONCLUSIONS Mild and asymptomatic severe acute respiratory syndrome coronavirus 2 infections in family clusters elicited higher nAbs among children.
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Affiliation(s)
- Francesco Bonfante
- Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Padua, Italy
| | - Paola Costenaro
- Division of Pediatric Infectious Diseases, Department for Women's and Children's Health, University of Padua, Padua, Italy
| | - Anna Cantarutti
- Laboratory of Healthcare Research and Pharmacoepidemiology, Division of Biostatistics, Epidemiology and Public Health, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy
| | - Costanza Di Chiara
- Division of Pediatric Infectious Diseases, Department for Women's and Children's Health, University of Padua, Padua, Italy
| | - Alessio Bortolami
- Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Padua, Italy
| | - Maria Raffaella Petrara
- Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padua, Padua, Italy
| | | | - Matteo Pagliari
- Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Padua, Italy
| | - Chiara Cosma
- Department of Laboratory Medicine, University Hospital of Padua, Padua, Italy
| | - Sandra Cozzani
- Division of Pediatric Infectious Diseases, Department for Women's and Children's Health, University of Padua, Padua, Italy
| | - Eva Mazzetto
- Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Padua, Italy
| | - Giovanni Di Salvo
- Department for Women's and Children's Health, University of Padua, Italy
| | - Liviana Da Dalt
- Department for Women's and Children's Health, University of Padua, Italy
| | - Paolo Palma
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, Rome, Rome, Italy.,Department of Systems Medicine, Tor Vergata University of Rome, Rome, Italy
| | - Luisa Barzon
- Department of Molecular Medicine, University of Padua, Italy
| | - Giovanni Corrao
- National Centre for Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy.,Laboratory of Healthcare Research and Pharmacoepidemiology, Division of Biostatistics, Epidemiology and Public Health, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy
| | - Calogero Terregino
- Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Padua, Italy
| | - Andrea Padoan
- Department of Medicine-DIMED, University of Padua, Italy, Padua, Italy
| | - Mario Plebani
- Department of Medicine-DIMED, University of Padua, Italy, Padua, Italy.,Department of Laboratory Medicine, University Hospital of Padua, Padua, Italy
| | - Anita De Rossi
- Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padua, Padua, Italy.,Istituto Oncologico Veneto, IRCCS, Padua, Italy
| | - Daniele Donà
- Division of Pediatric Infectious Diseases, Department for Women's and Children's Health, University of Padua, Padua, Italy
| | - Carlo Giaquinto
- Division of Pediatric Infectious Diseases, Department for Women's and Children's Health, University of Padua, Padua, Italy
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46
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A Retrospective Survey among SARS-CoV-1 Infected Healthcare Workers after Three Years Post-Infection. Pathogens 2021; 10:pathogens10091078. [PMID: 34578111 PMCID: PMC8465910 DOI: 10.3390/pathogens10091078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 08/12/2021] [Accepted: 08/23/2021] [Indexed: 11/26/2022] Open
Abstract
Healthcare workers (HCWs) are on the frontline fighting several infectious diseases including SARS-CoV-1 and COVID-19. Coronavirus neutralizing antibodies (nAbs) were recently reported to last for a certain period. The factors affecting nAbs’ existence remain unclear. Here, we retrospectively analyzed the factors correlating with nAbs’ from SARS-CoV-1 long-term convalescence HCWs in Taiwan. One hundred and thirty SARS-CoV-1 convalescent patients were recruited between August 2006 and March 2007. Blood samples were collected to determine the anti-nucleocapsid (N) and anti-spike (S) antibodies’ existence status and neutralization ability. Neutralization ability was measured using SARS-CoV-1 pseudotyped viruses. Statistical analysis of factors associated with anti-SARS-CoV-1 antibodies’ existence status was determined using SAS software. 46.2% SARS-CoV-1 convalescent patients presented anti-N antibody after three years post-infection. Among sixty participants, ten participants co-presented anti-S antibodies. Eight participants with anti-S antibody displayed neutralization ability to SARS-CoV-1. The gender, age, and disease severity of participants did not affect the anti-N antibody existence status, whereas the anti-S antibody is significantly reduced in participants with old age (>50 years, p = 0.0434) after three years post SARS-CoV-1 infection. This study suggests that age is an important factor correlated with the duration of SARS-CoV-1 protective antibody existence status.
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47
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Hosseini SA, Zahedipour F, Mirzaei H, Kazemi Oskuee R. Potential SARS-CoV-2 vaccines: Concept, progress, and challenges. Int Immunopharmacol 2021; 97:107622. [PMID: 33895475 PMCID: PMC8006194 DOI: 10.1016/j.intimp.2021.107622] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/25/2021] [Accepted: 03/25/2021] [Indexed: 02/07/2023]
Abstract
Since September 2020, the world has had more than 28 million cases of coronavirus disease 2019 (COVID-19). Many countries are facing a second wave of the COVID-19 outbreak. A pressing need is evident for the development of a potent vaccine to control the SARS-CoV-2. Institutions and companies in many countries have announced their vaccine research programs and progress against the COVID-19. While most vaccines go through the designation and preparation stages, some of them are under evaluation for efficacy among animal models and clinical trials, and three approved vaccine candidates have been introduced for limited exploitation in Russia and China. An effective vaccine must induce a protective response of both cell-mediated and humoral immunity and should meet the safety and efficacy criteria. Although the emergence of new technologies has accelerated the development of vaccines, there are several challenges on the way, such as limited knowledge about the pathophysiology of the virus, inducing humoral or cellular immunity, immune enhancement with animal coronavirus vaccines, and lack of an appropriate animal model. In this review, we firstly discuss the immune responses against SARS-CoV-2 disease, subsequently, give an overview of several vaccine platforms for SARS-CoV-2 under clinical trials and challenges in vaccine development against this virus.
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Affiliation(s)
- Seyede Atefe Hosseini
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran,Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Zahedipour
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran,Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran,Corresponding authors
| | - Reza Kazemi Oskuee
- Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran,Corresponding authors
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48
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Rella SA, Kulikova YA, Dermitzakis ET, Kondrashov FA. Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains. Sci Rep 2021; 11:15729. [PMID: 34330988 PMCID: PMC8324827 DOI: 10.1038/s41598-021-95025-3] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 07/20/2021] [Indexed: 12/21/2022] Open
Abstract
Vaccines are thought to be the best available solution for controlling the ongoing SARS-CoV-2 pandemic. However, the emergence of vaccine-resistant strains may come too rapidly for current vaccine developments to alleviate the health, economic and social consequences of the pandemic. To quantify and characterize the risk of such a scenario, we created a SIR-derived model with initial stochastic dynamics of the vaccine-resistant strain to study the probability of its emergence and establishment. Using parameters realistically resembling SARS-CoV-2 transmission, we model a wave-like pattern of the pandemic and consider the impact of the rate of vaccination and the strength of non-pharmaceutical intervention measures on the probability of emergence of a resistant strain. As expected, we found that a fast rate of vaccination decreases the probability of emergence of a resistant strain. Counterintuitively, when a relaxation of non-pharmaceutical interventions happened at a time when most individuals of the population have already been vaccinated the probability of emergence of a resistant strain was greatly increased. Consequently, we show that a period of transmission reduction close to the end of the vaccination campaign can substantially reduce the probability of resistant strain establishment. Our results suggest that policymakers and individuals should consider maintaining non-pharmaceutical interventions and transmission-reducing behaviours throughout the entire vaccination period.
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Affiliation(s)
- Simon A Rella
- Institute of Science and Technology Austria, 1 Am Campus, 3400, Klosterneuburg, Austria
| | | | - Emmanouil T Dermitzakis
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
| | - Fyodor A Kondrashov
- Institute of Science and Technology Austria, 1 Am Campus, 3400, Klosterneuburg, Austria.
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49
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Gong F, Wei HX, Li Q, Liu L, Li B. Evaluation and Comparison of Serological Methods for COVID-19 Diagnosis. Front Mol Biosci 2021; 8:682405. [PMID: 34368226 PMCID: PMC8343015 DOI: 10.3389/fmolb.2021.682405] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 06/30/2021] [Indexed: 12/16/2022] Open
Abstract
The worldwide pandemic of COVID-19 has become a global public health crisis. Various clinical diagnosis methods have been developed to distinguish COVID-19-infected patients from healthy people. The nucleic acid test is the golden standard for virus detection as it is suitable for early diagnosis. However, due to the low amount of viral nucleic acid in the respiratory tract, the sensitivity of nucleic acid detection is unsatisfactory. As a result, serological screening began to be widely used with the merits of simple procedures, lower cost, and shorter detection time. Serological tests currently include the enzyme-linked immunosorbent assay (ELISA), lateral flow immunoassay (LFIA), and chemiluminescence immunoassay (CLIA). This review describes various serological methods, discusses the performance and diagnostic effects of different methods, and points out the problems and the direction of optimization, to improve the efficiency of clinical diagnosis. These increasingly sophisticated and diverse serological diagnostic technologies will help human beings to control the spread of COVID-19.
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Affiliation(s)
- Fanwu Gong
- Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Hua-Xing Wei
- Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Qiangsheng Li
- Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Liu Liu
- Department of General Surgery, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
| | - Bofeng Li
- Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
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50
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Alvarez MM, Bravo-González S, Trujillo-de Santiago G. Modeling vaccination strategies in an Excel spreadsheet: Increasing the rate of vaccination is more effective than increasing the vaccination coverage for containing COVID-19. PLoS One 2021; 16:e0254430. [PMID: 34280210 PMCID: PMC8289062 DOI: 10.1371/journal.pone.0254430] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 06/22/2021] [Indexed: 01/08/2023] Open
Abstract
We have investigated the importance of the rate of vaccination to contain COVID-19 in urban areas. We used an extremely simple epidemiological model that is amenable to implementation in an Excel spreadsheet and includes the demographics of social distancing, efficacy of massive testing and quarantine, and coverage and rate of vaccination as the main parameters to model the progression of COVID-19 pandemics in densely populated urban areas. Our model predicts that effective containment of pandemic progression in densely populated cities would be more effectively achieved by vaccination campaigns that consider the fast distribution and application of vaccines (i.e., 50% coverage in 6 months) while social distancing measures are still in place. Our results suggest that the rate of vaccination is more important than the overall vaccination coverage for containing COVID-19. In addition, our modeling indicates that widespread testing and quarantining of infected subjects would greatly benefit the success of vaccination campaigns. We envision this simple model as a friendly, readily accessible, and cost-effective tool for assisting health officials and local governments in the rational design/planning of vaccination strategies.
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Affiliation(s)
- Mario Moisés Alvarez
- Centro de Biotecnología-FEMSA, Tecnologico de Monterrey, Monterrey, NL, México
- Departamento de Bioingeniería, Escuela de Ingeniería y Ciencias, Tecnologico de Monterrey, Monterrey, NL, México
- * E-mail:
| | - Sergio Bravo-González
- Centro de Biotecnología-FEMSA, Tecnologico de Monterrey, Monterrey, NL, México
- Departamento de Bioingeniería, Escuela de Ingeniería y Ciencias, Tecnologico de Monterrey, Monterrey, NL, México
| | - Grissel Trujillo-de Santiago
- Centro de Biotecnología-FEMSA, Tecnologico de Monterrey, Monterrey, NL, México
- Departamento de Ingeniería Mecatrónica y Eléctrica, Escuela de Ingeniería y Ciencias, Tecnologico de Monterrey, Monterrey, NL, México
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