Figure 1.

Kinetics of SARS-CoV-2 replication and the antiviral immune response. The median incubation period of SARS-CoV-2 is 4-5 days, and symptoms usually start appearing by 11.5 days. Within a week of symptoms appearing, viral load reaches its peak and becomes detectable in RT-PCR tests. A non-robust viral replication is associated with a regulated and protective immune response. Early IFN (interferon) response, optimal monocyte-macrophage and neutrophil infiltration, optimal secretion of pro-inflammatory cytokines and chemokines, and optimal lymphocyte responses result in effective viral clearance. The inflammatory response resolves within 4-5 weeks after symptom appearance, viral particles go below the detection limit, but viral RNA may persist in low amount, and the person recovers. However, robust SARS-CoV-2 replication may lead to delayed IFN response, excess monocyte-macrophage and neutrophil infiltrations, sub-optimal lymphocyte response, and impaired viral clearance. The resulting aberrant inflammatory response known as hyperinflammation is associated with excessive secretion of pro-inflammatory cytokines and chemokines (hypercytokinemia) and accumulation of inflammatory cells in the lungs. Hyperinflammation and hypercytokinemia may lead to diffused alveolar damage (DAD), acute respiratory distress syndrome (ARDS), and multiorgan failure. Created with BioRender.com.