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The benefits of remdesivir in the treatment of hospitalized patients with COVID-19 remain debated with the National Institutes of Health and the World Health Organization providing contradictory recommendations for and against use. To evaluate the role of remdesivir for hospitalized inpatients as a function of oxygen requirements. Beginning with our prior systematic review, we searched MEDLINE using PubMed from 15 January 2021 through 5 May 2022. Randomised controlled trials; all languages. All hospitalized adults with COVID-19. Remdesivir, in comparison to either placebo, or standard of care. We used the ROB-2 criteria. The primary outcome was mortality, stratified by oxygen use (none, supplemental oxygen without mechanical ventilation, and mechanical ventilation). We conducted a frequentist random effects meta-analysis on the risk ratio scale and, to contextualize the probabilistic benefits, we also performed a Bayesian random effects meta-analysis on the risk difference scale. A ≥1% absolute risk reduction was considered clinically important. We identified eight randomized trials, totaling 10 751 participants. The risk ratio for mortality comparing remdesivir vs. control was 0.77 (95% CI, 0.5–1.19) in the patients who did not require supplemental oxygen; 0.89 (95% CI, 0.79–0.99) for nonventilated patients requiring oxygen; and 1.08 (95% CI, 0.88–1.31) in the setting of mechanical ventilation. Using neutral priors, the probabilities that remdesivir reduces mortality were 76.8%, 93.8%, and 14.7%, respectively. The probability that remdesivir reduced mortality by ≥ 1% was 77.4% for nonventilated patients requiring oxygen. Based on this meta-analysis, there is a high probability that remdesivir reduces mortality for nonventilated patients with COVID-19 requiring supplemental oxygen therapy. Treatment guidelines should be re-evaluated. [ABSTRACT FROM AUTHOR]

• A Bayesian re-analysis of remdesivir and corticosteroid randomized controlled trials was conducted. • Probabilities that remdesivir and corticosteroids reduced mortality by ≥1% were estimated. • Patients needing mechanical ventilation – 4% for remdesivir and 93% for corticosteroids. • Patients needing supplemental oxygen without mechanical ventilation – 81% for remdesivir and 93% for dexamethasone. • Patients who did not need oxygen support – neither remdesivir nor corticosteroids were likely to decrease mortality meaningfully. The global death toll from coronavirus disease 2019 (COVID-19) has exceeded 2 million, and treatments to decrease mortality are needed urgently. To examine the probabilities of a clinically meaningful reduction in mortality for remdesivir and systemic corticosteroids. This was a probabilistic re-analysis of clinical trial data for corticosteroids and remdesivir in the treatment of hospitalized patients with COVID-19 using a Bayesian random effects meta-analytic approach. Studies were identified from existing meta-analyses performed by the World Health Organization. Posterior probabilities of an absolute decrease in mortality compared with control patients, by subgroups based on oxygen requirements, were calculated for corticosteroids and remdesivir. Probabilities of ≥1%, ≥2% and ≥5% absolute decrease in mortality were quantified. For patients needing mechanical ventilation, the probability of ≥1% absolute decrease in mortality was 4% for remdesivir and 93% for corticosteroids. For patients needing supplemental oxygen without mechanical ventilation, the probability of ≥1% absolute decrease in mortality was 81% for remdesivir and 93% for dexamethasone. Finally, for patients who did not need oxygen support, the probability of ≥1% absolute decrease in mortality was 29% for remdesivir and 4% for dexamethasone. Using a Bayesian analytic approach, remdesivir had low probability of achieving a clinically meaningful reduction in mortality, except for patients needing supplemental oxygen without mechanical ventilation. Corticosteroids were more promising for patients needing oxygen support, especially mechanical ventilation. While awaiting more definitive studies, this probabilistic interpretation of the evidence will help to guide treatment decisions for clinicians, as well as guideline and policy makers. [ABSTRACT FROM AUTHOR]

Background: International COVID-19 guidelines recommend thromboprophylaxis for non-critically ill inpatients to prevent thrombotic complications. It is still debated whether full-dose thromboprophylaxis reduces all-cause mortality. The main aim of this updated systematic review and meta-analysis is to evaluate the effect of full-dose heparin-based thromboprophylaxis on survival in hospitalized non-critically ill COVID-19 patients. Methods: A systematic review was performed across Pubmed/Medline, EMBASE, Cochrane Central Register of clinical trials, Clinicaltrials.gov, and medRxiv.org from inception to November 2022. We conducted a meta-analysis of randomized clinical trials (RCTs) comparing full-dose heparin-based anticoagulation to prophylactic or intermediate dose anticoagulation or standard treatment in hospitalized non-critically ill COVID-19 patients. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations Assessment, Development and Evaluation was applied. The primary outcome was all-cause mortality at the longest follow-up available. Results: We identified 6 multicenter RCTs involving 3297 patients from 13 countries across 4 continents. The rate of all-cause mortality was 6.2% (103/1662) in the full-dose group vs 7.7% (126/1635) in the prophylactic or intermediate dose group (Risk Ratio [RR] = 0.76; 95% confidence interval [CI] = 0.59–0.98; P = 0.037). The probabilities of any mortality difference and of NNT ≤ 100 were estimated at 98.2% and 84.5%, respectively. The risk of bias was low for all included RCTs and the strength of the evidence was "moderate." Conclusion: Our meta-analysis of high-quality multicenter RCTs suggests that full-dose anticoagulation with heparin or low molecular weight heparin reduces all-cause mortality in hospitalized non-critically ill COVID-19 patients. Study registration: PROSPERO, review no. CRD42022348993. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCT) established the mortality reduction by tocilizumab (Actemra), baricitinib (Olumiant), and sarilumab (Kevzara) in hospitalized COVID-19 patients. However, uncertainty remains about which treatment performs best in patients receiving corticosteroids. To estimate probabilities of noninferiority between baricitinib and sarilumab compared to tocilizumab in patients treated with corticosteroids. PubMed, Embase, Cochrane Library, and MedRxiv. Eligible RCTs assigning hospitalized adults with COVID-19 treated with corticosteroids to tocilizumab or baricitinib or sarilumab versus standard of care or placebo (control). Reviewers independently abstracted published data and assessed study quality with the Risk of Bias 2 tool. Unpublished data, if required, were requested from authors of included studies. The outcome of interest was all-cause mortality at 28 days. Twenty-seven RCTs with 13 549 patients were included. Overall, the risk of bias was low. Bayesian pairwise meta-analyses were used to aggregate results of each treatment versus control. The average odds ratio for mortality was 0.78 (95% credible interval [CrI]: 0.65, 0.94) for tocilizumab; 0.78 (95% CrI: 0.56, 1.03) for baricitinib; and 0.91 (95% CrI: 0.60, 1.40) for sarilumab. The certainty of evidence (GRADE) ranged from moderate to low. Bayesian meta-regressions with multiple priors were used to estimate probabilities of noninferiority (margin of 13% greater effect by tocilizumab). Compared to tocilizumab, there were ≤94% and 90% probabilities of noninferiority with baricitinib and sarilumab, respectively. All but two studies included data with only indirect evidence for the comparison of interest. Among hospitalized COVID-19 treated with corticosteroids, there are high probabilities that both baricitinib and sarilumab are associated with similar mortality reductions in comparison to tocilizumab. [ABSTRACT FROM AUTHOR]