A multicenter real-life study to determine the efficacy of corticosteroids and olfactory training in improving persistent COVID-19-related olfactory dysfunction.

Background: No definitive treatment exists to effectively restore function in patients with persistent post-infectious olfactory dysfunction (OD). Corticosteroids have been considered as a therapeutic option in post-infectious OD but their benefit in COVID-19-related OD remains unexplored. We aim to determine the role of the combination of corticosteroids plus olfactory training (OT) in improving persistent COVID-19-related OD. Methods: A multicenter real-life cohort study was conducted between December 2020 and April 2022 on patients with reported COVID-19-related OD. Only patients with confirmed OD at Sniffin' Sticks (S'S) and those who attended their 6-month follow-up were included. Patients were started on a combined treatment of corticosteroids and OT. Patients refusing corticosteroids or not doing any treatment formed the control groups. Visual analogue scale (VAS) for sense of smell and SNOT-22 were used to assess patients reported symptoms. Results: Sixty-seven subjects with reported COVID-19-related OD were initially seen. Normosmic patients at S'S (n = 14) and those not attending their follow-up (n = 9) were excluded. Of the 44 patients included in the analysis, 19 patients had the combined treatment (group A), 16 patients refused to take corticosteroids and did the OT alone (group B) whereas 9 patients did not do any treatment (group C). An improvement of threshold + discrimination + identification (TDI) score (p = .01) and VAS for smell (p = .01) was found in group A whereas only the TDI score improved in group B (p = .04). Presence of comorbidities, age, sex (male), and length of OD negatively influenced olfactory recovery. Conclusions: Our study confirms the importance of OT in long-term OD suggesting that the addition of corticosteroids may give a benefit in terms of patient's perceived olfaction. Level of Evidence: 2b.

Parosmia as a predictor of a better olfactory function in COVID-19: a multicentric longitudinal study for upper respiratory tract infections.

PURPOSE: This study aimed to evaluate the course of olfactory dysfunction [OD] due to upper respiratory tract infections [URTI] especially for COVID-19 [C19] in a multicentric design and to investigate possible predictors for the outcome. METHODS: In a multicentric study, patients (n = 147, of which 96 were women) with OD due to URTI, including C19 and non-C19 were evaluated at two visits with a standardized medical history and "Sniffin' Sticks" extended psychophysical testing to examine the course and possible predictors for improvement of olfactory function. RESULTS: C19 patients showed better overall olfactory function (p < 0.001) compared to non-C19. Olfactory function (p < 0.001) improved over 3.5 ± 1.2 months in a comparable fashion for C19 and non-C19 comparable over time (p = 0.20) except for a more pronounced improvement of odour threshold (p = 0.03) in C19. C19 patients with parosmia exhibited a higher probability of clinically relevant improvement of odour threshold, a better threshold in the second visit, and tended to have a better TDI-score at the second visit. Further possible predictors for an improving olfactory function were younger age, female gender, and had lower scores in olfactory tests at the first visit. CONCLUSIONS: Patients with C19 and non-C19 URTI exhibit a similar improvement over 3-4 months except for the odour threshold, with a better TDI in both visits for C19. For C19 a better prognosis in terms of olfactory recovery was found for younger patients with parosmia and lower olfactory scores at the first visit. Still, for many patients with olfactory loss, an improvement that is experienced as complete may only occur over months and possibly years.

Genomic surveillance of SARS-CoV-2 in patients presenting neurological manifestations.

During the first wave of infections, neurological symptoms in Coronavirus Disease 2019 (COVID-19) patients raised particular concern, suggesting that, in a subset of patients, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could invade and damage cells of the central nervous system (CNS). Indeed, up to date several in vitro and in vivo studies have shown the ability of SARS-CoV-2 to reach the CNS. Both viral and/or host related features could explain why this occurs only in certain individuals and not in all the infected population. The aim of the present study was to evaluate if onset of neurological manifestations in COVID-19 patients was related to specific viral genomic signatures. To this end, viral genome was extracted directly from nasopharyngeal swabs of selected SARS-CoV-2 positive patients presenting a spectrum of neurological symptoms related to COVID-19, ranging from anosmia/ageusia to more severe symptoms. By adopting a whole genome sequences approach, here we describe a panel of known as well as unknown mutations detected in the analyzed SARS-CoV-2 genomes. While some of the found mutations were already associated with an improved viral fitness, no common signatures were detected when comparing viral sequences belonging to specific groups of patients. In conclusion, our data support the notion that COVID-19 neurological manifestations are mainly linked to patient-specific features more than to virus genomic peculiarities.

Altered brain regional homogeneity is associated with depressive symptoms in COVID-19.

BACKGROUND: COVID-19 is an infectious disease that has spread worldwide in 2020, causing a severe pandemic. In addition to respiratory symptoms, neuropsychiatric manifestations are commonly observed, including chronic fatigue, depression, and anxiety. The neural correlates of neuropsychiatric symptoms in COVID-19 are still largely unknown. METHODS: A total of 79 patients with COVID-19 (COV) and 17 healthy controls (HC) underwent 3 T functional magnetic resonance imaging at rest, as well as structural imaging. Regional homogeneity (ReHo) was calculated. We also measured depressive symptoms with the Patient Health Questionnaire (PHQ-9), anxiety using the General Anxiety Disorder 7-item scale, and fatigue with the Multidimension Fatigue Inventory. RESULTS: In comparison with HC, COV showed significantly higher depressive scores. Moreover, COV presented reduced ReHo in the left angular gyrus, the right superior/middle temporal gyrus and the left inferior temporal gyrus, and higher ReHo in the right hippocampus. No differences in gray matter were detected in these areas. Furthermore, we observed a negative correlation between ReHo in the left angular gyrus and PHQ-9 scores and a trend toward a positive correlation between ReHo in the right hippocampus and PHQ-9 scores. LIMITATIONS: Heterogeneity in the clinical presentation in COV, the different timing from the first positive molecular swab test to the MRI, and the cross-sectional design of the study limit the generalizability of our findings. CONCLUSIONS: Our results suggest that COVID-19 infection may contribute to depressive symptoms via a modulation of local functional connectivity in cortico-limbic circuits.

Olfactory Dysfunction in COVID-19 Patients Who Do Not Report Olfactory Symptoms: A Pilot Study with Some Suggestions for Dentists.

BACKGROUND: Smell and taste dysfunction are frequently reported by SARS-CoV-2 positive patients. The degree of olfactory and gustatory dysfunction varies from a very mild reduction to their complete loss. Several studies have been performed to determine their prevalence in COVID-19 patients, mostly using subjective measurement methods. The literature lacks long-term studies regarding duration and recovery. METHODS: We assessed olfactory performance, using the Sniffin' Sticks olfactory test, in a group of patients who had not reported olfactory dysfunction, around 131 days after their COVID-19 diagnosis. RESULTS: 11 out of 20 subjects showed no olfactory reduction (65%), while 9 subjects showed reduced TDI score (45%). A total of 13 subjects (65%) scored above the cutoff point for Threshold, 16 subjects (80%) scored above the cutoff point for discrimination and 13 subjects (65%) scored above the cutoff point for identification. CONCLUSION: Objective measurement methods of olfactory performance show a higher prevalence of olfactory reduction compared to patients' self-reported questionnaires. Olfactory dysfunction can last even months after its onset and because of its high prevalence, it could be a screening symptom for suspect COVID-19 cases.

Characteristics of taste dysfunction in COVID-19 subjects coming from two different countries.

Taste dysfunction (TD) has been recognised, together with olfactory dysfunction, as a key presenting symptom of COVID-19. The capability to recognise flavours, flavour intensities and aroma characteristics can be highly variable within the same population, as well as potentially diverse between culturally different populations. The aims of this study are to evaluate whether a difference in the types of TD presentation amongst COVID-19 positive subjects can be demonstrated and whether a difference exists between populations of different cultures.

Olfactory and taste dysfunction among mild-to-moderate symptomatic COVID-19 positive health care workers: An international survey.

OBJECTIVES: To determine the prevalence of olfactory and taste dysfunction (OD; TD) among COVID-19 positive health care workers (HCWs), their associated risk factors and prognosis. METHODS: Between May and June 2020, a longitudinal multicenter study was conducted on symptomatic COVID-19 PCR confirmed HCWs (COVID-19 positive) in London and Padua. RESULTS: Hundred and fourteen COVID-19 positive HCWs were surveyed with a response rate of 70.6% over a median follow-up period of 52 days. UK prevalence of OD and TD was 73.1% and 69.2%, respectively. There was a male to female ratio of 1:3 with 81.6% being white, 43.7% being nurses/health care assistants (HCAs), and 39.3% being doctors. In addition, 53.2% of them worked on COVID-19 wards. Complete recovery was reported in 31.8% for OD and 47.1% for TD with a 52 days follow-up. The job role of doctors and nurses negatively influenced smell (P = .04 and P = .02) and taste recovery (P = .02 and P = .01). Ethnicity (being white) showed to positively influence only taste recovery (P = .04). Sex (being female) negatively influenced OD and TD recovery only in Paduan HCWs (P = .02 and P = .011, respectively). Working on a COVID-19 ward did not influence prognosis. CONCLUSIONS: The prevalence of OD and TD was considerably higher in HCWs. The prognosis for OD and TD recovery was worse for nurses/HCAs and doctors but working on a COVID-19 ward did not influence prognosis. Sixty-eight percent of surveyed HCWs at 52 days continued to experience OD or TD requiring additional future medical management capacity. LEVEL OF EVIDENCE: 4.