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Functional Activity of the Complement System in Hospitalized COVID-19 Patients: A Prospective Cohort Study.
Charitos, Panteleimon; Heijnen, Ingmar A F M; Egli, Adrian; Bassetti, Stefano; Trendelenburg, Marten; Osthoff, Michael.
  • Charitos P; Division of Internal Medicine, University Hospital Basel, Basel, Switzerland.
  • Heijnen IAFM; Division of Medical Immunology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
  • Egli A; Clinical Bacteriology and Mycology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
  • Bassetti S; Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Trendelenburg M; Division of Internal Medicine, University Hospital Basel, Basel, Switzerland.
  • Osthoff M; Division of Internal Medicine, University Hospital Basel, Basel, Switzerland.
Front Immunol ; 12: 765330, 2021.
Article in English | MEDLINE | ID: covidwho-1518489
ABSTRACT

Aims:

Although the exact factors promoting disease progression in COVID-19 are not fully elucidated, unregulated activation of the complement system (CS) seems to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by SARS-CoV-2. In particular, the lectin pathway (LP) has been implicated in previous autopsy studies. The primary purpose of our study is to investigate the role of the CS in hospitalized COVID-19 patients with varying degrees of disease severity.

Methods:

In a single-center prospective observational study, 154 hospitalized patients with PCR-confirmed SARS-CoV-2 infection were included. Serum samples on admission to the COVID-19 ward were collected for analysis of CS pathway activities and concentrations of LP proteins [mannose-binding lectin (MBL) and ficolin-3 (FCN-3)] & C1 esterase inhibitor (C1IHN). The primary outcome was mechanical ventilation or in-hospital death.

Results:

The patients were predominately male and had multiple comorbidities. ICU admission was required in 16% of the patients and death (3%) or mechanical ventilation occurred in 23 patients (15%). There was no significant difference in LP activity, MBL and FCN-3 concentrations according to different peak disease severities. The median alternative pathway (AP) activity was significantly lower (65%, IQR 50-94) in patients with death/invasive ventilation compared to patients without (87%, IQR 68-102, p=0.026). An optimal threshold of <65.5% for AP activity was derived from a ROC curve resulting in increased odds for death or mechanical ventilation (OR 4,93; 95% CI 1.70-14.33, p=0.003) even after adjustment for confounding factors. Classical pathway (CP) activity was slightly lower in patients with more severe disease (median 101% for death/mechanical ventilation vs 109%, p=0.014). C1INH concentration correlated positively with length of stay, inflammatory markers and disease severity on admission but not during follow-up.

Conclusion:

Our results point to an overactivated AP in critically ill COVID-19 patients in vivo leading to complement consumption and consequently to a significantly reduced AP activity in vitro. The LP does not seem to play a role in the progression to severe COVID-19. Apart from its acute phase reaction the significance of C1INH in COVID-19 requires further studies.
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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Complement System Proteins / SARS-CoV-2 / COVID-19 Subject: Complement System Proteins / SARS-CoV-2 / COVID-19 Type of study: Etiology study / Observational study / Prognostic study Language: English Journal: Front Immunol Clinical aspect: Etiology / Prognosis Year: 2021

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Complement System Proteins / SARS-CoV-2 / COVID-19 Subject: Complement System Proteins / SARS-CoV-2 / COVID-19 Type of study: Etiology study / Observational study / Prognostic study Language: English Journal: Front Immunol Clinical aspect: Etiology / Prognosis Year: 2021
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