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[Preprint]. 2024 Jun 10:2023.10.25.564014. Originally published 2023 Oct 26. [Version 2] 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 infections1. 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. Functionality and quantity 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 symptom onset. Early CD4 T cell and CD8 T cell responses were strongly associated with reduced upper respiratory tract SARS2 viral RNA, independent of neutralizing antibody titers. Overall, these findings indicate a protective role for SARS2-specific T cells during acute COVID-19.

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