Smell and Taste in Children with Covid-19.

Objectives: To assess the frequency of loss of smell and taste in children during Covid-19 infection and their prevalence along with other symptoms, as well as the recovery of chemosensory function once healed. Methods: To evaluate symptoms during infection, we adapted the Scandinavian adaptation of the Multi-Clinic Smell and Taste Questionnaire and the modified Monel-Jefferson questionnaire. For smell analysis we used Odor Identification (OI) and two variants of the Odor Discrimination (OD) test, and we compared the results with those of a control group. Results: We enrolled nine patients in our experimental group and nine in our control group. Fever was the most frequent symptom (55% of cases), followed by anosmia and ageusia (44% of cases), muscle pain and asthenia (22% of cases) and diarrhea, abdominal pain, cough, and headache (11% of cases). In 11% of cases, olfactory symptoms were the only manifestation of the disease. There was no statistically significant difference in OI test and OD tests between the two groups (Children healed from Covid-19 and Control Group). Conclusion: Loss of smell and taste are the second most common symptoms of pediatric Covid-19, and they should always be tested because they can be the only manifestations of infection. Olfactory function in Covid-19 children decreases with increasing age and improves with the passage of time after illness.

The Impact of the COVID-19 Pandemic on the Prognosis of Laryngeal Adenoid Cystic Carcinoma: A Case Report and a Literature Review

Laryngeal adenoid cystic carcinoma (LACC) is a sporadic neoplasm, especially if supraglottic. The COVID-19 pandemic worsened the presenting stage of many cancers and impacted their prognosis negatively. Here, a case of a patient with adenoid cystic carcinoma (ACC) with delayed diagnosis and a rapid deterioration with distant metastasis due to the COVID-19 pandemic is illustrated. Next, we present a literature review of this rare glottic ACC. The COVID-19 pandemic worsened the stage of presentation of many cancers and adversely affected their prognosis. The present case had a rapidly lethal course, undoubtedly due to the diagnosis delay caused by the COVID-19 pandemic, which impacted the prognosis of this rare glottic ACC. Strict follow-up is recommended for any suspicious clinical findings, as an early diagnosis will improve the disease prognosis, and to consider the influence of the COVID-19 pandemic, especially on the timing of common diagnostic and therapeutic procedures for oncological diseases. In the post-COVID-19 era, it is important to generate new diagnostic scenarios to achieve an increasingly rapid diagnosis of oncological diseases, especially the rare ones, through screening or similar procedures.

The Impact of the COVID-19 Pandemic on the Prognosis of Laryngeal Adenoid Cystic Carcinoma: A Case Report and a Literature Review.

Laryngeal adenoid cystic carcinoma (LACC) is a sporadic neoplasm, especially if supraglottic. The COVID-19 pandemic worsened the presenting stage of many cancers and impacted their prognosis negatively. Here, a case of a patient with adenoid cystic carcinoma (ACC) with delayed diagnosis and a rapid deterioration with distant metastasis due to the COVID-19 pandemic is illustrated. Next, we present a literature review of this rare glottic ACC. The COVID-19 pandemic worsened the stage of presentation of many cancers and adversely affected their prognosis. The present case had a rapidly lethal course, undoubtedly due to the diagnosis delay caused by the COVID-19 pandemic, which impacted the prognosis of this rare glottic ACC. Strict follow-up is recommended for any suspicious clinical findings, as an early diagnosis will improve the disease prognosis, and to consider the influence of the COVID-19 pandemic, especially on the timing of common diagnostic and therapeutic procedures for oncological diseases. In the post-COVID-19 era, it is important to generate new diagnostic scenarios to achieve an increasingly rapid diagnosis of oncological diseases, especially the rare ones, through screening or similar procedures.

Targeting Neuroinflammation to Alleviate Chronic Olfactory Dysfunction in Long COVID: A Role for Investigating Disease-Modifying Therapy (DMT)?

Chronic olfactory dysfunction after SARS-CoV-2 infection occurs in approximately 10% of patients with COVID-19-induced anosmia, and it is a growing public health concern. A regimen of olfactory training and anti-neuroinflammatory therapy with co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT) has shown promising results in clinical trials; however, approximately 15% of treated patients do not achieve full recovery of a normal olfactory threshold, and almost 5% have no recovery. Disease-modifying therapies (DMTs), which are used to treat autoimmune neuroinflammation in multiple sclerosis (MS), have not been studied for treating persistent inflammation in refractory post-COVID-19 smell disorder. This study evaluated COVID-19-related smell loss and MS-related smell loss, comparing the responses to different therapies. Forty patients with MS and 45 reporting post-COVID-19 olfactory disorders were included in the study. All patients underwent nasal endoscopy and were evaluated by using validated Sniffin' Sticks testing. The patients with long COVID were treated for three months with um-PEA-LUT plus olfactory training. The patients with MS were treated with DMTs. Olfactory functions before and after treatment were analyzed in both groups. At the experimental endpoint, 13 patients in the COVID-19 group treated with um-PEA-LUT had residual olfactory impairment versus 10 patients in the MS group treated with DMTs. The severity of the persistent olfactory loss was lower in the MS group, and the patients with MS treated with IFN-beta and glatiramer acetate had the preservation of olfactory function. These data provide a rationale for considering prospective trials investigating the efficacy of DMTs for post-COVID-19 olfactory disorders that are refractory to um-PEA-LUT with olfactory training. This study is the first to consider the role of DMT in treating refractory post-viral olfactory loss in patients with long COVID.

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.

Investigational drugs for the treatment of olfactory dysfunction.

INTRODUCTION: Olfactory dysfunction could be the sign of acquired or degenerative diseases. The loss of the sense can be caused by a damage in the nasal structure (olfactory epithelium) or a neuro inflammation/degeneration in the superior olfactory pathway. The understanding of the origin of the smell alteration would be desirable for appropriate management of the problem. Unfortunately, clinical investigations do not always allow to define the exact cause. AREAS COVERED: This review discusses the treatments available and their mechanism of action based on the administration methods; in fact, just looking at the results obtained by the researcher using topic versus systemic treatment, might be possible to speculate about the peripheral or central origin of the olfactory disorder. EXPERT OPINION: Because COVID-19 causes olfactory loss and several treatments (topical and systemic) have been tested in this disease, we have decided to use this model of acquired olfactory loss to discuss the different therapeutical option. The authors believe these treatments might be an option also for treating olfactory disease related to neurodegeneration.

Sudden Sensorineural Hearing Loss after Third Dose Booster of COVID-19 Vaccine Administration.

Coronavirus disease 2019 (COVID-19) was declared a pandemic due to its rapid spread worldwide, and its vaccination campaign is considered one of the most historic public hygiene measures in modern medicine. Sudden sensorineural hearing loss (SSHL) is a common emergency that affects patient's quality of life and requires rapid treatment with steroids. The etiology could be viral or vascular even though in most cases it remains unknown (idiopathic SSHL). During the SARS-CoV-2 vaccination campaign, several rare but serious adverse events have been reported including thrombosis with thrombocytopenia syndrome, myocarditis, and Guillain-Barré Syndrome. ENT adverse events after vaccination were reported too, including cases of sudden sensorineural hearing loss (SSHL), vestibular neuronitis and audio vestibular disorders (such as tinnitus, dizziness, and vertigo). For the first time here, we reported two cases of SSHL after third administration of COVID-19 mRNA vaccine. Even if there is not clear evidence of an association between SSHL and vaccination, adverse effects should be kept in mind since viral infection could be the etiology of SSHL.

Long-Term Subjective and Objective Assessment of Smell and Taste in COVID-19.

Among the first clinical symptoms of the SARS-CoV-2 infection is olfactory-gustatory deficit; this continues for weeks and, in some cases, can be persistent. We prospectively evaluated 162 patients affected by COVID-19 using a visual analogue scale (VAS) for nasal and olfactory-gustatory symptoms. Patients were checked after 7, 14, 21, 28, 90, and 180 days. A total of 118 patients (72.8%) reported an olfactory VAS < 7 at baseline (group B), and 44 (27.2%) reported anosmia (VAS ≥ 7) (group A) and underwent the Brief Smell Identification Test (B-SIT) and Burghart Taste Strips (BTS) to quantify the deficit objectively and repeated the tests to confirm the sense recovery. Group A patients showed B-SIT anosmia and hyposmia in 44.2% and 55.8% of cases, respectively. A total of 88.6% of group A patients reported ageusia with VAS ≥ 7, and BTS confirmed 81.8% of ageusia and 18.2% of hypogeusia. VAS smell recovery was recorded starting from 14 days, with normalization at 28 days. The 28-day B-SIT score showed normosmia in 90.6% of group A patients. The mean time for full recovery (VAS = 0) was shorter in group B (22.9 days) than in group A (31.9 days). Chemosensory deficit is frequently the first symptom in patients with COVID-19, and, in most cases, recovery occurs after four weeks.

Exploring Mitochondrial Localization of SARS-CoV-2 RNA by Padlock Assay: A Pilot Study in Human Placenta.

The ongoing COVID-19 pandemic dictated new priorities in biomedicine research. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is a single-stranded positive-sense RNA virus. In this pilot study, we optimized our padlock assay to visualize genomic and subgenomic regions using formalin-fixed paraffin-embedded placental samples obtained from a confirmed case of COVID-19. SARS-CoV-2 RNA was localized in trophoblastic cells. We also checked the presence of the virion by immunolocalization of its glycoprotein spike. In addition, we imaged mitochondria of placental villi keeping in mind that the mitochondrion has been suggested as a potential residence of the SARS-CoV-2 genome. We observed a substantial overlapping of SARS-CoV-2 RNA and mitochondria in trophoblastic cells. This intriguing linkage correlated with an aberrant mitochondrial network. Overall, to the best of our knowledge, this is the first study that provides evidence of colocalization of the SARS-CoV-2 genome and mitochondria in SARS-CoV-2 infected tissue. These findings also support the notion that SARS-CoV-2 infection can reprogram mitochondrial activity in the highly specialized maternal-fetal interface.

Association Between Severity of COVID-19 Respiratory Disease and Risk of Obstructive Sleep Apnea.

OBJECTIVES: The purpose of this observational retrospective study was to evaluate, in patients with a severe acute respiratory syndrome coronavirus 2 infection, the association between the severity of coronavirus disease 2019 (COVID-19) respiratory illness and the risk of infected patients to develop obstructive sleep apnea (OSA). METHODS: Ninety-six patients with confirmed COVID-19 infection were enrolled in the study. The STOP-BANG questionnaire to investigate the risk of the OSA syndrome was filled in by the patients at admission. The enrolled patients were divided into 2 groups according to the respiratory disease: group 1 (72 patients), hospitalized patients undergoing conventional oxygen therapy; group 2 (24 patients), patients requiring enhanced respiratory support. STOP-BANG results of these 2 groups were compared to observe whether patients with high OSA risk more frequently presented a severe form of COVID-19. RESULTS: 41.6% of the patients in group 2 had a STOP-BANG score between 5 and 8 (high risk of having apnea); in contrast, 20.8% of the patients in group 1 had a STOP-BANG score between 5 and 8, with a statistically significant difference between the 2 groups (P = .05). A complementary trend was observed regarding the proportion of patients in the range 0 to 2, which classifies patients at a low risk of OSA (48.6% vs 20.8% for groups 1 and 2, P = .01). CONCLUSIONS: According to our data, the chances of having a severe case of COVID-19 should be considered in patients at high risk of OSA. CURRENT KNOWLEDGE/STUDY RATIONALE: Emerging research suggests that OSA could represent a potentially important risk factor for the severe forms of COVID-19. The purpose of this observational retrospective study was to evaluate the potential association between OSA and the severity of COVID-19 disease. STUDY IMPACT: According to our data, the likelihood of contracting a severe form of COVID-19 disease should be considered in patients at high risk of OSA.

Impact of COVID-19 pandemic on the incidence of otitis media with effusion in adults and children: a multicenter study.

PURPOSE: To compare and analyze the incidence of otitis media with effusion (OME), before and during the COVID-19-related pandemic period, to evaluate the effects of the social changes (lockdown, continuous use of facial masks, social distancing, reduction of social activities) in the OME incidence in children and adults. METHODS: The number of diagnosed OME in e five referral centers, between 1 March 2018 and 1 March 2021, has been reviewed and collected. To estimate the reduction of OME incidence in children and adults during the COVID-19 pandemic period the OME incidence in three period of time were evaluated and compared: group 1-patients with OME diagnosis achieved between 1/03/2018 and 01/03/2019 (not pandemic period). Group 2-patients with OME diagnosis achieved between 1/03/2019 and 1/03/2020 (not pandemic period). Group 3-patients with OME diagnosis achieved between 1/03/2020 and 1/03/2021 (COVID-19 pandemic period). RESULTS: In the non-pandemic periods (group 1 and 2), the incidence of OME in the five referral centers considered was similar, with 482 and 555 diagnosed cases, respectively. In contrast, the OME incidence in the same centers, during the pandemic period (group 3) was clearly reduced with a lower total number of 177 cases of OME estimated. Percentage variation in OME incidence between the first non-pandemic year considered (group 1) and the pandemic period (group 3) was-63, 3%, with an absolute value decrease value of-305 cases. Similarly, comparing the second non-pandemic year (group 2) and the pandemic year (group 3) the percentage variation of OME incidence was-68, 1% with an absolute value of-305 cases decreased. CONCLUSIONS: Our findings showed a lower incidence of OME during the pandemic period compared with 2 previous non pandemic years. The drastic restrictive anti-contagion measures taken by the Italian government to contain the spread of COVID-19 could have had a positive impact on the lower OME incidence during the last pandemic year.

Otolaryngology activity in two hospitals in northern and central Italy differently affected by COVID-19 pandemic.

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic had a significant impact on the Italian healthcare system, although geographical differences were present; regions in northern Italy have been the most severely affected while regions in the south of the country were relatively spared. Otolaryngologists were actively involved in the management of the pandemic. In this work, we analyzed and compared the otolaryngology surgical activity performed during the pandemic in two large public hospitals located in different Italian regions. In northern Italy, otolaryngologists were mainly involved in performing surgical tracheotomies in COVID-19 positive patients and contributed to the management of these patients in intensive care units. In central Italy, where the burden of the infection was significantly lower, otolaryngologists focused on diagnosis and treatment of emergency and oncology patients. This analysis confirms the important role of the otolaryngology specialists during the pandemic, but also highlights specific differences between two large hospitals in different Italian regions.

Clinical Recommendations for Epistaxis Management During the COVID-19 Pandemic.

Epistaxis is a common complaint in the general population, and its treatment is a common procedure in emergency departments. In the COVID-19 era, procedures involving airway management are a particular risk for health care workers due to the high virulence of the virus, the transmission through aerosol, and the risk of contagion from asymptomatic patients. In this article, we propose a simple memorandum of clinical recommendations to minimize the risk of operator infection deriving from epistaxis management. The correct use of personal protective equipment and strict compliance with the behavioral guidelines are essential to reduce the potential risk of infection. In particular, the use of filtering masks is strongly recommended since all patients, including those referring for epistaxis, should be treated as being COVID-19 positive in the emergency department. The safety of health care workers is essential not only to safeguard continuous patient care but also to limit virus transmission.

The Effects of the COVID-19/SARS-CoV-2 Pandemic Outbreak on Otolaryngology Activity in Italy.

The coronavirus disease 2019 (COVID-19) pandemic during the first months of 2020 is causing profound changes in worldwide health care systems, resulting in a major reduction of surgical interventions and routine non-urgent outpatient diagnostic procedures. The lockdown due to the COVID-19 pandemic in Italy, one of the most affected countries in Europe, is having severe effects on the otolaryngology medical and surgical activities. The main changes are represented by the postponement of outpatient visits and scheduled surgery, while the only guaranteed service is reserved to diagnostics and surgery for oncology and urgent patients. In these cases, given the sites of action typical of the otolaryngology practice, physicians and nurses are exposed to a high risk of contagion through virus aerosol transmission. Furthermore, as the current measures of lockdown continue, it will be difficult to perform scheduled and new diagnostic assessments, medical treatments and surgical procedures in a timely manner favoring the risk of diagnostic and therapeutic delays with severe impact on patients' health.