While olfactory dysfunction associated with coronavirus disease 2019 (COVID-19) has attracted considerable interest, few studies have tracked outcomes at serial time points or beyond 2 weeks. Furthermore, data are conflicting regarding whether COVID-19 severity correlates with degree of olfactory dysfunction. This prospective case-control study analyzed prevalence and severity of subjective loss of smell in outpatients (n = 23) and inpatients (n = 20) with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vs healthy controls (n = 25). Olfactory dysfunction was reported more commonly in COVID-19 patients than in healthy controls ( P < .001), and outpatients paradoxically reported loss of smell more commonly than inpatients ( P = .02). Headaches were present in 52% of patients with olfactory dysfunction. Anosmia or hyposmia persisted beyond 5 days but most of the patients recovered by 30 days, suggesting favorable prognosis for olfaction. Differences between inpatients and outpatients are potentially reflective of timeline of olfactory symptoms and contextual factors, underscoring the importance of corroborative objective testing, coupled with careful tracking of temporal relationships.

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 anti-inflammatory/ 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. 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 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. (ITALIAN; Clinicaltrials.gov number: NCT04853836)

Smell alteration and cognitive impairment are common features of the Long-COVID Syndrome. Mental clouding, often described as brain fog, might affect smell by altering recollection of odors or through a share mechanism of neuroinflammation. We investigated mental clouding, headache, and cognitive function in adult patients with persistent COVID-19 olfactory dysfunction. This multi-center cross-sectional study enrolled 152 adults with self-reported olfactory dysfunction from 3 tertiary centers specialized in COVID-19 olfactory disorders. Inclusion criteria were smell alterations after COVID-19 persisting over 6 months from infection, age >18 and < 65. Exclusion criteria included smell alterations, headache, or memory problems prior to COVID-19 infection. The patients were evaluated by olfactometry, nasal endoscopy, headache scale, cognitive assessment, Mini Mental State Examination (MMSE), and self-reported measures. Smell dysfunction was stratified and classified based on olfactory deficit severity and presence of olfactory distortion (parosmia, cacosmia). Data on smell disorder, mental clouding, MMSE, and headache were analyzed to assess correlations. Among the 152 patients studied, 50 (32.8%) presented with anosmia, 25 (16.4%) with hyposmia, 10 (6.6%) with parosmia/cacosmia, and 58 patients (38.2%) with a combination of hyposmia and parosmia; seven (4.6%) patients suffered from headache exclusively, and two (1.4%) had headache and mental clouding as their primary symptom. Headache was reported by 76 (50%) patients, and mental clouding by 71 (46.7%). The patients reporting headache, mental clouding, or both, had significantly increased risk of suffering from anosmia and/or hyposmia when compared with their counterparts without these neurological symptoms. No patients had reduced MMSE scores. In our cohort of adult patients with post-COVID-19, smell alterations persisting over 6 months, cognitive impairment and headache were associated with more severe olfactory loss, consistent with neuroinflammatory mechanisms mediating a variety of Long-COVID symptoms.

We describe an Italian family in which two sisters have macrocephaly due to hydrocephalus, and sensorineural hearing loss in addition to other brain abnormalities demonstrated by Magnetic resonance imaging (MRI). The girls, born to healthy non-consanguineous parents, have borderline psychomotor development delay (probably due to hearing defect) and minor dysmorphisms. The clinical picture fits the Chudley-McCullough syndrome, an autosomal recessive condition, to date described in only five families. Our data, in particular the neuroradiological findings, include all brain anomalies variably reported in previous works (hydrocephalus, corpus callosum partial agenesis, interhemispheric cyst, cerebral and cerebellar cortex dysplasia), thus illustrating the full phenotype of the syndrome.

Objective. Interactions between SARS-CoV-2 and pharyngeal associated lymphoid tissue are thought to influence the manifestations of COVID-19. We aimed to determine whether a previous history of tonsillectomy, as a surrogate indicator of a dysfunctional pharyngeal associated lymphoid tissue, could predict the presentation and course of COVID-19. Methods. Multicentric cross-sectional observational study involving seven hospitals in Northern and Central Italy. Data on the clinical course and signs and symptoms of the infection were collected from 779 adults who tested positive for SARS-CoV-2, and analysed in relation to previous tonsillectomy, together with demographic and anamnestic data. Results. Patients with previous tonsillectomy showed a greater risk of fever, temperature higher than 39°C, chills and malaise. No significant differences in hospital admissions were found. Conclusions. A previous history of tonsillectomy, as a surrogate indicator of immunological dysfunction of the pharyngeal associated lymphoid tissue, could predict a more intense systemic manifestation of COVID-19. These results could provide a simple clinical marker to discriminate suspected carriers and to delineate more precise prognostic models.

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Although chronic sinusitis widely affects the adult population, the treatments currently used did not always satisfactorily solve the symptoms. Traditional therapy with steroids and antibiotics presents risks and benefits and the new drugs, i.e., monoclonal antibody, are valid solutions despite being quite expensive. Natural molecules could be a valid treatment that combines good efficacy and low price. We conducted a case -control study to evaluate the benefit of an oral supplement with Ribes nigrum, Boswellia serrata, Bromelain and Vitamin D on chronic sinusitis symptoms. 60 patients were randomly assigned to one of the three groups: control using nasal steroids only, treatment 1 using nasal steroid and 1 dose of the oral supplement for 30 days and treatment 2 in which patients used nasal steroid and two oral supplement doses daily for 15 days. Conditions of the nasal mucosa and a blood sample (WBC, IgE and CRP) were analyzed at T0, T1 (15 days after treatment) and T2 (30 days after treatment. Patients treated with the supplement improved their nasal findings (hyperemia of mucosa and rhinorrhea) with statistically significant differences from the control. Our preliminary data suggest that the addition of supplement containing Ribes nigrum, Boswellia serrata, Vitamin D and Bromelain to the traditional local therapy (nasal spray with cortisone) can be a supporting therapy to modulate the local inflammation in the nose in patients affected by chronic sinusitis.

Objective: Surgical/anesthetic management of patients undergoing surgical tracheostomy for Covid-19 pneumonia aiming at minimizing the risk of health care workers (HCWs) infection. Design, Setting and Paticipants: Twenty-three Caucasian patients, mean age 67 years, with long-term orotracheal intubation for severe acute respiratory syndrome Covid-19 pneumonia were submitted to surgical tracheostomy, between February 3rd and March 22nd 2020, according to our specific procedure. Main outcomes and Measures: Air exposure time (AET) and frequency of infection in HCWs. Results: No complication, in terms of bleeding or tracheostomy cannula displacement, was observed. No HCWs involved in the procedures contracted Covid-19. Conclusions: The tracheostomy technique we describe minimizes the risk of surgeon's exposure to patient's aerosol drops/expired air and the possibility of HCWs infection during the procedure carried out in patients with Covid-19 pneumonia. The details and advantages of our approach with respect to "standard" tracheotomy and percutaneous procedures are discussed.