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

• Published in: bioRxiv 2020-12
• Main Authors: Shambat, Srikanth Mairpady, Gómez-Mejia, Alejandro, Schweizer, Tiziano A, Huemer, Markus, Chun-Chi, Chang, Acevedo, Claudio, Judith Bergada Pijuan, Vulin, Clement, Miroshnikova, Nataliya, Hofmänner, Daniel A, Wendel Garcia, Pedro D, Hilty, Matthias P, Philipp Bühler Karl, Schüpbach, Reto A, Brugger, Silvio D, Zinkernagel, Annelies S
• Format: Article
• Language: English
• Subjects: Autocrine signalling; Bacteria; Bacterial infections; Cell surface; Coronaviruses; COVID-19; Cytokine storm; Immune status; Leukocytes (neutrophilic); Microbicides; Monocytes; Neutrophils; Paracrine signalling; Severe acute respiratory syndrome coronavirus 2
• DOI: 10.1101/2020.12.01.406306

Abstract 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 Competing Interest Statement The authors have declared no competing interest.