To the editor,
The World Health Organization has announced COVID-19 as a pandemic in March 2020. COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. It is presented by fever, sore throat and complicated by pneumonia and sever acute respiratory distress. It was showed that after the SARS-CoV-2 infection, CD4 + T lymphocytes are rapidly activated to become pathogenic T helper (Th) 1 cells and generate GM-CSF, interleukin “IL”-1 beta, IL-6, IL-8 and other cytokines. These cytokines environment stimulates inflammatory monocytes and accelerates the inflammation. These aberrant pathogenic Th1 cells and inflammatory monocytes may enter the pulmonary circulation in huge numbers and play a role in damaging the lung with functional disability and quick mortality [2].
Thus, we suggest that dapsone and doxycycline may be effective in blocking inflammatory storms and, therefore, be a promising treatment of severe COVID-19 patients. Dapsone, belongs to a class of drugs known as sulfones, suppresses production of specific cytokine signatures as IL1α, IL8, IL1β, IL6, and IL8 and tumor necrosis factor-α [3]. Doxycycline, a tetracycline antibiotic, is used for its antibiotic, anti-inflammatory properties and good safety profile. Doxycycline was demonstrated to have a bioavailability of over 80% [4] and impaired the neutrophil migration to the airspaces of the lung in mice exposed to intratracheal lipopolysaccharide [5]. Also, doxycycline showed efficacy in COPD by inhibiting the neutrophilic inflammation and proteolytic activity that can be present in late COVID-19 [6]. Given that cytokine storm and lung fibrosis sequalae are the devesting outcomes in COVID-19, we suggest that emerging clinical trials should assess the efficacy of dapsone, and/or doxycycline in improving pulmonary affection and the mortality outcome in COVID-19.
Funding sources
The article has no funding source.
Prior presentation
No data from this manuscript were presented in a scientific meeting before.
Conflict of interest
No conflict of interest.
References
- 1.Liu J., Liao X., Qian S., Yuan J., Wang F., Liu Y. Community transmission of severe acute respiratory syndrome coronavirus 2, Shenzhen, China, 2020. Emerg Infect Dis J. 2020;26(6) doi: 10.3201/eid2606.200239. Available from: https://wwwnc.cdc.gov/eid/article/26/6/20-0239_article. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Zhou Y, Fu B, Zheng X, Wang D, Sun R, Tian Z, et al. PERSPECTIVE Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients. [DOI] [PMC free article] [PubMed]
- 3.Debol S.M., Herron M.J., Nelson R.D. Anti-inflammatory action of dapsone: inhibition of neutrophil adherence is associated with inhibition of chemoattractant-induced signal transduction. J Leukoc Biol. 1997;62(6):827–836. doi: 10.1002/jlb.62.6.827. [DOI] [PubMed] [Google Scholar]
- 4.Henehan M., Montuno M., De Benedetto A. Doxycycline as an anti-inflammatory agent: updates in dermatology. J Eur Acad Dermatol Venereol. 2017;31(11):1800–1808. doi: 10.1111/jdv.14345. [DOI] [PubMed] [Google Scholar]
- 5.Moon A., Gil S., Gill S.E., Chen P., Matute-Bello G. Doxycycline impairs neutrophil migration to the airspaces of the lung in mice exposed to intratracheal lipopolysaccharide. J Inflamm (Lond) 2012;9(1):31. doi: 10.1186/1476-9255-9-31. Available from: https://pubmed.ncbi.nlm.nih.gov/22943365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Herath S.C., Normansell R., Maisey S., Poole P. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD) Cochrane Database Syst Rev. 2018;(10) doi: 10.1002/14651858.CD009764.pub3. [DOI] [PMC free article] [PubMed] [Google Scholar]