Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals

These GEITP pages continue to stay updated on papers dealing with SARS-CoV-2 transmission and possible preventions and treatments. Vaccines against this new virus are just beginning to be developed. An understanding of human T cell responses to SARS-CoV-2 is lacking, due to the rapid emergence of the pandemic; certainly, there is an urgent need for foundational information about T cell responses to this virus. The first steps for such an understanding would be the ability to quantify virus-specific CD4+ and CD8+ T cells. Such knowledge is of immediate relevance — because it will provide insights into immunity and pathogenesis of SARS-CoV-2 infections, and this knowledge would assist vaccine design and evaluation of candidate vaccines.

Estimations of immunity are also central to epidemiological-model calibration of future social-distancing pandemic-control measures. Such projections are stikingly different — depending on whether SARS-CoV-2 infection creates substantial immunity, and whether any crossreactive immunity exists between SARS-CoV-2 and circulating seasonal “common cold” human coronaviruses. Definition and assessment of human antigen-specific SARS-CoV-2 T cell responses are best made with direct ex vivo (i.e. cells taken from a live patient) T cell assays using broad-based epitope pools and assays capable of detecting T cells of any cytokine polarization. Authors [see attached preprint] have completed such an assessment with blood samples from COVID-19 patients.

There is also great uncertainty about whether adaptive immune responses to SARS-CoV-2 are protective or pathogenic, or whether both scenarios can occur depending on timing, composition, or magnitude of the adaptive immune response. Hypotheses range the full gamut — based on available clinical data from severe acute respiratory disease syndrome (SARS) or Middle East respiratory distress syndrome (MERS), as well as animal model data with SARS in mice, SARS in nonhuman primates, or feline infectious peritoneitis virus (FIPV) in cats.

Using HLA Class I and II predicted peptide “mega-pools”, authors [see attached] identified circulating SARS-CoV-2-specific CD8+, and CD4+ T cells, in ~70%, and 100%, respectively, of COVID-19 convalescent patients. CD4+ T cell responses to the virus spike protein (the main target of most vaccine efforts) were robust and correlated with the

magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. It was most noteworthy that the authors detected SARS-CoV-2-reactive CD4+ T cells in ~40-60% of unexposed individuals. These intriguing data suggest cross-reactive T cell recognition between various circulating “common cold” coronaviruses and SARS-CoV-2. 😊


Cell, preprint in press, May 2020;

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