SARS-CoV-2 Effects on Psychophysical Olfactory Scores: Prospective Study With Evaluation Before and 60-Days After Infection.

The aim of this study was to prospectively evaluate the olfactory function in a series of individuals infected with SARS-CoV-2 and who had undergone psychophysical olfactory assessment prior to infection. Individuals unexposed to SARS-CoV-2 infection underwent a psychophysical evaluation of smell with the Sniffin' Sticks test. The subjects were followed prospectively and included in the study if they developed SARS-CoV-2 infection with a second test 60 days after recovery. At the 60-day follow-up of the 41 included subjects, 2 (4.9%) self-reported persistent olfactory dysfunction (OD). The differences between TDI scores before and after infection were statistically significant (37 [interquartile range (IQR), 34.25-39.25] vs 34.75 [IQR, 32.25-38]; p = .021). Analyzing the individual olfactory domains, the differences were significant for threshold (T) (9.75 [IQR, 9-11.25] vs 8.25 [IQR, 7.25-10.25]; p = .009) but not for odor discrimination (D) (p = .443) and identification (I) (p = .159). SARS-CoV-2 causes a significant reduction in the olfactory function, in particular affecting the olfactory threshold, even in subjects who do not self-report an OD.

An Update of Carbazole Treatment Strategies for COVID-19 Infection

The Coronavirus disease 2019 (COVID-19) outbreak was declared by the World Health Organization (WHO) in March 2020 to be a pandemic and many drugs used at the beginning proved useless in fighting the infection. Lately, there has been approval of some new generation drugs for the clinical treatment of severe or critical COVID-19 infections. Nevertheless, more drugs are required to reduce the pandemic's impact. Several treatment approaches for COVID-19 were employed since the beginning of the pandemic, such as immunomodulatory, antiviral, anti-inflammatory, antimicrobial agents, and again corticosteroids, angiotensin II receptor blockers, and bradykinin B2 receptor antagonists, but many of them were proven ineffective in targeting the virus. So, the identification of drugs to be used effectively for treatment of COVID-19 is strongly needed. It is aimed in this review to collect the information so far known about the COVID-19 studies and treatments. Moreover, the observations reported in this review about carbazoles as a treatment can signify a potentially useful clinical application;various drugs that can be introduced into the therapeutic equipment to fight COVID-19 or their molecules can be used as the basis for designing new antivirals.

Post-Viral Olfactory Loss: What We Learned from the SARS-CoV-2 Pandemic.

Viral infections have always been one of the most frequent causes of persistent olfactory dysfunctions accounting for 18% to 45% of all cases [...].

Are Nutraceuticals Effective in COVID-19 and Post-COVID Prevention and Treatment?

The beginning of the end or the end of the beginning? After two years mastered by coronavirus disease 19 (COVID-19) pandemic, we are now witnessing a turnaround. The reduction of severe cases and deaths from COVID-19 led to increasing importance of a new disease called post-COVID syndrome. The term post-COVID is used to indicate permanency of symptoms in patients who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immune, antiviral, antimicrobial therapies, as well as ozone therapy have been used to treat COVID-19 disease. Vaccines have then become available and administered worldwide to prevent the insurgence of the disease. However, the pandemic is not over yet at all given the emergence of new omicron variants. New therapeutic strategies are urgently needed. In this view, great interest was found in nutraceutical products, including vitamins (C, D, and E), minerals (zinc), melatonin, probiotics, flavonoids (quercetin), and curcumin. This review summarizes the role of nutraceuticals in the prevention and/or treatment of COVID-19 disease and post-COVID syndrome.

Effect of Ultra-Micronized Palmitoylethanolamide and Luteolin on Olfaction and Memory in Patients with Long COVID: Results of a Longitudinal Study.

In this study, we investigated whether treatment with palmitoylethanolamide and luteolin (PEA-LUT) leads to improvement in the quantitative or qualitative measures of olfactory dysfunction or relief from mental clouding in patients affected by long COVID. Patients with long COVID olfactory dysfunction were allocated to different groups based on the presence ("previously treated") or absence ("naïve") of prior exposure to olfactory training. Patients were then randomized to receive PEA-LUT alone or in combination with olfactory training. Olfactory function and memory were assessed at monthly intervals using self-report measures and quantitative thresholds. A total of 69 patients (43 women, 26 men) with an age average of 40.6 + 10.5 were recruited. PEA-LUT therapy was associated with a significant improvement in validated odor identification scores at the baseline versus each subsequent month; assessment at 3 months showed an average improvement of 10.7 + 2.6, CI 95%: 6-14 (p < 0.0001). The overall prevalence of parosmia was 79.7% (55 patients), with a significant improvement from the baseline to 3 months (p < 0.0001), namely in 31 patients from the Naïve 1 group (72%), 15 from the Naïve 2 group (93.7%), and 9 from the remaining group (90%). Overall, mental clouding was detected in 37.7% (26 subjects) of the cases, with a reduction in severity from the baseline to three months (p = 0.02), namely in 15 patients from the Naïve 1 group (34.8%), 7 from the Naïve 2 group (43.7%), and 4 from the remaining group (40%). Conclusions. In patients with long COVID and chronic olfactory loss, a regimen including oral PEA-LUT and olfactory training ameliorated olfactory dysfunction and memory. Further investigations are necessary to discern biomarkers, mechanisms, and long-term outcomes.

The Effects of Persistent Olfactory and Gustatory Dysfunctions on Quality of Life in Long-COVID-19 Patients.

(1) Background: Persistent olfactory (POD) and gustatory (PGD) dysfunctions are one of the most frequent symptoms of long-Coronavirus Disease 2019 but their effect on the quality of life (QoL) of patients is still largely unexplored. (2) Methods: An online survey was administered to individuals who reported to have had SARS-CoV-2 infection at least 6 months prior with persisting COVID-19 symptoms (using the COVID symptom index), including ratings of POD and PGD, and their physical (PCS) and mental (MCS) components of quality of life were assessed using the standardized short form 12 questionnaire (SF-12). (3) Results: Responses from 431 unique individuals were included in the analyses. The most frequent persistent symptoms were: fatigue (185 cases, 42.9%), olfactory dysfunction (127 cases, 29.5%), gustatory dysfunction (96 cases, 22.3%) and muscle pain (83 cases, 19.3%). Respondents who reported persisting muscle pain, joint pain, fatigue, headache, gastrointestinal disturbances, and dyspnea had significantly worse PCS. Those experiencing persistent fatigue and dyspnea also showed significantly lower MCS. Respondents reporting POD or PGD showed significantly worse QoL, but only pertaining to the MCS. Multiple regressions predicted MCS based on olfactory and marginally on gustatory ratings, but not PCS. Age significantly affected the prediction of PCS but not MCS, and gender and temporal distance from the COVID-19 diagnosis had no effect. (4) Conclusions: POD and PGD are frequent symptoms of the long-COVID-19 syndrome and significantly reduce QoL, specifically in the mental health component. This evidence should stimulate the establishment of appropriate infrastructure to support individuals with persistent CD, while research on effective therapies scales up.

Bis-Thiourea Quaternary Ammonium Salts as Potential Agents against Bacterial Strains from Food and Environmental Matrices.

In recent years, the phenomenon of antibiotic resistance in hospitals, communities and the environment has increasingly grown, so antibiotic resistance has become an urgent problem that requires a decisive and global intervention. Incorrect/unnecessary use of antibiotics contributes to increase the ability of microorganisms to develop resistance faster and faster. Research efforts must, therefore, be made to ensure a future in which antibiotic drugs will still be useful in combating infectious diseases. The search for new antibacterial compounds is fundamental. In this study, the antimicrobial activity of the compounds was evaluated against selected bacterial strains from food and environmental matrices by using the Agar Well Diffusion Assay. A total of thirty-six Gram-positive and Gram-negative bacteria were employed to determine the action spectrum and the antimicrobial effectiveness of a small series of thiourea derivatives. Results showed that the highest activities were found for compounds 1 and 4. The important role of the alkyl chain length and/or guanidine moiety in the width of action spectrum was evidenced. Further studies will allow evaluating the efficacy of the inhibiting action and the molecular mechanisms underlying this activity in order to identify compounds capable of counteracting the phenomenon of antibiotic resistance and to identify possible future applications of these newly synthesized compounds that have shown a high bactericidal action potential.

Prevalence of Persistent Olfactory Disorders in Patients With COVID-19: A Psychophysical Case-Control Study With 1-Year Follow-up.

The purpose of this multicenter case-control study was to evaluate a group of patients at least 1 year after coronavirus disease 2019 (COVID-19) with Sniffin' Sticks tests and to compare the results with a control population to quantify the potential bias introduced by the underlying prevalence of olfactory dysfunction (OD) in the general population. The study included 170 cases and 170 controls. In the COVID-19 group, 26.5% of cases had OD (anosmia in 4.7%, hyposmia in 21.8%) versus 3.5% in the control group (6 cases of hyposmia). The TDI score (threshold, discrimination, and identification) in the COVID-19 group was significantly lower than in the control group (32.5 [interquartile range, 29-36.5] vs 36.75 [34-39.5], P < .001). The prevalence of OD was significantly higher in the COVID-19 group, confirming that this result is not due to the underlying prevalence of OD in the general population.

Short-Term Efficacy and Safety of Oral and Nasal Corticosteroids in COVID-19 Patients with Olfactory Dysfunction: A European Multicenter Study.

Background: The objective of this study was to investigate the efficacy and safety of early administration of oral corticosteroids (OC) or nasal corticosteroids (NC) as an add-on to olfactory training (OT) versus OT alone in patients with olfactory dysfunction (OD) related to coronavirus disease 2019 (COVID-19). Methods: Patients with a positive diagnosis of COVID-19 and OD were prospectively recruited from March 22 to December 15, 2020 from 4 European hospitals. Patients had confirmed OD on psychophysical testing. All patients undertook OT, with add-on 10 days of OC (group 1: OC + OT), or 1 month of NC (group 2: NC + OT) or olfactory training alone (group 3: OT). Olfactory evaluations (Sniffin'Sticks tests) were carried out at the time of inclusion, 1 and 2 months after the start of the therapeutic course. Results: A total of 152 hyposmic or anosmic patients completed the study. Group 1, 2 and 3 included 59, 22 and 71 patients, respectively and all patient groups were comparable regarding baseline Sniffin'Sticks tests. The median Sniffin'Sticks test values significantly improved from pre- to post-intervention in all groups. The increase of Sniffin'Sticks test values was higher in group 1 (OC + OT) compared with groups 2 and 3 (p < 0.001) at one month after treatment but did not remain so at 2 months. Groups 1, 2 and 3, respectively, presented parosmia in 20/71 (28.2%), 9/22 (40.9%) and 42/71 (59.2%) patients. This difference was statistically significant between group 1 and 3 (p < 0.001). There were no patients with a worsening of the disease or an increase of the severity of the COVID-19 symptoms. Conclusions: The use of OCs in patients with OD related to mild COVID-19 is generally well-tolerated without any case of deterioration of symptoms. OC is associated with greater improvement in psychophysical olfactory evaluations at 1-month post-treatment but there was no difference at 2 months. Parosmia may be reduced following treatment with OC and NC. On the basis of these preliminary results, it is possible to state that considering the 2 months efficacy of OC and NC with respect to the OT alone and the risk-benefit ratio, the benefit to start a specific treatment of COVID-19 related OD cannot be demonstrated and there is a need for a randomised controlled trial to assess this further.

Psychophysical Evaluation of the Olfactory Function: European Multicenter Study on 774 COVID-19 Patients.

BACKGROUND: The objective evaluation of the olfactory function of coronavirus disease 2019 patients is difficult because of logistical and operator-safety problems. For this reason, in the literature, the data obtained from psychophysical tests are few and based on small case series. METHODS: A multicenter, cohort study conducted in seven European hospitals between March 22 and August 20, 2020. The Sniffin-Sticks test and the Connecticut Chemosensory Clinical Research Center orthonasal olfaction test were used to objectively evaluate the olfactory function. RESULTS: This study included 774 patients, of these 481 (62.1%) presented olfactory dysfunction (OD): 280 were hyposmic and 201 were anosmic. There was a significant difference between self-reported anosmia/hyposmia and psychophysical test results (p = 0.006). Patients with gastroesophageal disorders reported a significantly higher probability of presenting hyposmia (OR 1.86; p = 0.015) and anosmia (OR 2.425; p < 0.001). Fever, chest pain, and phlegm significantly increased the likelihood of having hyposmia but not anosmia or an olfactory disturbance. In contrast, patients with dyspnea, dysphonia, and severe-to-critical COVID-19 were significantly more likely to have no anosmia, while these symptoms had no effect on the risk of developing hyposmia or an OD. CONCLUSIONS: Psychophysical assessment represents a significantly more accurate assessment tool for olfactory function than patient self-reported clinical outcomes. Olfactory disturbances appear to be largely independent from the epidemiological and clinical characteristics of the patients. The non-association with rhinitis symptoms and the high prevalence as a presenting symptom make olfactory disturbances an important symptom in the differential diagnosis between COVID-19 and common flu.

Surgical oncology of the head and neck district during COVID-19 pandemic.

PURPOSE: A new member of the Coronaviridae family caused a worldwide pandemic emergency called Coronavirus disease 2019 (COVID-19). Health care workers who come into contact with the upper aero-digestive tract during diagnostic and therapeutic procedures, such as otolaryngologists, oral and maxillofacial surgeons, and head and neck surgeons, may undergo profound changes in their activities and are particularly at risk. We analysed the impact of COVID-19 on our oncological surgical activity. METHODS: To address the emergency and guarantee safety of patients referred to our Unit, reproducible guidelines were followed. Surgical activity data during COVID-19 were compared to previous years (2018 and 2019). RESULTS: From 21st February to 25th of May 113 surgical procedures were performed. The average of the two selected years (2018-2019) is 84.5, showing an increase of 34.5% of our activities (statistically significant, p = 0.0011). No patient showed perioperative or postoperative contagion. CONCLUSION: Due to the conversion of regular Hospitals into COVID Centers, Cancer Centers may encounter an increased demand for procedures. Following strict guidelines, it seems possible to face surgical activity on cancer patients and respect standard procedures aimed at containing the spread of COVID-19 infection.

Have There Been any Changes in the Epidemiology and Etiology of Maxillofacial Trauma During the COVID-19 Pandemic? An Italian Multicenter Study.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a significant impact on people's behavior. The aim of this study has been to evaluate how the SARS-CoV-2 pandemic has impacted the incidence and the features of maxillofacial fractures presented at 6 Italian tertiary centers. Clinical records of all the patients diagnosed for facial fractures between February 23 and May 23, 2019 and 2020 were retrospectively reviewed. Any differences in patient number and characteristics and fracture etiology and site between the 2 groups were then statistically analyzed.There has been a 69.1% decrease in the number of incoming patients during the pandemic. The number of foreign patients has decreased significantly (23.3% versus 9.6%, P = 0.011) while the average age has increased (38.6 versus 45.6 years old, P = 0.01). Specific statistical significant differences for accidental falls (31.8% versus 50.1%, P = 0.005) and sports injuries (16.9% versus 1.4%, P < 0.001) were found. Concerning fracture sites, significant differences have been found in relation to nasal (22.5% versus 11.4%, P = 0.009) and frontal sinus (0.9% versus 4.4%, P = 0.037) fractures. In conclusion, SARS-CoV-2 pandemic has significantly changed the epidemiology and the etiology of facial traumas.

Gustatory Dysfunction: A Highly Specific and Smell-Independent Symptom of COVID-19.

Chemosensitive dysfunctions are now considered as frequent and early symptoms of coronavirus disease 2019 (COVID-19). In the last few weeks, researchers' greatest efforts have been focusing mainly on the analysis of olfactory disorders, neglecting taste dysfunctions. According to our psychophysical evaluations, it can be inferred that the pathogenesis of taste disorders in COVID-19 patients is largely smell-independent. Moreover, isolated gustatory disorders are highly specific of SARS-CoV-2 infection. For these reasons, it is essential that gustatory dysfunctions, like olfactory disorders, are included in the COVID-19 guidelines.