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).