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. 2022 Apr;94(4):1617-1626.
doi: 10.1002/jmv.27512. Epub 2021 Dec 18.

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

Qinglin Cheng  1   2 , Gang Zhao  1 , Junfang Chen  1 , Qingjun Jia  1 , Zijian Fang  1
Affiliations

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

Qinglin Cheng et al. J Med Virol. 2022 Apr.

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.

Keywords: efficacy; network meta-analysis; randomized controlled trials; safety; severe COVID-19.

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Conflict of interest statement

The authors declare that there are no conflict of interests.

Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta‐Analyses flowchart for study selection.
Figure 2
Figure 2
The quality for included randomized controlled trials. (A) Risk of bias summary (The yellow circle with a question mark represents “unclear risk of bias,” the red one with minus sign represents “high risk of bias” and the green one with plus sign represents “low risk of bias”). (B) Risk of bias graph
Figure 3
Figure 3
Network plot of eligible comparisons for all‐cause mortality (A), and the TEAEs ratio (B) of medications in patients with severe COVID‐19. ALA, α‐lipoic acid; COVID‐19, coronavirus disease 2019; SOC, standard of care; TEAEs, treatment‐emergent adverse events
Figure 4
Figure 4
Network meta‐analyses of the relative efficacy and safety of medications for patients with severe COVID‐19 infection. ALA, α‐lipoic acid; AZM, azithromycin; CI, confidence interval; CP, convalescent plasma; COVID‐19, coronavirus disease 2019; HS, high dosage sarilumab; IFN‐β, interferon beta; LPV/r, lopinavir–ritonavir; LS, low dosage sarilumab; OR, odds ratio; SOC, standard of care
Figure 5
Figure 5
Meta‐regression and sensitivity analyses for the efficacy and safety of medications in patients with severe COVID‐19 infection. (A) All‐cause mortality. (B) The ratio of treatment‐emergent adverse events. CD, crossover design; COVID‐19, coronavirus disease 2019; DS, duration of study; IS, industry sponsorship; MS, multicenter study; RRB, risk of reported bias; SS, sample size
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