Immunopathology of COVID-19.
Upon infection of the receptor-bearing host cells, viz. type 2 lung epithelial cells, nasal epithelial cells, gut enterocytes etc., the virus is expected to induce a type I interferon (IFN) response. The type I IFN response from the infected epithelial cells are assumed to be due to cytosolic RNA sensors like RIG-I. Nucleic acid-driven endosomal Toll-like receptor (TLR) activation in plasmacytoid dendritic cells (pDCs) and type I IFN induction has been shown to play central pathogenetic role in several systemic autoimmune diseases as well as in different components of metabolic disorders (Ganguly et al., 2018). Whether RNA-recognizing toll-like receptors, viz. TLR7 and TLR8, present primarily in plasmacytoid and conventional dendritic cells respectively, are also involved in the type I IFN response in case of SARS-CoV2 infection is not yet clear. But one report suggests considerable muting of type I IFN induction from the lung epithelial cells in response to SARS-CoV2 (Blanco-Melo et al., 2020). Apart from the viral RNA, danger signals released by stressed or dying host cells should also play a role in the innate immune activation. The ensuing adaptive immune response, following the innate immune activation, is primarily driven by the viral-antigen-specific T cells, which are presented with viral antigens by dendritic cells and macrophages. While SARS-CoV2-specific CD8+ cytotoxic T cells will be directed to kill the infected host cells to prevent virus replication to continue unabated, the CD4+ helper T cells will provide help to SARS-CoV2-specific B cells in mounting a humoral response , producing viral antigen-specific antibodies. In chronic viral infections, CD8+ T cells have been shown enter a stage of exhaustion. The recent data suggest that both CD4+ and CD8+ T cells in severe cases with COVID-19 are significantly below the normal levels, although the mechanism underlying this is far from clear. Evidences suggest that the severe COVID-19 patients experience a hyperimmune response due to high levels of proinflammatory cytokines such as MCP1, IL1-β, MIP1- α, IL-2R, IL-7, IL-8, IL-9, IL-10, IFNγ and TNFα production, dubbed the much talked about ‘cytokine storm’, which lead to inadvertent host tissue damage, and multi-organ involvements leading to untoward outcomes (Mehta et al., 2020; Li et al., 2020a).