key: cord-0919200-chvuw8bq authors: Medina-De la Garza, Carlos Eduardo; Salvador Flores-Torres, Armando; García-Hernández, Marisela; de los Ángeles Castro-Corona, María title: Diethylcarbamazine as potential treatment of COVID-19 lung fibrosis date: 2022-01-25 journal: Med Hypotheses DOI: 10.1016/j.mehy.2022.110774 sha: 58f757c1153f331fd1de821b2d6a4cafe27d14fd doc_id: 919200 cord_uid: chvuw8bq Diethylcarbamazine, the antiparasitic drug, also possesses anti-inflammatory and immunomodulatory activities. The anti-fibrotic activity of diethylcarbamazine makes it a potential candidate to treat coronavirus disease 2019 (COVID-19)-related pulmonary fibrosis. Experimental and clinical studies should assess this possible effect. Abstract: Diethylcarbamazine, the antiparasitic drug, also possesses anti-inflammatory and immunomodulatory activities. The anti-fibrotic activity of diethylcarbamazine makes it a potential candidate to treat coronavirus disease 2019 (COVID-19)-related pulmonary fibrosis. Experimental and clinical studies should assess this possible effect. Keywords: diethylcarbamazine, drug repurposing, pulmonary fibrosis, COVID-19-related pulmonary fibrosis , post-COVID-19 To the Editor We, with great interest, read the proposal by Abeygunasekera and Jayasinghe [1] describing the use of diethylcarbamazine (DEC; N, N-Diethyl-4-methyl-1-piperazincarboxamid, C10H21N3O) as an adjuvant for treating coronavirus disease 2019 (COVID-19)-related pulmonary fibrosis. DEC is a safe and non-expensive drug with side effects mainly related to parasitic infection. The recently reported activities of DEC include immunomodulatory [2, 3] , anti-inflammatory [4] , and antifibrotic activities [5] [6] ; hence, the potential of DEC is beyond its original use as an antifilarial agent. DEC protects against acute lung injury [7] and shows an antifibrotic effect in experimental liver fibrosis [5] [6] , a condition that shares common pathways with lung fibrosis [8] . We believe that the antifibrotic activity suggests a significant potential of DEC for treating COVID-19-related lung damage. DEC reduces the production of fibrotic factors and collagen [9] [10] [11] and the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) [11] , thus inhibiting the production of the profibrotic cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. IL-1β and IL-6 influence the inflammatory and fibrotic response by inducing the activation and accumulation of neutrophils and lymphocytes to the injury site and promoting the activation of fibroblasts and collagen synthesis [12] . DEC reduces the expression of transforming growth factor (TGF)-β [5] [6] , a potent profibrotic cytokine, that induces the production and deposition of extracellular matrix (ECM) [13] . Additionally, DEC decreases tissue inhibitor of metalloproteinase (TIMP)-1 expression, further increasing metalloproteinase (MMP)-2 expression, ECM accumulation, and fibrosis [5] [6] . It would be clinically relevant to determine whether DEC may reduce the tissue damage leading to fibrosis or act upon already established lesions in patients in the acute stage or those recovering from post-COVID-19 fibrosis. Evidence suggest that the effect of DEC is dose-dependent, hence determining the effective therapeutic dose is critical [2, 4] . We believe that the mechanisms described above suggest DEC as a potential alternative for treating COVID-19-related pulmonary fibrosis and even lung fibrosis of another origin. Extensive experimental and clinical testing, including in silico screening for additional mechanisms, may provide the degree of evidence necessary to repurpose [1, 14] this known, but remarkable and resourceful drug. Not required. The authors declare no known competing financial interests or personal relationships that could have influenced this letter. Is the anti-filarial drug diethylcarbamazine useful to treat COVID-19? 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