Efficacy and safety of antiviral therapy in critically ill patients with mechanical ventilation: a meta-analysis with trial sequential analysis of randomized controlled trials.

OBJECTIVES: Viral reactivation is frequently detected in critically ill patients undergoing mechanical ventilation and is associated with worse outcomes. However, the efficacy and safety of antiviral therapy in these patients remain unknown. This review aims to assess the effects of antiviral therapy on mortality, viral reactivation, and adverse events in critically ill patients undergoing mechanical ventilation. METHODS: Data sources were Medline, Embase, the Cochrane Library, and reference lists. The study included randomized controlled trials that compared antiviral therapy with placebo, standard care, or no treatment. Participants were critically ill patients undergoing mechanical ventilation. Intervention was antiviral therapy. Assessment of risk of bias used the Cochrane risk of bias tool. For methods of data synthesis, risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model for meta-analysis with trial sequential analysis. RESULTS: Nine trials with a broad spectrum of critically ill patients were included. No association was found between antiviral therapy and all-cause mortality at the longest follow-up (nine trials, 1790 patients, RR 0.93, 95%CI 0.79-1.11, I2 3%). Trial sequential analysis showed that the cumulative Z curve crossed the futility boundary establishing sufficient evidence. No association was also found between antiviral therapy and 28-day mortality, in-hospital mortality, 60-day mortality, or 90-day mortality. However, antiviral therapy was associated with a reduction in viral reactivation (five trials, 644 patients, RR 0.23, 95%CI 0.14-0.37, I2 0%). Trial sequential analysis showed that the cumulative Z curve crossed the trial sequential monitoring boundary for benefit establishing sufficient evidence. Antiviral therapy was not associated with an increased risk of renal insufficiency (eight trials, 1574 patients, RR 0.88, 95%CI 0.73-1.05, I2 0%). CONCLUSIONS: No association between antiviral therapy and mortality was found, but antiviral therapy reduced viral reactivation without increasing the risk of renal insufficiency in critically ill patients with mechanical ventilation.

A meta-analysis of the incidence of venous thromboembolic events and impact of anticoagulation on mortality in patients with COVID-19.

BACKGROUND: The incidence of venous thromboembolic events (VTE) in patients with COVID-19 is generally high but varies markedly. However, the relationship between anticoagulation and mortality in patients with COVID-19 is still unclear. METHODS: We performed a systematic review and meta-analysis to determine the incidence of VTE and evaluate the role of anticoagulation in patients with COVID-19. Random effects models were used to determine overall pooled estimates and 95% confidence intervals (CIs). RESULTS: After a database search, 25 observational studies (20 on VTE incidence and 5 on the relationship between anticoagulation and mortality) were included. The pooled incidence rates of VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) in hospitalised COVID-19 patients were 21% (95% CI 15-27%), 15% (95% CI 10-20%), and 27% (95% CI 19-36%), respectively. A meta-analysis of five studies found that anticoagulation was not associated with an increased risk of mortality in hospitalised COVID-19 patients (RR = 0.86, 95% CI, 0.69-1.09, P = 0.218; I2 = 47.4%). CONCLUSIONS: In conclusion, the incidence of VTE among hospitalised COVID-19 patients was high. Clinical trials are urgently needed to evaluate the roles of prophylactic and therapeutic anticoagulation in COVID-19.