Early antiviral CD4+ and CD8+ T cells are associated with upper airway clearance of SARS-CoV-2
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, we assessed samples 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 at 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.
Authors
- Kara W Chew (ORCID: https://orcid.org/0000-0003-4865-4348)
- Alessandro Sette (ORCID: https://orcid.org/0000-0001-7013-2250)
- Sydney I. Ramirez (ORCID: https://orcid.org/0000-0002-7166-5195)
- Bjoern Peters (ORCID: https://orcid.org/0000-0002-8457-6693)
- Joseph J. Eron (ORCID: https://orcid.org/0000-0002-4938-0644)
- Carlee Moser (ORCID: https://orcid.org/0000-0001-5601-9112)
- Shane Crotty (ORCID: https://orcid.org/0000-0002-6484-6262)
- Paul Klekotka
- Paul Lopez (ORCID: https://orcid.org/0000-0002-6437-1092)
- Amy Heaps (ORCID: https://orcid.org/0000-0003-4410-4007)
- Davey M. Smith (ORCID: https://orcid.org/0000-0003-3603-1733)
- Farhoud Faraji (ORCID: https://orcid.org/0000-0001-5078-813X)
- David A. Wohl (ORCID: https://orcid.org/0000-0002-7764-0212)
- Alexander L. Greninger (ORCID: https://orcid.org/0000-0002-7443-0527)
- Daniela Weiskopf (ORCID: https://orcid.org/0000-0003-2968-7371)
- Eric S. Daar (ORCID: https://orcid.org/0000-0003-1880-7331)
- Alba Grifoni (ORCID: https://orcid.org/0000-0002-2209-5966)
- Judith S. Currier (ORCID: https://orcid.org/0000-0003-4279-4737)
- Justin Ritz (ORCID: https://orcid.org/0000-0001-6307-4849)
- Urvi M. Parikh (ORCID: https://orcid.org/0000-0002-4016-0629)
- Michael D. Hughes (ORCID: https://orcid.org/0000-0001-8562-2316)
Institutions
- University of North Carolina at Chapel Hill (US)
- La Jolla Institute for Immunology (US)
- University of California, Los Angeles (US)
- Eli Lilly (United States) (US)
- University of Pittsburgh (US)
- UCLA Medical Center (US)
- University of Washington Medical Center (US)
- University of California San Diego (US)
- Cancer Research And Biostatistics (US)
- Center for Global Health (US)
- Harbor–UCLA Medical Center (US)
Publication Details
- Journal
- JCI Insight
- Published
- 2024-12-19
- DOI
- https://doi.org/10.1172/jci.insight.186078
- Citations
- 12
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 4.67
Funders
- U.S. Department of Health and Human Services
- A.P. Giannini Foundation
- Eli Lilly and Company
- Giannini Foundation of Agricultural Economics
- ACT Government
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases