Fig. 2. Host-directed immunotherapeutic intervention points for severe COVID-19.

If the initial interferon and inflammatory responses are insufficient to control SARS-CoV-2 infection, the inflammatory cascade may persist and become hyperactivated. This can lead to monocyte and neutrophil infiltration into the lung, high local and systemic levels of cytokines, tissue damage in the lung, formation of neutrophil extracellular traps (NETosis), complement hyperactivation, coagulation, and the formation of microthrombi. Immunotherapeutic interventions aim to improve virus control early in infection (indicated in green) or to limit immune-mediated tissue damage owing to uncontrolled inflammation (indicated in red). JAK, Janus kinase.