ArticleHaematologica2022
Complement dysregulation is associated with severe COVID-19 illness.
Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 33 citations in OpenAlex.
- The Complement System in the Setting of Critical Illness-A Narrative Review.Biomolecules · 2026Review
- SARS-CoV-2 nucleocapsid protein forms complexes with soluble complement regulatory proteins that can bind to the virion.Scientific reports · 2026Article
- Common and rare variants in complement genes as biomarkers of COVID-19 infection and severity. A lesson to learn for emerging pathogens.Frontiers in immunology · 2026Article
- Viral Prognosis Using Proteomics.Advances in experimental medicine and biology · 2026Review
- Impact of complement system proteins on the clinical progression of hospitalized patients with COVID-19.BMC infectious diseases · 2025Article
- The role of complement in long COVID pathogenesis.JCI insight · 2025Review
- Host transcriptome response to Mycoplasma bovis and bovine viral diarrhea virus in bovine tissues.BMC genomics · 2025Article
- Proteomic profiling of the serum of patients with COVID-19 reveals key factors in the path to clinical improvement.Clinical and translational medicine · 2025Article
- Atypical hemolytic uremic syndrome with aFrontiers in pediatrics · 2025Article
- Proteomic analysis of lung responses to SARS-CoV-2 infection in aged non-human primates: clinical and research relevance.GeroScience · 2024Article
- SARS-CoV-2 Protein Deposition Enhances Renal Complement Activation and Aggravates Kidney Injury in Membranous Nephropathy After COVID-19.Kidney international reports · 2024Article
- Serum proteomics for the identification of biomarkers to flag predilection of COVID19 patients to various organ morbidities.Clinical proteomics · 2024Article
- Systematic Review of Individual Patient Data COVID-19 Infection and Vaccination-Associated Thrombotic Microangiopathy.Kidney international reports · 2024Article
- Unbiased plasma profiling using pre-selected RNA aptamer pools predicts mortality in COVID-19 and identifies protein risk factors.Molecular therapy. Nucleic acids · 2024Article
- Genomic analysis ofiScience · 2024Article
- Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies.The EMBO journal · 2024Article
- The human factor H protein family - an update.Frontiers in immunology · 2024Review
- The Role of Adipsin, Complement Factor D, in the Pathogenesis of Graves' Orbitopathy.Investigative ophthalmology & visual science · 2023Article
- Complement and COVID-19: Three years on, what we know, what we don't know, and what we ought to know.Immunobiology · 2023Review
- Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may manifest as thrombosis, stroke, renal failure, myocardial infarction, and thrombocytopenia, reminiscent of other complement- mediated diseases. Multiple clinical and preclinical studies have implicated complement in the pathogenesis of COVID-19 illness. We previously found that the SARS-CoV-2 spike protein activates the alternative pathway of complement (APC) in vitro through interfering with the function of complement factor H, a key negative regulator of APC. Here, we demonstrated that serum from 58 COVID-19 patients (32 patients with minimal oxygen requirement, 7 on high flow oxygen, 17 requiring mechanical ventilation and 2 deaths) can induce complementmediated cell death in a functional assay (the modified Ham test) and increase membrane attack complex (C5b-9) deposition on the cell surface. A positive modified Ham assay (>20% cell-killing) was present in 41.2% COVID-19 patients requiring intubation (n=7/17) and only 6.3% in COVID-19 patients requiring minimal oxygen support (n=2/32). C5 and factor D inhibition effectively mitigated the complement amplification induced by COVID-19 patient serum. Increased serum factor Bb level was associated with disease severity in COVID-19 patients, suggesting that APC dysregulation plays an important role. Moreover, SARS-CoV-2 spike proteins directly block complement factor H from binding to heparin, which may lead to complement dysregulation on the cell surface. Taken together, our data suggest that complement dysregulation contributes to the pathogenesis of COVID-19 and may be a marker of disease severity.
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