Effect of bromhexine in hospitalized patients with COVID-19

Abstract

BackgroundBromhexine is a potent inhibitor of transmembrane serine protease 2 and appears to have an antiviral effect in controlling influenza and parainfluenza infection; however, its efficacy in COVID-19 is controversial.MethodsA group of hospitalized patients with confirmed COVID-19 pneumonia were randomized using 1:1 allocation to either standard treatment lopinavir/ritonavir and interferon beta-1a or bromhexine 8 mg four times a day in addition to standard therapy. The primary outcome was clinical improvement within 28 days, and the secondary outcome measures were time to hospital discharge, all-cause mortality, duration of mechanical ventilation, the temporal trend in 2019-nCoV reverse transcription-polymerase chain reaction positivity and the frequency of adverse drug events within 28 days from the start of medication.ResultsA total of 111 patients were enrolled in this randomized clinical trial and data from 100 patients (48 patients in the treatment arm and 52 patients in the control arm) were analyzed. There was no significant difference in the primary outcome of this study, which was clinical improvement. There was no significant difference in the average time to hospital discharge between the two arms. There were also no differences observed in the mean intensive care unit stay, frequency of intermittent mandatory ventilation, duration of supplemental oxygenation or risk of death by day 28 noted between the two arms.ConclusionBromhexine is not an effective treatment for hospitalized patients with COVID-19. The potential prevention benefits of bromhexine in asymptomatic postexposure or with mild infection managed in the community remain to be determined.

Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

“…Overall, 115 studies with 77,128 patients reported the number of patients requiring mechanical ventilation during the study period. We included ACEIs/ARBs, ammonium chloride, azithromycin, bamlanivimab, baricitinib plus remdesivir, bromhexine, budesonide, camostat mesilate, canakinumab, chloroquine, colchicine, convalescent plasma, dexamethasone, doxycycline, favipiravir, hydroxychloroquine, hydroxychloroquine plus azithromycin, hydroxychloroquine plus favipiravir, imatinib, INM005, interferon beta, intravenous immunoglobulin, ivermectin, lopinavir/ritonavir, methylprednisolone, recombinant human GCSF, remdesivir, sarilumab, sofosbuvir plus daclatasvir, sulodexide, tocilizumab, tofacitinib, vitamin D3 and SOC as treatment nodes in the NMA, for which observations came from 84 studies ( 3 , 6 , 22 – 26 , 28 – 31 , 35 , 42 , 43 , 46 , 47 , 50 , 53 , 55 , 57 – 61 , 63 , 64 , 66 , 67 , 71 , 73 – 77 , 79 , 80 , 82 , 83 , 85 – 87 , 89 , 92 – 94 , 96 – 100 , 102 , 105 – 107 , 109 , 111 – 118 , 120 – 124 , 126 , 128 – 132 , 134 , 135 , 139 , 140 , 145 , 151 , 152 , 154 – 156 ). About one-third (26/84) of the included studies were evaluated as low risk ( Supplementary Table 6 ).…”

The Transmembrane Protease TMPRSS2 as a Therapeutic Target for COVID-19 Treatment

“…In one trial, SOC treatment (n = 39) was compared with additional treatment with 24 mg of BHH per day for 14 days (n = 39) in patients with COVID-19 symptoms, and a significant decrease in the rate of ICU admission and need for ventilation in the BHH arm was reported [190]. However, in a later study, administration of 32 mg BHH per day for 14 days in 48 hospitalized COVID-19 patients failed to accelerate clinical improvement [191]. Li et al reported a non-significant trend towards improved clinical recovery in a BHH treatment cohort (n = 12) upon administration of the maximum recommended dose of 96 mg per day for 14 days [192].…”

“…Second, SOC therapy at the study site was different depending on local and/or temporal differences, which could affect the rate of clinical improvement. Third, the definitions and assessment of the primary clinical outcomes were not uniform, variously observing a decline in the clinical score, rate of ICU admission and mortality, or reduction in clinical symptoms [190][191][192]. Overall, larger clinical trials will be required to clarify the impact of BHH on COVID-19 [192].…”

Human Cell Organelles in SARS-CoV-2 Infection: An Up-to-Date Overview

“…A non-significant trend toward better clinical recovery upon administration of BHH was reported by Li et al [ 112 ]. BHH failed to accelerate the clinical improvement of COVID-19 patients in the Tolouian et al study [ 113 ]. Contradictory outcomes of the experiments may come as a result of various study designs and further clinical trials are required to formulate the applicability of BHH in COVID-19.…”