SARS-CoV-2-specific CD4+ T cells are likely important in immunity against COVID-19, but our understanding of CD4+ longitudinal dynamics following infection, and specific features that correlate with the maintenance of neutralizing antibodies, remains limited. We characterized SARS-CoV-2-specific CD4 + T cells in a longitudinal cohort of 109 COVID-19 outpatients. The quality of the SARS-CoV-2-specific CD4 + response shifted from cells producing IFNγ to TNFα from five days to four months post-enrollment, with IFNγ- IL21- TNFα+ CD4+ T cells the predominant population detected at later timepoints. Greater percentages of IFNγ- IL21- TNFα+ CD4+ T cells on day 28 correlated with SARS-CoV-2 neutralizing antibodies measured seven months post-infection (⍴=0.4, P=0.01). mRNA vaccination following SARS-CoV-2 infection boosted both IFNγ and TNFα producing, spike protein-specific CD4 + T cells. These data suggest that SARS-CoV-2-specific, TNFα-producing CD4 + T cells may play an important role in antibody maintenance following COVID-19.
Funding: This study was supported by NIH/NIAID (U01 AI150741-01S1 to Z.H., S.T., I.R.B., B.G., T.T.W., and P.J.), the Stanford’s Innovative Medicines Accelerator, and a Fastgrant (C.A.B.). The Lambda clinical trial was funded by anonymous donors to Stanford University, and Peginterferon Lambda provided by Eiger BioPharmaceuticals.
Declaration of Interests: The authors declare no competing interests.
Ethics Approval Statement: All participants gave written informed consent. The study protocol used was approved by the Institutional Review Board of Stanford University.
van der Ploeg, Kattria and Kirosingh, Adam Setori and Mori, Diego Alonzo Martinez and Chakraborty, Saborni and Hu, Zicheng and Seivers, Benjamin L. and Jacobson, Karen B. and Bonilla, Hector and Parsonnet, Julie and Andrews, Jason and Press, Kathleen D. and Ty, Maureen Caracena and Ruiz-Betancourt, Daniel R. and de la Parte, Lauren and Tan, Gene S. and Blish, Catherine and Takahashi, Saki and Rodriguez-Barraquer, Isabel and Greenhouse, Bryan and Singh, Upinder and Wang, Taia and Jagannathan, Prasanna, TNFα-Producing CD4
+ T Cells Dominate the SARS-CoV-2-Specific T Cell Response in COVID-19 Outpatients and Are Associated with Durable Antibodies. Available at SSRN: https://ssrn.com/abstract=4019718 or http://dx.doi.org/10.2139/ssrn.4019718
This version of the paper has not been formally peer reviewed.
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