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

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 seco...

Full description

Saved in:
Bibliographic Details
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
Citations: Items that cite this one
Online Access:Request full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
DOI:10.1101/2020.12.01.406306