OTC Antihistamine Drug Reduces COVID-19 Cases by 67%
A phase 2 double blind RCT conducted at a German university hospital between March 2023 and July 2024 among healthy adult participants (n = 450) found that Azelastine 0.1% nasal spray, administered 3x a day, reduced rapid antigen test and PCR confirmed SARS-cornavirus infections nearly 3x compared to the placebo group from a 6.7% infection rate to a 2.2% infection rate over the course of 56 days. That is a 69% relative risk reduction in COVID-19 cases compared to placebo. Azelastine nasal spray also delayed average time to infection from 19.5 days (placebo) to 31.2 days and infected participants given azelastine had fewer COVID-19 symptoms (21) compared to placebo participants (49). Azelastine nasal spray reduced the rapid antigen test rhinovirus (common cold) infection rate 3.5x compared to placebo from 6.3% to 1.8% with a similar rate of adverse events reported across both groups. This is sold under the brand names Astelin, Astepro and Dymista.
Another nasally administered antihistamine has also shown promising results against COVID-19.
A review of clinical trial results and in vitro studies found that treating COVID-19 patients with chlorpheniramine maleate (i.e. Chlorpheniramine) nasal spray for 7 days after diagnosis led to faster symptom resolution and lower disease severity scores compared to placebo over the same time frame in the ACCROS I and III phase double blind RCT (n = 45). None of the patients treated with intranasal chlorpheniramine maleate were hospitalized. Long COVID patients treated with intranasal chlorpheniramine maleate in the Phase III clinical trial (n = 180) experienced reduced symptom incidence compared to placebo group in the post intervention analysis. None of the intervention group patients experienced fatigue or mental confusion, compared to 14.2% and 18.3% in the placebo group. About 1% of the intervention group report difficulty performing daily activities compared to 32% of the placebo group and none of the participants in the intervention group reported seeking medical attention for post acute sequela symptoms compared to 40% of the placebo group. This review notes that Chlorpheniramine can inhibit the SARS-Coronavirus by interfering with viral absorption on the ACE2 (angiotensin converting enzyme-2) receptors, reduces viral RNA synthesis by forming hydrogen bonds with RNA-dependent RNA polymerase and the spike protein itself. More importantly, delivering this drug in a nasal spray appears to activate mucosal immunity through the bitter taste receptors in the upper respiratory tract and reduces pro-inflammatory cytokine production through H1 receptor antagonism which explains reduced symptom severity in the aforementioned treatment groups.