Tocilizumab and Systemic Corticosteroids in the Management of Patients with COVID-19: A Systematic Review and Meta-Analysis.
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ABSTRACT: Background
To date, there is no effective treatment for the new coronavirus disease (COVID-19). We aimed to systematically review the literature on the association between the combination of tocilizumab (TCZ) and systemic corticosteroid therapy (SCT) on outcomes of COVID-19 patients.Methods
We searched MEDLINE, Cochrane Central, and preprints, for studies in which health outcomes were compared between adults with severe COVID-19 who received TCZ and SCT and those who received standard of care without TCZ. Record screening, data extraction, and risk of bias assessment were performed in duplicate. Random effect models were used when pooling crude numbers and adjusted effect estimates of study outcomes.Results
Our search identified seventeen studies. The pooled crude mortality rate was lower in the combination arm (relative risk, RR=0.62, 95% confidence interval [CI]=0.42 - 0.91; I2=60%). The adjusted mortality rates were also lower in the combination arm (RR=0.58, 95% CI=0.42 - 0.81; I2=71%). The rate of superinfections did not differ between the two interventions.Conclusions
The findings of this study show that combination of TCZ and SCT compared to SOC has lower mortality rates. There is an urgent need for well-designed randomized trials to assess the safety and efficacy of this combination in subjects with severe COVID-19.
SUBMITTER: Alkofide H
PROVIDER: S-EPMC8278842 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCoronavirus disease 2019 (COVID-19) has killed over 2.5 million people worldwide, but effective care and therapy have yet to be discovered. We conducted this analysis to better understand tocilizumab treatment for COVID-19 patients.Main textWe searched major databases for manuscripts reporting the effects of tocilizumab on COVID-19 patients. A total of 25 publications were analyzed with Revman 5.3 and R for the meta-analysis. Significant better clinical outcomes were found in the tocilizumab treatment group when compared to the standard care group [odds ratio (OR) = 0.70, 95% confidential interval (C): 0.54-0.90, P = 0.007]. Tocilizumab treatment showed a stronger correlation with good prognosis among COVID-19 patients that needed mechanical ventilation (OR = 0.59, 95% CI, 0.37-0.93, P = 0.02). Among stratified analyses, reduction of overall mortality correlates with tocilizumab treatment in patients less than 65 years old (OR = 0.68, 95% CI: 0.60-0.77, P < 0.00001), and with intensive care unit patients (OR = 0.62, 95% CI: 0.55-0.70, P < 0.00001). Pooled estimates of hazard ratio showed that tocilizumab treatment predicts better overall survival in COVID-19 patients (HR = 0.45, 95% CI: 0.24-0.84, P = 0.01), especially in severe cases (HR = 0.58, 95% CI 0.49-0.68, P < 0.00001).ConclusionsOur study shows that tocilizumab treatment is associated with a lower risk of mortality and mechanical ventilation requirement among COVID-19 patients. Tocilizumab may have substantial effectiveness in reducing mortality among COVID-19 patients, especially among critical cases. This systematic review provides an up-to-date evidence of potential therapeutic role of tocilizumab in COVID-19 management.
| S-EPMC8128625 | biostudies-literature
Project description:This systemic review and meta-analysis aimed to assess the efficacy of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19). Candidate studies up to 24 May 2020 were identified from PubMed, Cochrane Library, Embase, medRxiv and bioRxiv. Treatment outcomes included mortality, risk of intensive care unit (ICU) admission and the requirement for mechanical ventilation (MV). Seven retrospective studies involving 592 adult patients with severe COVID-19, including 240 in the tocilizumab group and 352 in the control group, were enrolled. All-cause mortality of severe COVID-19 patients among the tocilizumab group was 16.3% (39/240), which was lower than that in the control group (24.1%; 85/352). However, the difference did not reach statistical significance [risk ratio (RR) = 0.62, 95% confidence interval (CI) 0.31-1.22; I2 = 68%]. Additionally, risk of ICU admission was similar between the tocilizumab and control groups (35.1% vs. 15.8%; RR = 1.51, 95% CI 0.33-6.78; I2 = 86%). The requirement for MV was similar between the tocilizumab and control groups (32.4% vs. 28.6%; RR = 0.82, 95% CI 0.14-4.94; I2 = 91%). However, these non-significant differences between the tocilizumab and control groups may have been the result of baseline characteristics of the tocilizumab group, which were more severe than those of the control group. Based on low-quality evidence, there is no conclusive evidence that tocilizumab would provide any additional benefit to patients with severe COVID-19. Therefore, further recommendation of tocilizumab for COVID-19 cases should be halted until high-quality evidence from randomised controlled trials is available.
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Project description:BackgroundThe majority of patients with coronavirus disease 2019 (COVID-19) have good prognoses, but some develop a critical illness that can lead to death. Evidence shows severe acute respiratory syndrome is closely related to the induced cytokine storm. Interleukin-6 is a key player; its role in systemic inflammation is well known.AimTo evaluate the effect of tocilizumab (TCZ), an interleukin-6 receptor antagonist, on the outcomes for patients with COVID-19 pneumonia.MethodsPubMed, EMBASE, SCOPUS, Web of Science, MedRxiv, Science Direct, and the Cochrane Library were searched from inception to 9th June 2020 for observational or prospective studies reporting results of hospitalized adult patients with COVID-19 infection treated with TCZ. Effect sizes were reported as odds ratios (ORs) with 95% confidence intervals (CIs), and an OR less than 1 was associated with a better outcome in those treated with TCZ.ResultsOverall 13476 patients (33 studies; n = 3264 received TCZ) with COVID-19 pneumonia and various degree of severity were included. Outcome was improved with TCZ. In the primary analysis (n = 19 studies reporting data), mortality was reduced in patients treated with TCZ (OR = 0.64, 95%CI: 0.47-0.87; P < 0.01). In 9 studies where risk of death with TCZ use was controlled for other variables mortality was reduced by 57% (OR = 0.43, 95%CI: 0.27-0.7; P < 0.01). Intensive care need (mechanical ventilation) was also reduced (OR = 0.36, 95%CI: 0.14-0.89; P = 0.02).ConclusionIn COVID-19-infected patients treated with TCZ, outcome may be improved compared to those not treated with TCZ.
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Project description:OBJECTIVES:COVID-19 has become a global epidemic, and effective therapies have not been discovered up to now. We conducted this study to explore the effectiveness and safety of tocilizumab recently used for treating COVID-19. METHOD:A comprehensive search was conducted (up to September 27, 2020), and 19 eligible records were identified according to the inclusion and exclusion criteria. The data of the studies were extracted by 2 independent reviewers and were analyzed to evaluate the safety and availability of tocilizumab for treating COVID-19. RESULTS:Thirteen retrospective case-control studies (n =?2285 patients) and 6 retrospective single-armed studies (n =?208) were retrieved in this study. In the comparison of tocilizumab treatment group (TCZ) and standard treatment group (ST), significant associations with a lower risk of admission to ICU, use of ventilation, and mortality (OR, 95% CI: 0.53, 0.26~1.09; 0.66, 0.46~0.94; 0.44, 0.36~0.55) were found in the tocilizumab treatment group. What is more, patients treated with tocilizumab had better clinical improvement compared with the patients treated with ST (OR, 1.24; 95% CI, 0.96~1.62). After taking tocilizumab, the patients had lower C-reactive protein (CRP), white blood cell count (WBC), aspartate aminotransferase (AST) (WMD, 95% CI: -?99.66, -?156.24~-?43.09; -?0.95, -?1.8~-?0.11; -?12.58, -?18.88~-6.29) but higher troponin (WMD, 7.61; 95% CI, 3.06~12.15) than before. In addition, tocilizumab did not have significant influence on patients' neutrophil count (Neut), lymphocyte count (Lymp), platelet count (Plt), alanine aminotransferase (ALT), and creatine (WMD, 95% CI: -?0.29, -?2.91~2.33; 0.42, -?0.23~1.07; 5.2, -?2.85~13.25; 22.49, -?2.73~47.7; -?44.78, -?93.37~3.81). CONCLUSION:Tocilizumab may have potential effectiveness to treat COVID-19 according to the results of this study. However, more large-scale studies are needed for more accurate conclusions.
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Project description:The novel coronavirus disease 2019 (COVID-19) predisposes patients to venous thromboembolism (VTE) due to risk factors, severe infection, and severe inflammatory responses. The objective is to determine the risk of developing VTE after corticosteroid administration during COVID-19 treatment. Using PRISMA reporting guidelines, a review was conducted from inception until 20 September 2020 with MESH terms including "venous thromboembolism" and "covid-19," using MEDLINE, Scopus, CINAHL Plus, and WHO Global Database. The inclusion criteria included studies with COVID-19 patients aged 18 years and older with VTE diagnosed by duplex ultrasonography or computed tomography pulmonary angiography (CTPA). Exclusion criteria were studies with non COVID-19 patients and non-VTE patients aged less than 18 years. Quality appraisal was conducted of included studies using the Newcastle-Ottawa Scale (NOS). A random-effect model using 95% confidence intervals, and significance of findings was assessed using Review Manager V5.4.We included 12 observational studies with 2801 patients (VTE n = 434; non-VTE; n = 2367). Patients had a higher risk of presenting with VTE when being administered corticosteroids during treatment of COVID-19 (RR = 1.39, 95% CI = 1.10 to 1.77, I2 = 0%). A positive effect size was found (SMD = 1.00, 95% CI = 0.67 to 1.32, I2 = 85%) for D-dimer laboratory values (µg/mL) in the VTE group. While critically ill COVID-19 patients are more likely to require corticosteroid treatment, it may be associated with increased risk of VTE, and poor clinical prognosis. Risk assessment is warranted to further evaluate patients as case-by-case in reducing VTE and worsening clinical outcomes.
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Project description:ObjectivesCytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to perform a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients.MethodsData sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google up to October 8, 2020. Study eligibility criteria were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs and adjusted RRs from cohorts, separately. We evaluated inconsistency between studies with I2. We assessed the certainty of evidence using the GRADE approach.ResultsOf 1156 citations, 24 studies were eligible (five RCTs and 19 cohorts). Five RCTs at low risk of bias, with 1325 patients, examined the effect of tocilizumab on short-term mortality; pooled RR was 1.09 (95%CI 0.80-1.49, I2 = 0%). Four RCTs with 771 patients examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.71 (95%CI 0.52-0.96, I2 = 0%), with a corresponding number needed to treat of 17 (95%CI 9-100). Among 18 cohorts at moderate risk of bias with 9850 patients, the pooled adjusted RR for mortality was 0.58 (95%CI 0.51-0.66, I2 = 2.5%). This association was observed over all degrees of COVID-19 severity. Data from the RCTs did not show a higher risk of infections or adverse events with tocilizumab: pooled RR 0.63 (95%CI 0.38-1.06, five RCTs) and 0.83 (95%CI 0.55-1.24, five RCTs), respectively.ConclusionsCumulative moderate-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized COVID-19 patients. While RCTs showed that tocilizumab did not reduce short-term mortality, low-certainty evidence from cohort studies suggests an association between tocilizumab and lower mortality. We did not observe a higher risk of infections or adverse events with tocilizumab use. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.
| S-EPMC7644182 | biostudies-literature
Project description: Not available
| S-EPMC8604568 | biostudies-literature
Project description:BackgroundCovid-19 disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although corticosteroids have shown some promising results in Covid-19 patients, their effectiveness remains controversial. In this systematic review, we evaluated the effect of corticosteroids in mortality, Hospitalization, ICU admission, intubation, and mechanical ventilation in Covid-19 patients.MethodsWe searched major databases from March-2020 to Jan-2021. Twenty-nine studies were included after evaluating the eligibility of the literature. The extracted data for mortality, hospitalization, admission to the ICU, intubation, and mechanical ventilation were analyzed with RevMan® 5.4. Categorical variables are presented with odds ratios (OR), and numerical variables are shown with the mean difference.ResultCorticosteroid treatment had no impact on mortality in 18,190 covid patients with OR = 1.12[0.83-1.50]. When we include the randomized controlled trials, corticosteroids reduced the mortality by 20% (OR = 0.80 [0.73, 0.88]; P < 0.001). Additionally, the risk of admission to the ICU, the need for endotracheal intubation, and mechanical ventilation were comparable between patients receiving corticosteroids and controls. The duration of hospitalization was also similar in the two groups.ConclusionCorticosteroid therapy may not be effective for reducing mortality, length of hospitalization, the likelihood of intubation and mechanical ventilation, and ICU admission in patients suffering from Covid-19 pneumonia.
| S-EPMC8684054 | biostudies-literature
Project description:BackgroundTo systematically review the literature about the association between systemic corticosteroid therapy (CST) and outcomes of COVID-19 patients.MethodsWe searched Medline, Embase, EBM Reviews, Scopus, Web of Science, and preprints up to July 20, 2020. We included observational studies and randomized controlled trials (RCT) that assessed COVID-19 patients treated with CST. We pooled adjusted effect estimates of mortality and other outcomes using a random effect model, among studies at low or moderate risk for bias. We assessed the certainty of evidence for each outcome using the GRADE approach.ResultsOut of 1067 citations screened for eligibility, one RCT and 19 cohort studies were included (16,977 hospitalized patients). Ten studies (1 RCT and 9 cohorts) with 10,278 patients examined the effect of CST on short term mortality. The pooled adjusted RR was 0.92 (95% CI 0.69-1.22, I2 = 81.94%). This effect was observed across all stages of disease severity. Four cohort studies examined the effect of CST on composite outcome of death, ICU admission and mechanical ventilation need. The pooled adjusted RR was 0.41(0.23-0.73, I2 = 78.69%). Six cohort studies examined the effect of CST on delayed viral clearance. The pooled adjusted RR was 1.47(95% CI 1.11-1.93, I2 = 43.38%).ConclusionIn this systematic review, as of July 2020, heterogeneous and low certainty cumulative evidence based on observational studies and one RCT suggests that CST was not associated with reduction in short-term mortality but possibly with a delay in viral clearance in patients hospitalized with COVID-19 of different severities. However, the discordant results between the single RCT and observational studies as well as the heterogeneity observed across observational studies, call for caution in using observational data and suggests the need for more RCTs to identify the clinical and biochemical characteristics of patients' population that could benefit from CST.
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