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COVID-19 progression is potentially driven by T cell immunopathogenesis
dc.contributor.author | Anft, Moritz et al. | |
dc.date.accessioned | 2020-05-21T12:18:41Z | |
dc.date.available | 2020-05-21T12:18:41Z | |
dc.date.issued | 2020-05-19 | |
dc.identifier.uri | https://doi.org/10.1101/2020.04.28.20083089 | en_US |
dc.identifier.uri | https://hdl.handle.net/20.500.12663/1571 | |
dc.description.abstract | Background: The role of cellular immunity in pathogenesis of COVID-19 is unclear and conflicting data points to insufficient or pathogenic immunity as drivers of COVID-19 progression. Here we aimed to delineate the phenotype and function of the immune system in patients with moderate, severe, and critical COVID-19. Methods: In this prospective study, we included 53 patients with moderate (n=21), severe (n=18), and critical (n=14) COVID-19 manifestations. Using multiparametric flow cytometry we compared quantitative, phenotypic, and functional characteristics of circulating immune cells, SARS-CoV-2 antigen-reactive T-cells, and humoral immunity. Results: Deep phenotypic profiling revealed a depletion of circulating bulk CD8+ T-cells, CD4+ and CD8+ T-cell subsets with activated memory/effector T-cells expressing CD57+, HLA-DR+, and the key activation and migration molecule CD11a++ in critical COVID-19. Importantly, survival from acute respiratory distress syndrome was accompanied by a recovery of the depleted CD11++ T-cell subsets including T-cells expressing CD28, CD57, HLA-DR activation/effector molecules. We further observed a stronger response of S-protein specific T-cells producing inflammatory cytokines in critical COVID-19 cases. This seemingly contradictory observation is in fact confirmation of the underlying immunopathogenesis in patients with critical COVID-19. Conclusion: Our findings suggest a CD11a-based immune signature as a possible prognostic marker for disease development. Our data further reveal that increased rather than decreased SARS-CoV-2 specific T cell immunity is associated with adverse outcome in COVID-19. Tissue migration of activated effectors T-cells may constitute a crucial cornerstone in the immunopathogenesis of SARS-CoV-2 associated tissue injury. | en_US |
dc.language | English | en_US |
dc.subject | COVID-19 | en_US |
dc.subject | Coronavirus | en_US |
dc.subject | Infectious Diseases | en_US |
dc.subject | Immunity, Cellular | en_US |
dc.subject | Immune System | en_US |
dc.subject | SARS-CoV | en_US |
dc.subject | T-Lymphocytes | en_US |
dc.subject | CD11 Antigens | en_US |
dc.subject | CD4-CD8 Ratio | en_US |
dc.title | COVID-19 progression is potentially driven by T cell immunopathogenesis | en_US |
eihealth.country | Global (WHO/OMS) | en_US |
eihealth.category | Clinical characterization and management | en_US |
eihealth.type | Published Article | en_US |
eihealth.maincategory | Save Lives / Salvar Vidas | en_US |
dc.relation.ispartofjournal | medRxiv | en_US |
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