Neutrophil and monocyte dysfunctional effector response towards bacterial challenge in critically-ill COVID-19 patients

Shambat, Srikanth Mairpady; Gómez-Mejia, Alejandro; Schweizer, Tiziano A.; Huemer, Markus; Chang, Chun-Chi; Acevedo, Claudio; Pijuan, Judith Bergada; Vulin, Clement; Miroshnikova, Nataliya; Hofmänner, Daniel A.; Wendel Garcia, Pedro D.; Hilty, Matthias P; Karl, Philipp Bühler; Schüpbach, Reto A.; Brugger, Silvio D.; Zinkernagel, Annelies S.

COVID-19 displays diverse disease severities and symptoms. Elevated inflammation mediated by hypercytokinemia induces a detrimental dysregulation of immune cells. However, there is limited understanding of how SARS-CoV-2 pathogenesis impedes innate immune signaling and function against secondary bacterial infections. We assessed the influence of COVID-19 hypercytokinemia on the functional responses of neutrophils and monocytes upon bacterial challenges from acute and corresponding recovery COVID-19 ICU patients. We show that severe hypercytokinemia in COVID-19 patients correlated with bacterial superinfections. Neutrophils and monocytes from acute COVID-19 patients showed severely impaired microbicidal capacity, reflected by abrogated ROS and MPO production as well as reduced NETs upon bacterial challenges. We observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes leading to a suppressive autocrine and paracrine signaling during bacterial challenges. Our data provide insights into the innate immune status of COVID-19 patients mediated by their hypercytokinemia and its transient effect on immune dysregulation upon subsequent bacterial infections