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

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.

Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients.

The histamine-1 receptor antagonist azelastine was recently found to impact SARS-CoV-2 viral kinetics in a Phase 2 clinical trial (CARVIN). Thus, we investigated the relationship between intranasal azelastine administrations and viral load, as well as symptom severity in COVID-19 patients and analyzed the impact of covariates using non-linear mixed-effects modeling. For this, we developed a pharmacokinetic (PK) model for the oral and intranasal administration of azelastine. A one-compartment model with parallel absorption after intranasal administration described the PK best, covering both the intranasal and the gastro-intestinal absorption pathways. For virus kinetic and symptoms modeling, viral load and symptom records were gathered from the CARVIN study that included data of 82 COVID-19 patients receiving placebo or intranasal azelastine. The effect of azelastine on viral load was described by a dose-effect model targeting the virus elimination rate. An extension of the model revealed a relationship between COVID-19 symptoms severity and the number of infected cells. The analysis revealed that the intranasal administration of azelastine led to a faster decline in viral load and symptoms severity compared to placebo. Moreover, older patients showed a slower decline in viral load compared to younger patients and male patients experienced higher peak viral loads than females.

Eye Infection with SARS-CoV-2 as a Route to Systemic Immunization?

Infectious diseases of the conjunctiva and cornea usually leave behind both broad local and systemic immunity. Case reports of SARS-CoV-2-positive conjunctivitis with subsequent systemic immunity suggest a new route of immunization preventing the primary infection of the airways. MATERIAL AND METHODS: A total of 24 Syrian field hamsters were treated. In systematic animal experiments, we infected the eyes of n = 8 animals (group 1) and the airways of another n = 8 animals (group 2) with SARS-CoV-2 (Wuhan type); n = 8 hamsters served as controls (group 3). The weight development of the animals was recorded. After two weeks of observation of disease symptoms, all animals were re-exposed to SARS-CoV-2 in the respiratory tract (challenge) to determine whether immunity to the virus had been achieved. RESULTS: The epi-ocularly infected animals (group 1) showed no clinically visible disease during the ocular infection phase. At most, there was a slightly reduced weight gain compared to the control group (group 3), while the respiratory infected animals (group 2) all lost weight, became lethargic, and slowly recovered after two weeks. After the challenge, none of the animals in groups 1 and 2 became ill again. The animals in the negative control (group 3) all became ill. Cytotoxic antibodies were detectable in the blood of the infected groups before and after challenge, with higher titers in the epi-ocularly infected animals. CONCLUSION: By epi-ocular infection with SARS-CoV-2, the development of systemic immunity with formation of cytotoxic antibodies without severe general disease could be observed in the experimental animals, which did not induce any more disease upon a second infection in the respiratory tract. Therefore, it can be concluded that a purely epi-ocular infection with SARS-CoV2 only induces a weak disease pattern followed by systemic immunity.