Histamine receptors and COVID-19

Inflamm Res. 2021 Jan;70(1):67-75. doi: 10.1007/s00011-020-01422-1. Epub 2020 Nov 18.


Objective: Reports that the over-the-counter histamine H2 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, H1 and H2 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 H2 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 H2 receptor-mediated immunomodulatory actions on mast cell histamine-cytokine cross-talk, rather than a direct action on SARS-CoV-2.

Keywords: COVID-19; Histamine; Histamine receptor; Immunomodulation; Mast cells; SARS-CoV-2.

Publication types

  • Systematic Review

MeSH terms

  • COVID-19 / metabolism
  • COVID-19 Drug Treatment*
  • Histamine Antagonists / therapeutic use*
  • Histamine H2 Antagonists / therapeutic use
  • Humans
  • Receptors, Histamine / drug effects*
  • Receptors, Histamine / metabolism
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / metabolism


  • Histamine Antagonists
  • Histamine H2 Antagonists
  • Receptors, Histamine