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      Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans

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          Abstract

          Many unknowns exist about human immune responses to the SARS-CoV-2 virus. SARS-CoV-2 reactive CD4 + T cells have been reported in unexposed individuals, suggesting pre-existing cross-reactive T cell memory in 20-50% of people. However, the source of those T cells has been speculative. Using human blood samples derived before the SARS-CoV-2 virus was discovered in 2019, we mapped 142 T cell epitopes across the SARS-CoV-2 genome to facilitate precise interrogation of the SARS-CoV-2-specific CD4 + T cell repertoire. We demonstrate a range of pre-existing memory CD4 + T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63, or HCoV-HKU1. Thus, variegated T cell memory to coronaviruses that cause the common cold may underlie at least some of the extensive heterogeneity observed in COVID-19 disease.

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          Most cited references 22

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          The three-dimensional structure of peptide-MHC complexes.

           Thomas Madden (1994)
          The ability of MHC molecules to present a broad spectrum of peptide antigens for T cell recognition requires a compromise between high affinity and broad specificity. Three-dimensional atomic structures of several class I and class II MHC molecules reveal a unique structural solution to this problem: Tight binding to the peptide main chain is supplemented by more or less restrictive interactions with peptide side chains. In spite of these contacts, peptide side-chain and conformational variability ensures that the resulting peptide-MHC complex presents an antigenically unique surface to T cell receptors. Extension of this understanding to other peptide-MHC complexes, including agonist/antagonist peptides and the identification of antigenic peptides within protein sequences, however, requires a detailed analysis of the interactions that determine both peptide-MHC binding affinity and the conformations of bound peptides. While many of these interactions can be modeled by homology with known structures, their specificity can depend sensitively on subtle and long-range structural effects. Structurally and immunologically important distinctions are also found between the class I and class II peptide-binding strategies. Taken together, these interactions ultimately determine the ability of an individual to respond successfully to immune challenges.
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            Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients

             Jing Liu,  Sumeng Li,  Jia Liu (2020)
            Background The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. Methods Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays. Findings Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts [0•6 (0•6-0•8)] but increases in neutrophil counts [4•7 (3•6-5•8)] than 27 mild cases [1.1 (0•8-1•4); 2•0 (1•5-2•9)]. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8+ T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-lymphocyte ratio (NLR) (AUC=0•93) and neutrophil-to-CD8+ T cell ratio (N8R) (AUC =0•94) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19. Interpretation The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R and NLR may serve as a useful prognostic factor for early identification of severe COVID-19 cases. Funding The National Natural Science Foundation of China, the National Science and Technology Major Project, the Health Commission of Hubei Province, Huazhong University of Science and Technology, and the Medical Faculty of the University Hospital Essen, Germany.
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              Clinical Impact of Human Coronaviruses 229E and OC43 Infection in Diverse Adult Populations

              Abstract Background.  The incidence and clinical impact of coronavirus (CoV) infection in elderly persons and those with underlying cardiopulmonary disease over a long duration is not well described. We determined the incidence and clinical impact of 229E and OC43 CoV in this population during 4 consecutive winters, and compared illnesses to influenza A, respiratory syncytial virus, and human metapneumovirus. Methods.  CoV 229E and OC43 were detected by reverse transcription polymerase chain reaction and serology in 4 adult populations under surveillance for acute respiratory illness during the winters of 1999–2003. Cohorts included healthy young adults, healthy elderly adults, high-risk adults with underlying cardiopulmonary disease, and a hospitalized group. Results.  Three hundred ninety-eight CoV infections were identified, with annual infection rates ranging from 2.8% to 26% in prospective cohorts, and prevalence ranging from 3.3% to 11.1% in the hospitalized cohort. The incidence of infections with each strain was similar, although asymptomatic infection and viral coinfection was significantly more common with 229E than OC43 infection. Although the incidence and clinical manifestations were similar for each strain, OC43-infected subjects tended to seek more medical care, as OC43 was twice as common as 229E among the hospitalized cohort. Conclusions.  CoV infections in the elderly are frequent, likely causing substantial medical disease burden.
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                Journal
                Science
                Science
                American Association for the Advancement of Science (AAAS)
                0036-8075
                1095-9203
                August 04 2020
                : eabd3871
                Affiliations
                [1 ]Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
                [2 ]Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA.
                [3 ]Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA 6150, Australia.
                [4 ]Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
                [5 ]Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
                Article
                10.1126/science.abd3871
                © 2020

                https://creativecommons.org/licenses/by/4.0/

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