Abstract
COVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals. Evidence of a deleterious role of the innate immune system is accumulating, but the precise mechanisms involved remain unclear. In this study, we investigated the links between circulating innate phagocytes and severity in COVID-19 patients. We performed in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, anti-microbial functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Neutrophils and monocytes had a strikingly disturbed phenotype, and elevated concentrations of activation markers (calprotectin, myeloperoxidase, and neutrophil extracellular traps) were measured in plasma. Critical patients had increased CD13low immature neutrophils, LOX-1 + and CCR5 + immunosuppressive neutrophils, and HLA-DRlow downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity. Moreover, neutrophils and monocytes of critical patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.
Highlights
COVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals
We investigated the links between circulating innate phagocyte phenotype and functions and severity in COVID-19 patients
ICU patients presented a distinct set of parameters suggestive of immunosuppressive and immature neutrophils that clearly distinguished them from non-ICU patients
Summary
COVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals. We first assessed surface and soluble activation markers of blood neutrophils and monocytes in COVID-19 patients (Fig. 1). As for ICU patients, we identified a cluster of variables correlated with severity (higher O 2 requirement and longer stay; cluster A), which contained neutrophil activation markers like circulating MMP9 and NETs, and low expression of CD62L.
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