Although COVID-19 has many manifestations, lung injury and severe acute respiratory failure (SRF) are more common.
The cornerstone of this condition is MAS/sHLH, or immune dysregulation. Alveolar macrophages secrete IL-6, which causes excessive production of pro-inflammatory cytokines by monocytes, and lymphocyte dysregulation, characterized by CD4 lymphopenia and consequently B-cell lymphopenia.
In parallel, the number of absolute natural killer (NK) cells is depleted, probably as a result of the rapidly replicating virus. IL-6 also reduces membrane HLA-DR expression and IFN-γ production by CD4 cells.
In conclusion, it appears that innate immunity, characterized by neutrophils and pro-inflammatory cytokines in the form of a cytokine storm, attempts to limit the infection and defeat the virus; however, it leads to an excessive inflammatory response rather than harming the virus. This leads to lung injury with tissue damage and life-threatening edema, enriched with mucin and fibrin, which unfortunately causes SRF and death in severely ill patients.
