ArticleThe Journal of allergy and clinical immunology2022
Severe COVID-19 is associated with hyperactivation of the alternative complement pathway.
Article in The Journal of allergy and clinical immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Activation of the Lectin Pathway Drives Persistent Complement Dysregulation in Long COVID.Immunology · 2026Article
- Complement Hyperactivation Is Mediated by Alternative and Lectin Pathways During Early Phase of Severe Vaccination-Omicron BA.5 Infection.Journal of medical virology · 2026Article
- Small extracellular vesicles proteome reveals persistent inflammatory and coagulopathic dysregulation in long-COVID.Frontiers in immunology · 2026Article
- In vitro complement activation via nucleocapsid and spike proteins of SARS-CoV-2 in COVID-19 patients.Scientific reports · 2025Article
- Impact of complement system proteins on the clinical progression of hospitalized patients with COVID-19.BMC infectious diseases · 2025Article
- Differences in biomarker levels and proteomic survival prediction across two COVID-19 cohorts with distinct treatments.iScience · 2025Article
- Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long-Term Cardiovascular Mortality.Journal of the American Heart Association · 2025Article
- The complement system: A key player in the host response to infections.European journal of immunology · 2024Review
- Complement activation and lung injury in Japanese patients with COVID-19: a prospective observational study.Scientific reports · 2024Observational
- Atypical hemolytic-uremic syndrome after COVID-19 vaccine: A case report.Immunity, inflammation and disease · 2024Article
- IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition.Nature communications · 2024Article
- A Clinical Qualification Protocol Highlights Overlapping Genomic Influences and Neuro-Autonomic Mechanisms in Ehlers-Danlos and Long COVID-19 Syndromes.Current issues in molecular biology · 2023Article
- Heme Interactions as Regulators of the Alternative Pathway Complement Responses and Implications for Heme-Associated Pathologies.Current issues in molecular biology · 2023Review
- Complement-Mediated Thrombotic Microangiopathy Related to COVID-19 or SARS-CoV-2 Vaccination.Kidney international reports · 2023Article
- Complement and COVID-19: Three years on, what we know, what we don't know, and what we ought to know.Immunobiology · 2023Review
- Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review.Biomedicines · 2023Review
- Missense Variants of von Willebrand Factor in the Background of COVID-19 Associated Coagulopathy.Genes · 2023Article
- Xuanfei Baidu Decoction suppresses complement overactivation and ameliorates IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB signaling pathway.Phytomedicine : international journal of phytotherapy and phytopharmacology · 2023Article
- Complement activation predicts negative outcomes in COVID-19: The experience from Northen Italian patients.Autoimmunity reviews · 2023Review
- Targeting the Complement-Sphingolipid System in COVID-19 and Gaucher Diseases: Evidence for a New Treatment Strategy.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSevere coronavirus disease 2019 (COVID-19) is characterized by impaired type I interferon activity and a state of hyperinflammation leading to acute respiratory distress syndrome. The complement system has recently emerged as a key player in triggering and maintaining the inflammatory state, but the role of this molecular cascade in severe COVID-19 is still poorly characterized.
objectiveWe aimed at assessing the contribution of complement pathways at both the protein and transcriptomic levels.
methodsTo this end, we systematically assessed the RNA levels of 28 complement genes in the circulating whole blood of patients with COVID-19 and healthy controls, including genes of the alternative pathway, for which data remain scarce.
resultsWe found differential expression of genes involved in the complement system, yet with various expression patterns: whereas patients displaying moderate disease had elevated expression of classical pathway genes, severe disease was associated with increased lectin and alternative pathway activation, which correlated with inflammation and coagulopathy markers. Additionally, properdin, a pivotal positive regulator of the alternative pathway, showed high RNA expression but was found at low protein concentrations in patients with a severe and critical disease, suggesting its deposition at the sites of complement activation. Notably, low properdin levels were significantly associated with the use of mechanical ventilation (area under the curve = 0.82; P = .002).
conclusionThis study sheds light on the role of the alternative pathway in severe COVID-19 and provides additional rationale for the testing of drugs inhibiting the alternative pathway of the complement system.
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