Age, ethnic and genetic risk factors and senescence of the immune system
In the context of SARS-CoV-2 age seems to be one of the highest predictors of the probability to get infected as well as of the extent of symptoms and severity of COVID-19. One reason besides a higher number of comorbidities and drugs take in the group of elder patients might be that ACE2 expression increases with age (34 ). Younger age groups seem to be not only at lower risk but maybe even protected from infection or severe viral spreading within the body. This could be managed for example by the presence of cross-reactive antibodies derived from other rather mild coronavirus infections in the past and an immunocompetent viral defense system at different immunologic levels. Another reason might be the presence of allelic variants interfering with the binding of the S-protein of SARS-CoV-2 to ACE2 and putative protection of the carriers from SARS-CoV-2 infection (35 ). In contrast, higher allele frequencies of variants in the ACE2coding gene region, which go along with higher ACE2 expression in the tissue, have been observed in populations from east Asia (36 ) and might indicated a specific risk, related to ethnic groups.
Finally, senescence of the immune system with lower antigen response of T and B cells from elder individuals as well as weaker effector functions and limited number of CD8+ memory cells capable to react do different pathogens might among other factors play a role for attenuated virus clearance and lower number of anti-inflammatory cytokines and mediators, innate immune regulatory proteins or regulatory cell mechanisms in higher age groups (37, 38).