Intranasal Chlorpheniramine Maleate for the treatment of COVID-19: Translational and Clinical Evidence

Abstract

Recently, the nasal cavity has been highlighted as an ideal route of administration for interventions as it is the portal of entry of the severe acute respiratory syndrome coronavirus (SARS-CoV-2). The present study aimed to demonstrate the feasibility and efficacy of intranasally administered Chlorpheniramine Maleate (CPM) spray to treat coronavirus disease 2019 (COVID-19). Methods: The present study used a two-phase, non-clinical to clinical approach. The non-clinical phase evaluated CPM’s antiviral activity against SARS-CoV-2 delta (B.1.617.2) strain via a highly differentiated three-dimensional in vitro model of normal, human-derived tracheal/bronchial epithelial cells. CPM was tested in duplicate inserts of the tissue models of the human airway. Virus yield reduction assays measured antiviral activity on day six after infection. For the clinical phase, COVID-19 symptomatic (polymerase chain reaction positive) patients were recruited and assigned to a 7-day CPM treatment (n=32) or placebo (PLB; n=13). Close safety monitoring of all patients was conducted before and after administering the drug. The primary outcomes monitored were time to symptom resolution (days), progression to hospitalization, emergency room visits, and symptoms of the severity of the disease using a visual analog scale (VAS) on a scale of 1-10 (no symptoms to worst symptoms). Results: The virus yielded a reduction in the assay such that the CPM solution log reduction value was 2.69 and Remdesivir 0.12, demonstrating much high antiviral activity of CPM. Results of the clinical phase demonstrate that VAS scores between the groups were evident after using CPM for two days (day 3). The CPM group VAS were significantly lower (P<0.001) starting from day three compared with day one. In contrast, there were no statistically significant (P>0.05) changes in the PLB during the 7-day treatment window. No subjects in the intervention group were hospitalized, while two in the PLB required hospitalization (15.4%; X2=5.15, P=0.023). Besides some mild discomfort felt by subjects immediately after applying the spray, the participants reported neither adverse reactions nor side effects. Conclusion: If taken together, the results of the present two-phase study point towards the conclusion that CPM is an antiviral agent that can be administered intranasally to treat COVID-19 effectively.

Chlorpheniramine Intranasal Spray to Accelerate COVID-19 Clinical Recovery in an Outpatient Setting: The ACCROS Trials

“…Early intervention to treat COVID-19 has been recognized as a strategy for reducing hospitalization and mortality [7,8]. CPM is an effective intranasal agent to address SARS-CoV-2 infection early in the course of the disease (viremic phase) when symptoms are usually mild [6,7,[9][10][11]. Faster recovery will allow individuals to return to daily life quicker, reducing economic stress, healthcare overutilization, and medical centers over ow during outbreaks.…”

“…The atomizer was designed to generate a swirling effect by opening a spray cone from a tapered nozzle bottle to ensure the most e cient and enhanced drug delivery and aid in patient compliance. Subjects were instructed to use the atomizer following a 12-15º angle to augment the medication deposition in the nasopharynx, the focal point of viral infection, as previously described [11,25,26].…”

“…For instance, antiviral therapies, monoclonal antibody treatments, and steroids have been accepted as standards of care for COVID-19. Evidence suggests that EMT of symptomatic high-risk COVID-19 patients, with both oral and intranasal antihistamines, reduces fatality rate and hospitalizations [9][10][11][12]. A recent study showed that EMT in nursing homes could dramatically reduce hospitalization rates and improve survival [6].…”

“…Chlorphenamine Maleate (CPM) is a rst-generation antihistamine that relieves symptoms associated with allergies, hay fever, common cold, cough, and nasal congestion, probably owing to the antiin ammatory and immunomodulatory properties of the drug [16,17]. Various studies have documented the antiviral properties of CPM against SARS-Cov-2 [11,[18][19][20]. Previously, our group reported the safety and e cacy of intranasally administered CPM to treat COVID-19 [11] and allergic rhinitis [21].…”

“…Various studies have documented the antiviral properties of CPM against SARS-Cov-2 [11,[18][19][20]. Previously, our group reported the safety and e cacy of intranasally administered CPM to treat COVID-19 [11] and allergic rhinitis [21]. Since the nasal cavity is the portal of entry of the disease and many early manifestations are in the upper respiratory tract [22], it is plausible that an intranasal-administered therapy could decrease clinical symptomatology and accelerate clinical recovery.…”