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dc.contributor.authorAli, Youssif M
dc.contributor.authorLynch, Nicholas
dc.contributor.authorKhatri, Priyanka
dc.contributor.authorBamigbola, Ifeoluwa E
dc.contributor.authorChan, Andrew CY
dc.contributor.authorYabuki, Munehisa
dc.contributor.authorDemopulos, Gregory A
dc.contributor.authorHeeney, Jonathan L
dc.contributor.authorPai, Sumita
dc.contributor.authorBaxendale, Helen
dc.contributor.authorSchwaeble, Wilhelm J
dc.date.accessioned2022-05-11T19:00:14Z
dc.date.available2022-05-11T19:00:14Z
dc.date.issued2022
dc.date.submitted2021-12-22
dc.identifier.issn1664-3224
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337041
dc.description.abstractA 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.
dc.languageen
dc.publisherFrontiers Media SA
dc.subjectImmunology
dc.subjectK. pneumoniae
dc.subjectCOVID-19
dc.subjectSARS-CoV-2
dc.subjectcomplement system
dc.subjectbacterial infection
dc.subjectS. aureus
dc.titleSecondary Complement Deficiency Impairs Anti-Microbial Immunity to Klebsiella pneumoniae and Staphylococcus aureus During Severe Acute COVID-19.
dc.typeArticle
dc.date.updated2022-05-11T19:00:13Z
prism.publicationNameFront Immunol
prism.volume13
dc.identifier.doi10.17863/CAM.84464
dcterms.dateAccepted2022-03-21
rioxxterms.versionofrecord10.3389/fimmu.2022.841759
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidLynch, Nicholas [0000-0003-3803-3329]
dc.identifier.eissn1664-3224
cam.issuedOnline2022-04-27


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