Summary of COVID-19 azelastine studies
1. Lehr et al., Azelastine Nasal Spray for Prevention of SARS-CoV-2 Infections
450 patient azelastine prophylaxis RCT: 72% fewer symptomatic cases (p=0.02), 69% fewer cases (p=0.03), and 34% faster viral clearance (p<0.0001).RCT 450 healthy adults showing lower PCR-confirmed and symptomatic SARS-CoV-2 infections with azelastine 0.1% nasal spray (1 puff/nostril 3x/day for 56 days) versus placebo. The placebo formulation (hypromellose) may also have efficacy via barrier and mechanical effects, there is potential unblinding from azelastine’s bitter taste, and per-protocol exclusions were common due to visit schedule/adherence.
Sep 2025, JAMA Internal Medicine, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2838335, https://c19p.org/lehr
2. Klussmann et al., Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients
61 patient azelastine early treatment RCT: 14% improved viral clearance (p=0.22).RCT 90 outpatients showing potential benefit of azelastine nasal spray for reducing viral load. Patients were randomized to receive placebo, 0.02%, or 0.1% azelastine nasal spray for 11 days. The 0.1% azelastine group showed greater viral load reduction compared to placebo (p=0.007) and achieved PCR negativity earlier (48.2% vs 23.1% negative by day 11). Symptoms improved across all groups, with the 0.1% group showing slightly greater improvement (12.74 point reduction vs 11.12 for placebo) and significantly better improvement in shortness of breath on days 3-4. No significant differences were found in quality of life measures or WHO clinical progression scores.
Apr 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-32546-z, https://c19p.org/klussmannazl
3. Reznikov et al., Identification of antiviral antihistamines for COVID-19 repurposing
azelastine prophylaxis study: 45% fewer cases (p=0.03).Retrospective 219,000 patients showing lower risk of COVID-19 with antihistamine H1RA use. In vitro study showing these drugs exhibit direct antiviral activity against SARS-CoV-2. Molecular docking suggests hydroxyzine and azelastine may exert antiviral effects by binding ACE2 and the sigma-1 receptor.
Jan 2021, Biochemical and Biophysical Research Communications, https://www.sciencedirect.com/science/article/pii/S0006291X20321409, https://c19p.org/reznikovazl
251 patient azelastine late treatment RCT: 13% improved recovery (p=0.42) and 6% improved viral clearance (p<0.0001).
RCT 294 low-risk subjects with mild COVID-19 showing significantly greater reduction in viral load with azelastine 0.1% nasal spray vs. placebo. There was no COVID-19 related hospitalization in either group. The reduction in viral load was significantly higher in the azelastine group at day 3, 6 and 11. Authors report that treatment was associated with significant improvement in fever, weakness, and hypoxia compared to placebo, however detailed results are not provided for these and other symptoms. Treatment delay from symptom onset is not specified, however the baseline viral load, lack of progression, and recovery profile are consistent with relatively late treatment among low-risk patients. Time to recovery results are not clear, with an inconsistent HR and 95% CI reported 0.32 [0.83-2.32].
Oct 2024, Viruses, https://www.mdpi.com/1999-4915/16/12/1914, https://c19p.org/meiserazl