Cytokine release syndrome in severe COVID-1921 Apr, 2020
SARS-CoV-2 is a betacoronavirus that is most closely related to SARS-CoV. Both viruses use the angiotensin-converting enzyme–related carboxypeptidase (ACE2) receptor to gain entry to cells. This receptor is widely expressed in cardiopulmonary tissues but also in some hematopoietic cells, including monocytes and macrophages. A key feature of COVID-19 infection is lymphopenia (low blood lymphocyte count), which correlates with clinical severity. SARS-CoV efficiently infects primary human monocytes and dendritic cells, whereas MERS-CoV infects monocytes and T cells via dipeptidyl peptidase 4 (DPP4). It is possible that SARS-CoV-2 also infects dendritic cells. T cell apoptosis and exhaustion resulting from defective activation due to dendritic cell dysfunction might contribute to the immunopathology of COVID-19. However, lymphopenia as a biomarker of poor prognosis for COVID-19 is not specific because it was also a biomarker that correlated with fatality in the 2009 influenza A (H1N1) pandemic.
CRS was found to be the major cause of morbidity in patients infected with SARS-CoV and MERS-CoV. Elevated serum concentrations of the cytokine interleukin-6 (IL-6) and other inflammatory cytokines are hallmarks of severe MERS-CoV infections. CRS is common in patients with COVID-19, and elevated serum IL-6 correlates with respiratory failure, ARDS, and adverse clinical outcomes. Elevated serum C-reactive protein (CRP), a protein whose expression is driven by IL-6, is also a biomarker of severe betacoronavirus infection.