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[Preprint]. 2024 Aug 19:2023.10.25.564014. Originally published 2023 Oct 26. [Version 3] doi: 10.1101/2023.10.25.564014

Early antiviral CD4 and CD8 T cell responses and antibodies are associated with upper respiratory tract clearance of SARS-CoV-2

Sydney I Ramirez, Paul G Lopez, Farhoud Faraji, Urvi M Parikh, Amy Heaps, Justin Ritz, Carlee Moser, Joseph J Eron, David A Wohl, Judith S Currier, Eric S Daar, Alex L Greninger, Paul Klekotka, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Bjoern Peters, Michael D Hughes, Kara W Chew, Davey M Smith, Shane Crotty; ACTIV-2/A5401 Study Team
PMCID: PMC10634820  PMID: 37961119

Abstract

T cells are involved in protective immunity against numerous viral infections. Data regarding functional roles of human T cells in SARS-CoV-2 (SARS2) viral clearance in primary COVID-19 are limited. To address this knowledge gap, samples were assessed for associations between SARS2 upper respiratory tract viral RNA levels and early virus-specific adaptive immune responses for 95 unvaccinated clinical trial participants with acute primary COVID-19 aged 18-86 years old, approximately half of whom were considered high risk for progression to severe COVID-19. Functionality and magnitude of acute SARS2-specific CD4 and CD8 T cell responses were evaluated, in addition to antibody responses. Most individuals with acute COVID-19 developed SARS2-specific T cell responses within 6 days of COVID-19 symptom onset. Early CD4 T cell and CD8 T cell responses were polyfunctional, and both strongly associated with reduced upper respiratory tract SARS2 viral RNA, independent of neutralizing antibody titers. Overall, these findings provide evidence for protective roles for circulating SARS2-specific CD4 and CD8 T cells during acute COVID-19.

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