Complement levels at admission as a reflection of coronavirus disease 2019 (COVID-19) severity state
© 2021 Wiley Periodicals LLC..
Complement system hyperactivation has been proposed as a potential driver of adverse outcomes in severe acute respiratory syndrome coronavirus 2 infected patients, given prior research of complement deposits found in tissue and blood samples, as well as evidence of clinical improvement with anticomplement therapy. Its role in augmenting thrombotic microangiopathy mediated organ damage has also been implicated in coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement parameters and progression to severe COVID-19 illness, as well as correlations with other systems. Blood samples of COVID-19 patients presenting to the emergency department (ED) were analyzed for a wide panel of complement and inflammatory biomarkers. The primary outcome was COVID-19 severity at index ED visit, while the secondary outcome was peak disease severity over the course of illness. Fifty-two COVID-19 patients were enrolled. C3a (p = 0.018), C3a/C3 ratio (p = 0.002), and sC5b-9/C3 ratio (p = 0.021) were significantly elevated in with severe disease at ED presentation. Over the course of illness, C3a (p = 0.028) and C3a/C3 ratio (p = 0.003) were highest in the moderate severity group. In multivariate regression controlled for confounders, complement hyperactivation failed to predict progression to severe disease. C3a, C3a/C3 ratio, and sC5b-9/C3 ratio were correlated positively with numerous inflammatory biomarkers, fibrinogen, and VWF:Ag, and negatively with plasminogen and ADAMTS13 activity. We found evidence of complement hyperactivation in COVID-19, associated with hyperinflammation and thrombotic microangiopathy. Complement inhibition should be further investigated for potential benefit in patients displaying a hyperinflammatory and microangiopathic phenotype.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:93 |
|---|---|
| Enthalten in: |
Journal of medical virology - 93(2021), 9 vom: 10. Sept., Seite 5515-5522 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Henry, Brandon Michael [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 02.08.2021 Date Revised 05.10.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1002/jmv.27077 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM325258325 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM325258325 | ||
| 003 | DE-627 | ||
| 005 | 20231225192049.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/jmv.27077 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1084.xml |
| 035 | |a (DE-627)NLM325258325 | ||
| 035 | |a (NLM)33974276 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Henry, Brandon Michael |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Complement levels at admission as a reflection of coronavirus disease 2019 (COVID-19) severity state |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.08.2021 | ||
| 500 | |a Date Revised 05.10.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 Wiley Periodicals LLC. | ||
| 520 | |a Complement system hyperactivation has been proposed as a potential driver of adverse outcomes in severe acute respiratory syndrome coronavirus 2 infected patients, given prior research of complement deposits found in tissue and blood samples, as well as evidence of clinical improvement with anticomplement therapy. Its role in augmenting thrombotic microangiopathy mediated organ damage has also been implicated in coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement parameters and progression to severe COVID-19 illness, as well as correlations with other systems. Blood samples of COVID-19 patients presenting to the emergency department (ED) were analyzed for a wide panel of complement and inflammatory biomarkers. The primary outcome was COVID-19 severity at index ED visit, while the secondary outcome was peak disease severity over the course of illness. Fifty-two COVID-19 patients were enrolled. C3a (p = 0.018), C3a/C3 ratio (p = 0.002), and sC5b-9/C3 ratio (p = 0.021) were significantly elevated in with severe disease at ED presentation. Over the course of illness, C3a (p = 0.028) and C3a/C3 ratio (p = 0.003) were highest in the moderate severity group. In multivariate regression controlled for confounders, complement hyperactivation failed to predict progression to severe disease. C3a, C3a/C3 ratio, and sC5b-9/C3 ratio were correlated positively with numerous inflammatory biomarkers, fibrinogen, and VWF:Ag, and negatively with plasminogen and ADAMTS13 activity. We found evidence of complement hyperactivation in COVID-19, associated with hyperinflammation and thrombotic microangiopathy. Complement inhibition should be further investigated for potential benefit in patients displaying a hyperinflammatory and microangiopathic phenotype | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a SARS-CoV-2 hyperinflammation | |
| 650 | 4 | |a complement system | |
| 650 | 4 | |a coronavirus disease 2019 | |
| 650 | 4 | |a thrombotic microangiopathy | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Complement C3 |2 NLM | |
| 650 | 7 | |a Complement Membrane Attack Complex |2 NLM | |
| 650 | 7 | |a SC5b-9 protein complex |2 NLM | |
| 650 | 7 | |a ADAMTS13 Protein |2 NLM | |
| 650 | 7 | |a EC 3.4.24.87 |2 NLM | |
| 650 | 7 | |a ADAMTS13 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.24.87 |2 NLM | |
| 700 | 1 | |a Szergyuk, Ivan |e verfasserin |4 aut | |
| 700 | 1 | |a de Oliveira, Maria Helena Santos |e verfasserin |4 aut | |
| 700 | 1 | |a Lippi, Giuseppe |e verfasserin |4 aut | |
| 700 | 1 | |a Benoit, Justin L |e verfasserin |4 aut | |
| 700 | 1 | |a Vikse, Jens |e verfasserin |4 aut | |
| 700 | 1 | |a Benoit, Stefanie W |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of medical virology |d 1990 |g 93(2021), 9 vom: 10. Sept., Seite 5515-5522 |w (DE-627)NLM000285676 |x 1096-9071 |7 nnns |
| 773 | 1 | 8 | |g volume:93 |g year:2021 |g number:9 |g day:10 |g month:09 |g pages:5515-5522 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/jmv.27077 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 93 |j 2021 |e 9 |b 10 |c 09 |h 5515-5522 | ||