Cytokine storm with rapidly elevated interleukin-6 indicates sudden death in patients with critical COVID-19.
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ABSTRACT:
SUBMITTER: Hu Z
PROVIDER: S-EPMC7445135 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Data suggest that interleukin (IL)-6 blockade could reduce mortality in severe COVID-19, yet IL-6 is only modestly elevated in most patients. Chen et al. describe the role of soluble interleukin-6 receptor (sIL-6R) in IL-6 trans-signaling and how understanding the IL-6:sIL-6R axis might help define and treat COVID-19 cytokine storm syndrome.
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Project description:Corona virus disease 2019 (COVID-19) has caused a global outbreak and severely posed threat to people's health and social stability. Mounting evidence suggests that immunopathological changes, including diminished lymphocytes and elevated cytokines, are important drivers of disease progression and death in coronavirus infections. Cytokine storm not only limits further spread of virus in the body but also induces secondary tissue damage through the secretion of large amounts of active mediators and inflammatory factors. It has been determined that cytokine storm is a major cause of deaths in COVID-19; therefore, in order to reverse the deterioration of severe and critically ill patients from this disease, the cytokine storm has become a key therapeutic target. Although specific mechanisms of the occurrences of cytokine storms in COVID-19 have not been fully illuminated, hyper-activated innate immune responses, and dysregulation of ACE2 (angiotensin converting enzyme 2) expression and its downstream pathways might provide possibilities. Tailored immunoregulatory therapies have been applied to counteract cytokine storms, such as inhibition of cytokines, corticosteroids, blood purification therapy, and mesenchymal stem cell therapy. This review will summarize advances in the research of cytokine storms induced by COVID-19, as well as potential intervention strategies to control cytokine storms.
| S-EPMC7734084 | biostudies-literature
Project description:A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by a deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading, in the most severe cases, even to death. The term cytokine storm was first used in 1993 to describe the graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. It was then reused to define the adverse syndromes secondary to the administration of immunostimulating agents, such as anti-CD28 antibodies or bioengineered immune cells, i.e., CAR T-cell therapy. Currently, the concept of cytokine storm has been better elucidated and extended to the pathogenesis of many other conditions, such as sepsis, autoinflammatory disease, primary and secondary hemophagocytic lymphohistiocytosis, and multicentric Castleman disease. Moreover, cytokine storm has recently emerged as a key aspect in the novel Coronavirus disease 2019, as affected patients show high levels of several key pro-inflammatory cytokines, such as IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, and IL-10, some of which also correlate with disease severity. Therefore, since the onset of the pandemic, numerous agents have been tested in the effort to mitigate the cytokine storm in COVID-19 patients, some of which are effective in reducing mortality, especially in critically ill patients, and are now becoming standards of care, such as glucocorticoids or some cytokine inhibitors. However, the challenge is still far from being met, and other therapeutic strategies are being tested in the hope that we can eventually overcome the disease.
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Project description:BackgroundAngiotensin receptor blockers (ARBs) reducing inflammation and protecting lung and brain function, could be of therapeutic efficacy in COVID-19 patients.MethodsUsing GSEA, we compared our previous transcriptome analysis of neurons injured by glutamate and treated with the ARB Candesartan (GSE67036) with transcriptional signatures from SARS-CoV-2 infected primary human bronchial epithelial cells (NHBE) and lung postmortem (GSE147507), PBMC and BALF samples (CRA002390) from COVID-19 patients.ResultsHundreds of genes upregulated in SARS-CoV-2/COVID-19 transcriptomes were similarly upregulated by glutamate and normalized by Candesartan. Gene Ontology analysis revealed expression profiles with greatest significance and enrichment, including proinflammatory cytokine and chemokine activity, the NF-kappa B complex, alterations in innate and adaptive immunity, with many genes participating in the COVID-19 cytokine storm.ConclusionsThere are similar injury mechanisms in SARS-CoV-2 infection and neuronal injury, equally reduced by ARB treatment. This supports the hypothesis of a therapeutic role for ARBs, ameliorating the COVID-19 cytokine storm.
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Project description:Acute cardiac injuries occur in 20%–25% of hospitalized COVID‐19 patients. Herein, we demonstrate that human cardiac organoids (hCOs) are a viable platform to model the cardiac injuries caused by COVID‐19 hyperinflammation. As IL‐1β is an upstream cytokine and a core COVID‐19 signature cytokine, it was used to stimulate hCOs to induce the release of a milieu of proinflammatory cytokines that mirror the profile of COVID‐19 cytokine storm. The IL‐1β treated hCOs recapitulated transcriptomic, structural, and functional signatures of COVID‐19 hearts. The comparison of IL‐1β treated hCOs with cardiac tissue from COVID‐19 autopsies illustrated the critical roles of hyper‐inflammation in COVID‐19 cardiac insults and indicated the cardioprotective effects of endothelium. The IL‐1β treated hCOs thus provide a defined and robust model to assess the efficacy and potential side effects of immunomodulatory drugs, as well as the reversibility of COVID‐19 cardiac in- juries at baseline and simulated exercise conditions.
2023-12-20 | GSE250520 | GEO
Project description:Severe COVID-19 may progress into acute respiratory distress syndrome (ARDS) with high mortality risk. Its exact pathological mechanism, therapeutic obstacles and the clinical sequelae are critical and unresolved issues. Here, we reported a representative COVID-19 induced ARDS case experienced initially stable, then suddenly deteriorating up to final respiratory failure courses, until his death despite of lung transplantation. His lung pathology showed necrosis of parenchymal tissues, extensive immune cell infiltration and lung fibrosis. Single-cell RNA sequencing revealed various immune cell populations were largely expanded in his lung, and manifested inflammatory/activated functions. We also showed that cell-crosstalk between lung macrophages and fibroblasts promoted pulmonary fibrosis through IL-1B and TGF-Β signaling pathways. Although SARS-CoV-2 RNA remained undetectable in his respiratory tract specimens including BALF at the later stage of his disease, the presence of SARS-CoV-2 was definitely confirmed in his lung tissues. Thus, this case indicates the pathological mechanism of severe COVID-19 includes pulmonary SARS-CoV-2 persistence, deranged inflammation and the extensive lung fibrosis which set the barriers for effective treatments and indicate potential health complications for severe COVID-19 patients.
2020-12-01 | GSE149878 | GEO
Project description: Not available
| S-EPMC7484610 | biostudies-literature
Project description:The newly emerging coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, but has rapidly spread all over the world. Some COVID-19 patients encounter a severe symptom of acute respiratory distress syndrome (ARDS) with high mortality. This high severity is dependent on a cytokine storm, most likely induced by the interleukin-6 (IL-6) amplifier, which is hyper-activation machinery that regulates the nuclear factor kappa B (NF-κB) pathway and stimulated by the simultaneous activation of IL-6-signal transducer and activator of transcription 3 (STAT3) and NF-κB signaling in non-immune cells including alveolar epithelial cells and endothelial cells. We hypothesize that IL-6-STAT3 signaling is a promising therapeutic target for the cytokine storm in COVID-19, because IL-6 is a major STAT3 stimulator, particularly during inflammation. We herein review the pathogenic mechanism and potential therapeutic targets of ARDS in COVID-19 patients.
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