Fig. 1: Simplified model schematic depicting the influence of key mediators.

The model describes the productive viral infection of susceptible Type II alveolar cells - infected cells together with free virus activate proinflammatory mediators of the innate and adaptive immune systems (chiefly Type I interferons and CD8 + T cells) to clear the infected cells. The activation of this proinflammatory response engages anti-inflammatory mediators such as Treg cells, IL-10, and TGF-β, which contribute to resolve the proinflammatory response. Importantly, the proinflammatory response also causes the accumulation of tissue damage as a result of the inflammatory death of infected and bystander alveolar cells. This can lead to positive feedback leading to a sustained immune response indicative of the more severe outcomes of COVID-19. Finally, these processes are linked to certain circulating biomarkers of interest including IL-6, C-reactive protein [CRP], ferritin, and surfactant protein D. A more detailed model schematic can be found in Fig. 1 of ref. ¹⁹ and in Supplementary Fig. 1.