Disease severity, comorbidities and innate immunity
SARS-CoV-2 exploits many strategies to subvert innate immune responses allowing the virus to replicate and disseminate within the host. The extent to which the virus replicates within the host, and the efficacy of the host innate immune response to eradicate the infection and trigger effective adaptive immune responses, but not hyper-responses of innate immunity strongly determines the disease outcome [Table 3]. The severity of infection has been linked to age, smoking, comorbidities such as cancer, immune suppression, autoimmune diseases, inflammatory disease, neurodegenerative diseases, obesity, gender and race (96–105). For example, in a large cohort of 72,314 cases the case fatality ratio for over 80 years was 14.8% versus 2.3% in the total cohort (96). This is likely higher due to inflamm-ageing, an aberrant innate immune response such as lower production of IFNβ (97) and increased oxidative stress (98). Likewise, obesity, gender, race, blood groups and comorbidities have all been reported to influence the response to SARS-CoV-2 infection [Table 4; (99–110)] although few studies have fully examined the extent to which subversion and activation of innate immune components contribute to susceptibility in these cases. Understanding the innate immune factors that exacerbate vascular complications will be crucial to control severe disease following SARS-CoV-2 infection.