Famotidine with Celecoxib Adjuvant Therapy on Hospitalized COVID-19 Patients: A Case Series
23 Pages Posted: 24 Jul 2020
Date Written: July 8, 2020
Background: Up to 80% of SARS-CoV-2 positive patients are asymptomatic and do not appear to progress to COVID-19. Therefore, SARS-CoV-2 infection is necessary but not sufficient for development of COVID-19 disease; individual inflammatory response differences determine each patient’s outcome. It has been hypothesized that SARS-CoV-2 infection-associated mast cell degranulation plays a role in development of COVID-19, and that dexamethasone-responsive hyperinflammatory processes are involved in the later phase of the disease. Famotidine, a histamine H2 receptor antagonist/inverse agonist (commonly prescribed to treat mast cell activation syndrome) reduced COVID-19 mortality in one hospital-based retrospective study. Prostaglandin E2 (PGE2) modulates a wide variety of innate and adaptive immune responses including mast cell activation. In a prospective study of hospitalized COVID-19 cases, administration of the COX-2 antagonist celecoxib dampened PGE2 levels, prevented clinical deterioration, and was associated with rapid CT-chest improvement. We hypothesize that adjuvant therapy with a combination of celecoxib with famotidine may improve outcomes in hospitalized COVID-19 patients.
Methods: We report a single institution, consecutive case series of 14 COVID-19 hospitalized patients treated with high dose famotidine together with celecoxib as adjuvant therapy. All patients were administered oral famotidine 80mg four times a day (QID) and oral celecoxib 200mg twice daily (BID) following a 400mg loading dose. Summarized outcome measurements include time to discharge, changes in supplemental oxygen requirements, CT-chest findings, and laboratory changes in peripheral blood lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, lymphocyte levels, and D-dimer.
Results: All patients in the series survived hospitalized COVID-19 and were discharged without oxygen with a median of 5 days (range 1-14 days). Improvement was noted in supplemental oxygen requirements, ground-glass CT findings, LDH, ferritin, CRP, D-dimer, and lymphocyte levels.
Discussion: The data support performing blinded and randomized placebo-controlled trials to further examine the hypothesis that high dose famotidine with celecoxib may prevent clinical deterioration in adult hospitalized COVID-19 patients. In this series, concomitant improvement in CRP and/or ferritin preceded partial resolution of typical thoracic CT findings. The 5 patients with extremely high LDH (>365, Wuhan model prediction of 98% mortality) survived and were discharged. In previously published COVID-19 clinical intervention studies, therapeutic agents that report positive results have not shown consistent laboratory or radiological improvement. In this series, the treatment combination of oral famotidine and celecoxib was associated with 100% survival as well as improvements in clinical, biomarker and radiographic outcome measures.
Note: Funding: Support was provided by the Department of Defense (DoD),
Defense Threat Reduction Agency (DTRA), and the Joint Science and
Technology Office (JSTO) of the Chemical and Biological Defense
Program (CBDP) under the Discovery of Medical countermeasures Against
Novel Entities (DOMANE) initiative. This support has been provided
under Air Force Contract No. FA8702-15-D-0001. Any opinions, findings,
conclusions or recommendations expressed in this material are those of
the author(s) and do not necessarily reflect the views of the U.S. Air
Conflict of interest: none
Ethical statement: This study was approved by the institutional review board of Beloit Memorial Hospital.
Keywords: coronavirus 2019; SARS-CoV-2; famotidine; histamine-2 receptor antagonists, celecoxib, Cox-2 receptor antagonist, COVID-19, immunomodulators
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