Efficacy and safety of current treatment interventions for patients with severe COVID‐19 infection: A network meta‐analysis of randomized controlled trials

Abstract

This study aimed to assess the efficacy and safety of different medications available at present for severe coronavirus disease 2019 (COVID‐19) infection. We searched databases for randomized controlled trials (RCTs) published up to April 30, 2021, with Chinese or English language restriction, of medications recommended for patients (aged 18 years or older) with severe COVID‐19 infection. We extracted data on trials and patient characteristics, and the following primary outcomes: all‐cause mortality (ACM), and treatment‐emergent adverse events (TEAEs). We identified 1855 abstracts and of these included 15 RCTs comprising 3073 participants through database searches and other sources. In terms of efficacy, compared with the standard of care (SOC) group, no significant decrease in ACM was found in α‐lipoic acid, convalescent plasma (CP), azithromycin, tocilizumab, methylprednisolone, interferon beta, CP/SOC, high dosage sarilumab, low dosage sarilumab, remdesivir, lopinavir–ritonavir, auxora, and placebo group. Compared with placebo, we found that a significant decrease in ACM was only found in methylprednisolone (odds ratio [OR]: 0.16, 95% confidence interval [CI]: 0.03–0.75]. With respect to TEAEs, the CP group showed lower TEAEs than placebo (OR: 0.07, 95% CI: 0.01–0.58) or SOC (OR: 0.05, 95% CI: 0.01–0.42) group for the therapy of severe COVID‐19 patients. This study only demonstrated that methylprednisolone was superior to placebo in treating patients with severe COVID‐19 infection. Meanwhile, this further confirmed that the safety of other treatment interventions might be inferior to CP for the therapy of severe COVID‐19 patients.

Comparative efficacy and safety of pharmacological interventions for severe COVID-19 patients: An updated network meta-analysis of 48 randomized controlled trials

“…Curiously, our findings differed from our earlier pilot studies, [ 14 , 60 ] which have only indicated 2 effective medications (i.e., IG and methylprednisolone) in the decreased ACM for severe COVID-19 patients. In addition, the CP group showed lower TEAEs than the placebo for severe COVID-19 infection in our earlier NMAs.…”

High-cited favorable studies for COVID-19 treatments ineffective in large trials

“…with this interpretation. [67][68][69][70][71] For hydroxychloroquine, a recent collaborative meta-analysis even shows nominally statistically significantly increased mortality. 72 Prior experience from the in-depth analysis of persistent high citations of non-validated papers in other fields may offer us insights on why this situation arose also for COVID-19 treatments.…”

Clinical prediction models in hospitalized patients with COVID-19: A multicenter cohort study

“…During the first wave, in-hospital mortality ranged from 21% to 29%, and admission to intensive care units (ICUs) from 14% to 16% [ [1] , [2] , [3] , [4] ]. It should be noted that the efficacy of immunomodulatory and antiviral agents in reducing death or adverse outcome is still debated in COVID-19 patients, mainly when used in advanced phases of the disease [ [5] , [6] , [7] ]. Despite vaccination and spreading of several new variants may have impacted on severity of the disease, caution is required in inferring a reduced severity of COVID-19 infection [ 8 , 9 ].…”