Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4 + T cells are likely important in immunity against coronavirus 2019 (COVID-19), but our understanding of CD4 + longitudinal dynamics following infection and of specific features that correlate with the maintenance of neutralizing antibodies remains limited. Here, we characterize SARS-CoV-2-specific CD4 + T cells in a longitudinal cohort of 109 COVID-19 outpatients enrolled during acute infection. The quality of the SARS-CoV-2-specific CD4 + response shifts from cells producing interferon gamma (IFNγ) to tumor necrosis factor alpha (TNF-α) from 5 days to 4 months post-enrollment, with IFNγ – IL-21 – TNF-α + CD4 + T cells the predominant population detected at later time points. Greater percentages of IFNγ – IL-21 – TNF-α + CD4 + T cells on day 28 correlate with SARS-CoV-2-neutralizing antibodies measured 7 months post-infection (⍴ = 0.4, p = 0.01). mRNA vaccination following SARS-CoV-2 infection boosts both IFNγ- and TNF-α-producing, spike-protein-specific CD4 + T cells. These data suggest that SARS-CoV-2-specific, TNF-α-producing CD4 + T cells may play an important role in antibody maintenance following COVID-19.
Trial registration: ClinicalTrials.gov NCT04331899 .
Keywords: CD4; COVID-19; SARS-CoV-2; T cells; TNF-α; Tfh; antibodies; cytokines; longitudinal; neutralizing antibodies.
【저자키워드】 COVID-19, antibodies, SARS-CoV-2, Cytokines, T cells, CD4, longitudinal, neutralizing antibodies., TNF-α, Tfh, 【초록키워드】 severe acute respiratory syndrome coronavirus 2, neutralizing antibody, Necrosis, Tumor, mRNA vaccination, coronavirus, Cytokines, Immunity, Neutralizing antibodies, antibody, T cells, SARS-COV-2 infection, Infection, severe acute respiratory syndrome Coronavirus, Cohort, T cell, tumor necrosis factor, mRNA, acute infection, Alpha, Coronavirus 2019, respiratory, boost, TNF-α, SARS-CoV-2-neutralizing antibodies, IL-21, interferon gamma, maintenance, tumor necrosis, Post-infection, tumor necrosis factor alpha, acute respiratory syndrome, acute respiratory syndrome coronavirus, These data, IFNγ, NCT04331899, feature, Cell, enrolled, producing, predominant, COVID-19 outpatient, percentage, SARS-CoV-2-neutralizing antibody, 【제목키워드】 antibody, T cell, T cell response, COVID-19 outpatient, the SARS-CoV-2,