Exploratory Study on Chemosensory Event-Related Potentials in Long COVID-19 and Mild Cognitive Impairment: A Common Pathway?

People affected by the Long COVID-19 (LC) syndrome often show clinical manifestations that are similar to those observed in patients with mild cognitive impairments (MCI), such as olfactory dysfunction (OD), brain fog, and cognitive and attentional diseases. This study aimed to investigate the chemosensory-evoked related potentials (CSERP) in LC and MCI to understand if there is a common pathway for the similarity of symptoms associated with these disorders. Eighteen LC patients (mean age 53; s.d. = 7), 12 patients diagnosed with MCI (mean age 67; s.d. = 6), and 10 healthy control subjects (mean age 66; s.d. = 5, 7) were recruited for this exploratory study. All of them performed a chemosensory event-related potentials (CSERP) task with the administration of trigeminal stimulations (e.g., the odorants cinnamaldehyde and eucalyptus). Study results highlighted that MCI and LC showed reduced N1 amplitude, particularly in the left frontoparietal network, involved in working memory and attentional deficits, and a reduction of P3 latency in LC. This study lays the foundations for evaluating aspects of LC as a process that could trigger long-term functional alterations, and CSERPs could be considered valid biomarkers for assessing the progress of OD and an indicator of other impairments (e.g., attentional and cognitive impairments), as they occur in MCI.

Psychophysical assessment of olfactory and gustatory function in post-mild COVID-19 patients: A matched case-control study with 2-year follow-up.

BACKGROUND: The aim of this study was to psychophysically evaluate the prevalence of smell and taste dysfunction 2 years after mildly symptomatic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection compared to that observed at 1-year follow-up and while considering the background of chemosensory dysfunction in the no-coronavirus disease 2019 (COVID-19) population. METHOD: This is a prospective case-control study on 93 patients with polymerase chain reaction (PCR)-positive SARS-CoV-2 infection and 93 matched controls. Self-reported olfactory and gustatory dysfunction was assessed by 22-item Sino-Nasal-Outcome Test (SNOT-22), item "Sense of smell or taste." Psychophysical orthonasal and retronasal olfactory function and gustatory performance were estimated using the extended Sniffin' Sticks test battery, 20 powdered tasteless aromas, and taste strips test, respectively. Nasal trigeminal sensitivity was assessed by sniffing a 70% solution of acetic acid. RESULTS: The two psychophysical assessments of chemosensory function took place after a median of 409 days (range, 366-461 days) and 765 days (range, 739-800 days) from the first SARS-CoV-2-positive swab, respectively. At 2-year follow-up, cases exhibited a decrease in the prevalence of olfactory (27.9% vs. 42.0%; absolute difference, -14.0%; 95% confidence interval [CI], -21.8% to -2.6%; p = 0.016) and gustatory dysfunction (14.0% vs. 25.8%; absolute difference, -11.8%; 95% CI, -24.2% to 0.6%; p = 0.098). Subjects with prior COVID-19 were more likely than controls to have an olfactory dysfunction (27.9% vs. 10.8 %; absolute difference, 17.2%; 95% CI, 5.2% to 28.8%) but not gustatory dysfunction (14.0% vs. 9.7%; absolute difference, 4.3%; 95% CI, -5.8% to 14.4% p = 0.496) still 2 years after the infection. Overall, 3.2% of cases were still anosmic 2 years after the infection. CONCLUSIONS: Although a proportion of subjects recovered from long-lasting smell/taste dysfunction more than 1 year after COVID-19, cases still exhibited a significant excess of olfactory dysfunction 2 years after SARS-CoV-2 infection when compared to matched controls.

Early Negativization of SARS-CoV-2 Infection by Nasal Spray of Seawater plus Additives: The RENAISSANCE Open-Label Controlled Clinical Trial.

Background: COVID-19 is an asymptomatic condition in 40% of cases, and most symptomatic patients present with mild/moderate disease not requiring hospitalization or intensive care, especially during the Omicron wave, when the hospitalization rate was estimated to be 0.3%. The main port of entry for SARS-CoV-2 in the human body is the nasal cavity and the upper respiratory tract is affected since the early stages of the infection. Nasal irrigation or aerosol by isotonic or hypertonic saline solution is a traditional therapeutic approach for respiratory or nasal inflammation, also featured by prophylactic properties against upper respiratory infections. Methods: We conducted a prospective open-label controlled study to assess the superiority of an already existing medication (Tonimer Lab Panthexyl 800)-a sterile hypertonic solution containing seawater, xylitol, panthenol and lactic acid-to reduce the viral shedding time in patients affected by asymptomatic or mild COVID-19. COVID-19 patients (N = 108) were split into two groups: a treatment arm (50 participants receiving standard of care plus nasal spray 3 times/day with Tonimer Lab Panthexyl 800) and a control arm (58 participants receiving standard of care but nasal spray with Tonimer Lab Panthexyl 800). The two groups, both testing initially positive for SARS-CoV-2 at real-time PCR (RT-PCR) on nasal swab, were followed up over time to assess the daily number of positive swab tests turning negative (study endpoint). Treatment effectiveness at various time lags since the first positive RT-PCR swab test was measured by rate of events in the experimental arm (EER) and in the control arm (CER), absolute risk increase (ARI) = (EER - CER), and number needed to treat (NNT) = (1/ARI). To investigate the endpoint, we used logistic and Cox regression models, expressing the result as odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (95%CI), respectively. The symptoms recorded with a modified COVID-Q questionnaire at both diagnosis and first negative antigenic swab test were compared in each group (treated versus controls) by exact symmetry test. Results: During the first five days of treatment, COVID-19 patients treated with Tonimer Lab Panthexyl 800 were more likely to become negative two days before controls. According to NNT, four subjects had to be treated for five days to achieve the study endpoint in one individual. The negativization rate in patients treated with Tonimer Lab Panthexyl 800 was significantly higher than patients' treated with standard of care alone (OR = 7.39, 95%CI: 1.83-29.8; HR = 6.12, 95%CI: 1.76-21.32). There was no evidence of side effects. Conclusions: Nasal spray with Tonimer Lab Panthexyl 800 was effective against SARS-CoV-2, stopping viral shedding in the treatment arm two days before the control group. This treatment should be continued for at least five days after the first positive swab test for SARS-CoV-2.

A singular case of hyposmia and transient audiovestibular post-vaccine disorders: case report and literature review.

Introduction: Rare and mild adverse effects on cranial nerves have been reported after vaccination. Here, we report a singular case of smell and taste disorder associated with tinnitus that occurred after Oxford-AstraZeneca vaccination together with a review of the available literature. Case presentation: A 76-year-old patient experienced smell disorder, ear fullness and tinnitus 2 days after the first dose of Oxford-AstraZeneca vaccine. The patient then underwent a complete audiological and Ear, Nose and Throat evaluation, nasal endoscopy, Sniffin'Sticks battery, audiometric test battery, and cerebral magnetic resonance imaging (MRI). The exams revealed hyposmia and bilateral reduction of the volume of the olfactory bulbs (OB). At the follow-up, tinnitus was completely resolved while olfactory dysfunction only partially reduced. Review of the literature: A PubMed search was conducted on olfactory and gustatory dysfunctions after COVID-19 vaccination resulting in four case reports with a total of 10 patients. The main symptoms were hyposmia, parosmia, and dysgeusia developed after 1-9 days from vaccination with complete resolution occurring within 1 month. Notably, none of the considered articles reported reduction of OB volumes at cerebral MRI. Discussion: So far, no definitive cause-effect relationship has been established between anti-COVID19 vaccination and otolaryngologic adverse reactions. The persistence of hyposmia in our patient could possibly be explained by the reduction in OB volume, even though also the advanced age of the patient needs to be taken into account. This is a first indication of a cause-effect relation between hyposmia and Covid19 vaccination, even though a more robust study is needed to confirm the autoimmunological mechanisms responsible for these rare adverse reactions. However, it is worth highlighting that benefits of the anti-COVID-19 vaccination clearly outweigh the risk of rare adverse events.

A Viable Alternative. Comment on Kohmer et al. Self-Collected Samples to Detect SARS-CoV-2: Direct Comparison of Saliva, Tongue Swab, Nasal Swab, Chewed Cotton Pads and Gargle Lavage. J. Clin. Med. 2021, 10, 5751.

We read with great interest and would like to comment on the article "Self-Collected Samples to Detect SARS-CoV-2: Direct Comparison of Saliva, Tongue Swab, Nasal Swab, Chewed Cotton Pads and Gargle Lavage" [...].

Magnetic Resonance Imaging Confirmed Olfactory Bulb Reduction in Long COVID-19: Literature Review and Case Series.

An altered sense of smell and taste was recognized as one of the most characteristic symptoms of coronavirus infection disease (COVID-19). Despite most patients experiencing a complete functional resolution, there is a 21.3% prevalence of persistent alteration at 12 months after infection. To date, magnetic resonance imaging (MRI) findings in these patients have been variable and not clearly defined. We aimed to clarify radiological alterations of olfactory pathways in patients with long COVID-19 characterized by olfactory dysfunction. A comprehensive review of the English literature was performed by analyzing relevant papers about this topic. A case series was presented: all patients underwent complete otorhinolaryngology evaluation including the Sniffin' Sticks battery test. A previous diagnosis of SARS-CoV-2 infection was confirmed by positive swabs. The MRIs were acquired using a 3.0T MR scanner with a standardized protocol for olfactory tract analysis. Images were first analysed by a dedicated neuroradiologist and subsequently reviewed and compared with the previous available MRIs. The review of the literature retrieved 25 studies; most cases of olfactory dysfunction more than 3 months after SARS-CoV-2 infection showed olfactory bulb (OB) reduction. Patients in the personal case series had asymmetry and a reduction in the volume of the OB. This evidence was strengthened by the comparison with a previous MRI, where the OBs were normal. The results preliminarily confirmed OB reduction in cases of long COVID-19 with an altered sense of smell. Further studies are needed to clarify the epidemiology, pathophysiology and prognosis.

Magnetic Resonance Imaging Confirmed Olfactory Bulb Reduction in Long COVID-19: Literature Review and Case Series

An altered sense of smell and taste was recognized as one of the most characteristic symptoms of coronavirus infection disease (COVID-19). Despite most patients experiencing a complete functional resolution, there is a 21.3% prevalence of persistent alteration at 12 months after infection. To date, magnetic resonance imaging (MRI) findings in these patients have been variable and not clearly defined. We aimed to clarify radiological alterations of olfactory pathways in patients with long COVID-19 characterized by olfactory dysfunction. A comprehensive review of the English literature was performed by analyzing relevant papers about this topic. A case series was presented: all patients underwent complete otorhinolaryngology evaluation including the Sniffin' Sticks battery test. A previous diagnosis of SARS-CoV-2 infection was confirmed by positive swabs. The MRIs were acquired using a 3.0T MR scanner with a standardized protocol for olfactory tract analysis. Images were first analysed by a dedicated neuroradiologist and subsequently reviewed and compared with the previous available MRIs. The review of the literature retrieved 25 studies;most cases of olfactory dysfunction more than 3 months after SARS-CoV-2 infection showed olfactory bulb (OB) reduction. Patients in the personal case series had asymmetry and a reduction in the volume of the OB. This evidence was strengthened by the comparison with a previous MRI, where the OBs were normal. The results preliminarily confirmed OB reduction in cases of long COVID-19 with an altered sense of smell. Further studies are needed to clarify the epidemiology, pathophysiology and prognosis.

The Effect of Isotonic Saline Nasal Lavages in Improving Symptoms in SARS-CoV-2 Infection: A Case-Control Study.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mainly colonizes nasopharynx. In upper airways acute infections, e.g., the common cold, saline nasal irrigations have a significant efficacy in reducing symptoms. The present study aimed to test the efficacy of nasal lavages in upper airways symptoms of Coronavirus Disease 2019 (COVID-19). Methods: A series of consecutive adult subjects who tested positive for SARS-CoV-2 from December 2020 to February 2021 performed daily nasal lavages with saline solution (Lavonase®-Purling, Lugo di Romagna, Italy) for 12 days, starting on the day after the SARS-CoV-2 positive swab. A control group included a historical series of patients who were infected in February-March 2020 and who did not perform lavages. An ad hoc questionnaire regarding symptoms was administered to each subjects at base-line and 10 days after diagnosis (i.e., on the same day of the control swab) in both cases and controls. Results: A total of 140 subjects were enrolled. 68 participants in the treatment group and 72 in the control group were included. 90% of respondents declared the lavages were simple to use and 70% declared they were satisfied. Symptoms of blocked nose, runny nose, or sneezing decreased by an average of 24.7% after the treatment. Blocked nose and sneezing increased in the same period of time in the control group. Ears and eyes symptoms, anosmia/ageusia symptoms, and infection duration (10.53 days in the treatment group and 10.48 days in the control group) didn't vary significantly among the two groups. Conclusion: Nasal lavages resulted to significantly decrease nasal symptoms in newly diagnosed SARS-CoV-2 patients. These devices proved to be well-tolerated and easy to be used. Further studies on a larger number of subjects are needed in order to possibly confirm these preliminary results.

COVID-Q: Validation of the first COVID-19 questionnaire based on patient-rated symptom gravity.

OBJECTIVES: The aim of the present study was to develop and validate the CoronaVirus-Disease-2019 (COVID-19) Questionnaire (COVID-Q), a novel symptom questionnaire specific for COVID-19 patients, to provide a comprehensive evaluation that may be helpful for physicians, and evaluate the questionnaire's performance in identifying subjects at higher risk of testing positive. MATERIALS AND METHODS: Consecutive non-hospitalised adults who underwent nasopharyngeal-throat swab for severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) detection at Treviso Hospital in March 2020, were enrolled. Subjects were divided into positive (cases) and negative (controls). All subjects answered the COVID-Q. Patients not able to answer COVID-Q because of clinical conditions were excluded. Parallel Analysis and Principal Component Analysis identified items measuring the same dimension. The Item Response Theory (IRT)-based analyses evaluated the functioning of item categories, the presence of clusters of local dependence among items, item fit within the model and model fit to the data. RESULTS: Answers obtained from 230 cases (113 males; mean age 55 years, range 20-99) and 230 controls (61 males; mean age 46 years, range 21-89) were analysed. Six components were extracted with parallel analysis: asthenia, influenza-like symptoms, ear and nose symptoms, breathing issues, throat symptoms, and anosmia/ageusia. The final IRT models retained 27 items as significant for symptom assessment. The total questionnaire's score was significantly associated with positivity to the molecular test: subjects with multiple symptoms were more likely to be affected (P < .001). Older age, male gender presence of breathing issues and anosmia/ageusia were significantly related to positivity (P < .001). Comorbidities had not a significant association with the COVID-19 diagnosis. CONCLUSION: COVID-Q could be validated since the evaluated aspects were overall significantly related to infection. The application of the questionnaire to clinical practice may help to identify subjects who are likely to be affected by COVID-19 and address them to a nasopharyngeal swab in order to achieve an early diagnosis.

A Severe Acute Respiratory Syndrome Coronavirus 2 detection method based on nasal and nasopharyngeal lavage fluid: A pilot feasibility study.

OBJECTIVE: Nose and nasopharyngeal swab is the preferred and worldwide-accepted method to detect the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) within the nose and nasopharynx. This method may be linked with possible difficulties, such as patient's discomfort or complications. This article shows a pilot study of SARS-CoV-2 detection with nasal and nasopharyngeal lavage fluids (level of evidence: 3). METHODS: Nasal lavage fluid was collected from patients who were submitted to SARS-CoV-2 screening test, due to a preceding positive rapid antigen test. A control group was enrolled among health care professionals whose nasopharyngeal swab tested negative. Nasal lavages were performed using isotonic saline solution injected through a nasal fossa. Both lavage fluid and traditional nasopharyngeal swab were analyzed by real-time (RT) PCR and antigenic test. RESULTS: A total of 49 positive subjects were enrolled in the study. Results of the analysis on lavages and nasopharyngeal swabs were concordant for 48 cases, regardless of the antigenic and molecular test performed. RT-PCR resulted weakly positive at swab in one case and negative at lavage fluid. Among the control group (44 subjects), nasopharyngeal swab and lavage fluid analyses returned a negative result. Sensitivity of the molecular test based on nasal lavage fluid, compared to traditional nasal swab, was 97.7%, specificity was 100%, and accuracy was 98.9%, with high agreement (Cohen's κ, 0.978). CONCLUSION: Nasal and nasopharyngeal lavages resulted to be highly reliable and well tolerated. A larger series is needed to confirm these results. This approach may potentially represent a valid alternative to the traditional swab method in selected cases. LEVEL OF EVIDENCE: 3.

Tinnitus following COVID-19 vaccination: report of three cases.

OBJECTIVE: To ensure the safety and quality of vaccines, especially the newest RNA-vaccines against COVID-19, is one of the World Health Organization's current highest priorities. DESIGN: Case description. STUDY SAMPLE: We report three cases of sudden unilateral tinnitus following BNT162b2 mRNA-vaccine injection, which rapidly resolved in 2 out of 3 cases. RESULTS: The mechanism responsible for its development remains unclear. A hypersensitivity reaction with an abnormal autoimmune response or a vasculitic event may be implicated. CONCLUSIONS: Large-scale and well-designed studies are needed to improve surveillance of the COVID-19 vaccine and better define possible adverse reactions involving the cochleo-vestibular system and/or immunisation anxiety-related reactions.

Correct Execution of the Nasopharyngeal Swab: A Fundamental Method to Improve Diagnosis of SARS-CoV-2 Infection.

BACKGROUND: Severe acute respiratory infection Coronavirus 2 (SARS-CoV-2) infection has spread all over the world since December 2019. Treatment of the syndrome represents an important challenge for all physicians. Spread prevention relies on a correct diagnosis which is performed with nasopharyngeal swabs. OBJECTIVE: To describe the proper execution of the swab with a few simple steps. METHODS: Figures and video recording. RESULTS: A few simple steps are presented within this paper in order to perform easily nasopharyngeal swab for SARS-Cov-2 diagnosis and for other possible infectious diseases of the airways tract. CONCLUSIONS AND IMPLICATION FOR NURSING: Nasopharyngeal swab may be performed in an easier way than usually thought. This method may also be used for any other microorganism detection. By following simple steps, a correct diagnosis can easily be obtained.

The importance of early detection of ENT symptoms in mild-to-moderate COVID-19.

OBJECTIVES: Patients with coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may present with a wide range of symptoms. In this paper, a detailed characterisation of mild-to-moderate ear, nose nd throat (ENT) symptoms is presented with the aim of recognising the disease early to help reduce further spread and progression. METHODS: A total of 230 cases testing positive for SARS-CoV-2 and 134 negative controls were recruited for a case-control analysis. Symptoms were analysed using the Acute Respiratory Tract Infections Questionnaire, while other symptoms were investigated by ad hoc questions. RESULTS: Among the study samples (n = 364), 149 were males and 215 were females with age ranging from 20 to 89 years (mean 52.3). Four main groups of symptoms were obtained: influenza-like symptoms, ENT-symptoms, breathing issues and asthenia-related symptoms, representing 72%, 69%, 64% and 53% of overall referred clinical manifestations, respectively. ENT symptoms, breathing issues and influenza-like symptoms were associated with positivity to SARS-CoV-2, whereas asthenia-related symptoms did not show a significant association with SARS-CoV-2 infection after controlling for other symptoms, comorbidities and demographic characteristics. CONCLUSIONS: ENT symptoms are equally represented with influenza-like ones as presenting symptoms of COVID-19. Patients with ENT symptoms should be investigated for early identification and prevention of SARS-CoV-2 spread.

COVID-19 in the tonsillectomised population.

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.

Risk management during COVID-19: safety procedures for otolaryngologists.

The pandemic caused by SARS-CoV2 has stressed health care systems worldwide. The high volume of patients, combined with an increased need for intensive care and potential transmission, has forced reorganization of hospitals and care delivery models. In this article, are presented approaches to minimize risk to Otolaryngologists during their patients infected with COVID-19 care. We performed a narrative literature review among PubMed, Scopus and Web of Science electronic databases, searching for studies on SARS-CoV2 and Risk Management. Standard operating procedures have been adapted both for facilities and for health care workers, including the development of well-defined and segregated patient care areas for treating those affected by COVID-19. Personal protective equipment (PPEs) availability and adequate healthcare providers training on their use should be ensured. Preventive measures are especially important in Otolaryngology-Head and Neck Surgery, as the exposure to saliva suspensions, droplets and aerosols are increased in the upper aero-digestive tract routine examination. Morever, the frequent invasive procedures, such as laryngoscopy, intubation or tracheotomy placement and care, represent a high risk of contracting COVID-19.

Six-Month Psychophysical Evaluation of Olfactory Dysfunction in Patients with COVID-19.

This study prospectively assessed the 6-month prevalence of self-reported and psychophysically measured olfactory dysfunction in subjects with mild-to-moderate COVID-19. Self-reported smell or taste impairment was prospectively evaluated by SNOT-22 at diagnosis, 4-week, 8-week, and 6-month. At 6 months from the diagnosis, psychophysical evaluation of olfactory function was also performed using the 34-item culturally adapted University of Pennsylvania Smell Identification Test (CA-UPSIT). 145 completed both the 6-month subjective and psychophysical olfactory evaluation. According to CA-UPSIT, 87 subjects (60.0%) exhibited some smell dysfunction, with 10 patients being anosmic (6.9%) and seven being severely microsmic (4.8%). At the time CA-UPSIT was administered, a weak correlation was observed between the self-reported alteration of the sense of smell or taste and olfactory test scores (Spearman's r = -0.26). Among 112 patients who self-reported normal sense of smell at last follow-up, CA-UPSIT revealed normal smell in 46 (41.1%), mild microsmia in 46 (41.1%), moderate microsmia in 11 (9.8%), severe microsmia in 3 (2.3%), and anosmia in 6 (5.4%) patients; however, of those patients self-reporting normal smell but who were found to have hypofunction on testing, 62 out of 66 had a self-reported reduction in sense of smell or taste at an earlier time point. Despite most patients report a subjectively normal sense of smell, we observed a high percentage of persistent smell dysfunction at 6 months from the diagnosis of syndrome coronavirus 2 (SARS-CoV-2) infection, with 11.7% of patients being anosmic or severely microsmic. These data highlight a significant long-term rate of smell alteration in patients with previous SARS-COV-2 infection.