Histamine 4 receptor is a Potential Target for COVID-19 Treatment

COVID-19 pandemic started in December 2019, and is a worldwide health disaster today, pulmonary fibrosis and cytokine storm are two major complications in COVID-19 patients which can decrease life quality after recovery, and cause death. Histamine effects on the immune system through 4 histamine receptors. The function pattern of histamine 4 receptor has many similarities to COVID-19 pathogenesis pattern.H4R antagonists prevent lung fibrosis in bleomycine-induced lung fibrosis murine models, it can reduce TNF-α and IL-6 secretion in several immunemediated diseases such as asthma, colitis and dermatitis.H4R stimulation also decreases IL-12 which is not detected to be high in COVID-19 patients.TH- 17 acts as an important inflammatory effector in COVID-19 pathogenesis, through IL-17 secretion which results in TNF-α and IL-6 secretion, and also IL-17 promotes tissue remodeling and fibrosis via matrix metalloproteinase induction.TH-17 expresses H4R which can be stimulated by H4R antagonist and results in IL-17 production, this process can explain the relation between H4R and COVID-19 pathogenesis. The other content supporting this theory is the compatibility of gastrointestinal, neurologic, and dermatologic signs and symptoms of COVID-19 with the H4R function pattern.in addition to the previous evidences, clusters of Kawasaki-like disease are reported recently, these patients were highly infected with SARS- COV2, and this can be explained by the important role of IL-17 in Kawasaki disease and the stimulatory effect of H4R on TH-17. According to the above content the author hypothesis that H4R stimulation by SARS-COV2 results in IL-17 expression which is associated with cytokine release, and H4R is a potential target point for COVID-19 treatment. This hypothesis can be evaluated by a clinical trial study of the therapeutic and preventive effect of H4R antagonists in COVID-19 patient’s complication, severity progression, and mortality