Immunology of COVID-19

Abstract

SARS-CoV-2 is a new human pathogen belonging to a yet-evolving extended family of coronaviruses. The extraordinary global spread of SARS-CoV-2 through naïve populations provides compelling evidence of both the strengths and limitations of the human immune response: on the one hand, recognizing and eliminating a novel viral pathogen, while on the other, causing potentially lethal immunopathological conditions. The virus is easily transmitted, yet only a minority of adults with COVID-19 develop the full-blown severe syndrome characterized by hypoxemic respiratory failure, with diffuse alveolar damage, inflammatory infiltrates, and intravascular thrombosis (involving both large and small blood vessels), often associated with lymphopenia and markedly increased levels of inflammatory markers. The interplay of innate, humoral, and cellular immunity is now better understood as investigators create models of infection and disease to find better means of protecting people and treating patients exposed to SARS-CoV-2. Variations in the character and timing of the immune response give us clues to the relationship and relative roles of the innate and adaptive immune systems in defenses against COVID-19. Severe disease is understood to be due to delayed interferon responses, heightened early viral replication, and exaggerated subsequent late innate responses, yet further studies are needed to fully understand this phenomenon and the role of vaccines and therapeutics in mitigating severe disease while the virus undergoes mutational changes.