Olfactory-related quality of life impacts psychological distress in people with COVID-19: The affective implications of olfactory dysfunctions.

BACKGROUND: Coronavirus disease 2019 (COVID-19) often causes chemosensory impairment, and olfactory dysfunctions may have negative consequences on psychological distress. This study aimed at assessing which dimension of perceived olfactory disfunctions (i.e., subjective olfactory capability, smell-related problems, or olfactory-related quality of life [QoL]) was most associated with psychological distress in people diagnosed with COVID-19. METHODS: 364 participants (65 men and 299 women) diagnosed with COVID-19 on average 7 months prior to the beginning of the study were recruited between June 5 and 21, 2021, to take part in an online cross-sectional survey. Participants answered questions on demographics, clinical factors, perceived olfactory functioning, and psychological distress. Hierarchical multiple linear regression analysis was conducted, assessing the role of demographics, clinical factors, and perceived olfactory functioning dimensions on psychological distress. RESULTS: More than half of the participants met the cut-off for all perceived olfactory dysfunctions scales and psychological distress. Being women, smoker, with comorbidities, and greater severity of COVID-19 symptoms were associated with higher scores on psychological distress. Among perceived olfactory functioning scales, only impairment in olfaction QoL was associated with psychological distress. LIMITATIONS: Limitations concerned the cross-sectional nature of the study and the unbalanced sample in terms of gender. CONCLUSIONS: The study confirmed the core intertwining between mood, perceived QoL, and olfactory functioning, showing how impairments in olfactory processing are strongly correlated with psychological distress through the impact they have on the perceived QoL.

Parosmia COVID-19 Related Treated by a Combination of Olfactory Training and Ultramicronized PEA-LUT: A Prospective Randomized Controlled Trial

During COVID-19 pandemic, clinicians have had to deal with an ever-increasing number of cases of olfactory disturbances after SARS-CoV-2 infections and in some people this problem persisted for long time after negativization from virus. This a prospective randomized controlled trial aims at evaluating the efficacy of ultramicronized palmitoylethanolamide (PEA) and Luteolin (LUT) (umPEA-LUT) and olfactory training (OT) compared to OT alone for the treatment of smell disorders in Italian post-COVID population. We included patients with smell loss and parosmia who were randomized and assigned to Group 1 (intervention group;daily treatment with umPEA-LUT oral supplement and OT) or Group 2 (control group;daily treatment with placebo and OT). All subjects were treated for 90 consecutive days. The Sniffin' Sticks identification test was used to assess the olfactory functions at the baseline (T0) and the end of the treatment (T1). Patients were queried regarding any perception of altered olfaction (parosmia) or aversive smell, such as cacosmia, gasoline-type smell, or otherwise at the same observational points. This study confirmed the efficacy of combination of umPEA-LUT and olfactory training as treatment of quantitative smell alteration COVID-19 related, but the efficacy of the supplement for parosmia was limited. UmpEA-LUT is useful for the treatment of brain neuro-inflammation (origin of quantity smell disorders) but has limited/no effect on peripheral damage (olfactory nerve, neuro-epithelium) that is responsible of quality disorders.

Quantitative but not qualitative flavor recognition impairments in COVID-19 patients.

BACKGROUND: Smell and taste dysfunctions (STDs) are symptoms associated with COVID-19 syndrome, even if their incidence is still uncertain and variable. AIMS: In this study, the effects of SARS-CoV-2 infection on chemosensory function have been investigated using both a self-reporting questionnaire on smell and flavor perception, and a simplified flavor test. METHODS: A total of 111 subjects (19 hospitalized [HOS] and 37 home-isolated [HI] COVID-19 patients, and 55 healthy controls [CTRL]) were enrolled in the study. They received a self-evaluation questionnaire and a self-administered flavor test kit. The flavor test used consists in the self-administration of four solutions with a pure olfactory stimulus (coffee), a mixed olfactory-trigeminal stimulus (peppermint), and a complex chemical mixture (banana). RESULTS: After SARS-CoV-2 infection, HOS and HI patients reported similar prevalence of STDs, with a significant reduction of both smell and flavor self-estimated perception. The aromas of the flavor test were recognized by HI and HOS COVID-19 patients similarly to CTRL; however, the intensity of the perceived aromas was significantly lower in patients compared to controls. CONCLUSION: Data reported here suggests that a chemosensory impairment is present after SARS-CoV-2 infection, and the modified "flavor test" could be a novel self-administering objective screening test to assess STDs in COVID-19 patients. CLINICAL TRIAL REGISTRATION NO: NCT04840966; April 12, 2021, retrospectively registered.

Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo- Controlled Clinical Trial.

BACKGROUND: Olfactory training is the only evidence-based treatment for post-viral olfactory dysfunction. Smell disorders after SARS-CoV-2 infection have been attributed to neuroinflammatory events within the olfactory bulb and the central nervous system. Therefore, targeting neuroinflammation is one potential strategy for promoting recovery from post-COVID-19 chronic olfactory dysfunction. Palmitoylethanolamide and luteolin (PEA-LUT) are candidate antiinflammatory/ neuroprotective agents. OBJECTIVE: To investigate recovery of olfactory function in patients treated with PEA-LUT oral supplements plus olfactory training versus olfactory training plus placebo. METHODS: Multicenter double-blinded randomized placebo-controlled clinical trial was held. Eligible subjects had prior COVID-19 and persistent olfactory impairment >6 months after follow-up SARS-CoV-2 negative testing, without prior history of olfactory dysfunction or other sinonasal disorders. Participants were randomized to daily oral supplementation with ultramicronized PEA-LUT 770 mg plus olfactory training (intervention group) or olfactory training with placebo (control). Sniffin' Sticks assessments were used to test the patients at baseline and 90 days. RESULTS: A total of 185 patients, including intervention (130) and control (55) were enrolled. The intervention group showed significantly greater improvement in olfactory threshold, discrimination, and identification scores compared to controls (p=0.0001). Overall, 92% of patients in the intervention group improved versus 42% of controls. Magnitude of recovery was significantly greater in the intervention group versus control (12.8 + 8.2 versus mean 3.2 + 3), with >10-fold higher prevalence of anosmia in control versus intervention groups at the 90-day endpoint. CONCLUSION: Among individuals with olfactory dysfunction post-COVID-19, combining PEA-LUT with olfactory training resulted in greater recovery of smell than olfactory training alone.

Corrigendum: Age-Related Differences in the Expression of Most Relevant Mediators of SARS-CoV-2 Infection in Human Respiratory and Gastrointestinal Tract.

[This corrects the article DOI: 10.3389/fped.2021.697390.].

Assessing the extent and timing of chemosensory impairments during COVID-19 pandemic.

Chemosensory impairments have been established as a specific indicator of COVID-19. They affect most patients and may persist long past the resolution of respiratory symptoms, representing an unprecedented medical challenge. Since the SARS-CoV-2 pandemic started, we now know much more about smell, taste, and chemesthesis loss associated with COVID-19. However, the temporal dynamics and characteristics of recovery are still unknown. Here, capitalizing on data from the Global Consortium for Chemosensory Research (GCCR) crowdsourced survey, we assessed chemosensory abilities after the resolution of respiratory symptoms in participants diagnosed with COVID-19 during the first wave of the pandemic in Italy. This analysis led to the identification of two patterns of chemosensory recovery, partial and substantial, which were found to be associated with differential age, degrees of chemosensory loss, and regional patterns. Uncovering the self-reported phenomenology of recovery from smell, taste, and chemesthetic disorders is the first, yet essential step, to provide healthcare professionals with the tools to take purposeful and targeted action to address chemosensory disorders and their severe discomfort.

Age-Related Differences in the Expression of Most Relevant Mediators of SARS-CoV-2 Infection in Human Respiratory and Gastrointestinal Tract.

Background: Clinical features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection seem to differ in children compared to that in adults. It has been hypothesized that the lower clinical severity in children could be influenced by differential expression of the main host functional receptor to SARS-CoV-2, the angiotensin-converting enzyme 2 (ACE2), but data are still conflicting. To explore the origin of age-dependent clinical features of coronavirus disease 2019 (COVID-19), we comparatively evaluated the expression in children and adult subjects of the most relevant mediators of the SARS-CoV-2 infection: ACE2, angiotensin-converting enzyme 1 (ACE1), transmembrane serine protease-2 (TMPRSS2), and neuropilin-1 (NRP1), at upper respiratory tract and small intestine level. Methods: The expression of ACE2, ACE1, TMPRSS2, and NRP1 in nasal epithelium and in small intestine epithelium was investigated by quantitative real-time PCR analysis. Results: We found no differences in ACE2, ACE1, and TMPRSS2 expression in the nasal epithelium comparing children and adult subjects. In contrast, nasal epithelium NRP1 expression was lower in children compared to that in adults. Intestinal ACE2 expression was higher in children compared to that in adults, whereas intestinal ACE1 expression was higher in adults. Intestinal TMPRSS2 and NRP1 expression was similar comparing children and adult subjects. Conclusions: The lower severity of SARS-CoV-2 infection observed in children may be due to a different expression of nasal NRP1, that promotes the virus interaction with ACE2. However, the common findings of intestinal symptoms in children could be due to a higher expression of ACE2 at this level. The insights from these data will be useful in determining the treatment policies and preventive measures for COVID-19.