CHARM: COVID-19 Health Action Response for Marines-Association of antigen-specific interferon-gamma and IL2 responses with asymptomatic and symptomatic infections after a positive qPCR SARS-CoV-2 test

PLoS One. 2022 Apr 7;17(4):e0266691. doi: 10.1371/journal.pone.0266691. eCollection 2022.

Abstract

SARS-CoV-2 T cell responses are associated with COVID-19 recovery, and Class I- and Class II-restricted epitopes have been identified in the spike (S), nucleocapsid (N) and membrane (M) proteins and others. This prospective COVID-19 Health Action Response for Marines (CHARM) study enabled assessment of T cell responses against S, N and M proteins in symptomatic and asymptomatic SARS-CoV-2 infected participants. At enrollment all participants were negative by qPCR; follow-up occurred biweekly and bimonthly for the next 6 weeks. Study participants who tested positive by qPCR SARS-CoV-2 test were enrolled in an immune response sub-study. FluoroSpot interferon-gamma (IFN-γ) and IL2 responses following qPCR-confirmed infection at enrollment (day 0), day 7 and 14 and more than 28 days later were measured using pools of 17mer peptides covering S, N, and M proteins, or CD4+CD8 peptide pools containing predicted epitopes from multiple SARS-CoV-2 antigens. Among 124 asymptomatic and 105 symptomatic participants, SARS-CoV-2 infection generated IFN-γ responses to the S, N and M proteins that persisted longer in asymptomatic cases. IFN-γ responses were significantly (p = 0.001) more frequent to the N pool (51.4%) than the M pool (18.9%) among asymptomatic but not symptomatic subjects. Asymptomatic IFN-γ responders to the CD4+CD8 pool responded more frequently to the S pool (55.6%) and N pool (57.1%), than the M pool (7.1%), but not symptomatic participants. The frequencies of IFN-γ responses to the S and N+M pools peaked 7 days after the positive qPCR test among asymptomatic (S pool: 22.2%; N+M pool: 28.7%) and symptomatic (S pool: 15.3%; N+M pool 21.9%) participants and dropped by >28 days. Magnitudes of post-infection IFN-γ and IL2 responses to the N+M pool were significantly correlated with IFN-γ and IL2 responses to the N and M pools. These data further support the central role of Th1-biased cell mediated immunity IFN-γ and IL2 responses, particularly to the N protein, in controlling COVID-19 symptoms, and justify T cell-based COVID-19 vaccines that include the N and S proteins.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibodies, Viral
  • Asymptomatic Infections
  • CD8-Positive T-Lymphocytes
  • COVID-19 Vaccines
  • COVID-19* / diagnosis
  • COVID-19* / immunology
  • Epitopes
  • Humans
  • Interferon-gamma* / immunology
  • Interleukin-2* / immunology
  • Military Personnel
  • SARS-CoV-2 / genetics
  • Spike Glycoprotein, Coronavirus / genetics

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • Epitopes
  • Interleukin-2
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Interferon-gamma

Grants and funding

AGL received a grant (9700130) from the Defense Health Agency through the Naval Medical Research Center and SCS a contract from the Defense Advanced Research Projects Agency (N6600119C4022). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.