ObjectiveTo compare the effects of treatments for coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis.Data sourcesUS Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020.Study selectionRandomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.Results23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference −4.5 days, low certainty), remdesivir (−2.6 days, moderate certainty), and lopinavir-ritonavir (−1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not substantially increase the risk of adverse effects leading to drug discontinuation. No other interventions included enough patients to meaningfully interpret adverse effects leading to drug discontinuation.ConclusionGlucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations.Systematic review registrationThis review was not registered. The protocol is included as a supplement.Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Objective To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis, with pairwise meta-analysis for outcomes with insufficient data. Data sources WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, and six Chinese databases (up to 21 July 2021). Study selection Trials randomising people with suspected, probable, or confirmed covid-19 to antiviral antibody therapies, blood products, or standard care or placebo. Paired reviewers determined eligibility of trials independently and in duplicate. Methods After duplicate data abstraction, we performed random effects bayesian meta-analysis, including network meta-analysis for outcomes with sufficient data. We assessed risk of bias using a modification of the Cochrane risk of bias 2.0 tool. The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. We meta-analysed interventions with ≥100 patients randomised or ≥20 events per treatment arm. Results As of 21 July 2021, we identified 47 trials evaluating convalescent plasma (21 trials), intravenous immunoglobulin (IVIg) (5 trials), umbilical cord mesenchymal stem cells (5 trials), bamlanivimab (4 trials), casirivimab-imdevimab (4 trials), bamlanivimab-etesevimab (2 trials), control plasma (2 trials), peripheral blood non-haematopoietic enriched stem cells (2 trials), sotrovimab (1 trial), anti-SARS-CoV-2 IVIg (1 trial), therapeutic plasma exchange (1 trial), XAV-19 polyclonal antibody (1 trial), CT-P59 monoclonal antibody (1 trial) and INM005 polyclonal antibody (1 trial) for the treatment of covid-19. Patients with non-severe disease randomised to antiviral monoclonal antibodies had lower risk of hospitalisation than those who received placebo: casirivimab-imdevimab (odds ratio (OR) 0.29 (95% CI 0.17 to 0.47); risk difference (RD) −4.2%; moderate certainty), bamlanivimab (OR 0.24 (0.06 to 0.86); RD −4.1%; low certainty), bamlanivimab-etesevimab (OR 0.31 (0.11 to 0.81); RD −3.8%; low certainty), and sotrovimab (OR 0.17 (0.04 to 0.57); RD −4.8%; low certainty). They did not have an important impact on any other outcome. There was no notable difference between monoclonal antibodies. No other intervention had any meaningful effect on any outcome in patients with non-severe covid-19. No intervention, including antiviral antibodies, had an important impact on any outcome in patients with severe or critical covid-19, except casirivimab-imdevimab, which may reduce mortality in patients who are seronegative. Conclusion In patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescent plasma, IVIg, and other antibody and cellular interventions may not confer any meaningful benefit. Systematic review registration This review was not registered. The protocol established a priori is included as a data supplement. Funding This study was supported by the Canadian Institutes of Health Research (grant CIHR- IRSC:0579001321). Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Interim updates and additional study data will be posted on our website ( www.covid19lnma.com ).

Lymphovascular space invasion is an overall poor prognostic factor in T1N0 endometrial cancer. After adjusting for other factors, LVSI remains an independent risk factor for worse overall survival. Therefore, estimation of overall survival in patients with early-stage, node-negative endometrial cancer should take into account LVSI status.

Most trials addressing the treatment of patients with COVID-19 have targeted patients admitted to hospital with severe or critical disease. 1 However, more recently, several treatments, including antiviral drugs, antidepressants, monoclonal anti bodies and inhaled corticosteroids, have been studied for patients with nonsevere COVID-19. 2 Preliminary evidence from ongoing or recently completed trials suggests that 2 novel antiviral drugsmolnupiravir and nirmatrelvir-ritonavir (Paxlovid) -may be effective at reducing risk of hospital admission. [3][4][5] To date, evidence on antiviral drugs for nonsevere COVID-19 has not been systematically synthesized or appraised. Furthermore, although efficacy data from trials of molnupiravir, nirmatrelvir-ritonavir and remdesivir are promising, no head-to-head trials have compared these drugs.A network meta-analysis allows for comparison of treatments that have not been compared in randomized controlled trials (RCTs), using pooled estimates from direct and indirect evidence.They can provide guidance to clinicians and evidence users in determining which treatments are superior. This is particularly important as health care systems attempt to prioritize access to effective COVID-19 treatments in the early stages of the disease.We sought to compare the effectiveness of antiviral drugs for patients with nonsevere COVID-19. MethodsWe conducted a systematic review and network meta-analysis, that included a rigorous appraisal of the evidence. We registered a protocol on Open Science Framework and uploaded the data used for this analysis (https://osf.io/zbcf9). We report our systematic review and network meta-analysis in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) extension statement for reporting of sys tematic reviews incorporating network meta-analyses. 6