Pre-Clinical and Randomized Clinical Trial with Bromhexine and N-Acetylcysteine for COVID-19
Abstract
Roberto J Pires Neto*, Marco Clementino*, Rafael F Mesquita*, Mariana S Lima*, Ronaldo B Martins, Iasmin Ferreira, Jose Quirino Filho, Rafhaella N D G Gondim, Lyvia M V C Magalhães, Karene F Cavalcante, Vania A F Viana, Liana P Mello, Jose KSouza, Xhaulla M Q C Fonseca, Armenio A Santos, Pedro J C Magalhães, Alexandre Havt, Erico A G Arruda, Juliano P Souza, Marjorie Pontelli, Italo A Castro, Thais M Lima, Rosa M M Viana, Daniel M Jorge, Priscyla D Marcato, Hugo P Monteiro, Eurico Arruda and Aldo A M Lima*
Treatment options for mild to moderate COVID-19 is limited. N-acetylcysteine and bromhexine have antiviral activity and show potential as treatment options against SARS-CoV-2 infections. This study evaluates the in vitro antiviral effect of bromhexine (BMX) for SARS-CoV-2 and determines the efficacy of treatment with BMX in combination with N-acetylcysteine (NAC) to reduce clinical scores in patients with mild to moderate COVID-19. Upon evidence from pre- clinical studies, a single center randomized trial of BMX + NAC (ClinicalTrials.gov Identifier: NCT04928495) with 420 participants in total took place in Fortaleza, CE, Brazil. Out of the 420 participants 140 received placebo, 140 received NAC alone, and 140 received NAC + BMX. Patients were monitored for 10-14 days, where physicians recorded all signs and symptoms reported. Nasopharyngeal swabs and blood samples were collected for SARS-CoV-2 RNA testing during the first visit, as well as 3 and 10 days after. Blood samples were collected at first visit and 10 days after for immuno-inflammatory biomarkers measurements. Treatment with NAC+BMX reduced clinical scores and symptoms when compared to placebo group (2/26; 8% vs 7/18; 39%; p < 0.05). Fever (≥37.8°C) was reduced by NAC + BMX treatment when compared to treatment with NAC alone and placebo. This study was limited by a largely vaccinated population. Our analysis showed that BMX reduces SARS-CoV-2 infection in vitro. Clinical trial results suggested that combinatory treatment with NAC + BMX is beneficial in mild to moderate COVID-19.