The role of efferocytosis in tissue damage and hyperinflammation in SARS-CoV-2 infection

Controlling the multiplication of the pathogen and tolerating the impact of the damage caused during the infectious process, are essential to ensure the survival of the organism. Macrophages are a determining component of innate immunity to infectious processes, not only for identifying and eliminating the invading pathogen and activating the immune system, but also for acting to control the inflammatory response and reduce immunopathology. In this context, macrophages are responsible for eliminating dead cells (process of eferocytosis) and orchestrating the mechanisms of tissue repair. Patients infected with SARS-CoV-2 who evolve to the critical form of COVID-19 have symptoms consistent with the development of a hyperinflammatory syndrome that can cause fatal injuries to different organs. However, these critical patients often have a low viral load, suggesting that a failure in the tolerance mechanisms that culminate in exacerbated immunopathology is preponderant in the critical cases of COVID-19. Recent studies describing the clinical aspects of COVID-19 point to the occurrence of exacerbated cell death during infection: patients have acute leukopenia, in addition to high levels of inflammatory cell death markers in the bloodstream. The hypothesis on which this proposal is based is that the excess of cell death during the infection by SARS-Cov-2 and a possible failure in the elimination of these cells contributes to the hyperinflammation observed in patients with severe manifestation of COVID-19. In this sense, we propose to determine the potential of phagocytic cells of patients with COVID-19 to eliminate dead cells, determining the importance of this process for hyperinflammation and its association with the severity of the disease. Finally, we propose to investigate the potential of a possible biomarker associated with the phagocytic activity of macrophages to discriminate the response to therapy with immunosuppressive and anti-inflammatory drugs in critically ill patients. (AU)