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 cT(FH) 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‐γ 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.