Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19

Abstract

SUMMARY SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We here systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust, broad and highly functional memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.

Identification and characterization of an immunodominant SARS-CoV-2-specific CD8 T cell response

“…Accumulating information on the antibody response against SARS-CoV-2 demonstrates that structural proteins such as the spike and nucleoprotein serve as potent antibody targets in a substantial fraction of COVID-19 patients [2][3][4][5][6] . However, much less is currently known regarding the SARS-CoV-2-speci c T cell response, in particular which parts of the virus are targeted by T cells.…”

“…However, much less is currently known regarding the SARS-CoV-2-speci c T cell response, in particular which parts of the virus are targeted by T cells. Both CD4 and CD8 T cells can recognize SARS-CoV-2 derived antigens 4,[6][7][8][9][10][11][12][13] . Most studies have focused on limited parts of the viral proteome 6,8,12 , and in particular the spike protein 4,10,13 , which was found to be a very important antigen source for virus speci c T cell responses in SARS-CoV-1 14 and MERS 15 .…”

“…Both CD4 and CD8 T cells can recognize SARS-CoV-2 derived antigens 4,[6][7][8][9][10][11][12][13] . Most studies have focused on limited parts of the viral proteome 6,8,12 , and in particular the spike protein 4,10,13 , which was found to be a very important antigen source for virus speci c T cell responses in SARS-CoV-1 14 and MERS 15 . However, accumulating data provide evidence for a broader repertoire of the SARS-CoV-2 derived T cell antigens 6-9,11,12. The vast majority of studies demonstrating T cell reactivity against SARS-CoV-2 are based on large peptide pools [7][8][9]12,13 .…”

“…However, accumulating data provide evidence for a broader repertoire of the SARS-CoV-2 derived T cell antigens 6-9,11,12. The vast majority of studies demonstrating T cell reactivity against SARS-CoV-2 are based on large peptide pools [7][8][9]12,13 . Only few studies have identi ed exact T cell epitopes and their restriction elements, and these have mainly been focused on HLA-A*02:01 and a limited set of selected epitopes from the spike protein 2,6,10 . Therefore, broader efforts are needed to provide fundamental insights into which parts of the SARS-CoV-2 proteome induce potent CD8 T cell responses.…”

Are we underestimating seroprevalence of SARS-CoV-2?

“…However, within-individual variation has been observed in immune responses to viral exposure, particularly in those with mild or asymptomatic disease. For example, a pilot study from the Karolinska Institute found the percentage of people mounting T cell responses after mild covid-19, asymptomatic disease, or exposure to infected family members, consistently exceeded the percentage mounting detectable IgG serological responses against the virus 3. Such discordant results could have major implications for epidemiological modelling of disease transmission and herd immunity.…”