ReviewAutoimmunity reviews2023
Complement activation predicts negative outcomes in COVID-19: The experience from Northen Italian patients.
Review in Autoimmunity reviews, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 15 citations in OpenAlex.
- Article
- Mapping Interactions Between Cytokines, Chemokines, Growth Factors, and Conventional Biomarkers in COVID-19 ICU-Patients.International journal of molecular sciences · 2025Article
- Unique Features and Collateral Immune Effects of mRNA-LNP COVID-19 Vaccines: Plausible Mechanisms of Adverse Events and Complications.Pharmaceutics · 2025Review
- The role of complement in long COVID pathogenesis.JCI insight · 2025Review
- Aging-associated changes in immunological parameters: Implications for COVID-19 immune response in the elderly.Physiological reports · 2025Review
- Review
- Retrospective cohort analysis on predicting pulmonary fibrosis in elderly SARS-CoV-2-infected patients.Frontiers in cellular and infection microbiology · 2025Article
- Differential modulation of SARS-CoV-2 infection by complement factor H and properdin.Frontiers in immunology · 2025Article
- sMR and PTX3 levels associate with COVID-19 outcome and survival but not with Long COVID.iScience · 2024Article
- Article
- mRNA-LNP COVID-19 Vaccine Lipids Induce Complement Activation and Production of Proinflammatory Cytokines: Mechanisms, Effects of Complement Inhibitors, and Relevance to Adverse Reactions.International journal of molecular sciences · 2024Article
- Understanding COVID-19-associated endothelial dysfunction: role of PIEZO1 as a potential therapeutic target.Frontiers in immunology · 2024Review
- SUPER Score Contributes to Warning and Management in Early-Stage COVID-19.Infectious medicine · 2023Article
- The value of preoperative neutrophil/lymphocyte ratio in predicting the severity of cholecystolithiasis with cholecystitis in elderly patients.BMC surgery · 2023Article
- Complement and COVID-19: Three years on, what we know, what we don't know, and what we ought to know.Immunobiology · 2023Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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