ReviewCytokine2021
The cytokine storms of COVID-19, H1N1 influenza, CRS and MAS compared. Can one sized treatment fit all?
Review in Cytokine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 3 syntheses or guidelines pooled it, 100 citations in OpenAlex.
- Oral Janus kinase inhibitors for treating hospitalized patients with COVID-19: An updated systematic review and meta-analysis of randomized controlled trials.Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi · 2022Pooled it
- COVID-19 and the Immune Response: A Multi-Phasic Approach to the Treatment of COVID-19.International journal of molecular sciences · 2022Pooled it
- Janus kinase inhibitors and major COVID-19 outcomes: time to forget the two faces of Janus! A meta-analysis of randomized controlled trials.Clinical rheumatology · 2021Pooled it
- Trial
- The predictive value of the ratio of multi-dimensional inflammatory biomarkers in pediatric diseases from the perspective of pro-inflammatory/anti-inflammatory balance: a systematic review.Translational pediatrics · 2026Review
- The dynamic interplay of M1/M2-like macrophages and adenosine deaminase activity modulates COVID-19 severity.Open medicine (Warsaw, Poland) · 2026Article
- Dynamic monitoring of a core pro-inflammatory cytokine panel improves mortality prediction in severe influenza.Frontiers in immunology · 2026Article
- Pathogenic and Regulatory Roles of Fibrinolytic Factors in Autoimmune Diseases.Current issues in molecular biology · 2025Review
- Article
- Article
- The association between prolonged lymphopenia and in-hospital venous thromboembolism among different respiratory virus infections: a retrospective cohort study.Research and practice in thrombosis and haemostasis · 2025Article
- Severity of acute SARS-CoV-2 infection and risk of new-onset autoimmune disease: A RECOVER initiative study in nationwide U.S. cohorts.PloS one · 2025Article
- Innate immune role of IL-6 in influenza a virus pathogenesis.Frontiers in cellular and infection microbiology · 2025Review
- Characteristics of adults with influenza A virus pneumonia and co-infections identified by mNGS in Jilin, China during 2024-2025.Frontiers in cellular and infection microbiology · 2025Article
- Cytokine release syndrome induced by anti-programmed death-1 treatment in a psoriasis patient: A dark side of immune checkpoint inhibitors.World journal of clinical cases · 2024Article
- Interleukins in the pathogenesis of influenza and other acute respiratory viral infections.Epidemiology and infection · 2024Article
- Severe Bacterial Superinfection of Influenza Pneumonia in Immunocompetent Young Patients: Case Reports.Journal of clinical medicine · 2024Article
- Article
- Respiratory SARS-CoV-2 Infection Causes Skeletal Muscle Atrophy and Long-Lasting Energy Metabolism Suppression.Biomedicines · 2024Article
- Macrophage Activation Syndrome in Viral Sepsis.Viruses · 2024Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An analysis of published data appertaining to the cytokine storms of COVID-19, H1N1 influenza, cytokine release syndrome (CRS), and macrophage activation syndrome (MAS) reveals many common immunological and biochemical abnormalities. These include evidence of a hyperactive coagulation system with elevated D-dimer and ferritin levels, disseminated intravascular coagulopathy (DIC) and microthrombi coupled with an activated and highly permeable vascular endothelium. Common immune abnormalities include progressive hypercytokinemia with elevated levels of TNF-α, interleukin (IL)-6, and IL-1β, proinflammatory chemokines, activated macrophages and increased levels of nuclear factor kappa beta (NFκB). Inflammasome activation and release of damage associated molecular patterns (DAMPs) is common to COVID-19, H1N1, and MAS but does not appear to be a feature of CRS. Elevated levels of IL-18 are detected in patients with COVID-19 and MAS but have not been reported in patients with H1N1 influenza and CRS. Elevated interferon-γ is common to H1N1, MAS, and CRS but levels of this molecule appear to be depressed in patients with COVID-19. CD4+ T, CD8+ and NK lymphocytes are involved in the pathophysiology of CRS, MAS, and possibly H1N1 but are reduced in number and dysfunctional in COVID-19. Additional elements underpinning the pathophysiology of cytokine storms include Inflammasome activity and DAMPs. Treatment with anakinra may theoretically offer an avenue to positively manipulate the range of biochemical and immune abnormalities reported in COVID-19 and thought to underpin the pathophysiology of cytokine storms beyond those manipulated via the use of, canakinumab, Jak inhibitors or tocilizumab. Thus, despite the relative success of tocilizumab in reducing mortality in COVID-19 patients already on dexamethasone and promising results with Baricitinib, the combination of anakinra in combination with dexamethasone offers the theoretical prospect of further improvements in patient survival. However, there is currently an absence of trial of evidence in favour or contravening this proposition. Accordingly, a large well powered blinded prospective randomised controlled trial (RCT) to test this hypothesis is recommended.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.