A glimpse into the eye of the COVID-19 cytokine storm

Abstract

The pathogenesis of pandemic coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) likely depends heavily on disruption of immune and inflammatory processes. Thus far, the precise immune mechanisms have not been fully elucidated or studied in detail. In this issue of EBioMedicine, Liu and colleagues [1] showed that patients with severe COVID-19 had lymphopenia and increased neutrophil counts along with high levels of circulating pro-inflammatory cytokines compared to patients with mild COVID-19 illness. The investigators used flow cytometry to investigate immune phenotype and function of peripheral blood mononuclear cells (PBMC), as well as quantified plasma cytokine levels, from 40 COVID-19 patients. In particular, substantial depletion of CD8+ T cells were associated with disease severity, and both the ratios of neutrophils to CD8+ T cells (N8R) and neutrophils to lymphocytes (NLR) were predictive of COVID-19 outcome. These data suggest that depletion of lymphocytes, particularly cytotoxic T lymphocytes that function by eliminating infected cells, coupled with neutrophils capable of mediating a proinflammatory "cytokine storm" may be key players in COVID-19 pathogenesis.While "cytokine storms" have long been associated with acute respiratory distress syndrome (ARDS) caused by SARS coronavirus (SARS-CoV) and MERS coronavirus (MERS-CoV) [2], pro-inflammatory cytokine dynamics in the context of cellular immune responses in COVID-19 have not been well-characterized. This study clearly demonstrates that severe COVID-19 is associated with significant increases in pro-inflammatory cytokines such as IL-6 as well as significant reductions in CD8+ T cells. Th1 antiviral responses appear to be suppressed, which is supported by increases in the Th2 cytokine IL-10. A recent study in 21 patients also demonstrated that COVID-19

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