Abstract
SARS-CoV-2, the virus that causes COVID-19, has given rise to one of the largest pandemics, affecting millions worldwide. High neutrophil-to-lymphocyte ratios have been identified as an important correlate to poor recovery rates in severe COVID-19 patients. However, the mechanisms underlying this clinical outcome and the reasons for its correlation to poor prognosis are unclear. Furthermore, the mechanisms involved in healthy neutrophils acquiring a SARS-CoV-2-mediated detrimental role are yet to be fully understood. In this study, we isolated circulating neutrophils from healthy donors for treatment with supernates from infected epithelial cells and direct infection with SARS-CoV-2 in vitro. Infected epithelial cells induced a dysregulated degranulation of primary granules with a decrease in myeloperoxidase (MPO), but slight increase in neutrophil elastase release. Infection of neutrophils resulted in an impairment of both MPO and elastase release, even though CD16 receptor shedding was upregulated. Importantly, SARS-CoV-2-infected neutrophils had a direct effect on peripheral blood lymphocyte counts, with decreasing numbers of CD19+ B cells, CD8+ T cells, and CD4+ T cells. Together, this study highlights the independent role of neutrophils in contributing to the aberrant immune responses observed during SARS-CoV-2 infection that may be further dysregulated in the presence of other immune cells.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a β coronavirus with a single-stranded RNA genome
Many comorbidities have been associated with mortality in COVID-19 patients
A recent study comparing COVID-19 and influenza patients showed that higher rates of bacterial infections were present in COVID-19 patients [29]
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a β coronavirus with a single-stranded RNA genome. Compared to infections by other commonly circulating viruses such as influenza, SARS-CoV-2 infection has higher chances of progressing to a critical state requiring oxygen therapy and ventilatory support. This suggests SARS-CoV-2 may have a systemic aspect to its infection that is accompanied by severe inflammation [9,10,11,12]
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