Inactivated Wild-Type Human Coronavirus (NL63)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19. People over the age of 60 are at particularly high risk for severe or even fatal illness. In fact, more than 95% of all deaths from SARS-CoV-2 infection have been reported in this age group. Here, researchers hypothesize that differences in SARS-CoV-2 cross-reactive cellular immunity elicited after infection with human coronaviruses (HCoVs), such as OC43 and NL63, underlie the differences in mortality (and morbidity) observed after SARS-CoV-2 infection, as a small fraction of HCoV-specific T cells cross-react with SARS-CoV-2. Data suggest that pre-existing T cell immunity induced by circulating human α and β HCoVs is present in young adult individuals but virtually absent in older adults. Thus, the frequency of cross-reactive T cells against the novel pandemic SARS-CoV-2 is minimal in most older adults.

For both Human Coronavirus NL63 (HCoV-NL63) and Human Coronavirus OC43 (HCoV-OC43), the frequency of HCoV-specific T cells secreting IFN-γ was significantly higher in young adults than in older adults (Figure 1a), and overall, responses elicited by NL63 stimulation were more robust than those elicited by OC43 stimulation. A higher proportion of subjects with positive responses were observed in young adults than in older adults (Figure 1b). Researchers then sought to identify the T cell subsets responsible for IFN-γ secretion in response to inactivated HCoV-NL63 and HCoV-OC43 preparations by flow cytometry. The frequency of HCoV-specific T cells was very low, so virus-specific T cells could not be detected by intracellular IFN-γ staining. Therefore, five high responders (HR) were selected from the young group, and their PBMCs were restimulated in vitro with inactivated HCoV preparations. Despite the variable intensity of the responses, virus-specific CD4+ and CD8+ IFN-γ+ T cells were present in all young high-risk subjects tested. Thus, inactivated HCoV preparations induced IFN-γ production by CD4+ and CD8+ T cells (Figure 1c). In addition, the levels of NL63- and OC43-specific antibodies were similar in young and elderly people, and the level of OC43 antibodies was lower (Figure 1d), suggesting that other factors contribute to the lower frequency of HCoV-specific T cells in the elderly population.

Figure 1. HCoV-NL63 and HCoV-OC43-specific immunity in young and older adults. (Saletti G, et al., 2020)