https://orcid.org/0000-0002-2741-9755
Figures & data
Figure 1 Simplified depiction of the apoptotic/efferocytic process in SARS-COV-2 infection.
Notes: The phosphatidylserine (PS) in the envelope of the virus attaches to the PS receptors (PSRs) on the target cell, facilitating the binding of the viral spike protein to the host ACE2 receptor. In the cell, the viral ORF3a protein initiates the apoptotic process by the caspase-3 activation. While activated caspase-3 inhibits cellular innate immune response, caspase-3-driven permanent activation of the Xkr8 scramblase causes PS expression in the membrane outer leaflet of apoptotic cells. Caspase-3 also oxidizes PS and phosphatidylcholine (PC). PS binds to efferocytic cells via PSRs, facilitating the binding of oxidized PC-CRP and PS to CD36 and engulfment of the apoptotic cell. Successfully induced efferocytosis is a sterile process with the secretion of anti-inflammatory mediators. In addition, antigenic viral epitopes, which arise due to phago-lysosomal degradation of the virus in antigen-presenting cells, can initiate T- and B-cell-mediated adaptive immunity. Reproduced from Erol A. Defective efferocytosis as a predictor of COVID-19 mortality. OSF Preprints. 2021; September 13:1-18.Citation119
Figure 2 The common characteristics of co-morbid diseases responsible for the severity of COVID-19 are increased PS expression and ADAM-17 (A17) activity in cells.
Notes: ADAM-17 renders efferocytosis as defective due to the shedding of the receptors required for the engulfment of apoptotic cells. PS expressed on the surface of endothelial cells, PS in the SARS-CoV-2 envelope, and microvesicles (Mv) detached from apoptotic cells reason in coagulopathy seen in COVID-19. Reproduced from Erol A. Defective efferocytosis as a predictor of COVID-19 mortality. OSF Preprints. 2021; September 13:1-18.Citation119
