Cytokine Storm May Not Be the Chief Culprit for the Deterioration of COVID-19

Gao, Yang; Wang, Changsong; Kang, Kai; Peng, Yahui; Luo, Yunpeng; Liu, Haitao; Yang, Wei; Zhao, Mingyan; Yu, Kaijiang

doi:10.1089/vim.2020.0243

Cited by 14 publications

(14 citation statements)

References 39 publications

(38 reference statements)

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“…The mean IL-6 levels were recorded to be significantly higher in patients with severe COVID-19 compared with non-severe COVID-19 patients [15,16,[88][89][90][91][92][93][94]. Additionally, IL-6 was also reported as an independent predictor of ICU admission [95].…”

Section: Discussionmentioning

confidence: 92%

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The Association between TNF-α, IL-6, and Vitamin D Levels and COVID-19 Severity and Mortality: A Systematic Review and Meta-Analysis

2022

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Background: An increasing number of scientific journals have proposed a connection between tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the severity of COVID-19. Vitamin D has been discussed as a potential therapy for COVID-19 due to its immunomodulatory effects. This meta-analysis aims to determine the relationship, if any, between TNF-α, IL-6, vitamin D, and COVID-19 severity and mortality. Methods: The design of the study is a systematic review and meta-analysis. A literature search is performed using PubMed, Cochrane, ProQuest, and Google Scholar. Results: TNF-α insignificantly increases the risk of COVID-19 severity (adjusted odds ratio (aOR) = 1.0304; 95% CI 0.8178–1.2983; p = 0.80) but significantly increases the risk of COVID-19 mortality (crude hazard ratio (HR) = 1.0640; 95% CI 1.0259–1.1036; p = 0.0009). IL-6 significantly increases the risk of COVID-19 severity (aOR = 1.0284; 95% CI 1.0130–1.0441; p = 0.0003) and mortality (aOR = 1.0076; 95% CI 1.0004–1.0148; p = 0.04; adjusted hazard ratio (aHR) = 1.0036; 95% CI 1.0010–1.0061; p = 0.006). There is a statistically insignificant difference of the mean vitamin D levels between patients with severe COVID-19 and non-severe COVID-19 (mean difference (MD) = −5.0232; 95% CI 11.6832–1.6368; p = 0.14). A vitamin D deficiency insignificantly increases the risk of mortality of COVID-19 patients (aOR = 1.3827; 95% CI 0.7103–2.6916; p = 0.34). Conclusion: IL-6 is an independent prognostic factor towards COVID-19 severity and mortality.

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Section: Discussionmentioning

confidence: 92%

“…TNF-α is one of the endogenous pyrogens that increases the body temperature and causes fever [80] (pp. [88][89]. Large quantities of TNF-α are pathological to the organ systems.…”

Section: Discussionmentioning

confidence: 99%

The Association between TNF-α, IL-6, and Vitamin D Levels and COVID-19 Severity and Mortality: A Systematic Review and Meta-Analysis

2022

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“…Excessive and uncontrolled systemic immune responses are the real culprit of disease deterioration and death in patients with Coronavirus disease 2019 (COVID-19), and not fatal virus infection (Gao et al, 2021). Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection can trigger the excessive production and release of a series of circulating cytokines and inflammatory chemokines, especially marked by IL-6, IL-10, and TNF-α, also known as cytokine release syndrome (CRS) or cytokine storm, which have been revealed to be closely associated with organ injury, disease severity and death in patients with COVID-19 (Copaescu et al, 2020;Del Valle et al, 2020;Huang et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Continuous Renal Replacement Therapy With oXiris Filter May Not be an Effective Resolution to Alleviate Cytokine Release Syndrome in Non-AKI Patients With Severe and Critical COVID-19

et al. 2022

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In this study, we aimed to determine whether continuous renal replacement therapy (CRRT) with oXiris filter may alleviate cytokine release syndrome (CRS) in non-AKI patients with severe and critical coronavirus disease 2019 (COVID-19). A total of 17 non-AKI patients with severe and critical COVID-19 treated between February 14 and March 26, 2020 were included and randomly divided into intervention group and control group according to the random number table. Patients in the intervention group immediately received CRRT with oXiris filter plus conventional treatment, while those in the control group only received conventional treatment. Demographic data were collected and collated at admission. During ICU hospitalization, the concentrations of circulating cytokines and inflammatory chemokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, were quantitatively measured daily to reflect the degree of CRS induced by SARS-CoV-2 infection. Clinical data, including the severity of COVID-19 white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet (PLT), C-reaction protein (CRP), high sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), albumin (ALB), serum creatinine (SCr), D-Dimer, fibrinogen (FIB), IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, number of hospital days and sequential organ failure assessment (SOFA) score were obtained and collated from medical records, and then compared between the two groups. Age, and SCr significantly differed between the two groups. Besides the IL-2 concentration that was significantly lower on day 2 than that on day 1 in the intervention group, and the IL-6 concentrations that were significantly higher on day 1, and day 2 in the intervention group compared to the control group, similar to the IL-10 concentration on day 5, there were no significant differences between the two groups. To sum up, CRRT with oXiris filter may not effectively alleviate CRS in non-AKI patients with severe and critical COVID-19. Thus, its application in these patients should be considered with caution to avoid increasing the unnecessary burden on society and individuals and making the already overwhelmed medical system even more strained (IRB number: IRB-AF/SC-04).

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“…Accumulating evidence showed that the high level of cytokines indicates a poor prognosis in COVID-19, although there are some controversy supported by a few clinical studies ( 118 ). Here, we propose a potential therapeutic strategy to fight against cytokine storm in COVID-19 infection, namely activating organism’s intrinsic CAP.…”

Section: Discussionmentioning

confidence: 99%

Activation of the Cholinergic Anti-Inflammatory Pathway as a Novel Therapeutic Strategy for COVID-19

Qin

Xiang

et al. 2021

Front. Immunol.

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The outbreak of coronavirus disease 2019 (COVID-19) underlined the urgent need for alleviating cytokine storm. We propose here that activating the cholinergic anti-inflammatory pathway (CAP) is a potential therapeutic strategy. However, there is currently no approved drugs targeting the regulatory pathway. It is evident that nicotine, anisodamine and some herb medicine, activate the CAP and exert anti-inflammation action in vitro and in vivo. As the vagus nerve affects both inflammation and specific immune response, we propose that vagus nerve stimulation by invasive or non-invasive devices and acupuncture at ST36, PC6, or GV20, are also feasible approaches to activate the CAP and control COVID-19. It is worth to investigate the efficacy and safety of the strategy in patients with COVID-19.

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Cytokine Storm May Not Be the Chief Culprit for the Deterioration of COVID-19

Cited by 14 publications

References 39 publications

The Association between TNF-α, IL-6, and Vitamin D Levels and COVID-19 Severity and Mortality: A Systematic Review and Meta-Analysis

The Association between TNF-α, IL-6, and Vitamin D Levels and COVID-19 Severity and Mortality: A Systematic Review and Meta-Analysis

Continuous Renal Replacement Therapy With oXiris Filter May Not be an Effective Resolution to Alleviate Cytokine Release Syndrome in Non-AKI Patients With Severe and Critical COVID-19

Activation of the Cholinergic Anti-Inflammatory Pathway as a Novel Therapeutic Strategy for COVID-19

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