Secondary Complement Deficiency Impairs Anti-Microbial Immunity to Klebsiella pneumoniae and Staphylococcus aureus During Severe Acute COVID-19
Ali, Youssif M
Lynch, Nicholas J
Bamigbola, Ifeoluwa E
Chan, Andrew CY
Demopulos, Gregory A
Heeney, Jonathan L
Schwaeble, Wilhelm J
Frontiers in Immunology
Frontiers Media S.A.
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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. Frontiers in Immunology, 13 https://doi.org/10.3389/fimmu.2022.841759
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.
Immunology, K. pneumoniae, COVID-19, SARS-CoV-2, complement system, bacterial infection, S. aureus
External DOI: https://doi.org/10.3389/fimmu.2022.841759
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337041