Secondary Complement Deficiency Impairs Anti-Microbial Immunity to Klebsiella pneumoniae and Staphylococcus aureus During Severe Acute COVID-19

• Published in: Frontiers in immunology Vol. 13; p. 841759
• Main Authors: Ali, Youssif M., Lynch, Nicholas J., Khatri, Priyanka, Bamigbola, Ifeoluwa E., Chan, Andrew C. Y., Yabuki, Munehisa, Demopulos, Gregory A., Heeney, Jonathan L., Pai, Sumita, Baxendale, Helen, Schwaeble, Wilhelm J.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 27.04.2022
• Subjects: bacterial infection; complement system; Complement System Proteins; COVID-19; Hereditary Complement Deficiency Diseases; Humans; Immunology; K. pneumoniae; Klebsiella pneumoniae; S. aureus; SARS-CoV-2; Staphylococcal Infections; Staphylococcus aureus; COVID-19; K. pneumoniae; SARS-CoV-2; S. aureus; bacterial infection; complement system
• ISSN: 1664-3224; 1664-3224
• DOI: 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.