Contribution of Coronavirus-Specific Immunoglobulin G Responses to Complement Overactivation in Patients with Severe Coronavirus Disease 2019
© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America..
BACKGROUND: Excessive complement activation has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19), but the mechanisms leading to this response remain unclear.
METHODS: We measured plasma levels of key complement markers, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies against SARS-CoV-2 and seasonal human common cold coronaviruses (CCCs) in hospitalized patients with COVID-19 of moderate (n = 18) and critical severity (n = 37) and in healthy controls (n = 10).
RESULTS: We confirmed that complement activation is systemically increased in patients with COVID-19 and is associated with a worse disease outcome. We showed that plasma levels of C1q and circulating immune complexes were markedly increased in patients with severe COVID-19 and correlated with higher immunoglobulin (Ig) G titers, greater complement activation, and higher disease severity score. Additional analyses showed that the classical pathway was the main arm responsible for augmented complement activation in severe patients. In addition, we demonstrated that a rapid IgG response to SARS-CoV-2 and an anamnestic IgG response to the nucleoprotein of the CCCs were strongly correlated with circulating immune complex levels, complement activation, and disease severity.
CONCLUSIONS: These findings indicate that early, nonneutralizing IgG responses may play a key role in complement overactivation in severe COVID-19. Our work underscores the urgent need to develop therapeutic strategies to modify complement overactivation in patients with COVID-19.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:226 |
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| Enthalten in: |
The Journal of infectious diseases - 226(2022), 5 vom: 13. Sept., Seite 766-777 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Castanha, Priscila M S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.09.2022 Date Revised 06.09.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/infdis/jiac091 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM337978905 |
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| 100 | 1 | |a Castanha, Priscila M S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Contribution of Coronavirus-Specific Immunoglobulin G Responses to Complement Overactivation in Patients with Severe Coronavirus Disease 2019 |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 15.09.2022 | ||
| 500 | |a Date Revised 06.09.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. | ||
| 520 | |a BACKGROUND: Excessive complement activation has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19), but the mechanisms leading to this response remain unclear | ||
| 520 | |a METHODS: We measured plasma levels of key complement markers, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies against SARS-CoV-2 and seasonal human common cold coronaviruses (CCCs) in hospitalized patients with COVID-19 of moderate (n = 18) and critical severity (n = 37) and in healthy controls (n = 10) | ||
| 520 | |a RESULTS: We confirmed that complement activation is systemically increased in patients with COVID-19 and is associated with a worse disease outcome. We showed that plasma levels of C1q and circulating immune complexes were markedly increased in patients with severe COVID-19 and correlated with higher immunoglobulin (Ig) G titers, greater complement activation, and higher disease severity score. Additional analyses showed that the classical pathway was the main arm responsible for augmented complement activation in severe patients. In addition, we demonstrated that a rapid IgG response to SARS-CoV-2 and an anamnestic IgG response to the nucleoprotein of the CCCs were strongly correlated with circulating immune complex levels, complement activation, and disease severity | ||
| 520 | |a CONCLUSIONS: These findings indicate that early, nonneutralizing IgG responses may play a key role in complement overactivation in severe COVID-19. Our work underscores the urgent need to develop therapeutic strategies to modify complement overactivation in patients with COVID-19 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a and antibodies | |
| 650 | 4 | |a classical pathway | |
| 650 | 4 | |a common cold coronaviruses | |
| 650 | 4 | |a complement system | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Coronavirus Nucleocapsid Proteins |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 700 | 1 | |a Tuttle, Dylan J |e verfasserin |4 aut | |
| 700 | 1 | |a Kitsios, Georgios D |e verfasserin |4 aut | |
| 700 | 1 | |a Jacobs, Jana L |e verfasserin |4 aut | |
| 700 | 1 | |a Braga-Neto, Ulisses |e verfasserin |4 aut | |
| 700 | 1 | |a Duespohl, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Rathod, Sanjay |e verfasserin |4 aut | |
| 700 | 1 | |a Marti, Michelle M |e verfasserin |4 aut | |
| 700 | 1 | |a Wheeler, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Naqvi, Asma |e verfasserin |4 aut | |
| 700 | 1 | |a Staines, Brittany |e verfasserin |4 aut | |
| 700 | 1 | |a Mellors, John |e verfasserin |4 aut | |
| 700 | 1 | |a Morris, Alison |e verfasserin |4 aut | |
| 700 | 1 | |a McVerry, Bryan J |e verfasserin |4 aut | |
| 700 | 1 | |a Shah, Faraaz |e verfasserin |4 aut | |
| 700 | 1 | |a Schaefer, Caitlin |e verfasserin |4 aut | |
| 700 | 1 | |a Macatangay, Bernard J C |e verfasserin |4 aut | |
| 700 | 1 | |a Methe, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Fernandez, Christian A |e verfasserin |4 aut | |
| 700 | 1 | |a Barratt-Boyes, Simon M |e verfasserin |4 aut | |
| 700 | 1 | |a Burke, Donald |e verfasserin |4 aut | |
| 700 | 1 | |a Marques, Ernesto T A |e verfasserin |4 aut | |
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