The amount of cytokine-release defines different shades of Sars-Cov2 infection

Abstract

The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: "mild",symbolized as a "drizzle" of cytokines, severe as a "storm", and critical as a "hurricane". In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a "cytokine-release syndrome", SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.

Keywords: COVID-19; CRS; HLH/MAS; SARS-CoV2; cytokines.

Figure 1.

The drizzle, the storm, and the hurricane: three different phenotypes of disease severity for COVID-19. The three main clinical phenotypes are represented. (a) Normal immunological response against viral infection. The clinical picture is typical of mild and self-limiting SARS-CoV2 infection. (b) The cytokine release syndrome (CRS) caused by the lysis of the immune cells may worse the clinical picture and lead to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). This immunological condition is typical of severe COVID-19 patients. (c) Critical patients present with a phenotype similar to a secondary Hemophagocytic Lymphohistyocitosis. The inflammasome is constantly triggered and produces large amounts of pro-inflammatory mediators which lead to life-threatening manifestations and multi organ failure (MOF). CRS: cytokine release syndrome; HLH: hemophagocyic lymphohistyocitosis; MAS: macrophage activation syndrome; MOF: multi organ failure; NLR: nod-like receptor; TLR: toll-like receptor. (A color version of this figure is available in the online journal.)