In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 1 ( 2022-1-10), p. e1010176-
Abstract:
COVID-19 displays diverse disease severities and symptoms including acute systemic inflammation and hypercytokinemia, with subsequent dysregulation of immune cells. Bacterial superinfections in COVID-19 can further complicate the disease course and are associated with increased mortality. However, there is limited understanding of how SARS-CoV-2 pathogenesis and hypercytokinemia impede the innate immune function against bacterial superinfections. We assessed the influence of COVID-19 plasma hypercytokinemia on the functional responses of myeloid immune cells upon bacterial challenges from acute-phase COVID-19 patients and their corresponding recovery-phase. We show that a severe hypercytokinemia status in COVID-19 patients correlates with the development of bacterial superinfections. Neutrophils and monocytes derived from COVID-19 patients in their acute-phase showed an impaired intracellular microbicidal capacity upon bacterial challenges. The impaired microbicidal capacity was reflected by abrogated MPO and reduced NETs production in neutrophils along with reduced ROS production in both neutrophils and monocytes. Moreover, we observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes, in line with suppressed autocrine and paracrine cytokine signaling. This phenotype was characterized by a high expression of CD66b, CXCR4 and low expression of CXCR1, CXCR2 and CD15 in neutrophils and low expression of HLA-DR, CD86 and high expression of CD163 and CD11b in monocytes. Furthermore, the impaired antibacterial effector function was mediated by synergistic effect of the cytokines TNF-α, IFN-γ and IL-4. COVID-19 patients receiving dexamethasone showed a significant reduction of overall inflammatory markers in the plasma as well as exhibited an enhanced immune response towards bacterial challenge ex vivo . Finally, broad anti-inflammatory treatment was associated with a reduction in CRP, IL-6 levels as well as length of ICU stay and ventilation-days in critically ill COVID-19 patients. Our data provides insights into the transient functional dysregulation of myeloid immune cells against subsequent bacterial infections in COVID-19 patients and describe a beneficial role for the use of dexamethasone in these patients.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010176
DOI:
10.1371/journal.ppat.1010176.g001
DOI:
10.1371/journal.ppat.1010176.g002
DOI:
10.1371/journal.ppat.1010176.g003
DOI:
10.1371/journal.ppat.1010176.g004
DOI:
10.1371/journal.ppat.1010176.g005
DOI:
10.1371/journal.ppat.1010176.g006
DOI:
10.1371/journal.ppat.1010176.g007
DOI:
10.1371/journal.ppat.1010176.g008
DOI:
10.1371/journal.ppat.1010176.g009
DOI:
10.1371/journal.ppat.1010176.s001
DOI:
10.1371/journal.ppat.1010176.s002
DOI:
10.1371/journal.ppat.1010176.s003
DOI:
10.1371/journal.ppat.1010176.s004
DOI:
10.1371/journal.ppat.1010176.s005
DOI:
10.1371/journal.ppat.1010176.s006
DOI:
10.1371/journal.ppat.1010176.s007
DOI:
10.1371/journal.ppat.1010176.s008
DOI:
10.1371/journal.ppat.1010176.s009
DOI:
10.1371/journal.ppat.1010176.s010
DOI:
10.1371/journal.ppat.1010176.s011
DOI:
10.1371/journal.ppat.1010176.s012
DOI:
10.1371/journal.ppat.1010176.s013
DOI:
10.1371/journal.ppat.1010176.s014
DOI:
10.1371/journal.ppat.1010176.s015
DOI:
10.1371/journal.ppat.1010176.s016
DOI:
10.1371/journal.ppat.1010176.s017
DOI:
10.1371/journal.ppat.1010176.s018
DOI:
10.1371/journal.ppat.1010176.s019
DOI:
10.1371/journal.ppat.1010176.s020
DOI:
10.1371/journal.ppat.1010176.s021
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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