tetano
Editor, Senior Moderator
Autoimmun Rev
. 2022 Nov 19;103232.
doi: 10.1016/j.autrev.2022.103232. Online ahead of print.
Complement activation predicts negative outcomes in COVID-19: The experience from Northen Italian patients
Pier Luigi Meroni[SUP] 1 [/SUP], Stefania Croci[SUP] 2 [/SUP], Paola Adele Lonati[SUP] 3 [/SUP], Francesca Pregnolato[SUP] 3 [/SUP], Lucia Spaggiari[SUP] 4 [/SUP], Giulia Besutti[SUP] 5 [/SUP], Martina Bonacini[SUP] 2 [/SUP], Ilaria Ferrigno[SUP] 6 [/SUP], Alessandro Rossi[SUP] 2 [/SUP], Geir Hetland[SUP] 7 [/SUP], Ivana Hollan[SUP] 8 [/SUP], Massimo Cugno[SUP] 9 [/SUP], Francesco Tedesco[SUP] 3 [/SUP], Maria Orietta Borghi[SUP] 10 [/SUP], Carlo Salvarani[SUP] 11 [/SUP]
Affiliations
Abstract
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.
Keywords: Complement; Covid-19; Cytokines; Disease outcome; Disease severity.
. 2022 Nov 19;103232.
doi: 10.1016/j.autrev.2022.103232. Online ahead of print.
Complement activation predicts negative outcomes in COVID-19: The experience from Northen Italian patients
Pier Luigi Meroni[SUP] 1 [/SUP], Stefania Croci[SUP] 2 [/SUP], Paola Adele Lonati[SUP] 3 [/SUP], Francesca Pregnolato[SUP] 3 [/SUP], Lucia Spaggiari[SUP] 4 [/SUP], Giulia Besutti[SUP] 5 [/SUP], Martina Bonacini[SUP] 2 [/SUP], Ilaria Ferrigno[SUP] 6 [/SUP], Alessandro Rossi[SUP] 2 [/SUP], Geir Hetland[SUP] 7 [/SUP], Ivana Hollan[SUP] 8 [/SUP], Massimo Cugno[SUP] 9 [/SUP], Francesco Tedesco[SUP] 3 [/SUP], Maria Orietta Borghi[SUP] 10 [/SUP], Carlo Salvarani[SUP] 11 [/SUP]
Affiliations
- PMID: 36414219
- DOI: 10.1016/j.autrev.2022.103232
Abstract
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.
Keywords: Complement; Covid-19; Cytokines; Disease outcome; Disease severity.