Celecoxib with HD famotidine may reverse and prevent clinical deterioration in adult hospitalized COVID-19 patients.
Hypothesis that celecoxib with HD famotidine as adjuvant therapy may reverse and prevent clinical deterioration in adult hospitalized COVID-19 patients.
BACKGROUND: Up to 80% of SARS-CoV-2 positive patients are asymptomatic and do not appear to progress to COVID-19. SARS-CoV-2 infection is not sufficient for development of COVID-19 disease; this may reflect differences in host inflammatory responses to infection.
A randomized trial of hospitalized COVID-19 cases has demonstrated that COX-2 protein antagonist celecoxib dampened systemic Prostaglandin E2 levels, prevented clinical deterioration, and was associated with rapid pulmonary CT chest improvement. High doses of famotidine, a histamine H2 receptor antagonist/inverse agonist reduces severity of COVID-19 symptoms.
We hypothesize that adjuvant therapy with a combination of celecoxib and high dose (HD) famotidine may improve COVID-19 outcomes.
At a single institution, consecutive case series of 30 COVID-19 hospitalized patients treated with celecoxib and HD famotidine as adjuvant therapy.
RESULTS: All 30 patients in the series survived hospitalized COVID-19 without mechanical ventilation or renal replacement therapy (RRT) and were discharged on room air within a median of 3 days (range 1-16 days). Statistically significant improvements from admission to discharge were observed for all aggregated outcome measures.
In this series, combined treatment with oral celecoxib and HD famotidine in an adjuvant setting was associated with 100% survival and improved radiographic outcomes, as well as statistically significant improvements in clinical, biomarker, and renal function measurements. The 9 patients with extremely high LDH (>365, Wuhan model prediction of 98% mortality) survived and were discharged on room air.
These results support that celecoxib treatment may mitigate the effects of direct viral transactivation of COX-2 expression in infected cells. HD famotidine acts to reduce cellular effects of local histamine via H2 receptor antagonism. Acute kidney injury was either prevented or mitigated by treatment; HD famotidine contributes to this effect.
In contrast to these findings, previously published COVID19 clinical intervention studies have not shown consistent laboratory or radiographic improvement.