Secondary Complement Deficiency Impairs Anti-Microbial Immunity to Klebsiella pneumoniae and Staphylococcus aureus During Severe Acute COVID-19
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 |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
|---|---|
| Enthalten in: |
Frontiers in Immunology - 13(2022) |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Youssif M. Ali [VerfasserIn] |
|---|
| Links: |
doi.org [kostenfrei] |
|---|
| Themen: |
Bacterial infection |
|---|
| doi: |
10.3389/fimmu.2022.841759 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
DOAJ038367246 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ038367246 | ||
| 003 | DE-627 | ||
| 005 | 20230308021438.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230227s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fimmu.2022.841759 |2 doi | |
| 035 | |a (DE-627)DOAJ038367246 | ||
| 035 | |a (DE-599)DOAJbdabafda1e954e61aed144f91d79873b | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 050 | 0 | |a RC581-607 | |
| 100 | 0 | |a Youssif M. Ali |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Secondary Complement Deficiency Impairs Anti-Microbial Immunity to Klebsiella pneumoniae and Staphylococcus aureus During Severe Acute COVID-19 |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 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 K. pneumoniae | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a complement system | |
| 650 | 4 | |a bacterial infection | |
| 650 | 4 | |a S. aureus | |
| 653 | 0 | |a Immunologic diseases. Allergy | |
| 700 | 0 | |a Youssif M. Ali |e verfasserin |4 aut | |
| 700 | 0 | |a Nicholas J. Lynch |e verfasserin |4 aut | |
| 700 | 0 | |a Priyanka Khatri |e verfasserin |4 aut | |
| 700 | 0 | |a Ifeoluwa E. Bamigbola |e verfasserin |4 aut | |
| 700 | 0 | |a Andrew C. Y. Chan |e verfasserin |4 aut | |
| 700 | 0 | |a Munehisa Yabuki |e verfasserin |4 aut | |
| 700 | 0 | |a Gregory A. Demopulos |e verfasserin |4 aut | |
| 700 | 0 | |a Jonathan L. Heeney |e verfasserin |4 aut | |
| 700 | 0 | |a Sumita Pai |e verfasserin |4 aut | |
| 700 | 0 | |a Helen Baxendale |e verfasserin |4 aut | |
| 700 | 0 | |a Wilhelm J. Schwaeble |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t Frontiers in Immunology |d Frontiers Media S.A., 2011 |g 13(2022) |w (DE-627)DOAJ000031690 |x 16643224 |7 nnns |
| 773 | 1 | 8 | |g volume:13 |g year:2022 |
| 856 | 4 | 0 | |u https://doi.org/10.3389/fimmu.2022.841759 |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/bdabafda1e954e61aed144f91d79873b |z kostenfrei |
| 856 | 4 | 0 | |u https://www.frontiersin.org/articles/10.3389/fimmu.2022.841759/full |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/1664-3224 |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 951 | |a AR | ||
| 952 | |d 13 |j 2022 | ||