Histamine receptors and COVID-19

• Published in: Inflammation research Vol. 70; no. 1; pp. 67 - 75
• Main Authors: Ennis, Madeleine, Tiligada, Katerina
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.01.2021; Springer Nature B.V
• Subjects: Allergology; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Cimetidine; Clinical trials; Coronaviridae; Coronaviruses; COVID-19; COVID-19 - metabolism; COVID-19 Drug Treatment; Crosstalk; Cytokines; Dermatology; Famotidine; Histamine; Histamine Antagonists - therapeutic use; Histamine H2 Antagonists - therapeutic use; Histamine H2 receptors; Histamine receptors; Humans; Immunology; Immunomodulation; Inflammation; Neurology; Pharmacology/Toxicology; Receptors; Receptors, Histamine - drug effects; Receptors, Histamine - metabolism; Review; Rheumatology; SARS-CoV-2 - drug effects; SARS-CoV-2 - metabolism; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Viral diseases; COVID-19; Histamine; SARS-CoV-2; Mast cells; Histamine receptor; Immunomodulation
• ISSN: 1023-3830; 1420-908X; 1420-908X
• DOI: 10.1007/s00011-020-01422-1

Objective Reports that the over-the-counter histamine H 2 receptor antagonist famotidine could help treat the novel coronavirus disease (COVID-19) appeared from April 2020. We, therefore, examined reports on interactions between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and histamine receptor antagonists. Methods A systematic literature search was performed by 19 September 2020, and updated on 28 October 2020, in PubMed, Scopus, Cochrane Library and Google Scholar using (COVID-19 OR coronavirus OR SARS-CoV-2) AND (histamine antagonist OR famotidine OR cimetidine). ClinicalTrials.gov was searched for COVID-19 and (famotidine or histamine). Results Famotidine may be a useful addition in COVID-19 treatment, but the results from prospective randomized trials are as yet awaited. Bioinformatics/drug repurposing studies indicated that, among several medicines, H 1 and H 2 receptor antagonists may interact with key viral enzymes. However, in vitro studies have to date failed to show a direct inhibition of famotidine on SARS-CoV-2 replication. Conclusions Clinical research into the potential benefits of H 2 receptor antagonists in managing COVID-19 inflammation began from a simple observation and now is being tested in multi-centre clinical trials. The positive effects of famotidine may be due to H 2 receptor-mediated immunomodulatory actions on mast cell histamine–cytokine cross-talk, rather than a direct action on SARS-CoV-2.