Efficacy and safety of current medications for treating severe and non-severe COVID-19 patients: an updated network meta-analysis of randomized placebo-controlled trials

Abstract

Background: Many recent studies have investigated the role of drug interventions for coronavirus disease 2019 (COVID-19) infection. However, an important question has been raised about how to select the effective and secure medications for COVID-19 patients. The aim of this analysis was to assess the efficacy and safety of the various medications available for severe and non-severe COVID-19 patients based on randomized placebo-controlled trials (RPCTs). Methods: We did an updated network meta-analysis. We searched the databases from inception until July 31, 2021, with no language restrictions. We included RPCTs comparing 49 medications and placebo in the treatment of severe and non-severe patients (aged 18 years or older) with COVID-19 infection. We extracted data on the trial and patient characteristics, and the following primary outcomes: all-cause mortality, the ratios of virological cure, and treatment-emergent adverse events. Odds ratio (OR) and their 95% confidence interval (CI) were used as effect estimates. Results: From 3,869 publications, we included 61 articles related to 73 RPCTs (57 in non-severe COVID-19 patients and 16 in severe COVID-19 patients), comprising 20,680 patients. The mean sample size was 160 (interquartile range 96–393) in this study. The median duration of follow-up drugs intervention was 28 days (interquartile range 21–30). For increase in virological cure, we only found that proxalutamide (OR 9.16, 95% CI 3.15–18.30), ivermectin (OR 6.33, 95% CI 1.22–32.86), and low dosage bamlanivimab (OR 5.29, 95% CI 1.12–24.99) seemed to be associated with non-severe COVID-19 patients when compared with placebo, in which proxalutamide seemed to be better than low dosage bamlanivimab (OR 5.69, 95% CI 2.43–17.65). For decrease in all-cause mortality, we found that proxalutamide (OR 0.13, 95% CI 0.09–0.19), imatinib (OR 0.49, 95% CI 0.25–0.96), and baricitinib (OR 0.58, 95% CI 0.42–0.82) seemed to be associated with non-severe COVID-19 patients; however, we only found that immunoglobulin gamma (OR 0.27, 95% CI 0.08–0.89) was related to severe COVID-19 patients when compared with placebo. For change in treatment-emergent adverse events, we only found that sotrovimab (OR 0.21, 95% CI 0.13–0.34) was associated with non-severe COVID-19 patients; however, we did not find any medications that presented a statistical difference when compared with placebo among severe COVID-19 patients. Conclusion: We conclude that marked variations exist in the efficacy and safety of medications between severe and non-severe patients with COVID-19. It seems that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. Clinical decisions to use preferentially medications should carefully consider the risk-benefit profile based on efficacy and safety of all active interventions in patients with COVID-19 at different levels of infection.

SARS-CoV-2 reinfections: Overview of efficacy and duration of natural and hybrid immunity

“…The efficacy and duration of natural immunity will definitely be crucial for current policy deliberations and even more for the future ( Cheng et al, 2021 ; Dunkle et al, 2021 ; Gentile et al, 2021 ; Gupta et al, 2021 ; Ingram et al, 2021 ; Krause et al, 2021 ; Weinreich et al, 2021 ; Zemb et al, 2020 ). Nevertheless, huge knowledge gaps regarding natural immunity remain, that pose a challenge for health policy makers and require additional investigations.…”

SARS-CoV-2: Recent Variants and Clinical Efficacy of Antibody-Based Therapy

“…In a recent study published in The New England Journal of Medicine, researchers theorized that a monoclonal antibody that neutralizes all SARS-CoV-2 would target a highly conserved epitope that would remain effective as SARS-CoV-2 mutates ( Aschenbrenner, 2021 ). In the phase III, multicenter, double-blind, placebo-controlled study, SARS-CoV-2 Monoclonal Antibody Efficacy Trial–Intent to Care Early (COMET-ICE), Researchers evaluated the impact of a single intravenous infusion of sotrovimab 500 mg on mild-to-moderate SARS-CoV-2 in high-risk, non-hospitalized patients ( Cheng et al., 2021 ). The risk of severe SARS-CoV-2 is higher in patients over 55 years old or in those who have diabetes, obesity, chronic kidney disease, chronic obstructive pulmonary disease, congestive heart failure, or moderate-to-severe asthma.…”

“…Overall, 1% (3/291) of patients in the sotrovimab group and 7% (21/292) of patients in the placebo group had disease progression requiring hospitalization or death. In high-risk adults with symptomatic SARS-CoV-2, a single 500 mg dose of sotrovimab was found to minimize the probability of hospitalization or mortality by 85% ( Aschenbrenner, 2021 ; Cheng et al., 2021 ; Gupta et al., 2021 ). COMET-ICE, which compared monoclonal antibodies to SARS-CoV-2 and the subsequent variants, was apparent as evidence that sotrovimab neutralized SARS-CoV-2 and its variants.…”

“…Sotrovimab has also shown efficacity against variant lineages B.1.1.7, B.1.351, P.1, B.1.617, B.1.427/B.1.429 and B.1.526. Preclinical data suggest it could both block viral entry into healthy cells and clear infected cells by binding to an epitope on SARS-CoV-2 that’s participated with SARS-CoV-1 ( Cheng et al., 2021 ; Gupta et al., 2021 ).…”

Emerging small molecule antivirals may fit neatly into COVID-19 treatment

“…Along with dexamethasone, remdesivir is often now the “standard of care” (SOC) comparator in clinical trials (Table 4 ). Lopinavir/ritonavir or hydroxychloroquine were common early SOCs [ 59 ], but newer meta-analyses and reviews do not support their use in COVID-19 [ 60 – 62 ]…”