Complement activation predicts negative outcomes in COVID-19 : The experience from Northen Italian patients
Copyright © 2022 Elsevier B.V. All rights reserved..
Coronavirus disease 19 (COVID-19) may present as a multi-organ disease with a hyperinflammatory and prothrombotic response (immunothrombosis) in addition to upper and lower airway involvement. Previous data showed that complement activation plays a role in immunothrombosis mainly in severe forms. The study aimed to investigate whether complement involvement is present in the early phases of the disease and can be predictive of a negative outcome. We enrolled 97 symptomatic patients with a positive RT-PCR for SARS-CoV-2 presenting to the emergency room. The patients with mild symptoms/lung involvement at CT-scan were discharged and the remaining were hospitalized. All the patients were evaluated after a 4-week follow-up and classified as mild (n. 54), moderate (n. 17) or severe COVID-19 (n. 26). Blood samples collected before starting any anti-inflammatory/immunosuppressive therapy were assessed for soluble C5b-9 (sC5b-9) and C5a plasma levels by ELISA, and for the following serum mediators by ELLA: IL-1β, IL-6, IL-8, TNFα, IL-4, IL-10, IL-12p70, IFNγ, IFNα, VEGF-A, VEGF-B, GM-CSF, IL-2, IL-17A, VEGFR2, BLyS. Additional routine laboratory parameters were measured (fibrin fragment D-dimer, C-reactive protein, ferritin, white blood cells, neutrophils, lymphocytes, monocytes, platelets, prothrombin time, activated partial thromboplastin time, and fibrinogen). Fifty age and sex-matched healthy controls were also evaluated. SC5b-9 and C5a plasma levels were significantly increased in the hospitalized patients (moderate and severe) in comparison with the non-hospitalized mild group. SC5b9 and C5a plasma levels were predictive of the disease severity evaluated one month later. IL-6, IL-8, TNFα, IL-10 and complement split products were higher in moderate/severe versus non-hospitalized mild COVID-19 patients and healthy controls but with a huge heterogeneity. SC5b-9 and C5a plasma levels correlated positively with CRP, ferritin values and the neutrophil/lymphocyte ratio. Complement can be activated in the very early phases of the disease, even in mild non-hospitalized patients. Complement activation can be observed even when pro-inflammatory cytokines are not increased, and predicts a negative outcome.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
Autoimmunity reviews - 22(2023), 1 vom: 01. Jan., Seite 103232 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Meroni, Pier Luigi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.01.2023 Date Revised 28.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.autrev.2022.103232 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM349273383 |
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| 520 | |a Copyright © 2022 Elsevier B.V. All rights reserved. | ||
| 520 | |a Coronavirus disease 19 (COVID-19) may present as a multi-organ disease with a hyperinflammatory and prothrombotic response (immunothrombosis) in addition to upper and lower airway involvement. Previous data showed that complement activation plays a role in immunothrombosis mainly in severe forms. The study aimed to investigate whether complement involvement is present in the early phases of the disease and can be predictive of a negative outcome. We enrolled 97 symptomatic patients with a positive RT-PCR for SARS-CoV-2 presenting to the emergency room. The patients with mild symptoms/lung involvement at CT-scan were discharged and the remaining were hospitalized. All the patients were evaluated after a 4-week follow-up and classified as mild (n. 54), moderate (n. 17) or severe COVID-19 (n. 26). Blood samples collected before starting any anti-inflammatory/immunosuppressive therapy were assessed for soluble C5b-9 (sC5b-9) and C5a plasma levels by ELISA, and for the following serum mediators by ELLA: IL-1β, IL-6, IL-8, TNFα, IL-4, IL-10, IL-12p70, IFNγ, IFNα, VEGF-A, VEGF-B, GM-CSF, IL-2, IL-17A, VEGFR2, BLyS. Additional routine laboratory parameters were measured (fibrin fragment D-dimer, C-reactive protein, ferritin, white blood cells, neutrophils, lymphocytes, monocytes, platelets, prothrombin time, activated partial thromboplastin time, and fibrinogen). Fifty age and sex-matched healthy controls were also evaluated. SC5b-9 and C5a plasma levels were significantly increased in the hospitalized patients (moderate and severe) in comparison with the non-hospitalized mild group. SC5b9 and C5a plasma levels were predictive of the disease severity evaluated one month later. IL-6, IL-8, TNFα, IL-10 and complement split products were higher in moderate/severe versus non-hospitalized mild COVID-19 patients and healthy controls but with a huge heterogeneity. SC5b-9 and C5a plasma levels correlated positively with CRP, ferritin values and the neutrophil/lymphocyte ratio. Complement can be activated in the very early phases of the disease, even in mild non-hospitalized patients. Complement activation can be observed even when pro-inflammatory cytokines are not increased, and predicts a negative outcome | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Croci, Stefania |e verfasserin |4 aut | |
| 700 | 1 | |a Lonati, Paola Adele |e verfasserin |4 aut | |
| 700 | 1 | |a Pregnolato, Francesca |e verfasserin |4 aut | |
| 700 | 1 | |a Spaggiari, Lucia |e verfasserin |4 aut | |
| 700 | 1 | |a Besutti, Giulia |e verfasserin |4 aut | |
| 700 | 1 | |a Bonacini, Martina |e verfasserin |4 aut | |
| 700 | 1 | |a Ferrigno, Ilaria |e verfasserin |4 aut | |
| 700 | 1 | |a Rossi, Alessandro |e verfasserin |4 aut | |
| 700 | 1 | |a Hetland, Geir |e verfasserin |4 aut | |
| 700 | 1 | |a Hollan, Ivana |e verfasserin |4 aut | |
| 700 | 1 | |a Cugno, Massimo |e verfasserin |4 aut | |
| 700 | 1 | |a Tedesco, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a Borghi, Maria Orietta |e verfasserin |4 aut | |
| 700 | 1 | |a Salvarani, Carlo |e verfasserin |4 aut | |
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