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Effect of therapeutic versus prophylactic anticoagulation therapy on clinical outcomes in COVID-19 patients: a systematic review with an updated meta-analysis
Duo H, Li Y, Sun Y, Wei L, Wang Z, Fang F, Zhong Y, Huang J, Luo L, Peng Z, et al
Thrombosis journal. 2022;20(1):47
Abstract
BACKGROUND Previous studies demonstrate a reduced risk of thrombosis and mortality with anticoagulant treatment in patients with COVID-19 than in those without anticoagulation treatment. However, an open question regarding the efficacy and safety of therapeutic anticoagulation (T-AC) versus a lower dose, prophylaxis anticoagulation (P-AC) in COVID-19 patients is still controversial. METHODS We systematically reviewed currently available randomized clinical trials (RCTs) and observational studies (OBs) from January 8, 2019, to January 8, 2022, and compared prophylactic and therapeutic anticoagulant treatment in COVID-19 patients. The primary outcomes were risk of mortality, major bleeding, and the secondary outcomes included venous and arterial thromboembolism. Subgroup analysis was also performed between critically ill and non-critically ill patients with COVID-19 and between patients with higher and lower levels of D-dimer. Sensitivity analysis was performed to decrease the bias and the impact of population heterogeneity. RESULTS We identified 11 RCTs and 17 OBs fulfilling our inclusion criteria. In the RCTs analyses, there was no statistically significant difference in the relative risk of mortality between COVID-19 patients with T-AC treatment and those treated with P-AC (RR 0.95, 95% CI, 0.78-1.15, P = 0.60). Similar results were also found in the OBs analyses (RR 1.21, 95% CI, 0.98-1.49, P = 0.08). The pooling meta-analysis using a random-effects model combined with effect sizes showed that in the RCTs and OBs analyses, patients with COVID-19 who received T-AC treatment had a significantly higher relative risk of the major bleeding event than those with P-AC treatment in COVID-19 patients (RCTs: RR 1.76, 95% CI, 1.19-2.62, P = 0.005; OBs: RR 2.39, 95% CI, 1.56-3.68, P < 0.0001). Compared with P-AC treatment in COVID-19 patients, patients with T-AC treatment significantly reduced the incidence of venous thromboembolism (RR 0.51, 95% CI, 0.39-0.67, P<0.00001), but it is not associated with arterial thrombosis events (RR 0.97, 95% CI, 0.66-1.42, P = 0.87). The subgroup analysis of OBs shows that the mortality risk significantly reduces in critically ill COVID-19 patients treated with T-AC compared with those with P-AC treatment (RR 0.58, 95% CI, 0.39-0.86, P = 0.007), while the mortality risk significantly increases in non-critically ill COVID-19 patients treated with T-AC (RR 1.56, 95% CI, 1.34-1.80, P < 0.00001). In addition, T-AC treatment does not reduce the risk of mortality in COVID-19 patients with high d-dimer levels in RCTs. Finally, the overall sensitivity analysis after excluding two RCTs studies remains consistent with the previous results. CONCLUSIONS In our integrated analysis of included RCTs and OBs, there is no significant difference between the mortality of T-AC and P-AC treatment in unselected patients with COVID-19. T-AC treatment in COVID-19 patients significantly reduced the incidence of venous thromboembolism but showed a higher risk of bleeding than those with P-AC treatment. In addition, P-AC treatment was superior to T-AC treatment in non-critically ill COVID-19 patients, the evidence supporting the necessity for T-AC treatment in critically ill COVID-19 patients came only from OBs. TRIAL REGISTRATION Protocol registration: The protocol was registered at PROSPERO (CRD42021293294).
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Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review
Wang Z, Zhao S, Tang Y, Wang Z, Shi Q, Dang X, Gan L, Peng S, Li W, Zhou Q, et al
European journal of pediatrics. 2022;:1-12
Abstract
The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.Conclusions: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. What is Known: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. What is New: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.
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Efficacy and safety of recanalization therapy for acute ischemic stroke with COVID-19: A systematic review and meta-analysis
Wang Z, Teng H, Wu X, Yang X, Qiu Y, Chen H, Chen Z, Wang Z, Chen G
Frontiers in neurology. 2022;13:984135
Abstract
BACKGROUND The novel coronavirus disease 2019 (COVID-19) has rapidly spread worldwide and created a tremendous threat to global health. Growing evidence suggests that patients with COVID-19 have more severe acute ischemic stroke (AIS). However, the overall efficacy and safety of recanalization therapy for AIS patients infected by the SARS-CoV-2 virus is unknown. METHODS The PRISMA guideline 2020 was followed. Two independent investigators systematically searched databases and ClinicalTrials.gov to identify relevant studies published up to 31 March 2022. AIS patients who received any recanalization treatments were categorized into those with COVID-19 and those without COVID-19. The main efficacy outcomes were patients' functional independence on discharge and successful recanalization, and the safety outcomes were in-hospital mortality and symptomatic intracranial hemorrhage. Subgroup analyses were implemented to assess the influence of admission National Institutes of Health Stroke Scale and different recanalization treatments on the outcomes. STATA software 12.0 was used for the statistical analysis. RESULTS This systematic review and meta-analysis identified 10 studies with 7,042 patients, including 596 COVID-19 positive patients and 6,446 COVID-19 negative patients. Of the total patients, 2,414 received intravenous thrombolysis while 4,628 underwent endovascular thrombectomy. COVID-19 positive patients had significantly lower rates of functional independence at discharge [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.15 to 0.59, P = 0.001], lower rates of successful recanalization (OR 0.40, 95% CI 0.24 to 0.68, P = 0.001), longer length of hospital stay (weighted mean difference 5.09, 95% CI 1.25 to 8.94, P = 0.009) and higher mortality rates (OR 3.38, 95% CI 2.43 to 4.70, P < 0.0001). Patients with COVID-19 had a higher risk of symptomatic intracranial hemorrhage than the control group, although the difference did not reach statistical significance (OR 2.34, 95% CI 0.99 to 5.54, P = 0.053). CONCLUSIONS Compared with COVID-19 negative AIS patients who received recanalization treatments, COVID-19 positive patients turned out to have poorer outcomes. Particular attention needs to be paid to the treatments for these COVID-19 patients to decrease mortality and morbidity. Long-term follow-up is necessary to evaluate the recanalization treatments for AIS patients with COVID-19. SYSTEMATIC REVIEW REGISTRATION https://inplasy.com/inplasy-2022-4-0022/, identifier: INPLASY202240022.
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Rigorous Assessment of Guidelines on COVID-19-Related Thrombotic or Thromboembolic Disease: Implications for Clinical Practice of Prevention, Diagnosis, and Treatment
Liang J, Wang Z, Xie J, Liang H, Liang J, Jiang M, Li S
Evidence-based complementary and alternative medicine : eCAM. 2021;2021:5513744
Abstract
PURPOSE Severe COVID-19 patients were prone to develop venous thromboembolism. Unfortunately, to date, there is no evidence of any effective medications for thromboembolism in COVID-19. The management of the disease relies on symptomatic and supportive treatments, giving rise to a variety of guidelines. However, the quality of methodology and clinical recommendations remains unknown. MATERIALS AND METHODS We searched Medline, Cochrane Library, Web of Science, websites of international organizations and medical societies, and gray literature databases. Four well-trained appraisers independently evaluated the quality of eligible guidelines and extracted recommendations using well-recognized guideline appraisal tools. Furthermore, recommendations were extracted and reclassified according to a composite grading system. RESULTS The search identified 23 guidelines that offered 108 recommendations. Guidelines scored average on AGREE II criteria, with Scope and Purpose and Clarity of Presentation highest. Only five (22%) guidelines provided high-quality recommendations. The existed clinical recommendations were inconsistent in terms of prophylaxis, diagnosis, and treatment of thromboembolic disease to some extent. CONCLUSION Current guidelines for COVID-19 thromboembolism are generally of low quality, and clinical recommendations on thromboembolism are principally supported by insufficient evidence. There is still an urgent need for more well-designed clinical trials as evidence to prevent adverse events and improve prognosis during COVID-19 treatment.