Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients

Abstract

With the changing epidemiology of COVID-19 and its impact on our daily lives, there is still an unmet need of COVID-19 therapies treating early infections to prevent progression. The current study was a randomized, parallel, double-blind, placebo-controlled trial. Ninety SARS-CoV-2 positive patients were randomized into 3 groups receiving placebo, 0.02% or 0.1% azelastine nasal spray for 11 days, during which viral loads were assessed by quantitative PCR. Investigators assessed patients' status throughout the trial including safety follow-ups (days 16 and 60). Symptoms were documented in patient diaries. Initial viral loads were log₁₀ 6.85 ± 1.31 (mean ± SD) copies/mL (ORF 1a/b gene). After treatment, virus load was reduced in all groups (p < 0.0001) but was greater in the 0.1% group compared to placebo (p = 0.007). In a subset of patients (initial Ct < 25) viral load was strongly reduced on day 4 in the 0.1% group compared to placebo (p = 0.005). Negative PCR results appeared earlier and more frequently in the azelastine treated groups: being 18.52% and 21.43% in the 0.1% and 0.02% groups, respectively, compared to 0% for placebo on day 8. Comparable numbers of adverse events occurred in all treatment groups with no safety concerns. The shown effects of azelastine nasal spray may thus be suggestive of azelastine's potential as an antiviral treatment.Trial registration: The study was registered in the German Clinical Trial Register (DRKS-ID: DRKS00024520; Date of Registration in DRKS: 12/02/2021). EudraCT number: 2020-005544-34.

Figure 1

Patient disposition. ITT—intention to treat. Ct—cycle threshold.

Figure 2

Absolute changes in viral copy numbers (log₁₀ cp/mL) from baseline (day 1) over time based on the ORF 1a/b gene (ITT analysis set).

Figure 3

Absolute changes in viral copy numbers (log₁₀ cp/ml) from baseline (day 1) over time based on the ORF 1a/b gene (Ct < 25 analysis set). *p = 0.005 comparing the decrease of viral load on day 4 in the 0.1% azelastine group (log₁₀ 1.90 ± 1.03) compared to placebo (log₁₀ 1.05 ± 0.70; p = 0.005).

Figure 4

Area under the curve (AUC) reflecting changes in viral copy numbers (log₁₀ cp/mL) from baseline (day 1) over time (until day 11) based on the ORF 1a/b gene (ITT analysis set). The overall AUC of the Azelastine 0.1% group (red area) was significantly greater than that of placebo (green area), p = 0.007.

Figure 5

Kaplan–Meier analysis results regarding the ORF 1a/b gene from baseline (day 1) until day 11 of treatment (ITT analysis set).

Figure 6

Absolute changes of total symptom scores from baseline (day 1) until day 11 of treatment (ITT analysis set).