Efficacy of tocilizumab in the treatment of COVID‐19: An umbrella review

Tolzali, Mohammad Mahdi Rezaei; Noori, Maryam; Shokri, Pourya; Rahmani, Shayan; Khanzadeh, Shokoufeh; Nejadghaderi, Seyed Aria; Fazlollahi, Asra; Sullman, Mark J.M.; Singh, Kuljit; Kolahi, Ali‐Asghar; Arshi, Shahnam; Safiri, Saeid

doi:10.1002/rmv.2388

Cited by 9 publications

(3 citation statements)

References 143 publications

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“…Unfortunately, in numerous countries, several factors have limited the use of tocilizumab, such as drug shortages, high cost or late approval (December 2021 in Europe, December 2022 in the USA). Therefore, real-life data on tocilizumab treatment remain scarce, especially in patients infected with delta or omicron VOCs [13][14][15]. Moreover, its use is questionable in omicron cases.…”

Section: Introductionmentioning

confidence: 99%

Effect of Tocilizumab on Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta or Omicron Variants: A Propensity-Matched Analysis in Nimes University Hospital, France

et al. 2023

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We aimed to assess the factors associated with mortality in patients treated with tocilizumab for a SARS-CoV-2 pneumonia due to the delta or omicron variants of concern (VOC) and detect an effect of tocilizumab on mortality. We conducted a prospective cohort study in a tertiary hospital from 1 August 2021 to 31 March 2022 including patients with severe COVID-19, treated with tocilizumab. Factors associated with mortality were assessed in a Cox model; then, the 60-day mortality rates of COVID-19 patients treated with standard of care (SoC) +/− tocilizumab were compared after 1:1 propensity score matching. The mortality rate was 22% (N = 26/118) and was similar between delta and omicron cases (p = 0.6). The factors independently associated with mortality were age (HR 1.06; 95% CI (1.02–1.11), p = 0.002), Charlson index (HR 1.33; 95% CI (1.11–1.6), p = 0.002), WHO-CPS (HR 2.56; 95% CI (1.07–6.22) p = 0.03), and tocilizumab infusion within the first 48 h following hospital admission (HR 0.37, 95% CI (0.14–0.97), p = 0.04). No significant differences in mortality between the tocilizumab plus SoC and SoC alone groups (p = 0.5) were highlighted. However, the patients treated with tocilizumab within the 48 h following hospital admission had better survival (p = 0.04). In conclusion, our results suggested a protective effect on mortality of the early administration of tocilizumab in patients with severe COVID-19 regardless of the VOC involved.

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Section: Introductionmentioning

confidence: 99%

Effect of Tocilizumab on Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta or Omicron Variants: A Propensity-Matched Analysis in Nimes University Hospital, France

et al. 2023

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“…In another recent systematic review, they believed that immunosuppressants can significantly reduce mortality and have no effect on the increase of the risk of secondary infection ( 175 ). In terms of secondary infection, an umbrella review in August 2022 also put forward same views ( 176 , 177 ). Their research shows that the treatment of steroids or steroids plus tocilizumab did not confer a higher risk of bacterial infections and improved survival rates.…”

Section: The Attractive Therapeutic Approach To Prevent Mas In Covid-19mentioning

confidence: 90%

Advances in attractive therapeutic approach for macrophage activation syndrome in COVID-19

et al. 2023

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Nowadays, people have relaxed their vigilance against COVID-19 due to its declining infection numbers and attenuated virulence. However, COVID-19 still needs to be concern due to its emerging variants, the relaxation of restrictions as well as breakthrough infections. During the period of the COVID-19 infection, the imbalanced and hyper-responsive immune system plays a critical role in its pathogenesis. Macrophage Activation Syndrome (MAS) is a fatal complication of immune system disease, which is caused by the excessive activation and proliferation of macrophages and cytotoxic T cells (CTL). COVID-19-related hyperinflammation shares common clinical features with the above MAS symptoms, such as hypercytokinemia, hyperferritinemia, and coagulopathy. In MAS, immune exhaustion or defective anti-viral responses leads to the inadequate cytolytic capacity of CTL which contributes to prolonged interaction between CTL, APCs and macrophages. It is possible that the same process also occurred in COVID-19 patients, and further led to a cytokine storm confined to the lungs. It is associated with the poor prognosis of severe patients such as multiple organ failure and even death. The main difference of cytokine storm is that in COVID-19 pneumonia is mainly the specific damage of the lung, while in MAS is easy to develop into a systemic. The attractive therapeutic approach to prevent MAS in COVID-19 mainly includes antiviral, antibiotics, convalescent plasma (CP) therapy and hemadsorption, extensive immunosuppressive agents, and cytokine-targeted therapies. Here, we discuss the role of the therapeutic approaches mentioned above in the two diseases. And we found that the treatment effect of the same therapeutic approach is different.

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“…Tocilizumab is an IL6 receptor blocker that effectively blocks the IL6 signal transduction pathway and is an effective therapeutic drug for COVID-19 patients. Tocilizumab can reduce the intubation risk, mortality, and hospital stay in COVID-19 patients without increasing the risk of superimposed infections ( 26 ). Nifuroxazide improves myocardial oxidation and attenuates LPS-induced myocardial injury by interrupting TLR4/NALPR3/IL-1β signaling ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

High expression of IL6 and decrease in immune cells in COVID-19 patients combined with myocardial injury

Chen

et al. 2023

Front. Immunol.

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PurposeMyocardial injury, as a serious complication of coronavirus disease-2019 (COVID-19), increases the occurrence of adverse outcomes. Identification of key regulatory molecules of myocardial injury may help formulate corresponding treatment strategies and improve the prognosis of COVID-19 patients.MethodsGene Set Enrichment Analysis (GSEA) was conducted to identify co-regulatory pathways. Differentially expressed genes (DEGs) in GSE150392 and GSE169241 were screened and an intersection analysis with key genes of the co-regulatory pathway was conducted. A protein-protein interaction (PPI) network was constructed to screen for key regulatory genes. Preliminarily screened genes were verified using other datasets to identify genes with consistent expression. Based on the hierarchical cluster, we divided the patients from GSE177477 into high- and low-risk groups and compared the proportion of immune cells. A total of 267 COVID-19 patients from the Zhejiang Provincial Hospital of Chinese Medicine from December 26, 2022, to January 11, 2023, were enrolled to verify the bioinformatics results. Univariate and multivariate analyses were performed to analyze the risk factors for myocardial injury. According to high-sensitivity troponin (hsTnI) levels, patients with COVID-19 were divided into high- and low-sensitivity groups, and interleukin 6 (IL6) expression and lymphocyte subsets were compared. Patients were also divided into high and low groups according to the IL6 expression, and hsTnI levels were compared.ResultsInterleukin signaling pathway and GPCR ligand binding were shown to be co-regulatory pathways in myocardial injury associated with COVID-19. According to the hierarchical cluster analysis of seven genes (IL6, NFKBIA, CSF1, CXCL1, IL1R1, SOCS3, and CASP1), patients with myocardial injury could be distinguished from those without myocardial injury. Age, IL6 levels, and hospital stay may be factors influencing myocardial injury caused by COVID-19. Compared with COVID-19 patients without myocardial injury, the levels of IL6 in patients with myocardial injury increased, while the number of CD4+ T cells, CD8+ T cells, B cells, and NK cells decreased (P<0.05). The hsTnI levels in COVID-19 patients with high IL6 levels were higher than those in patients with low IL6 (P<0.05).ConclusionsThe COVID-19 patients with myocardial injury had elevated IL6 expression and decreased lymphocyte counts. IL6 may participate in myocardial injury through the interleukin signaling pathway.

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Efficacy of tocilizumab in the treatment of COVID‐19: An umbrella review

Cited by 9 publications

References 143 publications

Effect of Tocilizumab on Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta or Omicron Variants: A Propensity-Matched Analysis in Nimes University Hospital, France

Effect of Tocilizumab on Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta or Omicron Variants: A Propensity-Matched Analysis in Nimes University Hospital, France

Advances in attractive therapeutic approach for macrophage activation syndrome in COVID-19

High expression of IL6 and decrease in immune cells in COVID-19 patients combined with myocardial injury

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