Innate immunity during SARS-CoV-2: evasion strategies and activation
trigger hypoxia and vascular damage
Abstract
Innate immune sensing of viral molecular patterns is essential for
development of antiviral responses. Like many viruses SARS CoV-2 has
evolved strategies to circumvent innate immune detection including low
CpG levels in the genome, glycosylation to shield essential elements
including the receptor binding domain, RNA shielding and generation of
viral proteins that actively impede anti-viral interferon responses.
Together these strategies allow widespread infection and increased viral
load. Despite the efforts of immune subversion SARS-CoV-2 infection does
activate innate immune pathways inducing a robust type I/III interferon
response, production of proinflammatory cytokines, and recruitment of
neutrophils and myeloid cells. This may induce hyperinflammation or
alternatively, effectively recruit adaptive immune responses that help
clear the infection and prevent reinfection. The dysregulation of the
renin-angiotensin system due to downregulation of angiotensin converting
enzyme 2, the receptor for SARS-CoV-2, together with the activation of
type I/III interferon response, and inflammasome response converge to
promote free radical production and oxidative stress. This exacerbates
tissue damage in the respiratory system but also leads to widespread
activation of coagulation pathways leading to thrombosis. Here, we
review the current knowledge of the role of the innate immune response
following SARS-CoV-2 infection, much of which is based on the knowledge
from SARS-CoV and other coronaviruses. Understanding how the virus
subverts the initial immune response and how an aberrant innate immune
response contributes to the respiratory and vascular damage in COVID-19
may help explain factors that contribute to the variety of clinical
manifestations and outcome of SARS-CoV-2 infection.