Secondary Complement Deficiency Impairs Anti-Microbial Immunity to Klebsiella pneumoniae and Staphylococcus aureus During Severe Acute COVID-19.
Authors
Ali, Youssif M
Lynch, Nicholas J
Khatri, Priyanka
Bamigbola, Ifeoluwa E
Chan, Andrew CY
Yabuki, Munehisa
Demopulos, Gregory A
Heeney, Jonathan L
Pai, Sumita
Baxendale, Helen
Schwaeble, Wilhelm J
Publication Date
2022Journal Title
Front Immunol
ISSN
1664-3224
Publisher
Frontiers Media SA
Volume
13
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Ali, Y. M., Lynch, N. J., Khatri, P., Bamigbola, I. E., Chan, A. C., Yabuki, M., Demopulos, G. A., et al. (2022). Secondary Complement Deficiency Impairs Anti-Microbial Immunity to Klebsiella pneumoniae and Staphylococcus aureus During Severe Acute COVID-19.. Front Immunol, 13 https://doi.org/10.3389/fimmu.2022.841759
Abstract
A high incidence of secondary Klebsiella pneumoniae and Staphylococcus aureus infection were observed in patients with severe COVID-19. The cause of this predisposition to infection is unclear. Our data demonstrate consumption of complement in acute COVID-19 patients reflected by low levels of C3, C4, and loss of haemolytic activity. Given that the elimination of Gram-negative bacteria depends in part on complement-mediated lysis, we hypothesised that secondary hypocomplementaemia is rendering the antibody-dependent classical pathway activation inactive and compromises serum bactericidal activity (SBA). 217 patients with severe COVID-19 were studied. 142 patients suffered secondary bacterial infections. Klebsiella species were the most common Gram-negative organism, found in 58 patients, while S. aureus was the dominant Gram-positive organism found in 22 patients. Hypocomplementaemia was observed in patients with acute severe COVID-19 but not in convalescent survivors three months after discharge. Sera from patients with acute COVID-19 were unable to opsonise either K. pneumoniae or S. aureus and had impaired complement-mediated killing of Klebsiella. We conclude that hyperactivation of complement during acute COVID-19 leads to secondary hypocomplementaemia and predisposes to opportunistic infections.
Keywords
Immunology, K. pneumoniae, COVID-19, SARS-CoV-2, complement system, bacterial infection, S. aureus
Identifiers
External DOI: https://doi.org/10.3389/fimmu.2022.841759
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337041
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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