Mechanistic model of hyper-inflammation in COVID-19. After respiratory epithelial cells are infected (A), SARS-CoV-2 proteins block viral-recognition signaling and type I and III interferon (IFN) responses (B). The viral load increases (C) and myeloid cells, such as monocytes and macrophages, are stimulated by viral components via Toll-like receptors, producing type I and III IFNs (D). IFNs further stimulate the production of chemokines and induce the accumulation and activation of monocytes and macrophages, thus producing excessive amounts of pro-inflammatory cytokines (E). This process can be amplified by a positive feedback mechanism.
