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Herrero R, Fantin R, Loría V, Aparicio A, Prevots DR, Zúñiga M, Wong R, Morera M, Butt J, Binder M, Abdelnour A, Calderón A, Castro R, Cortes B, Ocampo R, Vanegas JC, Gail MH, Pfeiffer RM, Flock J, Remans K, Eberhardt L, Rastgou S, Magalhaes V, Porras C, Hildesheim A, Waterboer T. Time course and determinants of the antibody response to SARS-CoV-2 in Costa Rica: the RESPIRA study. BMC Infect Dis 2025; 25:376. [PMID: 40102764 PMCID: PMC11917050 DOI: 10.1186/s12879-025-10742-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 03/03/2025] [Indexed: 03/20/2025] Open
Abstract
BACKGROUND Antibodies to SARS-CoV-2 are essential for protection or reduction in severity of subsequent disease. We studied antibody responses to spike protein receptor-binding domain (S1-RBD) and nucleocapsid (N) in a population-based sample of COVID-19 cases in Costa Rica. METHODS As part of the RESPIRA study, we selected an age-stratified random sample of PCR-confirmed COVID-19 cases diagnosed from March 2020 to July 2021. Antibodies were determined with multiplex serology in 794 unvaccinated subjects diagnosed 3 days to 17 months before recruitment to investigate immune response to natural infection. In addition, neutralizing antibodies were determined in 136 randomly selected participants. We estimated antibody positivity and GMTs by time since diagnosis and explored determinants using multivariate regression. RESULTS Most participants tested 15-29 days after PCR diagnosis were seropositive for N (90%) and S1-RBD antibodies (96%) and had the highest GMTs for both antibodies. Only 42% of subjects tested one year after infection were seropositive for N antibodies, compared to 97% for S1-RBD. GMTs for neutralizing antibodies peaked 15-89 days after infection and declined but remained positive for 95% of subjects thereafter. In multivariate models, antibodies were significantly higher among men and increased with age and severity of the clinical presentation. The correlation of multiplex and neutralizing antibodies was high (0.72 [95% CI = 0.63-0.79]) and stronger among women. CONCLUSIONS A robust immune response against N and S1-RBD is elicited by COVID-19 a few days after infection. While S1-RBD antibodies are present after > 1 year, N antibodies decline significantly. Antibody levels are higher in men and increase with age and severity of disease. The different immune response patterns by sex warrant further investigation. TRIAL REGISTRATION RESPIRA Study ClinicalTrials.gov ID: NCT04537338 (3 September 2020).
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Affiliation(s)
- Rolando Herrero
- Agencia Costarricense de Investigaciones Biomédicas-Fundación INCIENSA (ACIB-FUNIN), San José, Costa Rica.
| | - Romain Fantin
- Agencia Costarricense de Investigaciones Biomédicas-Fundación INCIENSA (ACIB-FUNIN), San José, Costa Rica
| | - Viviana Loría
- Agencia Costarricense de Investigaciones Biomédicas-Fundación INCIENSA (ACIB-FUNIN), San José, Costa Rica
| | - Amada Aparicio
- Caja Costarricense del Seguro Social, San José, Costa Rica
| | - D Rebecca Prevots
- Epidemiology and Population Studies Unit, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, National Institutes of Health, Bethesda, MD, USA
| | - Michael Zúñiga
- Agencia Costarricense de Investigaciones Biomédicas-Fundación INCIENSA (ACIB-FUNIN), San José, Costa Rica
| | - Roy Wong
- Caja Costarricense del Seguro Social, San José, Costa Rica
| | - Melvin Morera
- Caja Costarricense del Seguro Social, San José, Costa Rica
| | - Julia Butt
- Infections and Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
| | - Marco Binder
- Virus-Associated Carcinogenesis, German Cancer Research Center, Heidelberg, Germany
| | | | | | | | - Bernal Cortes
- Agencia Costarricense de Investigaciones Biomédicas-Fundación INCIENSA (ACIB-FUNIN), San José, Costa Rica
| | - Rebeca Ocampo
- Agencia Costarricense de Investigaciones Biomédicas-Fundación INCIENSA (ACIB-FUNIN), San José, Costa Rica
| | - Juan Carlos Vanegas
- Agencia Costarricense de Investigaciones Biomédicas-Fundación INCIENSA (ACIB-FUNIN), San José, Costa Rica
| | - Mitchell H Gail
- Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Ruth M Pfeiffer
- Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Julia Flock
- European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
| | - Kim Remans
- European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
| | - Lukas Eberhardt
- Virus-Associated Carcinogenesis, German Cancer Research Center, Heidelberg, Germany
| | - Soheil Rastgou
- Virus-Associated Carcinogenesis, German Cancer Research Center, Heidelberg, Germany
| | - Vladimir Magalhaes
- Virus-Associated Carcinogenesis, German Cancer Research Center, Heidelberg, Germany
| | - Carolina Porras
- Agencia Costarricense de Investigaciones Biomédicas-Fundación INCIENSA (ACIB-FUNIN), San José, Costa Rica
| | - Allan Hildesheim
- Agencia Costarricense de Investigaciones Biomédicas-Fundación INCIENSA (ACIB-FUNIN), San José, Costa Rica
| | - Tim Waterboer
- Infections and Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
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Ling Z, Zheng Z, Xu L, Yi C, Dong X, Gu X, Sun X, Wu B, Sun B, Zhou W. Children exhibit a robust B-cell response to Omicron BA.2 after breakthrough infection with limited influence from the original antigenic sin. Cell Mol Immunol 2025; 22:127-130. [PMID: 39627611 PMCID: PMC11686154 DOI: 10.1038/s41423-024-01241-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Accepted: 11/16/2024] [Indexed: 01/01/2025] Open
Affiliation(s)
- Zhiyang Ling
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
| | | | - Lingli Xu
- Children's Hospital of Fudan University, Shanghai, China
| | - Chunyan Yi
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
| | - Xinran Dong
- Children's Hospital of Fudan University, Shanghai, China
| | - Xiaoqiong Gu
- Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xiaoyu Sun
- Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Bingbing Wu
- Children's Hospital of Fudan University, Shanghai, China.
| | - Bing Sun
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
| | - Wenhao Zhou
- Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.
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3
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Okuducu YK, Mall MA, Yonker LM. COVID-19 in Pediatric Populations. Clin Chest Med 2024; 45:675-684. [PMID: 39069330 DOI: 10.1016/j.ccm.2024.02.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
Abstract
The COVID-19 pandemic reshaped the landscape of respiratory viral illnesses, causing common viruses to fade as SARS-CoV-2 took precedence. By 2023, more than 96% of the children in the United States were estimated to have been infected with SARS-CoV-2, with certain genetic predispositions and underlying health conditions posing risk factors for severe disease in children. Children, in general though, exhibit immunity advantages, protecting against aspects of the SARS-CoV-2 infection known to drive increased severity in older adults. Post-COVID-19 complications such as multisystem inflammatory syndrome in children and long COVID have emerged, underscoring the importance of vaccination. Here, we highlight the risks of severe pediatric COVID-19, age-specific immunoprotection, comparisons of SARS-CoV-2 with other respiratory viruses, and factors contributing to post-COVID-19 complications in children.
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Affiliation(s)
- Yanki K Okuducu
- Department of Pediatrics, Pulmonary Division, Massachusetts General Hospital, 175 Cambridge Street, 5(th) floor, Boston, MA 02114, USA; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Marcus A Mall
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin Augustenburger Platz 1, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 13353, Germany; German Center for Lung Research (DZL), Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Lael M Yonker
- Department of Pediatrics, Pulmonary Division, Massachusetts General Hospital, 175 Cambridge Street, 5(th) floor, Boston, MA 02114, USA; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
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4
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Shahbazi E, Moradi A, Mollasalehi H, Mohebbi SR. Unravelling the diagnostic methodologies for SARS-CoV-2; the Indispensable need for developing point-of-care testing. Talanta 2024; 275:126139. [PMID: 38696900 DOI: 10.1016/j.talanta.2024.126139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 04/13/2024] [Accepted: 04/20/2024] [Indexed: 05/04/2024]
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused COVID-19 pandemic that continues to be a global menace and since its emergence in the late 2019, SARS-CoV-2 has been vigorously spreading throughout the globe putting the whole world into a multidimensional calamity. The suitable diagnosis strategies are on the front line of the battle against preventing the spread of infections. Since the clinical manifestation of COVID-19 is shared between various diseases, detection of the unique impacts of the pathogen on the host along with the diagnosis of the virus itself should be addressed. Employing the most suitable approaches to specifically, sensitively and effectively recognize the infected cases may be a real game changer in controlling the outbreak and the crisis management. In that matter, point-of-care assays (POC) appears to be the potential option, due to sensitivity, specificity, affordable, and availability. Here we brief the most recent findings about the virus, its variants, and the conventional methods that have been used for its detection, along with the POC strategies that have been applied to the virus diagnosis and the developing technologies which can accelerate the diagnosis procedure yet maintain its efficiency.
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Affiliation(s)
- Erfan Shahbazi
- Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Asma Moradi
- Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Hamidreza Mollasalehi
- Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
| | - Seyed Reza Mohebbi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Jia R, Li Z, Hu S, Chang H, Zeng M, Liu P, Lu L, Xu M, Zhai X, Qian M, Xu J. Immunological characterization and comparison of children with COVID-19 from their adult counterparts at single-cell resolution. Front Immunol 2024; 15:1358725. [PMID: 39148728 PMCID: PMC11325098 DOI: 10.3389/fimmu.2024.1358725] [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: 07/17/2024] [Indexed: 08/17/2024] Open
Abstract
Introduction The immunological characteristics that could protect children with coronavirus disease 2019 (COVID-19) from severe or fatal illnesses have not been fully understood yet. Methods Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on peripheral blood samples of 15 children (8 with COVID-19) and compared them to 18 adults (13 with COVID-19). Results The child-adult integrated single cell data indicated that children with the disease presented a restrained response to type I interferon in most of the major immune cell types, along with suppression of upstream interferon regulatory factor and toll-like receptor expression in monocytes, which was confirmed by in vitro interferon stimulation assays. Unlike adult patients, children with COVID-19 showed lower frequencies of activated proinflammatory CD14+ monocytes, possibly explaining the rareness of cytokine storm in them. Notably, natural killer (NK) cells in pediatric patients displayed potent cytotoxicity with a rich expression of cytotoxic molecules and upregulated cytotoxic pathways, whereas the cellular senescence, along with the Notch signaling pathway, was significantly downregulated in NK cells, all suggesting more robust cytotoxicity in NK cells of children than adult patients that was further confirmed by CD107a degranulation assays. Lastly, a modest adaptive immune response was evident with more naïve T cells but less activated and proliferated T cells while less naïve B cells but more activated B cells in children over adult patients. Conclusion Conclusively, this preliminary study revealed distinct cell frequency and activation status of major immune cell types, particularly more robust NK cell cytotoxicity in PBMC that might help protect children from severe COVID-19.
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Affiliation(s)
- Ran Jia
- Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Zifeng Li
- Department of Hematology and Oncology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Shiwen Hu
- Department of Hematology and Oncology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Hailing Chang
- Department of Infectious Diseases, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Mei Zeng
- Department of Infectious Diseases, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Pengcheng Liu
- Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Lijuan Lu
- Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Menghua Xu
- Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Xiaowen Zhai
- Department of Hematology and Oncology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Maoxiang Qian
- Institute of Pediatrics and Department of Hematology and Oncology, Children's Hospital of Fudan University, National Children's Medical Center, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Jin Xu
- Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
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Paniskaki K, Goretzki S, Anft M, Konik MJ, Lechtenberg K, Vogl M, Meister TL, Pfaender S, Zettler M, Jäger J, Dolff S, Westhoff TH, Rohn H, Felderhoff-Mueser U, Stervbo U, Witzke O, Dohna-Schwake C, Babel N. Fading SARS-CoV-2 humoral VOC cross-reactivity and sustained cellular immunity in convalescent children and adolescents. BMC Infect Dis 2023; 23:818. [PMID: 37993788 PMCID: PMC10664582 DOI: 10.1186/s12879-023-08805-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 11/08/2023] [Indexed: 11/24/2023] Open
Abstract
Cross-reactive cellular and humoral immunity can substantially contribute to antiviral defense against SARS-CoV-2 variants of concern (VOC). While the adult SARS-CoV-2 cellular and humoral immunity and its cross-recognition potential against VOC is broadly analyzed, similar data regarding the pediatric population are missing. In this study, we perform an analysis of the humoral and cellular SARS-CoV-2 response immune of 32 convalescent COVID-19 children (children), 27 convalescent vaccinated adults(C + V+) and 7 unvaccinated convalescent adults (C + V-). Similarly to adults, a significant reduction of cross-reactive neutralizing capacity against delta and omicron VOC was observed 6 months after SARS-CoV-2 infection. While SAR-CoV-2 neutralizing capacity was comparable among children and C + V- against all VOC, children demonstrated as expected an inferior humoral response when compared to C + V+. Nevertheless, children generated SARS-CoV-2 reactive T cells with broad cross-recognition potential. When compared to V + C+, children presented even comparable frequencies of WT-reactive CD4 + and CD8 + T cells with high avidity and functionality. Taking into consideration the limitations of study - unknown disease onset for 53% of the asymptomatic pediatric subjects, serological detection of SARS-CoV-2 infection-, our results suggest that following SARS-CoV-2 infection children generate a humoral SARS-CoV-2 response with neutralizing potential comparable to unvaccinated COVID-19 convalescent adults as well a sustained SARS-CoV-2 cellular response cross-reactive to VOC.
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Affiliation(s)
- Krystallenia Paniskaki
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
- Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Bochum, Germany.
| | - Sarah Goretzki
- Department of Pediatrics I, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Moritz Anft
- Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Bochum, Germany
| | - Margarethe J Konik
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Klara Lechtenberg
- Department of Pediatrics I, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Melanie Vogl
- Department of Pediatrics III, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Toni L Meister
- Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany
| | - Stephanie Pfaender
- Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany
| | - Markus Zettler
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Jasmin Jäger
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Bochum, Germany
| | - Sebastian Dolff
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Timm H Westhoff
- Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany
| | - Hana Rohn
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Ursula Felderhoff-Mueser
- Department of Pediatrics I, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Ulrik Stervbo
- Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Bochum, Germany
| | - Oliver Witzke
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Christian Dohna-Schwake
- Department of Pediatrics I, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Nina Babel
- Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Bochum, Germany
- Berlin Institute of Health at Charité - University Clinic Berlin, BIH Center for Regenerative Therapies (BCRT) Berlin, Berlin, Germany
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Gupta A, Marzook H, Ahmad F. Comorbidities and clinical complications associated with SARS-CoV-2 infection: an overview. Clin Exp Med 2023; 23:313-331. [PMID: 35362771 PMCID: PMC8972750 DOI: 10.1007/s10238-022-00821-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Accepted: 03/12/2022] [Indexed: 01/08/2023]
Abstract
The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes major challenges to the healthcare system. SARS-CoV-2 infection leads to millions of deaths worldwide and the mortality rate is found to be greatly associated with pre-existing clinical conditions. The existing dataset strongly suggests that cardiometabolic diseases including hypertension, coronary artery disease, diabetes and obesity serve as strong comorbidities in coronavirus disease (COVID-19). Studies have also shown the poor outcome of COVID-19 in patients associated with angiotensin-converting enzyme-2 polymorphism, cancer chemotherapy, chronic kidney disease, thyroid disorder, or coagulation dysfunction. A severe complication of COVID-19 is mostly seen in people with compromised medical history. SARS-CoV-2 appears to attack the respiratory system causing pneumonia, acute respiratory distress syndrome, which lead to induction of severe systemic inflammation, multi-organ dysfunction, and death mostly in the patients who are associated with pre-existing comorbidity factors. In this article, we highlighted the key comorbidities and a variety of clinical complications associated with COVID-19 for a better understanding of the etiopathogenesis of COVID-19.
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Affiliation(s)
- Anamika Gupta
- Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah, 27272, UAE
| | - Hezlin Marzook
- Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah, 27272, UAE
| | - Firdos Ahmad
- Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah, 27272, UAE.
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, 27272, UAE.
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Abdulla ZA, Al-Bashir SM, Alzoubi H, Al-Salih NS, Aldamen AA, Abdulazeez AZ. The Role of Immunity in the Pathogenesis of SARS-CoV-2 Infection and in the Protection Generated by COVID-19 Vaccines in Different Age Groups. Pathogens 2023; 12:329. [PMID: 36839601 PMCID: PMC9967364 DOI: 10.3390/pathogens12020329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/09/2023] [Accepted: 02/13/2023] [Indexed: 02/18/2023] Open
Abstract
This study aims to review the available data regarding the central role of immunity in combating SARS-CoV-2 infection and in the generation of protection by vaccination against COVID-19 in different age groups. Physiologically, the immune response and the components involved in it are variable, both functionally and quantitatively, in neonates, infants, children, adolescents, and adults. These immunological differences are mirrored during COVID-19 infection and in the post-vaccination period. The outcome of SARS-CoV-2 infection is greatly dependent on the reaction orchestrated by the immune system. This is clearly obvious in relation to the clinical status of COVID-19 infection, which can be symptomless, mild, moderate, or severe. Even the complications of the disease show a proportional pattern in relation to the immune response. On the contrary, the commonly used anti-COVID-19 vaccines generate protective humoral and cellular immunity. The magnitude of this immunity and the components involved in it are discussed in detail. Furthermore, many of the adverse effects of these vaccines can be explained on the basis of immune reactions against the different components of the vaccines. Regarding the appropriate choice of vaccine for different age groups, many factors have to be considered. This is a cornerstone, particularly in the following age groups: 1 day to 5 years, 6 to 11 years, and 12 to 17 years. Many factors are involved in deciding the route, doses, and schedule of vaccination for children. Another important issue in this dilemma is the hesitancy of families in making the decision about whether to vaccinate their children. Added to these difficulties is the choice by health authorities and governments concerning whether to make children's vaccination compulsory. In this respect, although rare and limited, adverse effects of vaccines in children have been detected, some of which, unfortunately, have been serious or even fatal. However, to achieve comprehensive control over COVID-19 in communities, both children and adults have to be vaccinated, as the former group represents a reservoir for viral transmission. The understanding of the various immunological mechanisms involved in SARS-CoV-2 infection and in the preparation and application of its vaccines has given the sciences a great opportunity to further deepen and expand immunological knowledge. This will hopefully be reflected positively on other diseases through gaining an immunological background that may aid in diagnosis and therapy. Humanity is still in continuous conflict with SARS-CoV-2 infection and will be for a while, but the future is expected to be in favor of the prevention and control of this disease.
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Affiliation(s)
| | - Sharaf M. Al-Bashir
- Department of Clinical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan
| | - Hiba Alzoubi
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan
| | - Noor S. Al-Salih
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan
| | - Ala A. Aldamen
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan
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Machura E, Krakowczyk H, Bąk-Drabik K, Szczepańska M. SARS-CoV-2 Infection as a Possible Trigger for IgA-Associated Vasculitis: A Case Report. CHILDREN (BASEL, SWITZERLAND) 2023; 10:children10020344. [PMID: 36832473 PMCID: PMC9955818 DOI: 10.3390/children10020344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 01/15/2023] [Accepted: 02/08/2023] [Indexed: 02/12/2023]
Abstract
BACKGROUND IgA-associated vasculitis (IgAV), formerly known as Henoch-Schönlein purpura (HSP) disease, is the most common type of systemic vasculitis observed during developmental age. Available published studies associate the outbreak of the disease with streptococci, adenovirus, parvovirus, mycoplasma, respiratory syncytial virus (RSV), and influenza infection in approximately 50% of patients with HSP, while some emerging reports have described a few cases of COVID-19 infection being associated with HSP in both adults and children. CASE PRESENTATION a 7-year-old girl was diagnosed with HSP, fulfilling the four required clinical criteria (palpable purpura and abdominal pain, arthralgia and edema, and periodic renal involvement). Infection with SARS-CoV-2 was confirmed via the presence of IgM and IgG antibodies. The disclosure of the Henoch-Schönlein purpura (HSP) disease was preceded by a mild, symptomatically treated infection of the upper respiratory tract. High levels of inflammatory markers were observed during hospitalization, including leukocytosis, an increased neutrophil count and a high neutrophil-to-lymphocyte ratio (NLR). All of these markers are associated with IgAV gastrointestinal bleeding, which was also associated with rotavirus diarrhea observed in the patient. CONCLUSIONS This case presented by us and similar cases presented by other authors indicate the possible role of SARS-CoV-2 in the development of HSP, but this assumption requires further research and evidence-based verification.
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Rajamanickam A, Nathella PK, Venkataraman A, Varadarjan P, Kannan S, Pandiarajan AN, Renji RM, Elavarasan E, Thimmaiah A, Sasidaran K, Krishnamoorthy N, Natarajan S, Ramaswamy G, Sundaram B, Putlibai S, Hissar S, Selladurai E, Uma Devi KR, Nutman TB, Babu S. Unique cellular immune signatures of multisystem inflammatory syndrome in children. PLoS Pathog 2022; 18:e1010915. [PMID: 36322537 PMCID: PMC9629618 DOI: 10.1371/journal.ppat.1010915] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 10/04/2022] [Indexed: 11/11/2022] Open
Abstract
The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8+ T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4+ and CD8+ T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6-9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242.
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Affiliation(s)
- Anuradha Rajamanickam
- National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai, India
- * E-mail: (AR); (NPV)
| | - Pavan Kumar Nathella
- ICMR-National Institute for Research in Tuberculosis, Chennai, India
- * E-mail: (AR); (NPV)
| | | | | | - Srinithi Kannan
- Institute of Child Health and Hospital for Children, Chennai, India
| | - Arul Nancy Pandiarajan
- National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai, India
| | - Rachel Mariam Renji
- National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai, India
| | | | | | | | | | | | | | | | | | - Syed Hissar
- ICMR-National Institute for Research in Tuberculosis, Chennai, India
| | | | | | - Thomas B. Nutman
- Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Subash Babu
- National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai, India
- Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
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11
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Peng Y, Wang S, Chai R, Chen Y, Li N, Zeng B, Tang Q, Zheng K, Liang Y, Xie S, Huang W, Wang S, Wang X. Clinical and Gene Features of SARS-CoV-2-Positive Recurrence in Patients Recovered From COVID-19. Front Mol Biosci 2022; 9:875418. [PMID: 35755819 PMCID: PMC9217101 DOI: 10.3389/fmolb.2022.875418] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 04/22/2022] [Indexed: 01/08/2023] Open
Abstract
There are still frequent reports that a number of recovered coronavirus disease 2019 (COVID-19) patients following discharge have re-detectable positive (RP) results by RT-PCR. Understanding the clinical and molecular characteristics of RP patients may have implications for curbing the COVID-19 pandemic. In this study, 318 COVID-19 convalescent patients, including 59 RP patients and 259 non-RP (NRP) patients, were enrolled. Among RP patients, women accounted for a significantly high proportion (67.8%), and the titers of IgG and IgM antibodies in this group were also significantly high. Differentially expressed genes (DEGs), including 692 upregulated and 383 downregulated genes, overlapped in two public GEO datasets containing RP and NRP blood cell samples. Enrichment analysis indicated that these DEGs were related to several key signaling pathways, such as viral infection, immune activation, and inflammatory responses. Importantly, 59 indicator genes constituting the core network exhibited high diagnostic values and were correlated with markers of different immune cells. Among these, 12 drug-related genes were associated with the RP results. Our work suggests that, in addition to clinically available features, blood cell transcriptome sequencing can be performed to obtain gene signatures for diagnosis of RP patients.
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Affiliation(s)
- Yuying Peng
- Department of Pharmacy, Shenzhen Key Laboratory of Prevention and Treatment of Severe Infection, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.,School of Pharmacy, Jinan University, Guangzhou, China
| | - Shaoqi Wang
- Department of Internal Medicine, Hubei Province Corps Hospital of The Chinese Armed Police Force (CAPF), Wuhan, China
| | - Ruihuan Chai
- School of Pharmaceutical Sciences, Shenzhen University Health Science Center, Shenzhen, China
| | - Yong Chen
- Chinese PLA Center for Disease Control and Prevention, Beijing, China
| | - Nan Li
- School of Pharmaceutical Sciences, Shenzhen University Health Science Center, Shenzhen, China
| | - Boning Zeng
- Department of Pharmacy, Shenzhen Key Laboratory of Prevention and Treatment of Severe Infection, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Qian Tang
- Department of Pharmacy, Shenzhen Key Laboratory of Prevention and Treatment of Severe Infection, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.,School of Pharmacy, Jinan University, Guangzhou, China
| | - Kai Zheng
- School of Pharmaceutical Sciences, Shenzhen University Health Science Center, Shenzhen, China
| | - Youfang Liang
- School of Pharmaceutical Sciences, Shenzhen University Health Science Center, Shenzhen, China
| | - Shouxia Xie
- Department of Pharmacy, Shenzhen Key Laboratory of Prevention and Treatment of Severe Infection, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Wei Huang
- Bacteriology and Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Shaoxiang Wang
- School of Pharmaceutical Sciences, Shenzhen University Health Science Center, Shenzhen, China
| | - Xiao Wang
- Department of Pharmacy, Shenzhen Key Laboratory of Prevention and Treatment of Severe Infection, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.,School of Pharmacy, Jinan University, Guangzhou, China
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12
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Kakos CD, Ziogas IA, Tsoulfas G. Pediatric transplantation during the COVID-19 pandemic. World J Transplant 2022; 12:88-99. [PMID: 35663540 PMCID: PMC9136715 DOI: 10.5500/wjt.v12.i5.88] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 03/16/2022] [Accepted: 04/20/2022] [Indexed: 02/06/2023] Open
Abstract
Children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seem to have a better prognosis than adults. Nevertheless, pediatric solid organ transplantation (SOT) has been significantly affected by the unprecedented coronavirus disease 2019 (COVID-19) pandemic during the pre-, peri-, and post-transplant period. Undoubtedly, immunosuppression constitutes a real challenge for transplant clinicians as increased immunosuppression may prolong disease recovery, while its decrease can contribute to more severe symptoms. To date, most pediatric SOT recipients infected by SARS-CoV-2 experience mild disease with only scarce reports of life-threatening complications. As a consequence, after an initial drop during the early phase of the pandemic, pediatric SOTs are now performed with the same frequency as during the pre-pandemic period. This review summarizes the currently available evidence regarding pediatric SOT during the COVID-19 pandemic.
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Affiliation(s)
| | - Ioannis A Ziogas
- Surgery Working Group, Society of Junior Doctors, Athens 15123, Greece
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, United States
| | - Georgios Tsoulfas
- Department of Transplantation Surgery, Aristotle University School of Medicine, Thessaloniki 54622, Greece
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13
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Han MS, Um J, Lee EJ, Kim KM, Chang SH, Lee H, Kim YK, Choi YY, Cho EY, Kim DH, Choi JH, Lee J, Kim M, Chung KH, Min HS, Choe YJ, Lim DG, Park JS, Choi EH. Antibody Responses to SARS-CoV-2 in Children With COVID-19. J Pediatric Infect Dis Soc 2022; 11:267-273. [PMID: 35275210 PMCID: PMC8992286 DOI: 10.1093/jpids/piac012] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 02/14/2022] [Indexed: 12/05/2022]
Abstract
BACKGROUND The immunologic features of children with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not clearly delineated. This study was conducted to evaluate SARS-CoV-2-specific antibody responses in children with COVID-19. METHODS The levels of anti-spike (S) IgG, anti-SARS-CoV-2 IgG, and neutralizing antibody (NAb) were measured during various time points in children <19 years of age with COVID-19 in South Korea from February 2020 to September 2020. RESULTS One hundred sixty-five blood samples from 114 children with COVID-19 (43.9% asymptomatic and 56.1% mildly symptomatic) were analyzed. In both asymptomatic and mildly symptomatic children, the positive rates of anti-S IgG, anti-SARS-CoV-2 IgG, and NAb were low within 7 days after onset, but they soon reached 100% 14 to <28 days after onset. In symptomatic children, the geometric mean titers (GMTs) of antibodies were all below the positive cutoff during the first 2 weeks from onset and peaked at 28 to <56 days (5.6 for anti-S IgG, 383.6 for anti-SARS-CoV-2 IgG, and 55.0 for NAb, P < .001, respectively). Antibody levels remained detectable up to 3 months after infection. The antibody GMTs during the period 14 to <56 days after symptom onset were highest in children aged 0-4 years. CONCLUSIONS These results collectively present the humoral immune responses during SARS-CoV-2 infection in children. A further longitudinal study is needed to thoroughly understand the immune system and for effective vaccine development in children during the COVID-19 pandemic.
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Affiliation(s)
- Mi Seon Han
- Department of Pediatrics, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea
| | - Jihye Um
- Research Institute of Public Health, National Medical Center, Seoul, South Korea
| | - Eun Joo Lee
- Department of Pediatrics, Seongnam Citizens Medical Center, Seongnam, South Korea
| | - Kyung Min Kim
- Department of Pediatrics, The Catholic University of Korea Daejeon St. Mary’s Hospital, Daejeon, South Korea
| | - Sung Hee Chang
- Department of Pediatrics, Seonam Hospital, Seoul, South Korea
| | - Hyunju Lee
- Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, South Korea,Department of Pediatrics, Seoul National University College of Medicine, Seoul, South Korea
| | - Ye Kyung Kim
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, South Korea
| | - Youn Young Choi
- Department of Pediatrics, National Medical Center, Seoul, South Korea
| | - Eun Young Cho
- Department of Pediatrics, Chungnam National University Hospital, Daejeon, South Korea
| | - Dong Hyun Kim
- Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon, South Korea
| | - Jae Hong Choi
- Department of Pediatrics, Jeju National University Hospital, Jeju, South Korea
| | - Jina Lee
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Misuk Kim
- Research Institute of Public Health, National Medical Center, Seoul, South Korea
| | - Ki-Hyun Chung
- Research Institute of Public Health, National Medical Center, Seoul, South Korea
| | - Hye Sook Min
- Research Institute of Public Health, National Medical Center, Seoul, South Korea
| | - Young June Choe
- Department of Pediatrics, Korea University Anam Hospital, Seoul, South Korea
| | - Dong-Gyun Lim
- Research Institute of Public Health, National Medical Center, Seoul, South Korea
| | - Jun-Sun Park
- Research Institute of Public Health, National Medical Center, Seoul, South Korea
| | - Eun Hwa Choi
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, South Korea,Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, South Korea,Corresponding Author: Eun Hwa Choi, MD, PhD, Department of Pediatrics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, South Korea. E-mail:
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14
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Grootemaat AE, van der Niet S, Scholl ER, Roos E, Schurink B, Bugiani M, Miller SE, Larsen P, Pankras J, Reits EA, van der Wel NN. Lipid and Nucleocapsid N-Protein Accumulation in COVID-19 Patient Lung and Infected Cells. Microbiol Spectr 2022; 10:e0127121. [PMID: 35171025 PMCID: PMC8849100 DOI: 10.1128/spectrum.01271-21] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 01/11/2022] [Indexed: 12/11/2022] Open
Abstract
The pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global outbreak and prompted an enormous research effort. Still, the subcellular localization of the coronavirus in lungs of COVID-19 patients is not well understood. Here, the localization of the SARS-CoV-2 proteins is studied in postmortem lung material of COVID-19 patients and in SARS-CoV-2-infected Vero cells, processed identically. Correlative light and electron microscopy on semithick cryo-sections demonstrated induction of electron-lucent, lipid-filled compartments after SARS-CoV-2 infection in both lung and cell cultures. In lung tissue, the nonstructural protein 4 and the stable nucleocapsid N-protein were detected on these novel lipid-filled compartments. The induction of such lipid-filled compartments and the localization of the viral proteins in lung of patients with fatal COVID-19 may explain the extensive inflammatory response and provide a new hallmark for SARS-CoV-2 infection at the final, fatal stage of infection. IMPORTANCE Visualization of the subcellular localization of SARS-CoV-2 proteins in lung patient material of COVID-19 patients is important for the understanding of this new virus. We detected viral proteins in the context of the ultrastructure of infected cells and tissues and discovered that some viral proteins accumulate in novel, lipid-filled compartments. These structures are induced in Vero cells but, more importantly, also in lung of patients with COVID-19. We have characterized these lipid-filled compartments and determined that this is a novel, virus-induced structure. Immunogold labeling demonstrated that cellular markers, such as CD63 and lipid droplet marker PLIN-2, are absent. Colocalization of lipid-filled compartments with the stable N-protein and nonstructural protein 4 in lung of the last stages of COVID-19 indicates that these compartments play a key role in the devastating immune response that SARS-CoV-2 infections provoke.
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Affiliation(s)
- Anita E. Grootemaat
- Electron Microscopy Centre Amsterdam, Medical Biology, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
| | - Sanne van der Niet
- Electron Microscopy Centre Amsterdam, Medical Biology, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
| | - Edwin R. Scholl
- Electron Microscopy Centre Amsterdam, Medical Biology, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
| | - Eva Roos
- Department of Pathology, Amsterdam University Medical Centers (UMC), VU University Amsterdam, Amsterdam, the Netherlands
| | - Bernadette Schurink
- Department of Pathology, Amsterdam University Medical Centers (UMC), VU University Amsterdam, Amsterdam, the Netherlands
| | - Marianna Bugiani
- Department of Pathology, Amsterdam University Medical Centers (UMC), VU University Amsterdam, Amsterdam, the Netherlands
| | - Sara E. Miller
- Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA
| | - Per Larsen
- Electron Microscopy Centre Amsterdam, Medical Biology, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
- Department of Pathology, Amsterdam University Medical Centers (UMC), VU University Amsterdam, Amsterdam, the Netherlands
| | - Jeannette Pankras
- Electron Microscopy Centre Amsterdam, Medical Biology, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
- Department of Pathology, Amsterdam University Medical Centers (UMC), VU University Amsterdam, Amsterdam, the Netherlands
| | - Eric A. Reits
- Electron Microscopy Centre Amsterdam, Medical Biology, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
| | - Nicole N. van der Wel
- Electron Microscopy Centre Amsterdam, Medical Biology, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
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15
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Kudlay D, Kofiadi I, Khaitov M. Peculiarities of the T Cell Immune Response in COVID-19. Vaccines (Basel) 2022; 10:242. [PMID: 35214700 PMCID: PMC8877307 DOI: 10.3390/vaccines10020242] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 01/11/2022] [Accepted: 01/27/2022] [Indexed: 02/06/2023] Open
Abstract
Understanding the T cell response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance, and control strategies for this disease. This review provides data from studies of the immune response in coronavirus infections. It describes general mechanisms of immunity, its T cell components, and presents a detailed scheme of the T cell response in SARS-CoV-2 infection, including from the standpoint of determining the most promising targets for assessing its level. In addition, we reviewed studies investigating post-vaccination immunity in the development of vaccines against COVID-19. This review also includes the peculiarities of immunity in different age and gender groups, and in the presence of a number of factors, for example, comorbidity or disease severity. This study summarizes the most informative methods for assessing the immune response to SARS-CoV-2 infection.
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Affiliation(s)
- Dmitry Kudlay
- NRC Institute of Immunology FMBA of Russia, 115522 Moscow, Russia
- Department of Pharmacology, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
| | - Ilya Kofiadi
- NRC Institute of Immunology FMBA of Russia, 115522 Moscow, Russia
- Department of Immunology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia
| | - Musa Khaitov
- NRC Institute of Immunology FMBA of Russia, 115522 Moscow, Russia
- Department of Immunology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia
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16
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Zheng J, Deng Y, Zhao Z, Mao B, Lu M, Lin Y, Huang A. Characterization of SARS-CoV-2-specific humoral immunity and its potential applications and therapeutic prospects. Cell Mol Immunol 2022; 19:150-157. [PMID: 34645940 PMCID: PMC8513558 DOI: 10.1038/s41423-021-00774-w] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 08/12/2021] [Indexed: 12/23/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic that poses a great threat to human health worldwide. As the humoral immune response plays essential roles in disease occurrence and development, understanding the dynamics and characteristics of virus-specific humoral immunity in SARS-CoV-2-infected patients is of great importance for controlling this disease. In this review, we summarize the characteristics of the humoral immune response after SARS-CoV-2 infection and further emphasize the potential applications and therapeutic prospects of SARS-CoV-2-specific humoral immunity and the critical role of this immunity in vaccine development. Notably, serological antibody testing based on the humoral immune response can guide public health measures and control strategies; however, it is not recommended for population surveys in areas with very low prevalence. Existing evidence suggests that asymptomatic individuals have a weaker immune response to SARS-CoV-2 infection, whereas SARS-CoV-2-infected children have a more effective humoral immune response than adults. The correlations between antibody (especially neutralizing antibody) titers and protection against SARS-CoV-2 reinfection should be further examined. In addition, the emergence of cross-reactions among different coronavirus antigens in the development of screening technology and the risk of antibody-dependent enhancement related to SARS-CoV-2 vaccination should be given further attention.
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Affiliation(s)
- Jiaxin Zheng
- Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yingying Deng
- Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Zhenyu Zhao
- Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Binli Mao
- Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Mengji Lu
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, 45122, Germany
| | - Yong Lin
- Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
| | - Ailong Huang
- Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
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17
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Adli A, Rahimi M, Khodaie R, Hashemzaei N, Hosseini SM. Role of Genetic Variants and Host Polymorphisms on COVID‐19: From Viral Entrance Mechanisms to Immunological Reactions. J Med Virol 2022; 94:1846-1865. [PMID: 35076118 PMCID: PMC9015257 DOI: 10.1002/jmv.27615] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/04/2022] [Accepted: 01/18/2022] [Indexed: 11/24/2022]
Abstract
Coronavirus disease 2019 (COVID‐19), caused by a highly pathogenic emerging virus, is called severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Knowledge regarding the pathogenesis of this virus is in infancy; however, investigation on the pathogenic mechanisms of the SARS‐CoV‐2 is underway. In COVID‐19, one of the most remarkable characteristics is the wide range of disease manifestation and severity seen across individuals of different ethnic backgrounds and geographical locations. To effectively manage COVID‐19 in the populations, beyond SARS‐CoV‐2 detection, serological response assessment, and analytic techniques, it is critical to obtain knowledge about at‐risk individuals and comprehend the identified variations in the disease's severity in general and also in the populations' levels. Several factors can contribute to variation in disease presentation, including population density, gender and age differences, and comorbid circumstances including diabetes mellitus, hypertension, and obesity. Genetic factors presumably influence SARS‐CoV‐2 infection susceptibility. Besides this, COVID‐19 has also been linked with a higher risk of mortality in men and certain ethnic groups, revealing that host genetic characteristics may affect the individual risk of death. Also, genetic variants involved in pathologic processes, including virus entrance into cells, antiviral immunity, and inflammatory response, are not entirely understood. Regarding SARS‐CoV‐2 infection characteristics, the present review suggests that various genetic polymorphisms influence virus pathogenicity and host immunity, which might have significant implications for understanding and interpreting the matter of genetics in SARS‐CoV‐2 pathogenicity and customized integrative medical care based on population investigation.
Genetic factors presumably influence SARS‐CoV‐2 infection susceptibility. Genetic variants were involved in the pathologic processes of SARS‐CoV‐2 infection. Various genetic polymorphisms influence virus pathogenicity and host immunity. Human leukocyte antigens (HLAs) may play a vital role in SARS‐CoV‐2 susceptibility. Polymorphisms in several genes such as IL‐6, TMPRSS2, IFITM3, CD26, ACE, and DBP were associated with the COVID‐19 severity.
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Affiliation(s)
- Abolfazl Adli
- Human Genetic Research Center, Baqiyatallah University of Medical SciencesTehran1435916471Iran
| | - Mandana Rahimi
- Department of Pathology, School of Medicine, Hasheminejad Kidney Center, Iran University of Medical SciencesTehranIran
| | - Reza Khodaie
- Department of Biology, East Tehran Branch, Islamic Azad UniversityTehranIran
| | | | - Sayed Mostafa Hosseini
- Human Genetic Research Center, Baqiyatallah University of Medical SciencesTehran1435916471Iran
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18
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In silico Design and Characterization of Multi-epitopes Vaccine for SARS-CoV2 from Its Spike Protein. Int J Pept Res Ther 2022; 28:37. [PMID: 35002585 PMCID: PMC8722413 DOI: 10.1007/s10989-021-10348-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/12/2021] [Indexed: 11/04/2022]
Abstract
COVID 19 is a disease caused by a novel coronavirus, SARS-CoV2 originated in China most probably of Bat origin. Multiepitopes vaccine would be useful in eliminating SARS-CoV2 infections as asymptomatic patients are in large numbers. In response to this, we utilized bioinformatic tools to develop an efficient vaccine candidate against SARS-CoV2. The designed vaccine has effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Predicted BCR and TCR epitopes found antigenic, non-toxic and probably non-allergen. Modeled and the refined tertiary structure predicted as valid for further use. Protein–Protein interaction prediction of TLR2/4 and designed vaccine indicates promising binding. The designed multiepitope vaccine has induced cell-mediated and humoral immunity along with increased interferon-gamma response. Macrophages and dendritic cells were also found to increase upon the vaccine exposure. In silico codon optimization and cloning in expression vector indicates that the vaccine can be efficiently expressed in E. coli. In conclusion, the predicted vaccine is a good antigen, probable no allergen, and has the potential to induce cellular and humoral immunity.
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19
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Abstract
Adaptive immune responses play critical roles in viral clearance and protection against re-infection, and SARS-CoV-2 is no exception. What is exceptional is the rapid characterization of the immune response to the virus performed by researchers during the first 20 months of the pandemic. This has given us a more detailed understanding of SARS-CoV-2 compared to many viruses that have been with us for a long time. Furthermore, effective COVID-19 vaccines were developed in record time, and their rollout worldwide is already making a significant difference, although major challenges remain in terms of equal access. The pandemic has engaged scientists and the public alike, and terms such as seroprevalence, neutralizing antibodies, antibody escape and vaccine certificates have become familiar to a broad community. Here, we review key findings concerning B cell and antibody (Ab) responses to SARS-CoV-2, focusing on non-severe cases and anti-spike (S) Ab responses in particular, the latter being central to protective immunity induced by infection or vaccination. The emergence of viral variants that have acquired mutations in S acutely highlights the need for continued characterization of both emerging variants and Ab responses against these during the evolving pathogen-immune system arms race.
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Affiliation(s)
- Xaquin Castro Dopico
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Sebastian Ols
- Department of Medicine, Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Karin Loré
- Department of Medicine, Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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20
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Xiao T, Cheng Y, Lu G, Zhou W. Pandemic considerations in pediatric critical care: what can we learn from COVID-19? Transl Pediatr 2021; 10:2875-2880. [PMID: 34765508 PMCID: PMC8578757 DOI: 10.21037/tp-20-129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 11/06/2020] [Indexed: 11/06/2022] Open
Affiliation(s)
- Tiantian Xiao
- Department of Neonatology, Children’s Hospital of Fudan University, Shanghai, China
| | - Ye Cheng
- Pediatric Intensive Care Unit, Children’s Hospital of Fudan University, Shanghai, China
| | - Gouping Lu
- Pediatric Intensive Care Unit, Children’s Hospital of Fudan University, Shanghai, China
| | - Wenhao Zhou
- Department of Neonatology, Children’s Hospital of Fudan University, Shanghai, China
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21
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Blanchard-Rohner G, Didierlaurent A, Tilmanne A, Smeesters P, Marchant A. Pediatric COVID-19: Immunopathogenesis, Transmission and Prevention. Vaccines (Basel) 2021; 9:1002. [PMID: 34579240 PMCID: PMC8473426 DOI: 10.3390/vaccines9091002] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 08/31/2021] [Accepted: 09/01/2021] [Indexed: 12/18/2022] Open
Abstract
Children are unique in the context of the COVID-19 pandemic. Overall, SARS-CoV-2 has a lower medical impact in children as compared to adults. A higher proportion of children than adults remain asymptomatic following SARS-CoV-2 infection and severe disease and death are also less common. This relative resistance contrasts with the high susceptibility of children to other respiratory tract infections. The mechanisms involved remain incompletely understood but could include the rapid development of a robust innate immune response. On the other hand, children develop a unique and severe complication, named multisystem inflammatory syndrome in children, several weeks after the onset of symptoms. Although children play an important role in the transmission of many pathogens, their contribution to the transmission of SARS-CoV-2 appears lower than that of adults. These unique aspects of COVID-19 in children must be considered in the benefit-risk analysis of vaccination. Several COVID-19 vaccines have been authorized for emergency use in adolescents and clinical studies are ongoing in children. As the vaccination of adolescents is rolled out in several countries, we shall learn about the impact of this strategy on the health of children and on transmission within communities.
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Affiliation(s)
- Geraldine Blanchard-Rohner
- Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland
- Pediatric Immunology and Vaccinology Unit, Division of General Pediatrics, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Hospitals, University of Geneva, 1205 Geneva, Switzerland;
- Children’s Hospital of Geneva, 6, Rue Willy-Donzé, 1211 Geneva, Switzerland
| | - Arnaud Didierlaurent
- Pediatric Immunology and Vaccinology Unit, Division of General Pediatrics, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Hospitals, University of Geneva, 1205 Geneva, Switzerland;
| | - Anne Tilmanne
- Children’s Hospital Queen Fabiola, Université libre de Bruxelles, 1020 Brussels, Belgium; (A.T.); (P.S.)
| | - Pierre Smeesters
- Children’s Hospital Queen Fabiola, Université libre de Bruxelles, 1020 Brussels, Belgium; (A.T.); (P.S.)
| | - Arnaud Marchant
- Institute for Medical Immunology, Université libre de Bruxelles, 1050 Charleroi, Belgium;
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22
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Filippatos F, Tatsi EB, Michos A. Immune response to SARS-CoV-2 in children: A review of the current knowledge. Pediatr Investig 2021; 5:217-228. [PMID: 34540321 PMCID: PMC8441939 DOI: 10.1002/ped4.12283] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 04/13/2021] [Indexed: 12/14/2022] Open
Abstract
Host immune responses to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), especially in children, are still under investigation. Children with coronavirus disease 2019 (COVID‐19) constitute a significant study group of immune responses as they rarely present with severe clinical manifestations, require hospitalization, or develop complications such as multisystem inflammatory syndrome in children (MIS‐C) associated with SARS‐CoV‐2 infection. The deciphering of children’s immune responses during COVID‐19 infection will provide information about the protective mechanisms, while new potential targets for future therapies are likely to be revealed. Despite the limited immunological studies in children with COVID‐19, this review compares data between adults and children in terms of innate and adaptive immunity to SARS‐CoV‐2, discusses the possible reasons why children are mostly asymptomatic, and highlights unanswered or unclear immunological issues. Current evidence suggests that the activity of innate immunity seems to be crucial to the early phases of SARS‐CoV‐2 infection and adaptive memory immunity is vital to prevent reinfection. Despite the limited immunological studies from children with COVID‐19, this review compares data between adults and children in terms of innate and adaptive immunity to SARS‐CoV‐2, discusses the possible reasons why children are mostly asymptomatic, and highlights unanswered or unclear immunological issues.
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Affiliation(s)
- Filippos Filippatos
- First Department of Pediatrics Infectious Diseases and Chemotherapy Research Laboratory Medical School National and Kapodistrian University of Athens "Aghia Sophia" Children's Hospital Athens Greece
| | - Elizabeth-Barbara Tatsi
- First Department of Pediatrics Infectious Diseases and Chemotherapy Research Laboratory Medical School National and Kapodistrian University of Athens "Aghia Sophia" Children's Hospital Athens Greece
| | - Athanasios Michos
- First Department of Pediatrics Infectious Diseases and Chemotherapy Research Laboratory Medical School National and Kapodistrian University of Athens "Aghia Sophia" Children's Hospital Athens Greece
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23
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Senapati S, Darling RJ, Ross KA, Wannemeuhler MJ, Narasimhan B, Mallapragada SK. Self-assembling synthetic nanoadjuvant scaffolds cross-link B cell receptors and represent new platform technology for therapeutic antibody production. SCIENCE ADVANCES 2021; 7:eabj1691. [PMID: 34348905 PMCID: PMC8336949 DOI: 10.1126/sciadv.abj1691] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 06/17/2021] [Indexed: 06/13/2023]
Abstract
Host antibody responses are pivotal for providing protection against infectious agents. We have pioneered a new class of self-assembling micelles based on pentablock copolymers that enhance antibody responses while providing a low inflammatory environment compared to traditional adjuvants. This type of "just-right" immune response is critical in the rational design of vaccines for older adults. Here, we report on the mechanism of enhancement of antibody responses by pentablock copolymer micelles, which act as scaffolds for antigen presentation to B cells and cross-link B cell receptors, unlike other micelle-forming synthetic block copolymers. We exploited this unique mechanism and developed these scaffolds as a platform technology to produce antibodies in vitro. We show that this novel approach can be used to generate laboratory-scale quantities of therapeutic antibodies against multiple antigens, including those associated with SARS-CoV-2 and Yersinia pestis, further expanding the value of these nanomaterials to rapidly develop countermeasures against infectious diseases.
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Affiliation(s)
- Sujata Senapati
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, USA
| | - Ross J Darling
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA
| | - Kathleen A Ross
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, USA
- Nanovaccine Institute, Iowa State University, Ames, IA, USA
| | - Michael J Wannemeuhler
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA
- Nanovaccine Institute, Iowa State University, Ames, IA, USA
| | - Balaji Narasimhan
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, USA.
- Nanovaccine Institute, Iowa State University, Ames, IA, USA
| | - Surya K Mallapragada
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, USA.
- Nanovaccine Institute, Iowa State University, Ames, IA, USA
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24
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L’Huillier AG, Danziger‐Isakov L, Chaudhuri A, Green M, Michaels MG, M Posfay‐Barbe K, van der Linden D, Verma A, McCulloch M, Ardura MI. SARS-CoV-2 and pediatric solid organ transplantation: Current knowns and unknowns. Pediatr Transplant 2021; 25:e13986. [PMID: 33689201 PMCID: PMC8237081 DOI: 10.1111/petr.13986] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 01/17/2021] [Accepted: 02/02/2021] [Indexed: 12/11/2022]
Abstract
The COVID-19 pandemic has proven to be a challenge in regard to the clinical presentation, prevention, diagnosis, and management of SARS-CoV-2 infection among children who are candidates for and recipients of SOT. By providing scenarios and frequently asked questions encountered in routine clinical practice, this document provides expert opinion and summarizes the available data regarding the prevention, diagnosis, and management of SARS-CoV-2 infection among pediatric SOT candidates and recipients and highlights ongoing knowledge gaps requiring further study. Currently available data are still lacking in the pediatric SOT population, but data have emerged in both the adult SOT and general pediatric population regarding the approach to COVID-19. The document provides expert opinion regarding prevention, diagnosis, and management of SARS-CoV-2 infection among pediatric SOT candidates and recipients.
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Affiliation(s)
- Arnaud G. L’Huillier
- Pediatric Infectious Diseases UnitGeneva University Hospitals and Faculty of MedicineGenevaSwitzerland
| | | | | | - Michael Green
- UPMC Children’s Hospital of PittsburghPittsburghPAUSA
| | | | - Klara M Posfay‐Barbe
- Pediatric Infectious Diseases UnitGeneva University Hospitals and Faculty of MedicineGenevaSwitzerland
| | - Dimitri van der Linden
- Pediatric Infectious DiseasesDepartment of PediatricsCliniques Universitaires Saint‐LucBrusselsBelgium
| | | | | | - Monica I. Ardura
- Department of Pediatrics, Infectious Diseases and Host DefenseNationwide Children’s HospitalThe Ohio State UniversityColumbusOHUSA
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25
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Subramaniam S, Ruf W, Bosmann M. Advocacy of targeting protease-activated receptors in severe coronavirus disease 2019. Br J Pharmacol 2021; 179:2086-2099. [PMID: 34235728 PMCID: PMC8794588 DOI: 10.1111/bph.15587] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 05/19/2021] [Accepted: 05/27/2021] [Indexed: 12/23/2022] Open
Abstract
Identifying drug targets mitigating vascular dysfunction, thrombo-inflammation and thromboembolic complications in COVID-19 is essential. COVID-19 coagulopathy differs from sepsis coagulopathy. Factors that drive severe lung pathology and coagulation abnormalities in COVID-19 are not understood. Protein-protein interaction studies indicate that the tagged viral bait protein ORF9c directly interacts with PAR2, which modulates host cell IFN and inflammatory cytokines. In addition to direct interaction of SARS-CoV-2 viral protein with PARs, we speculate that activation of PAR by proteases plays a role in COVID-19-induced hyperinflammation. In COVID-19-associated coagulopathy elevated levels of activated coagulation proteases may cleave PARs in association with TMPRSS2. PARs activation enhances the release of cytokines, chemokines and tissue factor expression to propagate IFN-dependent inflammation, leukocyte-endothelial interaction, vascular permeability and coagulation responses. This hypothesis, corroborated by in vitro findings and emerging clinical evidence, will focus targeted studies of PAR1/2 blockers as adjuvant drugs against cytokine release syndrome and COVID-19-associated coagulopathy.
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Affiliation(s)
- Saravanan Subramaniam
- Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Wolfram Ruf
- Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.,Department of Immunology and Microbiology, Scripps Research, La Jolla, California, USA
| | - Markus Bosmann
- Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.,Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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26
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Sahu U, Biswas D, Singh AK, Khare P. Mechanism involved in the pathogenesis and immune response against SARS-CoV-2 infection. Virusdisease 2021; 32:211-219. [PMID: 33969150 PMCID: PMC8096142 DOI: 10.1007/s13337-021-00687-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 04/08/2021] [Indexed: 12/18/2022] Open
Abstract
SARS CoV-2, a causative agent of human respiratory tract infection, was first identified in late 2019. It is a newly emerging viral disease with unsatisfactory treatments. The virus is highly contagious and has caused pandemic globally. The number of deaths is increasing exponentially, which is an alarming situation for mankind. The detailed mechanism of the pathogenesis and host immune responses to this virus are not fully known. Here we discuss an overview of SARS CoV-2 pathogenicity, its entry and replication mechanism, and host immune response against this deadly pathogen. Understanding these processes will help to lead the development and identification of drug targets and effective therapies.
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Affiliation(s)
- Utkarsha Sahu
- Department of Microbiology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh India
| | - Debasis Biswas
- Department of Microbiology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh India
| | - Anirudh Kumar Singh
- Department of Microbiology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh India
| | - Prashant Khare
- Department of Microbiology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh India
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27
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Khatiwada S, Subedi A. A Mechanistic Link Between Selenium and Coronavirus Disease 2019 (COVID-19). Curr Nutr Rep 2021; 10:125-136. [PMID: 33835432 PMCID: PMC8033553 DOI: 10.1007/s13668-021-00354-4] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/23/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Coronavirus disease 2019 (COVID-19) is a rapidly emerging disease caused by a highly contagious virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and this disease has affected millions of people across the world and led to hundreds of thousands of deaths worldwide. Nutrition is a key factor related to this disease, and nutritional status may determine the risk and outcomes of SARS-CoV-2 infection. Selenium is one of the major trace elements required for redox functions and has significant roles in viral infections. The purpose of this review was to examine the current evidence on the role of selenium in COVID-19. We reviewed studies on selenium and COVID-19, and other relevant studies to understand how selenium status can modify the risk of SARS-CoV-2 infection, and how selenium status might affect a person post-infection. RECENT FINDINGS We found that oxidative stress is a characteristic feature of COVID-19 disease, which is linked with the immunopathological disorder observed in individuals with severe COVID-19. Selenium plays a key role in strengthening immunity, reducing oxidative stress, preventing viral infections and supporting critical illness. Moreover, selenium deficiency is related to oxidative stress and hyperinflammation seen in critical illness, and selenium deficiency is found to be associated with the severity of COVID-19 disease. Selenium supplementation at an appropriate dose may act as supportive therapy in COVID-19. Future studies in large cohorts of COVID-19 are warranted to verify the benefits of selenium supplementation for reducing risk and severity of COVID-19.
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Affiliation(s)
| | - Astha Subedi
- Medicine ICU, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
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28
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Wehbe Z, Hammoud SH, Yassine HM, Fardoun M, El-Yazbi AF, Eid AH. Molecular and Biological Mechanisms Underlying Gender Differences in COVID-19 Severity and Mortality. Front Immunol 2021; 12:659339. [PMID: 34025658 PMCID: PMC8138433 DOI: 10.3389/fimmu.2021.659339] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 04/20/2021] [Indexed: 12/13/2022] Open
Abstract
Globally, over two million people have perished due to the recent pandemic caused by SARS-CoV-2. The available epidemiological global data for SARS-CoV-2 portrays a higher rate of severity and mortality in males. Analyzing gender differences in the host mechanisms involved in SARS-CoV-2 infection and progression may offer insight into the more detrimental disease prognosis and clinical outcome in males. Therefore, we outline sexual dimorphisms which exist in particular host factors and elaborate on how they may contribute to the pronounced severity in male COVID-19 patients. This includes disparities detected in comorbidities, the ACE2 receptor, renin-angiotensin system (RAS), signaling molecules involved in SARS-CoV-2 replication, proteases which prime viral S protein, the immune response, and behavioral considerations. Moreover, we discuss sexual disparities associated with other viruses and a possible gender-dependent response to SARS-CoV-2 vaccines. By specifically highlighting these immune-endocrine processes as well as behavioral factors that differentially exist between the genders, we aim to offer a better understanding in the variations of SARS-CoV-2 pathogenicity.
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Affiliation(s)
- Zena Wehbe
- Department of Biology, American University of Beirut, Beirut, Lebanon
| | - Safaa Hisham Hammoud
- Department of Pharmacology and Therapeutics, Beirut Arab University, Beirut, Lebanon
| | | | - Manal Fardoun
- Department of Biology, American University of Beirut, Beirut, Lebanon
| | - Ahmed F. El-Yazbi
- Department of Pharmacology and Toxicology, American University of Beirut, Beirut, Lebanon
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Ali H. Eid
- Department of Basic Medical Sciences, College of Medicine, Qatar University Health, Qatar University, Doha, Qatar
- Biomedical and Pharmaceutical Research Unit, Qatar University Health, Qatar University, Doha, Qatar
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29
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Amaral JL, Oliveira JTA, Lopes FES, Freitas CDT, Freire VN, Abreu LV, Souza PFN. Quantum biochemistry, molecular docking, and dynamics simulation revealed synthetic peptides induced conformational changes affecting the topology of the catalytic site of SARS-CoV-2 main protease. J Biomol Struct Dyn 2021; 40:8925-8937. [PMID: 33949286 PMCID: PMC8108194 DOI: 10.1080/07391102.2021.1920464] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 04/16/2021] [Indexed: 02/07/2023]
Abstract
The recent outbreak caused by SARS-CoV-2 continues to threat and take many lives all over the world. The lack of an efficient pharmacological treatments are serious problems to be faced by scientists and medical staffs worldwide. In this work, an in silico approach based on the combination of molecular docking, dynamics simulations, and quantum biochemistry revealed that the synthetic peptides RcAlb-PepI, PepGAT, and PepKAA, strongly interact with the main protease (Mpro) a pivotal protein for SARS-CoV-2 replication. Although not binding to the proteolytic site of SARS-CoV-2 Mpro, RcAlb-PepI, PepGAT, and PepKAA interact with other protein domain and allosterically altered the protease topology. Indeed, such peptide-SARS-CoV-2 Mpro complexes provoked dramatic alterations in the three-dimensional structure of Mpro leading to area and volume shrinkage of the proteolytic site, which could affect the protease activity and thus the virus replication. Based on these findings, it is suggested that RcAlb-PepI, PepGAT, and PepKAA could interfere with SARS-CoV-2 Mpro role in vivo. Also, unlike other antiviral drugs, these peptides have no toxicity to human cells. This pioneering in silico investigation opens up opportunity for further in vivo research on these peptides, towards discovering new drugs and entirely new perspectives to treat COVID-19.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Jackson L. Amaral
- Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil
| | - Jose T. A. Oliveira
- Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil
| | - Francisco E. S. Lopes
- Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil
- Center for Permanent Education in Health Care, CEATS/School of Public Health of Ceará-ESP-CE, Fortaleza, Brazil
| | - Cleverson D. T. Freitas
- Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil
| | - Valder N. Freire
- Department of Physics, Federal University of Ceará, Fortaleza, Brazil
| | - Leonardo V. Abreu
- Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil
| | - Pedro F. N. Souza
- Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil
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30
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Scott TM, Jensen S, Pickett BE. A signaling pathway-driven bioinformatics pipeline for predicting therapeutics against emerging infectious diseases. F1000Res 2021; 10:330. [PMID: 34868553 PMCID: PMC8607308 DOI: 10.12688/f1000research.52412.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/22/2021] [Indexed: 11/03/2023] Open
Abstract
Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of coronavirus disease-2019 (COVID-19), is a novel Betacoronavirus that was first reported in Wuhan, China in December of 2019. The virus has since caused a worldwide pandemic that highlights the need to quickly identify potential prophylactic or therapeutic treatments that can reduce the signs, symptoms, and/or spread of disease when dealing with a novel infectious agent. To combat this problem, we constructed a computational pipeline that uniquely combines existing tools to predict drugs and biologics that could be repurposed to combat an emerging pathogen. Methods: Our workflow analyzes RNA-sequencing data to determine differentially expressed genes, enriched Gene Ontology (GO) terms, and dysregulated pathways in infected cells, which can then be used to identify US Food and Drug Administration (FDA)-approved drugs that target human proteins within these pathways. We used this pipeline to perform a meta-analysis of RNA-seq data from cells infected with three Betacoronavirus species including severe acute respiratory syndrome coronavirus (SARS-CoV; SARS), Middle East respiratory syndrome coronavirus (MERS-CoV; MERS), and SARS-CoV-2, as well as respiratory syncytial virus and influenza A virus to identify therapeutics that could be used to treat COVID-19. Results: This analysis identified twelve existing drugs, most of which already have FDA-approval, that are predicted to counter the effects of SARS-CoV-2 infection. These results were cross-referenced with interventional clinical trials and other studies in the literature to identify drugs on our list that had previously been identified or used as treatments for COIVD-19 including canakinumab, anakinra, tocilizumab, sarilumab, and baricitinib. Conclusions: While the results reported here are specific to Betacoronaviruses, such as SARS-CoV-2, our bioinformatics pipeline can be used to quickly identify candidate therapeutics for future emerging infectious diseases.
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Affiliation(s)
- Tiana M. Scott
- Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, 84602, USA
| | - Sam Jensen
- Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, 84602, USA
| | - Brett E. Pickett
- Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, 84602, USA
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31
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Scott TM, Jensen S, Pickett BE. A signaling pathway-driven bioinformatics pipeline for predicting therapeutics against emerging infectious diseases. F1000Res 2021; 10:330. [PMID: 34868553 PMCID: PMC8607308 DOI: 10.12688/f1000research.52412.2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/18/2021] [Indexed: 01/08/2023] Open
Abstract
Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of coronavirus disease-2019 (COVID-19), is a novel Betacoronavirus that was first reported in Wuhan, China in December of 2019. The virus has since caused a worldwide pandemic that highlights the need to quickly identify potential prophylactic or therapeutic treatments that can reduce the signs, symptoms, and/or spread of disease when dealing with a novel infectious agent. To combat this problem, we constructed a computational pipeline that uniquely combines existing tools to predict drugs and biologics that could be repurposed to combat an emerging pathogen. Methods: Our workflow analyzes RNA-sequencing data to determine differentially expressed genes, enriched Gene Ontology (GO) terms, and dysregulated pathways in infected cells, which can then be used to identify US Food and Drug Administration (FDA)-approved drugs that target human proteins within these pathways. We used this pipeline to perform a meta-analysis of RNA-seq data from cells infected with three Betacoronavirus species including severe acute respiratory syndrome coronavirus (SARS-CoV; SARS), Middle East respiratory syndrome coronavirus (MERS-CoV; MERS), and SARS-CoV-2, as well as respiratory syncytial virus and influenza A virus to identify therapeutics that could be used to treat COVID-19. Results: This analysis identified twelve existing drugs, most of which already have FDA-approval, that are predicted to counter the effects of SARS-CoV-2 infection. These results were cross-referenced with interventional clinical trials and other studies in the literature to identify drugs on our list that had previously been identified or used as treatments for COIVD-19 including canakinumab, anakinra, tocilizumab, sarilumab, and baricitinib. Conclusions: While the results reported here are specific to Betacoronaviruses, such as SARS-CoV-2, our bioinformatics pipeline can be used to quickly identify candidate therapeutics for future emerging infectious diseases.
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Affiliation(s)
- Tiana M. Scott
- Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, 84602, USA
| | - Sam Jensen
- Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, 84602, USA
| | - Brett E. Pickett
- Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, 84602, USA
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32
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Jia W, Wang J, Sun B, Zhou J, Shi Y, Zhou Z. The Mechanisms and Animal Models of SARS-CoV-2 Infection. Front Cell Dev Biol 2021; 9:578825. [PMID: 33987176 PMCID: PMC8111004 DOI: 10.3389/fcell.2021.578825] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 04/12/2021] [Indexed: 01/08/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has aroused great public health concern worldwide. Currently, COVID-19 epidemic is spreading in many countries and regions around the world. However, the study of SARS-CoV-2 is still in its infancy, and there is no specific therapeutics. Here, we summarize the genomic characteristics of SARS-CoV-2. In addition, we focus on the mechanisms of SARS-CoV-2 infection, including the roles of angiotensin converting enzyme II (ACE2) in cell entry, COVID-19 susceptibility and COVID-19 symptoms, as well as immunopathology such as antibody responses, lymphocyte dysregulation, and cytokine storm. Finally, we introduce the research progress of animal models of COVID-19, aiming at a better understanding of the pathogenesis of COVID-19 and providing new ideas for the treatment of this contagious disease.
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Affiliation(s)
- Wenrui Jia
- Department of Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Juan Wang
- Department of Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Bao Sun
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Jiecan Zhou
- Institute of Clinical Medicine, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Yamin Shi
- Department of Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zheng Zhou
- Department of Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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33
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Villena J, Li C, Vizoso-Pinto MG, Sacur J, Ren L, Kitazawa H. Lactiplantibacillus plantarum as a Potential Adjuvant and Delivery System for the Development of SARS-CoV-2 Oral Vaccines. Microorganisms 2021; 9:683. [PMID: 33810287 PMCID: PMC8067309 DOI: 10.3390/microorganisms9040683] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/18/2021] [Accepted: 03/24/2021] [Indexed: 01/08/2023] Open
Abstract
The most important characteristics regarding the mucosal infection and immune responses against the Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) as well as the current vaccines against coronavirus disease 2019 (COVID-19) in development or use are revised to emphasize the opportunity for lactic acid bacteria (LAB)-based vaccines to offer a valid alternative in the fight against this disease. In addition, this article revises the knowledge on: (a) the cellular and molecular mechanisms involved in the improvement of mucosal antiviral defenses by beneficial Lactiplantibacillus plantarum strains, (b) the systems for the expression of heterologous proteins in L. plantarum and (c) the successful expressions of viral antigens in L. plantarum that were capable of inducing protective immune responses in the gut and the respiratory tract after their oral administration. The ability of L. plantarum to express viral antigens, including the spike protein of SARS-CoV-2 and its capacity to differentially modulate the innate and adaptive immune responses in both the intestinal and respiratory mucosa after its oral administration, indicates the potential of this LAB to be used in the development of a mucosal COVID-19 vaccine.
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Affiliation(s)
- Julio Villena
- Reference Centre for Lactobacilli (CERELA-CONICET), Laboratory of Immunobiotechnology, Tucuman CP4000, Argentina
- Laboratory of Animal Products Chemistry, Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
| | - Chang Li
- Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Military Veterinary Institute, Academy of Military Medical Sciences, Changchun 130122, China;
| | - Maria Guadalupe Vizoso-Pinto
- Infection Biology Laboratory, Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, Tucuman CP4000, Argentina; (M.G.V.-P.); (J.S.)
| | - Jacinto Sacur
- Infection Biology Laboratory, Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, Tucuman CP4000, Argentina; (M.G.V.-P.); (J.S.)
| | - Linzhu Ren
- College of Animal Sciences, Key Lab for Zoonoses Research, Ministry of Education, Jilin University, Changchun 130062, China
| | - Haruki Kitazawa
- Laboratory of Animal Products Chemistry, Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
- International Education and Research Center for Food Agricultural Immunology, Livestock Immunology Unit, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
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34
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Cotugno N, Ruggiero A, Bonfante F, Petrara MR, Zicari S, Pascucci GR, Zangari P, De Ioris MA, Santilli V, Manno EC, Amodio D, Bortolami A, Pagliari M, Concato C, Linardos G, Campana A, Donà D, Giaquinto C, Brodin P, Rossi P, De Rossi A, Palma P. Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies. Cell Rep 2021; 34:108852. [PMID: 33730580 PMCID: PMC7962998 DOI: 10.1016/j.celrep.2021.108852] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 12/28/2020] [Accepted: 02/19/2021] [Indexed: 12/11/2022] Open
Abstract
As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.
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Affiliation(s)
- Nicola Cotugno
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome "Tor Vergata," 00185 Rome, Italy
| | - Alessandra Ruggiero
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy
| | - Francesco Bonfante
- Laboratory of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, 35020 Legnaro, Italy
| | - Maria Raffaella Petrara
- Section of Oncology and Immunology, Department of Surgery, Oncology, and Gastroenterology, Unit of Viral Oncology and AIDS Reference Center, University of Padova, 35128 Padova, Italy
| | - Sonia Zicari
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy
| | - Giuseppe Rubens Pascucci
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy
| | - Paola Zangari
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy
| | | | - Veronica Santilli
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy
| | - E C Manno
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy
| | - Donato Amodio
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome "Tor Vergata," 00185 Rome, Italy
| | - Alessio Bortolami
- Laboratory of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, 35020 Legnaro, Italy
| | - Matteo Pagliari
- Laboratory of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, 35020 Legnaro, Italy
| | - Carlo Concato
- Department of Laboratories, Division of Virology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy
| | - Giulia Linardos
- Department of Laboratories, Division of Virology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy
| | - Andrea Campana
- Academic Department of Pediatrics, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy
| | - Daniele Donà
- Department of Mother and Child Health, University of Padova, 35128 Padova, Italy
| | - Carlo Giaquinto
- Department of Mother and Child Health, University of Padova, 35128 Padova, Italy
| | - Petter Brodin
- Pediatric Rheumatology, Karolinska University Hospital, 17177 Stockholm, Sweden
| | - Paolo Rossi
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome "Tor Vergata," 00185 Rome, Italy
| | - Anita De Rossi
- Section of Oncology and Immunology, Department of Surgery, Oncology, and Gastroenterology, Unit of Viral Oncology and AIDS Reference Center, University of Padova, 35128 Padova, Italy; Istituto Oncologico Veneto (IOV)-IRCCS, 35128 Padova, Italy
| | - Paolo Palma
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome "Tor Vergata," 00185 Rome, Italy.
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Huang KYA, Tan TK, Chen TH, Huang CG, Harvey R, Hussain S, Chen CP, Harding A, Gilbert-Jaramillo J, Liu X, Knight M, Schimanski L, Shih SR, Lin YC, Cheng CY, Cheng SH, Huang YC, Lin TY, Jan JT, Ma C, James W, Daniels RS, McCauley JW, Rijal P, Townsend AR. Breadth and function of antibody response to acute SARS-CoV-2 infection in humans. PLoS Pathog 2021; 17:e1009352. [PMID: 33635919 PMCID: PMC8130932 DOI: 10.1371/journal.ppat.1009352] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 05/18/2021] [Accepted: 02/02/2021] [Indexed: 12/31/2022] Open
Abstract
Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 3.5% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-receptor-binding domain (RBD), three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two recovered patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. Finally, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.
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Affiliation(s)
- Kuan-Ying A. Huang
- Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Tiong Kit Tan
- MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
| | - Ting-Hua Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Chung-Guei Huang
- Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Ruth Harvey
- Worldwide Influenza Centre, The Francis Crick Institute, 1 Midland Road, London, United Kingdom
| | - Saira Hussain
- Worldwide Influenza Centre, The Francis Crick Institute, 1 Midland Road, London, United Kingdom
| | - Cheng-Pin Chen
- Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, and National Yang-Ming University, Taipei, Taiwan
| | - Adam Harding
- Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
| | | | - Xu Liu
- Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
| | - Michael Knight
- Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
| | - Lisa Schimanski
- MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
- Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, United Kingdom
| | - Shin-Ru Shih
- Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Yi-Chun Lin
- Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, and Taipei Medical University, Taipei, Taiwan
| | - Chien-Yu Cheng
- Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, and National Yang-Ming University, Taipei, Taiwan
| | - Shu-Hsing Cheng
- Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, and Taipei Medical University, Taipei, Taiwan
| | - Yhu-Chering Huang
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Tzou-Yien Lin
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Jia-Tsrong Jan
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Che Ma
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - William James
- Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
| | - Rodney S. Daniels
- Worldwide Influenza Centre, The Francis Crick Institute, 1 Midland Road, London, United Kingdom
| | - John W. McCauley
- Worldwide Influenza Centre, The Francis Crick Institute, 1 Midland Road, London, United Kingdom
| | - Pramila Rijal
- MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
- Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, United Kingdom
| | - Alain R. Townsend
- MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
- Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, United Kingdom
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36
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Shrotri M, van Schalkwyk MCI, Post N, Eddy D, Huntley C, Leeman D, Rigby S, Williams SV, Bermingham WH, Kellam P, Maher J, Shields AM, Amirthalingam G, Peacock SJ, Ismail SA. T cell response to SARS-CoV-2 infection in humans: A systematic review. PLoS One 2021; 16:e0245532. [PMID: 33493185 PMCID: PMC7833159 DOI: 10.1371/journal.pone.0245532] [Citation(s) in RCA: 93] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 01/02/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Understanding the T cell response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance and disease control strategies. This systematic review critically evaluates and synthesises the relevant peer-reviewed and pre-print literature published from 01/01/2020-26/06/2020. METHODS For this systematic review, keyword-structured literature searches were carried out in MEDLINE, Embase and COVID-19 Primer. Papers were independently screened by two researchers, with arbitration of disagreements by a third researcher. Data were independently extracted into a pre-designed Excel template and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. RESULTS 61 articles were included. 55 (90%) studies used observational designs, 50 (82%) involved hospitalised patients with higher acuity illness, and the majority had important limitations. Symptomatic adult COVID-19 cases consistently show peripheral T cell lymphopenia, which positively correlates with increased disease severity, duration of RNA positivity, and non-survival; while asymptomatic and paediatric cases display preserved counts. People with severe or critical disease generally develop more robust, virus-specific T cell responses. T cell memory and effector function has been demonstrated against multiple viral epitopes, and, cross-reactive T cell responses have been demonstrated in unexposed and uninfected adults, but the significance for protection and susceptibility, respectively, remains unclear. CONCLUSION A complex pattern of T cell response to SARS-CoV-2 infection has been demonstrated, but inferences regarding population level immunity are hampered by significant methodological limitations and heterogeneity between studies, as well as a striking lack of research in asymptomatic or pauci-symptomatic individuals. In contrast to antibody responses, population-level surveillance of the T cell response is unlikely to be feasible in the near term. Focused evaluation in specific sub-groups, including vaccine recipients, should be prioritised.
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Affiliation(s)
- Madhumita Shrotri
- Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
- National Infection Service, Public Health England, London, United Kingdom
| | - May C. I. van Schalkwyk
- Department of Public Health, Environments and Society, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Nathan Post
- Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Danielle Eddy
- National Infection Service, Public Health England, London, United Kingdom
| | - Catherine Huntley
- Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - David Leeman
- National Infection Service, Public Health England, London, United Kingdom
| | - Samuel Rigby
- Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Sarah V. Williams
- Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - William H. Bermingham
- Department of Clinical Immunology, University Hospitals Birmingham, Birmingham, United Kingdom
| | - Paul Kellam
- Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - John Maher
- School of Cancer and Pharmaceutical Studies, King’s College London, London, United Kingdom
- Department of Immunology, Eastbourne Hospital, Eastbourne, United Kingdom
| | - Adrian M. Shields
- Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | | | - Sharon J. Peacock
- National Infection Service, Public Health England, London, United Kingdom
- Department of Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Sharif A. Ismail
- National Infection Service, Public Health England, London, United Kingdom
- Department of Primary Care and Public Health, Imperial College London, London, United Kingdom
- Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom
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37
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Souza PFN, Amaral JL, Bezerra LP, Lopes FES, Freire VN, Oliveira JTA, Freitas CDT. ACE2-derived peptides interact with the RBD domain of SARS-CoV-2 spike glycoprotein, disrupting the interaction with the human ACE2 receptor. J Biomol Struct Dyn 2021; 40:5493-5506. [PMID: 33427102 PMCID: PMC7876913 DOI: 10.1080/07391102.2020.1871415] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Vaccines could be the solution to the current SARS-CoV-2 outbreak. However, some studies have shown that the immunological memory only lasts three months. Thus, it is imperative to develop pharmacological treatments to cope with COVID-19. Here, the in silico approach by molecular docking, dynamic simulations and quantum biochemistry revealed that ACE2-derived peptides strongly interact with the SARS-CoV-2 RBD domain of spike glycoprotein (S-RBD). ACE2-Dev-PepI, ACE2-Dev-PepII, ACE2-Dev-PepIII and ACE2-Dev-PepIV complexed with S-RBD provoked alterations in the 3D structure of S-RBD, leading to disruption of the correct interaction with the ACE2 receptor, a pivotal step for SARS-CoV-2 infection. This wrong interaction between S-RBD and ACE2 could inhibit the entry of SARS-CoV-2 in cells, and thus virus replication and the establishment of COVID-19 disease. Therefore, we suggest that ACE2-derived peptides can interfere with recognition of ACE2 in human cells by SARS-CoV-2 in vivo. Bioinformatic prediction showed that these peptides have no toxicity or allergenic potential. By using ACE2-derived peptides against SARS-CoV-2, this study points to opportunities for further in vivo research on these peptides, seeking to discover new drugs and entirely new perspectives to treat COVID-19.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Pedro F N Souza
- Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil
| | - Jackson L Amaral
- Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil.,Department of Physics, Federal University of Ceará, Fortaleza, Brazil
| | - Leandro P Bezerra
- Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil
| | - Francisco E S Lopes
- Center for Permanent Education in Health Care, CEATS/School of Public Health of Ceará-ESP-CE, Fortaleza, Brazil
| | - Valder N Freire
- Department of Physics, Federal University of Ceará, Fortaleza, Brazil
| | - Jose T A Oliveira
- Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil
| | - Cleverson D T Freitas
- Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil
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38
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Kabeerdoss J, Pilania RK, Karkhele R, Kumar TS, Danda D, Singh S. Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management. Rheumatol Int 2021; 41:19-32. [PMID: 33219837 PMCID: PMC7680080 DOI: 10.1007/s00296-020-04749-4] [Citation(s) in RCA: 199] [Impact Index Per Article: 49.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Accepted: 11/03/2020] [Indexed: 02/07/2023]
Abstract
Multisystem inflammatory syndrome (MIS-C) is a pediatric hyperinflammation disorder caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It has now been reported from several countries the world over. Some of the clinical manifestations of MIS-C mimic Kawasaki disease (KD) shock syndrome. MIS-C develops 4-6 weeks following SARS-CoV-2 infection, and is presumably initiated by adaptive immune response. Though it has multisystem involvement, it is the cardiovascular manifestations that are most prominent. High titres of anti-SARS-CoV-2 antibodies are seen in these patients. As this is a new disease entity, its immunopathogenesis is not fully elucidated. Whether it has some overlap with KD is still unclear. Current treatment guidelines recommend use of intravenous immunoglobulin and high-dose corticosteroids as first-line treatment. Mortality rates of MIS-C are lower compared to adult forms of severe COVID-19 disease.
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Affiliation(s)
- Jayakanthan Kabeerdoss
- Department of Clinical Immunology and Rheumatology, Christian Medical College and Hospital, Vellore, Tamil Nadu, 632004, India
| | - Rakesh Kumar Pilania
- Allergy Immunology Unit, Department of Pediatrics and Chief, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India
| | - Reena Karkhele
- MGM Medical College and Hospital, Navi Mumbai, Maharashtra, India
| | - T Sathish Kumar
- Department of Child Health, Christian Medical College, Vellore, India
| | - Debashish Danda
- Department of Clinical Immunology and Rheumatology, Christian Medical College and Hospital, Vellore, Tamil Nadu, 632004, India.
| | - Surjit Singh
- Allergy Immunology Unit, Department of Pediatrics and Chief, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.
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39
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Alon R, Sportiello M, Kozlovski S, Kumar A, Reilly EC, Zarbock A, Garbi N, Topham DJ. Leukocyte trafficking to the lungs and beyond: lessons from influenza for COVID-19. Nat Rev Immunol 2021; 21:49-64. [PMID: 33214719 PMCID: PMC7675406 DOI: 10.1038/s41577-020-00470-2] [Citation(s) in RCA: 127] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/14/2020] [Indexed: 01/08/2023]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Understanding of the fundamental processes underlying the versatile clinical manifestations of COVID-19 is incomplete without comprehension of how different immune cells are recruited to various compartments of virus-infected lungs, and how this recruitment differs among individuals with different levels of disease severity. As in other respiratory infections, leukocyte recruitment to the respiratory system in people with COVID-19 is orchestrated by specific leukocyte trafficking molecules, and when uncontrolled and excessive it results in various pathological complications, both in the lungs and in other organs. In the absence of experimental data from physiologically relevant animal models, our knowledge of the trafficking signals displayed by distinct vascular beds and epithelial cell layers in response to infection by SARS-CoV-2 is still incomplete. However, SARS-CoV-2 and influenza virus elicit partially conserved inflammatory responses in the different respiratory epithelial cells encountered early in infection and may trigger partially overlapping combinations of trafficking signals in nearby blood vessels. Here, we review the molecular signals orchestrating leukocyte trafficking to airway and lung compartments during primary pneumotropic influenza virus infections and discuss potential similarities to distinct courses of primary SARS-CoV-2 infections. We also discuss how an imbalance in vascular activation by leukocytes outside the airways and lungs may contribute to extrapulmonary inflammatory complications in subsets of patients with COVID-19. These multiple molecular pathways are potential targets for therapeutic interventions in patients with severe COVID-19.
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Affiliation(s)
- Ronen Alon
- Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
| | - Mike Sportiello
- David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA
| | - Stav Kozlovski
- Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
| | - Ashwin Kumar
- David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA
| | - Emma C Reilly
- David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA
| | - Alexander Zarbock
- Department of Cellular Immunology, Institute of Experimental Immunology Medical Faculty, University of Bonn, Bonn, Germany
| | - Natalio Garbi
- Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany
| | - David J Topham
- David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA
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40
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Post N, Eddy D, Huntley C, van Schalkwyk MCI, Shrotri M, Leeman D, Rigby S, Williams SV, Bermingham WH, Kellam P, Maher J, Shields AM, Amirthalingam G, Peacock SJ, Ismail SA. Antibody response to SARS-CoV-2 infection in humans: A systematic review. PLoS One 2020; 15:e0244126. [PMID: 33382764 PMCID: PMC7775097 DOI: 10.1371/journal.pone.0244126] [Citation(s) in RCA: 237] [Impact Index Per Article: 47.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 12/03/2020] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. METHODS Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. RESULTS 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14-22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. CONCLUSIONS Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.
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Affiliation(s)
- Nathan Post
- Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Danielle Eddy
- National Infection Service, Public Health England, London, United Kingdom
| | - Catherine Huntley
- Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - May C. I. van Schalkwyk
- Department of Public Health, Environments and Society, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Madhumita Shrotri
- Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
- Department of Public Health, Environments and Society, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - David Leeman
- National Infection Service, Public Health England, London, United Kingdom
| | - Samuel Rigby
- Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Sarah V. Williams
- Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - William H. Bermingham
- Department of Clinical Immunology, University Hospitals Birmingham, Birmingham, United Kingdom
| | - Paul Kellam
- Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - John Maher
- School of Cancer and Pharmaceutical Studies, King’s College London, London, United Kingdom
- Department of Immunology, Eastbourne Hospital, Eastbourne, United Kingdom
| | - Adrian M. Shields
- Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | | | - Sharon J. Peacock
- National Infection Service, Public Health England, London, United Kingdom
- Department of Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Sharif A. Ismail
- National Infection Service, Public Health England, London, United Kingdom
- Department of Primary Care and Public Health, Imperial College London, London, United Kingdom
- Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom
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Ing RJ, Chatterjee D, Twite MD. Resuscitating Children with COVID-19: What the Pediatric Anesthesiologist Needs to Know. J Cardiothorac Vasc Anesth 2020; 34:3182-3185. [PMID: 32624434 PMCID: PMC7296315 DOI: 10.1053/j.jvca.2020.06.037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 06/09/2020] [Indexed: 12/24/2022]
Affiliation(s)
- Richard J Ing
- Department of Anesthesiology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO
| | - Debnath Chatterjee
- Department of Anesthesiology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO
| | - Mark D Twite
- Department of Anesthesiology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO
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Shah VK, Firmal P, Alam A, Ganguly D, Chattopadhyay S. Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past. Front Immunol 2020; 11:1949. [PMID: 32849654 PMCID: PMC7426442 DOI: 10.3389/fimmu.2020.01949] [Citation(s) in RCA: 296] [Impact Index Per Article: 59.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Accepted: 07/20/2020] [Indexed: 12/17/2022] Open
Abstract
After the 1918 flu pandemic, the world is again facing a similar situation. However, the advancement in medical science has made it possible to identify that the novel infectious agent is from the coronavirus family. Rapid genome sequencing by various groups helped in identifying the structure and function of the virus, its immunogenicity in diverse populations, and potential preventive measures. Coronavirus attacks the respiratory system, causing pneumonia and lymphopenia in infected individuals. Viral components like spike and nucleocapsid proteins trigger an immune response in the host to eliminate the virus. These viral antigens can be either recognized by the B cells or presented by MHC complexes to the T cells, resulting in antibody production, increased cytokine secretion, and cytolytic activity in the acute phase of infection. Genetic polymorphism in MHC enables it to present some of the T cell epitopes very well over the other MHC alleles. The association of MHC alleles and its downregulated expression has been correlated with disease severity against influenza and coronaviruses. Studies have reported that infected individuals can, after recovery, induce strong protective responses by generating a memory T-cell pool against SARS-CoV and MERS-CoV. These memory T cells were not persistent in the long term and, upon reactivation, caused local damage due to cross-reactivity. So far, the reports suggest that SARS-CoV-2, which is highly contagious, shows related symptoms in three different stages and develops an exhaustive T-cell pool at higher loads of viral infection. As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. A classical immunotherapy of convalescent plasma transfusion from recovered patients has also been initiated for the neutralization of viremia in terminally ill COVID-19 patients. Due to the limitations of plasma transfusion, researchers are now focusing on developing neutralizing antibodies against virus particles along with immuno-modulation of cytokines like IL-6, Type I interferons (IFNs), and TNF-α that could help in combating the infection. This review highlights the similarities of the coronaviruses that caused SARS and MERS to the novel SARS-CoV-2 in relation to their pathogenicity and immunogenicity and also focuses on various treatment strategies that could be employed for curing COVID-19.
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Affiliation(s)
- Vibhuti Kumar Shah
- Department of Biological Sciences, BITS Pilani, K. K. Birla Goa Campus, Goa, India
- National Centre for Cell Science, S. P. Pune University Campus, Pune, India
| | - Priyanka Firmal
- Department of Biological Sciences, BITS Pilani, K. K. Birla Goa Campus, Goa, India
- National Centre for Cell Science, S. P. Pune University Campus, Pune, India
| | - Aftab Alam
- National Centre for Cell Science, S. P. Pune University Campus, Pune, India
- Indian Institute of Chemical Biology, Kolkata, India
| | | | - Samit Chattopadhyay
- Department of Biological Sciences, BITS Pilani, K. K. Birla Goa Campus, Goa, India
- National Centre for Cell Science, S. P. Pune University Campus, Pune, India
- Indian Institute of Chemical Biology, Kolkata, India
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43
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Villena J, Kitazawa H. The Modulation of Mucosal Antiviral Immunity by Immunobiotics: Could They Offer Any Benefit in the SARS-CoV-2 Pandemic? Front Physiol 2020; 11:699. [PMID: 32670091 PMCID: PMC7326040 DOI: 10.3389/fphys.2020.00699] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 05/28/2020] [Indexed: 01/08/2023] Open
Abstract
Viral respiratory infections are of major importance because of their capacity to cause of a high degree of morbidity and mortality in high-risk populations, and to rapidly spread between countries. Perhaps the best example of this global threat is the infectious disease caused by the new SARS-CoV-2 virus, which has infected more than 4 million people worldwide, causing the death of 287,000 persons according to the WHO's situation report on May 13, 2020. The availability of therapeutic tools that would be used massively to prevent or mitigate the detrimental effects of emerging respiratory viruses on human health is therefore mandatory. In this regard, research from the last decade has reported the impact of the intestinal microbiota on the respiratory immunity. It was conclusively demonstrated how the variations in the intestinal microbiota affect the responses of respiratory epithelial cells and antigen presenting cells against respiratory virus attack. Moreover, the selection of specific microbial strains (immunobiotics) with the ability to modulate immunity in distal mucosal sites made possible the generation of nutritional interventions to strengthen respiratory antiviral defenses. In this article, the most important characteristics of the limited information available regarding the immune response against SARS-CoV-2 virus are revised briefly. In addition, this review summarizes the knowledge on the cellular and molecular mechanisms involved in the improvement of respiratory antiviral defenses by beneficial immunobiotic microorganisms such as Lactobacillus rhamnosus CRL1505. The ability of beneficial microorganisms to enhance type I interferons and antiviral factors in the respiratory tract, stimulate Th1 response and antibodies production, and regulate inflammation and coagulation activation during the course of viral infections reducing tissue damage and preserving lung functionally, clearly indicate the potential of immunobiotics to favorably influence the immune response against SARS-CoV-2 virus.
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Affiliation(s)
- Julio Villena
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), San Miguel de Tucumán, Argentina
- Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Haruki Kitazawa
- Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
- Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
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44
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Lippi G, Sanchis-Gomar F, Henry BM. COVID-19: unravelling the clinical progression of nature's virtually perfect biological weapon. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:693. [PMID: 32617313 PMCID: PMC7327324 DOI: 10.21037/atm-20-3989] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Coronavirus disease 2019 (COVID-19) pandemic has shocked the world and caused morbidity and mortality on an unprecedented level in the era of modern medicine. Evidence generated to-date on the virulence and pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that COVID-19 may be considered a perfect storm, caused by a nature's virtually perfect biological weapon. This conclusion is supported by an updated analysis of pathogenesis and clinical progression of this infectious disease. It is now readily apparent that COVID-19 is not a clear-cut disorder, but is instead a gradually evolving pathology, characterized by a series of stages sustained by different molecular and biological mechanisms. The disease can hence be divided in at least five different phases (incubation, respiratory, pro-inflammatory, pro-thrombotic, and death or remission). Whilst the virus triggers direct cytopathic injury during the initial stage of illness, in the following evolving phases, it is the host itself that undergoes an almost suicidal reaction, sustained, amplified and maintained by the immune, complement and hemostatic systems. Another peculiar property making SARS-CoV-2 a devious and vicious pathogen is the biophysical structure of its receptor biding domain, which needs to be primed by human proteases, thus being less efficiently targetable by the host immune system. The unique pathophysiology of COVID-19 requires the customization of therapy by individual patient characteristics and according to the phase-specific, evolving derangement of the multiple biological pathways.
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Affiliation(s)
- Giuseppe Lippi
- Section of Clinical Biochemistry, University of Verona, Verona, Italy
| | - Fabian Sanchis-Gomar
- Department of Physiology, Faculty of Medicine, University of Valencia and INCLIVA Biomedical Research Institute, Valencia, Spain.,Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Brandon M Henry
- Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children's Hospital Medical Center, Ohio, USA
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