Dual-histamine receptor blockade with cetirizine - famotidine reduces pulmonary symptoms in COVID-19 patients

Reed B Hogan Ii, Reed B Hogan Iii, Tim Cannon, Maria Rappai, John Studdard, Doug Paul, Thomas P Dooley, Reed B Hogan Ii, Reed B Hogan Iii, Tim Cannon, Maria Rappai, John Studdard, Doug Paul, Thomas P Dooley

Abstract

Background: The COVID-19 pandemic due to SARS-CoV-2 infection can produce Acute Respiratory Distress Syndrome as a result of a pulmonary cytokine storm. Antihistamines are safe and effective treatments for reducing inflammation and cytokine release. Combinations of Histamine-1 and Histamine-2 receptor antagonists have been effective in urticaria, and might reduce the histamine-mediated pulmonary cytokine storm in COVID-19. Can a combination of Histamine-1 and Histamine-2 receptor blockers improve COVID-19 inpatient outcomes?

Methods: A physician-sponsored cohort study of cetirizine and famotidine was performed in hospitalized patients with severe to critical pulmonary symptoms. Pulmonologists led the inpatient care in a single medical center of 110 high-acuity patients that were treated with cetirizine 10 mg b.i.d. and famotidine 20 mg b.i.d. plus standard-of-care.

Results: Of all patients, including those with Do Not Resuscitate directives, receiving the dual-histamine receptor blockade for at least 48 h, the combination drug treatment resulted in a 16.4% rate of intubation, a 7.3% rate of intubation after a minimum of 48 h of treatment, a 15.5% rate of inpatient mortality, and 11.0 days duration of hospitalization. The drug combination exhibited beneficial reductions in inpatient mortality and symptom progression when compared to published reports of COVID-19 inpatients. Concomitant medications were assessed and hydroxychloroquine was correlated with worse outcomes.

Conclusions: This physician-sponsored cohort study of cetirizine and famotidine provides proof-of-concept of a safe and effective method to reduce the progression in symptom severity, presumably by minimizing the histamine-mediated cytokine storm. Further clinical studies in COVID-19 are warranted of the repurposed off-label combination of two historically-safe histamine receptor blockers.

Keywords: ARDS; Antihistamine; COVID; Cytokine storm; Histamine; Lung.

Conflict of interest statement

Dr. Hogan II discloses a US patent application on dual-histamine receptor blockade in the treatment of COVID-19, issued patents on dual-histamine receptor blockade in the treatment of diarrhea, and ownership in a biomedical business related to the latter; Dr. Cannon none; Dr. Rappai none; Dr. Studdard reports personal fees from American College of Chest Physicians, unrelated to the submitted work; Dr. Hogan III none; Dr. Paul discloses ownership in unrelated biomedical-related businesses and consulting with numerous pharmaceutical companies; and Dr. Dooley discloses ownership in unrelated biomedical-related businesses.

Copyright © 2020 Elsevier Ltd. All rights reserved.

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