Abstract
Currently, infections with SARS-Coronavirus-2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, are responsible for substantial morbidity and mortality worldwide. Older adults subjects > 60 years of age account for > 95% of the over one million fatal cases reported to date. It is unclear why in this age group SARS-CoV-2 infection causes more severe disease than in young adults. We hypothesized that differences in SARS-CoV-2 cross-reactive cellular immunity induced after infection with human coronaviruses (HCoVs), like OC43 and NL63, were at the basis of the differential mortality (and morbidity) observed after SARS-CoV-2 infection, because a small proportion of HCoV-specific T cells cross-react with SARS-CoV-2. Our data demonstrate that pre-existing T cell immunity induced by circulating human alpha- and beta-HCoVs is present in young adult individuals, but virtually absent in older adult subjects. Consequently, the frequency of cross-reactive T cells directed to the novel pandemic SARS-CoV-2 was minimal in most older adults. To the best of our knowledge, this is the first time that the presence of cross-reactive T cells to SARS-CoV-2 is compared in young and older adults. Our findings provide at least a partial explanation for the more severe clinical outcome of SARS-CoV-2 infection observed in the elderly. Moreover, this information could help to design efficacious vaccines for this age group, aiming at the induction of cell-mediated immunity.
Highlights
Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19
peripheral blood mononuclear cells (PBMCs) obtained from forty-four healthy blood donors (Table 1 and Supplementary Table S1) divided into two age groups, young adults (N = 23) and older adults (N = 21) were stimulated with inactivated human coronaviruses (HCoVs)-NL63 and HCoV-OC43 or left unstimulated
Because there was an unequal distribution between males and females in the two age groups, we re-analyzed the data only using the male subjects and confirmed that older subjects displayed a lower response than young adults (NL63 p < 0.005; OC43 p < 0.05) (Supplementary Fig. S1)
Summary
Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19. The first cases of SARS-CoV-2 infection were reported in December 2019 and ever since the virus spread rapidly around the globe, causing mild to severe respiratory disease, which prompted the World Health Organization to declare the COVID-19 outbreak a pandemic on March 11th. The reason why SARS-CoV-2 infection causes more severe disease in older adults is largely unknown, but most likely has an immunological basis. It has been shown that infection with human coronaviruses (HCoVs), like OC43, HKU-1 (beta coronaviruses), NL63 and 229E (alpha coronaviruses) can induce virus-specific CD4+ and CD8+ T cell responses that display cross-reactivity with the novel emerging coronavirus SARS-CoV-2, to a limited e xtent[5,6]. SARS-CoV-2 specific T cells could not be demonstrated in Scientific Reports | (2020) 10:21447
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