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.

Impact of COVID-19-Mediated Olfactory Loss on Quality of Life.

INTRODUCTION: COVID-19 can be associated with a variety of longer-lasting impairments that can have a significant impact on patients' quality of life (QoL). While this is well described in the literature for limitations in lung capacity or permanent headaches, there is little research on the impact of olfactory dysfunction in the context of COVID-19 on patients' QoL. METHODS: In 65 patients with a history of COVID-19, the present olfactory ability was assessed using the Sniffin' Sticks test. In addition, olfactory QoL was assessed by the Questionnaire of Olfactory Disorders. Self-assessment was performed with visual analogue scales. The data were compared with the results obtained in healthy individuals and in patients with hyposmia due to other viral infections. RESULTS: The QoL of COVID-19 patients was significantly lower compared to the healthy control group. Even recovered subjects whose olfaction had already returned to the normal range still had a reduced QoL. The severity of the olfactory impairment correlated with the reduction in QoL. However, the olfactory QoL of COVID-19 patients was not worse than that of patients' olfactory loss due to other viral infections. Patients with parosmia had reduced QoL and rated their situation worse than patients without parosmia. CONCLUSION: QoL appears to be impaired in patients with long-lasting COVID-19 olfactory disorders several months after overcoming acute symptoms, even if olfaction has normalized. However, the impairment is not more pronounced than in patients with other postviral olfactory disorders of the same duration.

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.

Patients with COVID-19-associated olfactory impairment also show impaired trigeminal function.

OBJECTIVE: Next to olfactory function, the nose can also perceive chemestetic sensations mediated by the trigeminal nerve. While olfactory dysfunction as a symptom of COVID-19 is well described, there has been little research on the limitation of other nasal sensory inputs due to SARS-CoV-2 infection. The aim of this study was to determine possible limitations of nasal chemesthesis after COVID-19 infection by a psychophysiological diagnostic tool. METHODS: In 65 patients with a PCR-confirmed, former COVID-19 disease, olfaction was tested by means of a sniffin' sticks test, tasting by taste sprays and chemesthesis with a menthol dilution series. The subjective self-assessment of the patients was recorded via a questionnaire. RESULTS: We found a restriction of nasal chemesthesis and the extent correlated with the loss of smell, as well as with the values of the taste score, but not with subjective self-assessment. CONCLUSION: Not only the ability to smell and taste, but also nasal chemesthesis is affected by COVID-19.

Persisting olfactory dysfunction improves in patients 6 months after COVID-19 disease.

BACKGROUND: Smell disorders persist in about half of the patients with other symptoms of COVID-19 disease, but the exact duration of the symptoms is yet unknown. Especially, only a few studies used validated olfactory tests for this. AIMS/OBJECTIVES: The aim of this study was to investigate how many patients with olfactory function impairment, which was detected in a validated olfactory test 3 months after COVID-19 disease, showed improvement in olfactory function after 6 months. METHODS: About 26 patients with a PCR-confirmed, former COVID-19 disease, with an impaired olfactory function after three months, were included in the study. The olfactory function was evaluated with the sniffing sticks test, the taste function with taste sprays. RESULTS: Smelling function improved in all but one patient (96%). All measured subitems, i.e. olfactory threshold, identification and discrimination of odours significantly improved. In the whole mouth taste test all patients showed normal taste function. CONCLUSIONS AND SIGNIFICANCE: 6 months after COVID-19 disease, olfactory function improves in just about all patients. Long-term measurements must investigate whether complete regeneration of the olfactory function will occur in all patients.

[The COVID-19 pandemic and otolaryngology: What it comes down to?] / Die COVID-19-Pandemie und das HNO-Fachgebiet: Worauf kommt es aktuell an?

Here, we review the most recent findings on the effects COVID-19 pandemic for the work of otolaryngologists. The role of anosmia and hyposmia as a potential COVID-19 related symptom is presented. We discuss the clinical management of all ENT patients, but especially of COVID-19 patients from the ENT perspective. The impact of the infection on the ENT examination and ENT surgery is summarized.

Olfactory dysfunction in patients after recovering from COVID-19.

BACKGROUND: Smell and taste disorders occur in COVID-19 with a high prevalence, but little is known about the duration of the symptoms. In particular, studies using validated olfactory tests are very rare to date. AIMS/OBJECTIVES: The aim of this study was to determine the olfactory function of COVID-19 recoveries by a detailed olfactory test. METHODS: 91 patients with PCR-confirmed, past COVID-19 disease were included. Olfactory history was taken using a questionnaire. Olfactory function was evaluated with the sniffin' sticks test, tasting function with taste sprays. RESULTS: 80 patients had experienced sudden olfactory loss during the course of disease and at the time of testing, 33 patients subjectively still had an impaired olfactory sense. Around 8 weeks had passed since the onset of symptoms. 45.1% of the tested individuals were still hyposmic according to the olfactory test while 53.8% showed an olfactory performance within the normal range. Patients' self-assessment correlated poorly with the measured olfactory performance. CONCLUSIONS AND SIGNIFICANCE: Half of the patients with an olfactory loss as a symptom of COVID-19 still have olfactory impairments after two months, although not all of these patients subjectively notice a restriction. Long-term measurements must confirm whether all affected patients will make full recovery.

[Smell disorders at COVID-19 - the current level of knowledge]. / Riechstörungen bei COVID-19 ­ aktueller Wissensstand.

Early reports of SARS-CoV-2 infections only rarely mentioned smell and taste disorders. Several studies, particularly from Europe and the USA, have now confirmed these symptoms as an early key feature of COVID-19. About 70 % of patients seem to experience a reduction of smell and taste in the course of the disease, with most of the studies published to date based on questionnaires and anamnestic data. Validated smell tests have so far only been used in a few studies. A distinction between taste and taste disorders, i. e. a distinction between retronasal aroma taste and the olfactory system from the dysfunction of taste capsules and the further cranial nerves, was mostly not made in the studies available to date. Some reports associate olfactory disorders with a milder clinical course. At the same time, the olfactory system via the olfactory bulb represents an entry point into the central nervous system, and an olfactory disorder could be a predisposing factor for central neurological symptoms. The clinical significance of smell and taste disorders in COVID-19 patients is currently still unclear. Further open questions concern the exact prevalence and the prognosis, so that overall higher quality studies with validated smell tests and larger numbers of patients are required.