SARS-CoV-2 viral infection was found to not significantly trigger IFN expression and only activated 5 of 13 pro-inflammatory mediators, which play important roles in the body's innate immune response. The virus possesses an gene identified as ORF3b that produces an IFN-antagonizing protein which inhibits synthesis and signaling and leads to unchecked viral replication.

Virus entry triggers the generation of pro-inflammatory cytokines (IL-6, IP-10, macrophage inflammatory protein 1α (MIP1α), MIP1β and MCP1) which recruit monocytes, macrophages, and T-cells to the sites of infections. This promotes further inflammation and creation of a feedback loop leading to a cytokine storm.