AUTHOR=Lebourgeois Samuel , David Ambroise , Chenane Houssem Redha , Granger Vanessa , Menidjel Reyene , Fidouh Nadhira , Noël Benoît , Delelis Olivier , Richetta Clémence , Charpentier Charlotte , Chollet-Martin Sylvie , Descamps Diane , Visseaux Benoit , de Chaisemartin Luc TITLE=Differential activation of human neutrophils by SARS-CoV-2 variants of concern JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1010140 DOI=10.3389/fimmu.2022.1010140 ISSN=1664-3224 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.