Differential activation of human neutrophils by SARS-CoV-2 variants of concern
Samuel Lebourgeois, Ambroise David, Houssem Redha Chenane, Vanessa Granger, Reyene Menidjel, Nadhira Fidouh, Benoît Noël, Olivier Delelis, Clémence Richetta, Charlotte Charpentier, Sylvie Chollet‐Martin, Diane Descamps, Benoît Visseaux, Luc de Chaisemartin
Abstract
The emerging SARS-CoV-2 virus has affected the entire world with over 600 million confirmed cases and 6.5 million deaths as of September 2022. Since the beginning of the pandemic, several variants of SARS-CoV-2 have emerged, with different infectivity and virulence. Several studies suggest an important role of neutrophils in SARS-Cov-2 infection severity, but data about direct activation of neutrophils by the virus is scarce. Here, we studied the in vitro activation of human neutrophils by SARS-CoV-2 variants of concern (VOCs). In our work, we show that upon stimulation with SARS-Cov-2 infectious particles, human healthy resting neutrophils upregulate activation markers, degranulate IL-8, produce Reactive Oxygen Species and release Neutrophil Extracellular Traps. Neutrophil activation was dependent on TLR7/8 and IRF3/STING. We then compared the activation potential of neutrophils by SARS-CoV-2 variants and showed a significantly increased activation by the Delta variant and a decreased activation by the Omicron variant as compared to the initial strain. In this study, we demonstrate that the SARS-Cov-2 virus can directly activate neutrophils in COVID-19 and that the different VOCs had differences in neutrophil activation intensity that mirror the differences of clinical severity. These data highlight the need to address neutrophil-virus interactions as a potential target for therapeutic intervention in SARS-CoV-2 infection.