Decreased neutrophil-mediated bacterial killing in COVID-19 patients
File(s)covid phagocytosis- Accepted version.doc (3.26 MB)
Accepted version
Author(s)
Nomani, Masoumeh
Varahram, Mohammad
Tabarsi, Payam
Hashemian, Seyed MohammadReza
Jamaati, Hamidreza
Type
Journal Article
Abstract
The coronavirus disease COVID-19 was first described in December 2019. The peripheral blood of COVID-19 patients have increased numbers of neutrophils which are important in controlling the bacterial infections observed in COVID-19. We sought to evaluate the cytotoxic capacity of neutrophils in COVID-19 patients. 34 confirmed COVID-19 patients (29 severe, five mild disease), and nine healthy controls were recruited from the Masih Daneshvari Hospital (Tehran, Iran) from March to May 2020. Polymorphonuclear (PMN) cells were isolated from whole blood and incubated with green fluorescent protein (GFP)-labelled methicillin-resistant Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). Bacterial growth was determined by measuring the florescence of co-cultures of bacteria and neutrophils and reported as the lag time before exponential growth. The number of viable bacteria was determined after 70 hours as colony-forming units (CFU). The immunophenotype of tested cells was evaluated by flow cytometry. Isolated neutrophils have higher surface expression of CD16 and CD62L with negative markers for PMN-MDSC. Bacterial growth in the presence of SA (22 ± 0.9 versus 9.2 ± 0.5 h, P < .01) and PA (12.4 ± 0.6 versus 4.5 ± 0.22, P < .01) was significantly reduced in COVID-19 patients. After 70 h incubation of PMN with bacteria (SA and PA), CFUs were significant increased in COVID-19 patients SA (2.6 ± 0.09 × 108 CFU/mL-severe patients and 1.4 ± 0.06 × 108 CFU/mL-mild patients, P < .001) and PA (2.2 ± 0.09 × 109 CFU/mL-severe patients and 1.6 ± 0.03 × 109 CFU/mL-mild patients, P < .001). Gentamycin proliferation assays confirmed the presence of intracellular bacteria. Reduced bacterial killing by neutrophils from COVID-19 patients may be responsible for the high bacterial yield seen in these patients.
Date Issued
2021-05-31
Date Acceptance
2021-05-01
Citation
Scandinavian Journal of Immunology, 2021, 94 (3), pp.1-10
ISSN
0300-9475
Publisher
Wiley
Start Page
1
End Page
10
Journal / Book Title
Scandinavian Journal of Immunology
Volume
94
Issue
3
Copyright Statement
© 2021 The Scandinavian Foundation for Immunology. This is the accepted version of the following article: Nomani, M, Varahram, M, Tabarsi, P, et al. Decreased neutrophil-mediated bacterial killing in COVID-19 patients. Scand J Immunol. 2021; 00: 1– 10, which has been published in final form at https://doi.org/10.1111/sji.13083
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Medical Research Council (MRC)
Community Jameel Imperial College COVID-19 Excellence Fund
Engineering & Physical Science Research Council (EPSRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000660344900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
EP/T003189/1
MR/T010371/1
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EP/V052462/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
colony-forming unit
COVID-19
PMN-MDSCs
polymorphonuclear
Pseudomonas aeruginosa
Staphylococcus aureus
SUPPRESSOR-CELLS
STAPHYLOCOCCUS-AUREUS
PHARMACODYNAMICS
GENTAMICIN
RESPONSES
IMMUNITY
THERAPY
SUBSET
Publication Status
Published
Article Number
ARTN e13083
Date Publish Online
2021-05-31