Physician researchers from Beloit Memorial Hospital and a well-known drug development consultant out of the Washington DC Beltway reported on a case series from the Wisconsin-based hospital involving 25 COVID-19 hospitalized patients treated with celecoxib and HD famotidine as adjuvant therapy. The research team reports that all 25 patients in the series survived hospitalized COVID-19 without the need for mechanical ventilation or renal replacement therapy (RRT). The patients, report the authors, were discharged on room air within a median of three days with a range of 1-16 days. The researchers observed statistically significant improvements from admission to discharge.
As it turns out, according to the authors, 80% of all those individuals that become infected with SARS-CoV-2 in fact remain asymptomatic and don’t appear to progress to a more severe state (COVID-19). TrialSite cannot verify this claim but obviously a majority of those infected with SAR-CoV-2 report either no symptoms or mild and moderate ones. TrialSite provides a breakdown of this research.
What Makes Someone Infected with SARS-CoV-2 Progress to a Severe COVID-19 State?
The authors suggest this is possibly explained by “differences in host inflammatory responses to infection.”
What are Attributes & Elements Associated with Severe COVID-19?
The Beloit Memorial Hospital physician author-led team suggest COX-2 expression is transcriptionally upregulated by SARS nucleocapsid N protein, and that those afflicted with COVID-19 severe progression have markedly high levels of prostaglandin E2 (PGE2). As it turns out, PGE2 can regulate inflammatory responses such as mast cell activation. Hence, its possible that mast cell deregulation is associated with severe progression of SARS-CoV-2 to a possibly deadly form of COVID-19.
Why is a COX-2 protein antagonist such as Celecoxib Important in this Approach?
The authors refer to a randomized controlled trial that involves hospitalized COVID-19 cases; these patients treated with the COX-2 protein antagonist celecoxib experienced reduction in systemic PGE2 levels, along with a turnaround in clinical deterioration along with accelerated pulmonary CT-chest improvement.
What is the Wisconsin-based team Hypothesis?
That adjuvant therapy with a combination of celecoxib and high dose (HD) famotidine may improve COVID-19 outcomes.
Summary of Results
The authors report that the combined treatment with oral celecoxib and HD famotidine in an adjuvant setting was associated with 100% survival and better radiographic results; results showcase statistically significant improvement in clinical, biomarker and renal function measurements. All 9 patients that reported high LDH survived and were discharged on room air.
The authors declared, “Conservation of SARS and SARS-CoV-2 nucleocapsid N protein N2 sequences support that celecoxib treatment may mitigate the effects of direct viral transactivation of COX-2 expression in infected cells.” They go on that by the H2 receptor antagonism, high dose famotidine can potentially reduce the cellular impact of local histamine. Moreover, they posit that this regimen either mitigated or even prevented acute kidney injury in the patients—the argue that HD famotidine is a contributory factor to this success.
How was this Study Funded?
The study was funded by the Department of Defense (DoD), The 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. The actual contract for the study funding leveraged an Air Force Contract (No. FA8702-15-D-0001). The opinion from this report is of the author and not of the U.S. Air Force.
About Beloit Memorial Hospital
Beloit Memorial Hospital is part of the Beloit Health System and opened its doors in 1970. The health system and hospital provide a full range of compassionate healthcare for Stateline residents, involving important areas of medicine, including the Hendricks Family Heart Hospital. By 2010, the Beloit Health System reflected a partnership between Beloit Hospital and Beloit Clinic to form a seamlessly integrated healthcare offering. The goal: local residents access comprehensive and distinctive services reflecting the “big city hospital” to the clinic next door.
Kevin Tomera, MD, Beloit Memorial Hospital
Joseph Kittah, MD, Beloit Memorial Hospital
Robert Malone, MD, Robert W Malone MD, LLC
Call to Action: The authors call for randomized, placebo-controlled trials to continue this pursuit of investigating the hypothesis that celecoxib with HD famotidine as an adjuvant therapy to standard of care could potentially reverse and even prevent COVID-19-driven clinical deterioration in hospitalized patients.