biostudies-literatureUnknownYang HNIGMS NIH HHS<b>Background.</b> Severe COVID-19 is characterized by pro-inflammatory cytokine release syndrome (cytokine storm) which causes high morbidity and mortality. Recent observational and clinical studies suggest famotidine, a histamine 2 receptor (H2R) antagonist widely used to treat gastroesophageal reflux disease , attenuates the clinical course of COVID-19. Because evidence is lacking for a direct antiviral activity of famotidine, a proposed mechanism of action is blocking the effects of histamine released by mast cells. Here we hypothesized that famotidine activates the inflammatory reflex, a brain-integrated vagus nerve mechanism which inhibits inflammation via alpha 7 nicotinic acetylcholine receptor ( α7nAChR ) signal transduction, to prevent cytokine storm. <b>Methods.</b> The potentiaResearch squarers.3.rs-1493296https://www.ebi.ac.uk/biostudies/studies/S-EPMC9016653biostudies-literatureFamotidine activates the vagus nerve inflammatory reflex to attenuate cytokine storm.PMC9016653R35 GM118182R01 GM132672Yang HTynan AAndersson UTracey KJChang EPavlov VATsaava TChavan SSBrines MGeorge SJThompson DSilverman HAfalseFamotidine activates the vagus nerve inflammatory reflex to attenuate cytokine storm.<b>Background.</b> Severe COVID-19 is characterized by pro-inflammatory cytokine release syndrome (cytokine storm) which causes high morbidity and mortality. Recent observational and clinical studies suggest famotidine, a histamine 2 receptor (H2R) antagonist widely used to treat gastroesophageal reflux disease , attenuates the clinical course of COVID-19. Because evidence is lacking for a direct antiviral activity of famotidine, a proposed mechanism of action is blocking the effects of histamine released by mast cells. Here we hypothesized that famotidine activates the inflammatory reflex, a brain-integrated vagus nerve mechanism which inhibits inflammation via alpha 7 nicotinic acetylcholine receptor ( α7nAChR ) signal transduction, to prevent cytokine storm. <b>Methods.</b> The potentia2022-01-01T00:00:00Z2022 Apr2025-04-04T19:09:57.427Z2025-02-19T01:24:02.616ZS-EPMC90166533544117610.21203/rs.3.rs-1493296/v1