Famotidine with Celecoxib Adjuvant Therapy on Hospitalized COVID-19 Patients: A Case Series

Tomera, Kevin M.; Malone, Robert E.; Kittah, Joseph

doi:10.2139/ssrn.3646583

Cited by 10 publications

(8 citation statements)

References 71 publications

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“…It is noteworthy that more complications, severity and fatality rate were observed in the COVID-19 group of elders and with comorbidities; however, this phenomenon did not appear in this particular Celebrex adjunctive treatment study. This phenomenon was also observed in another Celebrex adjunctive therapy study for COVID-19 reported from Beloit Memorial Hospital, United States (Tomera et al, 2020). There were 25 hospitalized patients enrolled this study, in which 36% of them were with life-threatened high lactate dehydrogenase, 80% with obesity, 44% cardiovascular disease, 40% diabetes, and 32% renal disease and other medical conditions.…”

Section: Discussionsupporting

confidence: 70%

Celebrex Adjuvant Therapy on Coronavirus Disease 2019: An Experimental Study

et al. 2020

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Background: The pandemic of coronavirus disease 2019 (COVID-19) resulted in grave morbidity and mortality worldwide. There is currently no effective drug to cure COVID-19. Based on analyses of available data, we deduced that excessive prostaglandin E 2 (PGE 2) produced by cyclooxygenase-2 was a key pathological event of COVID-19. Methods: A prospective clinical study was conducted in one hospital for COVID-19 treatment with Celebrex to suppress the excessive PGE 2 production. A total of 44 COVID-19 cases were enrolled, 37 cases in the experimental group received Celebrex as adjuvant (full dose: 0.2 g, bid; half dose: 0.2 g, qd) for 7-14 days, and the dosage and duration was adjusted for individuals, while seven cases in the control group received the standard therapy. The clinical outcomes were evaluated by measuring the urine PGE 2 levels, lab tests, CT scans, vital signs, and other clinical data. The urine PGE 2 levels were measured by mass spectrometry. The study was registered and can be accessed at http://www. chictr.org.cn/showproj.aspx?proj 50474. Results: The concentrations of PGE 2 in urine samples of COVID-19 patients were significantly higher than those of PGE 2 in urine samples of healthy individuals (mean value: 170 ng/ml vs 18.8 ng/ml, p < 0.01) and positively correlated with the progression of COVID-19. Among those 37 experimental cases, there were 10 cases with age over 60 years (27%, 10/37) and 13 cases (35%, 13/37) with preexisting conditions including cancer, atherosclerosis, and diabetes. Twenty-five cases had full dose, 11 cases with half dose of Celebrex, and one case with ibuprofen. The remission rates in midterm were 100%, 82%, and 57% of the full dose, half dose, and control group, respectively, and the discharged rate was 100% at the endpoint with Celebrex treatment. Celebrex significantly reduced the PGE 2 levels and promoted recovery of ordinary and severe COVID-19. Furthermore, more complications, severity, and death rate were widely observed and reported in the COVID-19 group of elders and with comorbidities; however, this phenomenon did not appear in this particular Celebrex adjunctive treatment study.

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Section: Discussionsupporting

confidence: 70%

Celebrex Adjuvant Therapy on Coronavirus Disease 2019: An Experimental Study

et al. 2020

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“…administered p.o. within 24 h of admission) led to 100% survival and improvements in a number of clinical and biomarker measurements [82]. The authors suggested that a randomized trial of the combination of high-dose famotidine with celecoxib as adjuvant therapy to SOC should be performed [82].…”

Section: Further Publications Since the Time Of Submissionmentioning

confidence: 99%

Histamine receptors and COVID-19

Ennis

Tiligada

2020

Inflamm. Res.

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Objective Reports that the over-the-counter histamine H 2 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, H 1 and H 2 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 H 2 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 H 2 receptor-mediated immunomodulatory actions on mast cell histamine–cytokine cross-talk, rather than a direct action on SARS-CoV-2.

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“…One proposed step in COVID-19 disease progression involves the nucleocapsid protein binding to the prostaglandin-endoperoxide synthase 2 (PTGS2)/cyclooxygenase-2 (COX-2) promoter and upregulating expression resulting in elevated levels of prostaglandin E 2 (PGE 2 ) and other inflammatory molecules (3)(4)(5). Elevated PGE 2 may be driving hyper-activation of mast cells associated with excess release of histamine and additional inflammatory molecules (5). COVID-19 is predicted to be a mast cell disease (6).…”

Section: Introductionmentioning

confidence: 99%

Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies

Ricke

2021

Front. Immunol.

118

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COVID-19 (SARS-CoV-2) disease severity and stages varies from asymptomatic, mild flu-like symptoms, moderate, severe, critical, and chronic disease. COVID-19 disease progression include lymphopenia, elevated proinflammatory cytokines and chemokines, accumulation of macrophages and neutrophils in lungs, immune dysregulation, cytokine storms, acute respiratory distress syndrome (ARDS), etc. Development of vaccines to severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome coronavirus (MERS-CoV), and other coronavirus has been difficult to create due to vaccine induced enhanced disease responses in animal models. Multiple betacoronaviruses including SARS-CoV-2 and SARS-CoV-1 expand cellular tropism by infecting some phagocytic cells (immature macrophages and dendritic cells) via antibody bound Fc receptor uptake of virus. Antibody-dependent enhancement (ADE) may be involved in the clinical observation of increased severity of symptoms associated with early high levels of SARS-CoV-2 antibodies in patients. Infants with multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 may also have ADE caused by maternally acquired SARS-CoV-2 antibodies bound to mast cells. ADE risks associated with SARS-CoV-2 has implications for COVID-19 and MIS-C treatments, B-cell vaccines, SARS-CoV-2 antibody therapy, and convalescent plasma therapy for patients. SARS-CoV-2 antibodies bound to mast cells may be involved in MIS-C and multisystem inflammatory syndrome in adults (MIS-A) following initial COVID-19 infection. SARS-CoV-2 antibodies bound to Fc receptors on macrophages and mast cells may represent two different mechanisms for ADE in patients. These two different ADE risks have possible implications for SARS-CoV-2 B-cell vaccines for subsets of populations based on age, cross-reactive antibodies, variabilities in antibody levels over time, and pregnancy. These models place increased emphasis on the importance of developing safe SARS-CoV-2 T cell vaccines that are not dependent upon antibodies.

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Famotidine with Celecoxib Adjuvant Therapy on Hospitalized COVID-19 Patients: A Case Series

Cited by 10 publications

References 71 publications

Celebrex Adjuvant Therapy on Coronavirus Disease 2019: An Experimental Study

Celebrex Adjuvant Therapy on Coronavirus Disease 2019: An Experimental Study

Histamine receptors and COVID-19

Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies

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