Older adults lack SARS CoV-2 cross-reactive T lymphocytes directed to human coronaviruses OC43 and NL63

• Published in: Scientific reports Vol. 10; no. 1; pp. 21447 - 10
• Main Authors: Saletti, Giulietta, Gerlach, Thomas, Jansen, Janina M., Molle, Antonia, Elbahesh, Husni, Ludlow, Martin, Li, Wentao, Bosch, Berend-Jan, Osterhaus, Albert D. M. E., Rimmelzwaan, Guus F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.12.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326/596/2553; 631/326/596/4130; Adult; Age; Aged; Antibodies, Viral - immunology; Cell-mediated immunity; Coronaviridae; Coronavirus NL63, Human - immunology; Coronavirus OC43, Human - immunology; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - pathology; Cross Reactions - immunology; Humanities and Social Sciences; Humans; Immunity, Cellular - immunology; Infections; Lymphocytes; Lymphocytes T; Middle Aged; Morbidity; Mortality; multidisciplinary; Older people; Pandemics; SARS-CoV-2 - immunology; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Spike Glycoprotein, Coronavirus - immunology; T-Lymphocytes - immunology; Young Adult; Young adults
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-78506-9

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.