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Covid-19: a puzzle with many missing pieces

BMJ 2020; 368 doi: (Published 19 February 2020) Cite this as: BMJ 2020;368:m627

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Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2)

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Re: Covid-19: a puzzle with many missing pieces: Carbocisteine and COVID-19

Dear Editor

Carbocisteine as a mucolytic agent is currently indicated for reduction of sputum viscosity as per the BNF [1].

There is evidence in the literature that Carbocisteine reduces the frequency of common colds as well as the frequency of exacerbations in COPD reported to be caused by viral and bacterial infection [2]. Carbocisteine has also been shown in invitro studies to be able to modulate airway inflammation and reduce the quantity of viral particles in studies with Rhinoviruses [3] (in the Picornaviridae family of RNA viruses), Human Influenza Viruses [4] (in the Orthomyxoviridae family of RNA viruses) and Respiratory Syncytial Viruses [5,6] (in the Pneumoviridae family of RNA viruses).

From prior personal experience, Carbocisteine has also been shown to be effective in reducing the duration and severity of seasonal influenza in patients.

Given the lack of available proven therapies for SARS-CoV-2 infection (COVID-19) including awaited vaccines which will need to undergo trials, current strategies rely on considering existing drugs, and others are completely new but based on some existing scientific evidence of mechanistic approaches that are effective against either similar viral infections or the serious symptoms that are caused by COVID-19.

It would be useful for retrospective real-world data be collected to assess clinical outcomes and morbidity and mortality rates in patients with COVID-19 who were on Carbocisteine, and who in all likelihood would also have had compromised respiratory tracts such as with COPD.

Carbocisteine has been proven to reduce sputum viscosity, and has also been shown to modulate airway inflammation by reducing the cytokine storm and subsequent respiratory tract tissue damage [7], and we also believe it might possibly also be able to reduce the quantity of COVID-19 viral particles. Since Carbocisteine is readily available, cost-effective and has few serious side-effects in capsule form [8], we suggest that consideration be given to empirically add Carbocisteine to the current treatment regimen in patients infected with COVID-19 or those at high risk of infection since urgent clinical necessity and ethical considerations may not currently allow for the conduct of randomised trials with Carbocisteine in COVID-19 patients.

2. Yasuda H, Yamaya M, Sasaki T, et al. Carbocisteine Reduces Frequency Of Common Colds And Exacerbations In Patients With Chronic Obstructive Pulmonary Disease. Journal of the American Geriatrics Society 2006;54:378–80. doi:10.1111/j.1532-5415.2005.00592_9.x
3. Yasuda H. Carbocisteine inhibits rhinovirus infection in human tracheal epithelial cells. European Respiratory Journal 2006;28:51–8. doi:10.1183/09031936.06.00058505
4. Yamaya M, Nishimura H, Shinya K, et al. Inhibitory effects of carbocisteine on type A seasonal influenza virus infection in human airway epithelial cells. American Journal of Physiology-Lung Cellular and Molecular Physiology 2010;299. doi:10.1152/ajplung.00376.2009
5. Yamaya M, Hatachi Y, Kubo H, et al. L-Carbocisteine Inhibits Respiratory Syncytial Virus Infection In Human Airway Epithelial Cells. B55 Host Defense In Pulmonary Infection And Tuberculosis Published Online First: 2012. doi:10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a3292
6. Asada M, Yoshida M, Hatachi Y, et al. l-carbocisteine inhibits respiratory syncytial virus infection in human tracheal epithelial cells. Respiratory Physiology & Neurobiology 2012;180:112–8. doi:10.1016/j.resp.2011.10.017
7. Khomich O, Kochetkov S, Bartosch B, et al. Redox Biology of Respiratory Viral Infections. Viruses 2018;10:392. doi:10.3390/v10080392

Competing interests: No competing interests

16 March 2020
Imraan F. Jhetam
Section 12(2) Doctor
Ridwaan Jhetam (Pharmaceutical Physician) Maidenhead