The cytokine storms of COVID-19, H1N1 influenza, CRS and MAS compared. Can one sized treatment fit all?
Anti-Inflammatory Agents
/ therapeutic use
Antiviral Agents
/ therapeutic use
COVID-19
/ immunology
Cytokine Release Syndrome
/ drug therapy
Disease-Free Survival
Humans
Influenza A Virus, H1N1 Subtype
/ immunology
Influenza, Human
/ drug therapy
Janus Kinases
/ antagonists & inhibitors
Lymphocytes
/ immunology
SARS-CoV-2
/ immunology
Survival Rate
COVID-19 Drug Treatment
COVID-19
Cytokine storm
Immune
Inflammation
Interleukin-1
Interleukin-6
Journal
Cytokine
ISSN: 1096-0023
Titre abrégé: Cytokine
Pays: England
ID NLM: 9005353
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
04
03
2021
revised:
03
05
2021
accepted:
17
05
2021
pubmed:
3
6
2021
medline:
16
6
2021
entrez:
2
6
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34074585
pii: S1043-4666(21)00176-9
doi: 10.1016/j.cyto.2021.155593
pmc: PMC8149193
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Antiviral Agents
0
Janus Kinases
EC 2.7.10.2
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
155593Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
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