{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T20:07:07Z","timestamp":1772741227886,"version":"3.50.1"},"reference-count":106,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000659","name":"Research Trainees Coordinating Centre","doi-asserted-by":"publisher","award":["NIHR300156"],"award-info":[{"award-number":["NIHR300156"]}],"id":[{"id":"10.13039\/501100000659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["215654\/Z\/19\/Z"],"award-info":[{"award-number":["215654\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0245532","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T13:23:38Z","timestamp":1611581018000},"page":"e0245532","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":124,"title":["T cell response to SARS-CoV-2 infection in humans: A systematic review"],"prefix":"10.1371","volume":"16","author":[{"given":"Madhumita","family":"Shrotri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"May C. I.","family":"van Schalkwyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Post","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Eddy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Huntley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2517-1474","authenticated-orcid":true,"given":"David","family":"Leeman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Rigby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah V.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2213-5574","authenticated-orcid":true,"given":"William H.","family":"Bermingham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Kellam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Maher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian M.","family":"Shields","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gayatri","family":"Amirthalingam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon J.","family":"Peacock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7246-7337","authenticated-orcid":true,"given":"Sharif A.","family":"Ismail","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"pone.0245532.ref001","unstructured":"WHO. COVID-19 timeline. 2020 [cited 20 Aug 2020]. Available from: https:\/\/www.who.int\/news-room\/detail\/29-06-2020-covidtimeline"},{"key":"pone.0245532.ref002","unstructured":"WHO. WHO Coronavirus Disease (COVID-19) Dashboard. 2020 [cited 20 Aug 2020]. Available from: https:\/\/covid19.who.int\/"},{"key":"pone.0245532.ref003","article-title":"Immunology of COVID-19: current state of the science","author":"N Vabret","year":"2020","journal-title":"Immunity"},{"key":"pone.0245532.ref004","article-title":"Antibody response to SARS-CoV-2 infection in humans: a systematic review.","author":"N Post","year":"2020","journal-title":"PLoS One."},{"key":"pone.0245532.ref005","volume-title":"Covid-19 Daily Digest Endnote Library","author":"C De Brun","year":"2020"},{"key":"pone.0245532.ref006","unstructured":"WHO. Clinical management of COVID-19: interim guidance. Geneva; 2020."},{"key":"pone.0245532.ref007","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.puhe.2015.10.027","article-title":"The development and validation of a meta-tool for quality appraisal of public health evidence: Meta Quality Appraisal Tool (MetaQAT).","volume":"136","author":"L Rosella","year":"2016","journal-title":"Public Health."},{"key":"pone.0245532.ref008","article-title":"Expansion of myeloid-derived suppressor cells in patients with severe coronavirus disease (COVID-19).","author":"C Agrati","year":"2020","journal-title":"Cell Death Differ"},{"key":"pone.0245532.ref009","article-title":"SARS-CoV-2-reactive interferon-\u03b3-producing CD8+ T cells in patients hospitalized with coronavirus disease 2019.","author":"E Gim\u00e9nez","year":"2020","journal-title":"J Med Virol"},{"key":"pone.0245532.ref010","article-title":"Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals","author":"A Grifoni","year":"2020","journal-title":"Cell"},{"key":"pone.0245532.ref011","first-page":"104361","article-title":"The clinical course and its correlated immune status in COVID-19 pneumonia.","volume":"127","author":"R He","journal-title":"J Clin Virol. 2020"},{"key":"pone.0245532.ref012","article-title":"T-Cell Subset Counts in Peripheral Blood Can Be Used as Discriminatory Biomarkers for Diagnosis and Severity Prediction of Coronavirus Disease 2019.","author":"M Jiang","year":"2020","journal-title":"J Infect Dis"},{"key":"pone.0245532.ref013","article-title":"COVID-19 pneumonia: CD8+ T and NK cells are decreased in number but compensatory increased in cytotoxic potential","author":"Y Jiang","year":"2020","journal-title":"Clin Immunol"},{"key":"pone.0245532.ref014","article-title":"Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity","author":"CK Kang","year":"2020","journal-title":"Int J Infect Dis"},{"key":"pone.0245532.ref015","article-title":"Immune-related factors associated with pneumonia in 127 children with coronavirus disease 2019 in Wuhan.","author":"Y Li","year":"2020","journal-title":"Pediatr Pulmonol."},{"key":"pone.0245532.ref016","article-title":"Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients.","author":"J Liu","year":"2020","journal-title":"EBioMedicine"},{"key":"pone.0245532.ref017","article-title":"Correlation Between Relative Nasopharyngeal Virus RNA Load and Lymphocyte Count Disease Severity in Patients with COVID-19","author":"Y Liu","year":"2020","journal-title":"Viral Immunol"},{"key":"pone.0245532.ref018","article-title":"Decreased T cell populations contribute to the increased severity of COVID-19","author":"R Liu","year":"2020","journal-title":"Clin Chim Acta"},{"issue":"7","key":"pone.0245532.ref019","doi-asserted-by":"crossref","first-page":"e100","DOI":"10.1097\/INF.0000000000002740","article-title":"Clinical analysis of 25 COVID-19 infections in children.","volume":"39","author":"K Bai","year":"2020","journal-title":"Pediatr Infect Dis J"},{"issue":"2","key":"pone.0245532.ref020","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jinf.2020.03.054","article-title":"Lymphocyte subset (CD4+, CD8+) counts reflect the severity of infection and predict the clinical outcomes in patients with COVID-19.","volume":"81","author":"Z Liu","year":"2020","journal-title":"J Infect."},{"issue":"13","key":"pone.0245532.ref021","doi-asserted-by":"crossref","first-page":"e139024","DOI":"10.1172\/jci.insight.139024","article-title":"IL-6 combined with CD8+ T cell count early predict in-hospital mortality for patients with COVID-19.","volume":"5","author":"M Luo","year":"2020","journal-title":"JCI Insight."},{"issue":"9","key":"pone.0245532.ref022","doi-asserted-by":"crossref","first-page":"4694","DOI":"10.1172\/JCI138554","article-title":"Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent","volume":"130","author":"A Mazzoni","year":"2020","journal-title":"J Clin Invest"},{"key":"pone.0245532.ref023","article-title":"Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals","author":"L Ni","year":"2020","journal-title":"Immunity"},{"key":"pone.0245532.ref024","article-title":"Characteristics of inflammatory factors and lymphocyte subsets in patients with severe COVID-19","author":"M Ni","year":"2020","journal-title":"J Med Virol"},{"issue":"16","key":"pone.0245532.ref025","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1093\/cid\/ciaa462","article-title":"Down-regulated gene expression spectrum and immune responses changed during the disease progression in COVID-19 patients","volume":"71","author":"Y Ouyang","year":"2020","journal-title":"Clin Infect Dis"},{"key":"pone.0245532.ref026","article-title":"Dysregulation of immune response in patients with COVID-19 in Wuhan, China","volume":"12","author":"C Qin","year":"2020","journal-title":"Clin Infect Dis"},{"key":"pone.0245532.ref027","first-page":"23","article-title":"The laboratory tests and host immunity of COVID-19 patients with different severity of illness.","volume":"23","author":"F Wang","year":"2020","journal-title":"JCI Insight."},{"key":"pone.0245532.ref028","article-title":"High-dimensional immune profiling by mass cytometry revealed immunosuppression and dysfunction of immunity in COVID-19 patients","author":"W Wang","year":"2020","journal-title":"Cell Mol Immunol"},{"issue":"8","key":"pone.0245532.ref029","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/s41423-020-0483-y","article-title":"Systemically comparing host immunity between survived and deceased COVID-19 patients","volume":"17","author":"F Wang","year":"2020","journal-title":"Cell Mol Immunol."},{"key":"pone.0245532.ref030","article-title":"SARS-CoV-2 infection protects against rechallenge in rhesus macaques","author":"A Chandrashekar","year":"2020","journal-title":"Science"},{"key":"pone.0245532.ref031","article-title":"Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing.","author":"W Wen","year":"2020","journal-title":"Cell Discov."},{"key":"pone.0245532.ref032","article-title":"Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China.","author":"B Xu","year":"2020","journal-title":"J Infect."},{"key":"pone.0245532.ref033","article-title":"Protective humoral immunity in SARS-CoV-2 infected pediatric patients","author":"Y Zhang","year":"2020","journal-title":"Cellular and Molecular Immunology"},{"issue":"2","key":"pone.0245532.ref034","doi-asserted-by":"crossref","first-page":"428","DOI":"10.21037\/apm.2020.03.26","article-title":"Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus.","volume":"9","author":"Y Zhou","year":"2020","journal-title":"Ann Palliat Med."},{"issue":"4","key":"pone.0245532.ref035","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.gendis.2020.03.008","article-title":"The clinical and immunological features of pediatric COVID-19 patients in China.","volume":"7","author":"J Chen","year":"2020","journal-title":"Genes Dis."},{"issue":"1","key":"pone.0245532.ref036","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jaci.2020.05.003","article-title":"Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China","volume":"146","author":"R Chen","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"pone.0245532.ref037","article-title":"Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19).","author":"B Diao","year":"2020","journal-title":"Front Immunol."},{"issue":"3","key":"pone.0245532.ref038","doi-asserted-by":"crossref","first-page":"642","DOI":"10.14336\/AD.2020.0317","article-title":"Immune characteristics of patients with coronavirus disease 2019 (COVID-19).","volume":"11","author":"X Dong","year":"2020","journal-title":"Aging Dis."},{"key":"pone.0245532.ref039","article-title":"Clinical characteristics of 182 pediatric COVID\u201019 patients with different severities and allergic status","author":"H Du","year":"2020","journal-title":"Allergy"},{"key":"pone.0245532.ref040","doi-asserted-by":"crossref","first-page":"102437","DOI":"10.1016\/j.bcmd.2020.102437","article-title":"Increased expression of CD8 marker on T-cells in COVID-19 patients","volume":"83","author":"A Ganji","year":"2020","journal-title":"Blood Cells, Mol Dis"},{"key":"pone.0245532.ref041","article-title":"SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET\/CT imaging and prolonged shedding of infectious virus from both respiratory and gastrointestinal tracts.","author":"AL Hartman","year":"2020","journal-title":"bioRxiv"},{"key":"pone.0245532.ref042","article-title":"Presence of SARS-CoV-2 reactive T cells in COVID-19 patients and healthy donors.","author":"J Braun","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref043","article-title":"Epidemiological and clinical characteristics in patients with SARS-CoV-2 antibody negative probable COVID-19 in Wuhan.","author":"L Duan","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref044","article-title":"Immunogenic profile of SARS-CoV-2 spike in individuals recovered from COVID-19.","author":"JA Juno","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref045","article-title":"Persistent SARS-CoV-2 presence is companied with defects in adaptive immune system in non-severe COVID-19 patients.","author":"B Liu","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref046","article-title":"Broad and strong memory CD4 + and CD8 + T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients.","author":"Y Peng","year":"2020","journal-title":"bioRxiv"},{"key":"pone.0245532.ref047","article-title":"SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors.","author":"AS Shomuradova","year":"2020","journal-title":"medrxiv"},{"key":"pone.0245532.ref048","article-title":"Expansion of SARS-CoV-2-specific Antibody-secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients.","author":"R Varnait\u0117","year":"2020","journal-title":"bioRxiv"},{"key":"pone.0245532.ref049","article-title":"Phenotype of SARS-CoV-2-specific T-cells in COVID-19 patients with acute respiratory distress syndrome.","author":"D Weiskopf","year":"2020","journal-title":"Sci Immunol"},{"key":"pone.0245532.ref050","article-title":"Analysis of adaptive immune cell populations and phenotypes in the patients infected by SARS-CoV-2.","author":"X Yang","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref051","article-title":"Spectrum of innate and adaptive immune response to SARS CoV 2 infection across asymptomatic, mild and severe cases; a longitudinal cohort study.","author":"R Carsetti","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref052","article-title":"Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion.","author":"F Gallais","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref053","article-title":"The production of antibodies for SARS-CoV-2 and its clinical implication.","author":"Q Hu","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref054","article-title":"A consensus Covid-19 immune signature combines immuno-protection with discrete sepsis-like traits associated with poor prognosis.","author":"AG Laing","year":"2020","journal-title":"medRxiv."},{"key":"pone.0245532.ref055","article-title":"Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals","author":"N Le Bert","year":"2020","journal-title":"bioRxiv"},{"key":"pone.0245532.ref056","article-title":"Longitudinal immune profiling reveals distinct features of COVID-19 pathogenesis.","author":"ER Mann","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref057","article-title":"Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19.","author":"A Marcos-Jimenez","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref058","article-title":"Reappearance of Effector T Cells Predicts Successful Recovery from COVID-19.","author":"I Odak","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref059","article-title":"A longitudinal study of immune cells in severe COVID-19 patients.","author":"D Payen","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref060","article-title":"The SARS-COV-2 T-Cell Immunity is Directed Against the Spike, Membrane, and Nucleocapsid Protein and Associated with COVID 19 Severity.","author":"C Thieme","year":"2020","journal-title":"SSRN Electron J."},{"key":"pone.0245532.ref061","article-title":"Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19.","author":"B Zhang","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref062","article-title":"COVID-19 progression is potentially driven by T cell immunopathogenesis","author":"M Anft","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref063","article-title":"Prediction of the Clinical Outcome of COVID-19 Patients Using T Lymphocyte Subsets with 340 Cases from Wuhan, China: A Retrospective Cohort Study and a Web Visualization Tool.","author":"Q Liu","year":"2020","journal-title":"SSRN Electron J."},{"key":"pone.0245532.ref064","article-title":"Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection.","author":"AA Minervina","year":"2020","journal-title":"bioRxiv"},{"key":"pone.0245532.ref065","article-title":"Disruption of the CCL5\/RANTES-CCR5 Pathway Restores Immune Homeostasis and Reduces Plasma Viral Load in Critical COVID-19.","author":"B Patterson","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref066","unstructured":"Chinese National Health Commission. The Notice of Launching Guideline on Diagnosis and Treatment of the Novel Coronavirus Pneumonia (NCP). 5th ed [Internet]. 2020. Available from: http:\/\/www.nhc.gov.cn\/yzygj\/s7653p\/202002\/3b09b894ac9b4204a79db5b8912d4440\/files\/7260301a393845fc87fcf6dd52965ecb.pdf"},{"key":"pone.0245532.ref067","article-title":"Comparative analysis of laboratory indexes of severe and non-severe patients infected with COVID-19","author":"J Bao","year":"2020","journal-title":"Clin Chim Acta"},{"issue":"19","key":"pone.0245532.ref068","doi-asserted-by":"crossref","first-page":"11034","DOI":"10.1128\/JVI.01505-14","article-title":"Virus-Specific Memory CD8 T Cells Provide Substantial Protection from Lethal Severe Acute Respiratory Syndrome Coronavirus Infection","volume":"88","author":"R Channappanavar","year":"2014","journal-title":"J Virol"},{"issue":"6","key":"pone.0245532.ref069","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41577-020-0311-8","article-title":"The trinity of COVID-19: immunity, inflammation and intervention","volume":"20","author":"MZ Tay","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"pone.0245532.ref070","article-title":"Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19","author":"D Blanco-Melo","year":"2020","journal-title":"Cell"},{"key":"pone.0245532.ref071","article-title":"Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages","author":"M Merad","year":"2020","journal-title":"Nature Reviews Immunology"},{"key":"pone.0245532.ref072","unstructured":"NIH. Clinical Presentation of People with SARS-CoV-2 Infection. 2020 [cited 2020 Dec 11]. Available from: https:\/\/www.covid19treatmentguidelines.nih.gov\/overview\/clinical-presentation\/"},{"key":"pone.0245532.ref073","article-title":"SARS-CoV-2-specific T cells exhibit unique features characterized by robust helper function, lack of terminal differentiation, and high proliferative potential.","author":"J Neidleman","year":"2020","journal-title":"bioRxiv"},{"key":"pone.0245532.ref074","article-title":"Lymphopenia-induced T cell proliferation is a hallmark of severe COVID-19.","author":"S Adamo","year":"2020","journal-title":"bioRxiv"},{"issue":"3","key":"pone.0245532.ref075","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1182\/blood-2005-02-0456","article-title":"IL-6 blocks a discrete early step in lymphopoiesis","volume":"106","author":"K Maeda","year":"2005","journal-title":"Blood"},{"key":"pone.0245532.ref076","article-title":"The many faces of the anti-COVID immune response","author":"SA Vardhana","year":"2020","journal-title":"Journal of Experimental Medicine"},{"key":"pone.0245532.ref077","article-title":"Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity","author":"C Rydyznski Moderbacher","year":"2020","journal-title":"Cell"},{"key":"pone.0245532.ref078","article-title":"Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients.","author":"CA Pierce","year":"2020","journal-title":"Sci Transl Med."},{"key":"pone.0245532.ref079","article-title":"SARS-CoV-2 Uses CD4 to Infect T Helper Lymphocytes.","author":"GG Davanzo","year":"2020","journal-title":"medRxiv"},{"issue":"8","key":"pone.0245532.ref080","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/S2213-2600(20)30267-8","article-title":"Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities","volume":"8","author":"P Mehta","year":"2020","journal-title":"Lancet Respir Med."},{"key":"pone.0245532.ref081","article-title":"Efficacy of Tocilizumab in Patients Hospitalized with Covid-19","author":"JH Stone","year":"2020","journal-title":"N Engl J Med"},{"key":"pone.0245532.ref082","article-title":"SARS-CoV-2 T cell immunity: Specificity, function, durability, and role in protection.","author":"DM Altmann","year":"2020","journal-title":"Sci Immunol."},{"key":"pone.0245532.ref083","article-title":"Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection.","author":"J Zuo","year":"2020","journal-title":"bioRxiv"},{"key":"pone.0245532.ref084","article-title":"Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6\u20138 months after the infection.","author":"N Sherina","year":"2020","journal-title":"bioRxiv"},{"key":"pone.0245532.ref085","article-title":"SARS-CoV-2 responsive T cell numbers are associated with protection from COVID-19: A prospective cohort study in keyworkers.","author":"DH Wyllie","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref086","first-page":"1","article-title":"Correlates of protection against SARS-CoV-2 in rhesus macaques","author":"K McMahan","year":"2020","journal-title":"Nature"},{"key":"pone.0245532.ref087","article-title":"Cellular Immunity in COVID-19 Convalescents with PCR-Confirmed Infection but with Undetectable SARS-CoV-2\u2013Specific IgG","author":"S Schwarzkopf","year":"2021","journal-title":"Emerg Infect Dis"},{"key":"pone.0245532.ref088","article-title":"Characterization of pre-existing and induced SARS-CoV-2-specific CD8+","author":"I Schulien","year":"2020","journal-title":"T cells. Nat Med"},{"key":"pone.0245532.ref089","article-title":"SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition","author":"A Nelde","year":"2020","journal-title":"Nat Immunol"},{"key":"pone.0245532.ref090","article-title":"Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19","author":"T Sekine","year":"2020","journal-title":"Cell"},{"key":"pone.0245532.ref091","article-title":"Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans","author":"J Mateus","year":"2020","journal-title":"Science"},{"key":"pone.0245532.ref092","article-title":"Cross-reactive memory T cells and herd immunity to SARS-CoV-2","author":"M Lipsitch","year":"2020","journal-title":"Nature Reviews Immunology"},{"key":"pone.0245532.ref093","article-title":"T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses.","author":"A Ogbe","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref094","article-title":"T-cell responses and therapies against SARS-CoV-2 infection","author":"SM Toor","year":"2020","journal-title":"Immunology"},{"key":"pone.0245532.ref095","article-title":"T cell responses in patients with COVID-19","author":"Z Chen","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"pone.0245532.ref096","article-title":"A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease.","author":"AT Huang","year":"2020","journal-title":"medRxiv"},{"key":"pone.0245532.ref097","unstructured":"LSHTM. COVID-19 Vaccine Tracker. 2020 [cited 11 Dec 2020]. Available from: https:\/\/vac-lshtm.shinyapps.io\/ncov_vaccine_landscape\/"},{"key":"pone.0245532.ref098","article-title":"Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18\u201359 years: a randomised, double-blind, placebo-controlled, phase 1\/2 clinical trial.","author":"Y Zhang","year":"2020","journal-title":"Lancet Infect Dis."},{"key":"pone.0245532.ref099","article-title":"Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1\/2 trial.","author":"S Xia","year":"2020","journal-title":"Lancet Infect Dis."},{"key":"pone.0245532.ref100","article-title":"Randomized, double-blinded and placebo-controlled phase II trial of an inactivated SARS-CoV-2 vaccine in healthy adults","author":"Y Che","year":"2020","journal-title":"Clin Infect Dis"},{"key":"pone.0245532.ref101","article-title":"Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults","author":"EJ Anderson","year":"2020","journal-title":"N Engl J Med"},{"key":"pone.0245532.ref102","article-title":"COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses","author":"U Sahin","year":"2020","journal-title":"Nature"},{"key":"pone.0245532.ref103","article-title":"Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2\/3 trial.","author":"MN Ramasamy","year":"2020","journal-title":"Lancet"},{"key":"pone.0245532.ref104","article-title":"Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1\/2 studies from Russia.","author":"DY Logunov","year":"2020","journal-title":"Lancet"},{"key":"pone.0245532.ref105","article-title":"Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial","author":"FC Zhu","year":"2020","journal-title":"Lancet"},{"key":"pone.0245532.ref106","article-title":"Unbiased Screens Show CD8+ T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein","author":"AP Ferretti","year":"2020","journal-title":"Immunity"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0245532","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T13:24:05Z","timestamp":1611581045000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0245532"}},"subtitle":[],"editor":[{"given":"Stephen R.","family":"Walsh","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,1,25]]},"references-count":106,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0245532","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.08.24.20180679","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,25]]}}}