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Association of complement pathways with COVID-19 severity and outcomes.
Devalaraja-Narashimha, Kishor; Ehmann, Peter J; Huang, Cong; Ruan, Qin; Wipperman, Matthew F; Kaplan, Theodore; Liu, Chien; Afolayan, Simisola; Glass, David J; Mellis, Scott; Yancopoulos, George D; Hamilton, Jennifer D; MacDonnell, Scott; Hamon, Sara C; Boyapati, Anita; Morton, Lori.
  • Devalaraja-Narashimha K; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Ehmann PJ; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Huang C; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; Wesleyan University, Middletown, CT, USA.
  • Ruan Q; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Wipperman MF; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Kaplan T; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Liu C; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Afolayan S; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Glass DJ; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Mellis S; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Yancopoulos GD; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Hamilton JD; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • MacDonnell S; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Hamon SC; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Boyapati A; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Morton L; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Microbes Infect ; 25(4): 105081, 2023 05.
Article in English | MEDLINE | ID: covidwho-2314097
ABSTRACT

OBJECTIVES:

Complement activation has been implicated in COVID-19 pathogenesis. This study aimed to assess the levels of complement activation products and full-length proteins in hospitalized patients with COVID-19, and evaluated whether complement pathway markers are associated with outcomes.

METHODS:

Longitudinal measurements of complement biomarkers from 89 hospitalized adult patients, grouped by baseline disease severity, enrolled in an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial and treated with intravenous sarilumab (200 mg or 400 mg) or placebo (NCT04315298), were performed. These measurements were then correlated with clinical and laboratory parameters.

RESULTS:

All complement pathways were activated in hospitalized patients with COVID-19. Alternative pathway activation was predominant earlier in the disease course. Complement biomarkers correlated with multiple variables of multi-organ dysfunction and inflammatory injury. High plasma sC5b-9, C3a, factor Bb levels, and low mannan-binding lectin levels were associated with increased mortality. Sarilumab treatment showed a modest inhibitory effect on complement activation. Moreover, sera from patients spontaneously deposited C5b-9 complex on the endothelial surface ex vivo, suggesting a microvascular thrombotic potential.

CONCLUSION:

These results advance our understanding of COVID-19 disease pathophysiology and demonstrate the importance of specific complement pathway components as prognostic biomarkers in COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Adult / Humans Language: English Journal: Microbes Infect Journal subject: Allergy and Immunology / Microbiology Year: 2023 Document Type: Article Affiliation country: J.micinf.2022.105081

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Adult / Humans Language: English Journal: Microbes Infect Journal subject: Allergy and Immunology / Microbiology Year: 2023 Document Type: Article Affiliation country: J.micinf.2022.105081