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.