Secondary Complement Deficiency Impairs Anti-Microbial Immunity to Klebsiella pneumoniae and Staphylococcus aureus During Severe Acute COVID-19
Copyright © 2022 Ali, Lynch, Khatri, Bamigbola, Chan, Yabuki, Demopulos, Heeney, Pai, Baxendale and Schwaeble..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Frontiers in immunology - 13(2022) vom: 14., Seite 841759 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ali, Youssif M [VerfasserIn] |
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| Links: |
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| Themen: |
9007-36-7 |
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| Anmerkungen: |
Date Completed 19.05.2022 Date Revised 22.03.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2022.841759 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM340954264 |
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| 520 | |a Copyright © 2022 Ali, Lynch, Khatri, Bamigbola, Chan, Yabuki, Demopulos, Heeney, Pai, Baxendale and Schwaeble. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a K. pneumoniae | |
| 650 | 4 | |a S. aureus | |
| 650 | 4 | |a SARS-CoV-2 | |
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| 700 | 1 | |a Lynch, Nicholas J |e verfasserin |4 aut | |
| 700 | 1 | |a Khatri, Priyanka |e verfasserin |4 aut | |
| 700 | 1 | |a Bamigbola, Ifeoluwa E |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Andrew C Y |e verfasserin |4 aut | |
| 700 | 1 | |a Yabuki, Munehisa |e verfasserin |4 aut | |
| 700 | 1 | |a Demopulos, Gregory A |e verfasserin |4 aut | |
| 700 | 1 | |a Heeney, Jonathan L |e verfasserin |4 aut | |
| 700 | 1 | |a Pai, Sumita |e verfasserin |4 aut | |
| 700 | 1 | |a Baxendale, Helen |e verfasserin |4 aut | |
| 700 | 1 | |a Schwaeble, Wilhelm J |e verfasserin |4 aut | |
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