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

• Published in: PloS one Vol. 17; no. 4; p. e0266691
• Main Authors: Sedegah, Martha, Porter, Chad, Hollingdale, Michael R., Ganeshan, Harini, Huang, Jun, Goforth, Carl W., Belmonte, Maria, Belmonte, Arnel, Weir, Dawn L., Lizewski, Rhonda A., Lizewski, Stephen E., Sealfon, Stuart C., Jani, Vihasi, Cheng, Ying, Inoue, Sandra, Velasco, Rachael, Villasante, Eileen, Sun, Peifang, Letizia, Andrew G.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.04.2022; Public Library of Science (PLoS)
• Subjects: Analysis; Antibodies, Viral; Antigenic determinants; Antigens; Asymptomatic; Asymptomatic Infections; Biology and Life Sciences; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes; Coronaviruses; COVID-19; COVID-19 - diagnosis; COVID-19 - immunology; COVID-19 Vaccines; Enrollments; Epitopes; Evaluation; FDA approval; Humans; Immune response; Immune system; Infections; Interferon; Interferon-gamma - immunology; Interleukin 2; Interleukin-2 - immunology; Lymphocytes; Lymphocytes T; Medical research; Medical tests; Medicine and Health Sciences; Methods; Military Personnel; N protein; Nucleocapsids; Peptides; Pools; Proteins; SARS-CoV-2 - genetics; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Vaccines; Viral diseases; Virology; γ-Interferon; United States; United States > US; Peru
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0266691

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 Th 1 -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.