Cross-reactive cellular, but not humoral, immunity is detected between OC43 and SARS-CoV-2 NPs in people not infected with SARS-CoV-2: Possible role of cTFH cells

Multiple questions about SARS-CoV-2 humoral and cellular immunity remain unanswered. One key question is whether preexisting memory T or B cells, specific for related coronaviruses in SARS-CoV-2-unexposed individuals, can recognize and suppress COVID-19, but this issue remains unclear. Here, we demonstrate that antibody responses to SARS-CoV-2 antigens are restricted to serum samples from COVID-19 convalescent individuals. In contrast, cross-reactive T cell proliferation and IFN-gamma production responses were detected in PBMCs of around 30% of donor samples collected prepandemic, although we found that these prepandemic T cell responses only elicited weak cT(FH) activation upon stimulation with either HCoV-OC43 or SARS-CoV-2 NP protein. Overall, these observations confirm that T cell cross-reactive with SARS-CoV-2 antigens are present in unexposed people, but suggest that the T cell response to HCoV-OC43 could be deficient in some important aspects, like T-FH expansion, that might compromise the generation of cross-reactive T-FH cells and antibodies. Understanding these differences in cellular responses may be of critical importance to advance in our knowledge of immunity against SARS-CoV-2.

Automated summary

Several unanswered questions remain about humoral and cellular immunity to SARS-CoV-2, including whether preexisting memory T or B cells in unexposed individuals can recognize and suppress COVID-19. Research has shown that while some unexposed individuals have cross-reactive T cell responses, these responses are weak in aspects like T-FH expansion, which may impact the generation of effective antibodies against SARS-CoV-2. Understanding these differences in cellular responses is crucial for advancing our knowledge of immunity to SARS-CoV-2.