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Pre-clinical and randomized clinical trial with bromhexine and N-acetylcysteine for COVID-19
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  • Marco Clementino,
  • Roberto da Justa Pires Neto,
  • Rafael F. Mesquita,
  • Mariana S. Lima,
  • Ronaldo Martins,
  • Iasmin Ferreira,
  • M. Clementino,
  • Rafhaella Nogueira Della Guardia Gondim,
  • Lyvia Maria Vasconcelos Carneiro Magalhães,
  • Karene Ferreira Cavalcante,
  • Vania Angelica Feitosa Viana,
  • Liana Perdigão Mello,
  • José K. Souza,
  • Xhaulla M.Q.C. Fonseca,
  • Armênio Aguiar dos Santos,
  • Pedro Jorge Caldas Magalhães,
  • Alexandre Havt,
  • Érico Antônio Gomes de Arruda,
  • Juliano P. Souza,
  • Marjorie Pontelli,
  • Italo A. Castro,
  • Thais M. Lima,
  • Rosa Viana,
  • Daniel Macedo de Melo Jorge,
  • Priscyla D. Marcato,
  • Hugo P. Monteiro,
  • Eurico Arruda,
  • Aldo Lima
Marco Clementino
Universidade Federal do Ceara
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Roberto da Justa Pires Neto
Hospital Sao Jose de Doencas Infecciosas
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Rafael F. Mesquita
Hospital Sao Jose de Doencas Infecciosas
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Mariana S. Lima
Universidade Federal do Ceara
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Ronaldo Martins
Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto
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Iasmin Ferreira
Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto
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M. Clementino
Universidade Federal do Ceara
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Rafhaella Nogueira Della Guardia Gondim
Universidade Federal do Ceara
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Lyvia Maria Vasconcelos Carneiro Magalhães
Universidade Federal do Ceara
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Karene Ferreira Cavalcante
Secretaria de Vigilancia em Saude
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Vania Angelica Feitosa Viana
Secretaria de Vigilancia em Saude
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Liana Perdigão Mello
Secretaria de Vigilancia em Saude
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José K. Souza
Universidade Federal do Ceara
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Xhaulla M.Q.C. Fonseca
Universidade Federal do Ceara
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Armênio Aguiar dos Santos
Universidade Federal do Ceara
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Pedro Jorge Caldas Magalhães
Universidade Federal do Ceara
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Alexandre Havt
Universidade Federal do Ceara
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Érico Antônio Gomes de Arruda
Hospital Sao Jose de Doencas Infecciosas
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Juliano P. Souza
Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto
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Marjorie Pontelli
Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto
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Italo A. Castro
Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto
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Thais M. Lima
Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto
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Rosa Viana
Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto
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Daniel Macedo de Melo Jorge
Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto
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Priscyla D. Marcato
Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto
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Hugo P. Monteiro
Universidade Federal de Sao Paulo
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Eurico Arruda
Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto
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Aldo Lima
Universidade Federal do Ceara

Corresponding Author:alima@ufc.br

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Abstract

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.