Long COVID, audiovestibular symptoms and persistent chemosensory dysfunction: a systematic review of the current evidence.

Objective: The persistence of auditory, vestibular, olfactory, and gustatory dysfunction for an extended time after COVID-19 has been documented, which represents an emerging challenge of which ENT specialists must be aware. This systematic review aims to evaluate the prevalence of persistent audiovestibolar and olfactory/gustatory symptoms in patients with "long-COVID". Methods: The literature was systematically reviewed according to PRISMA guidelines; PubMed, Scopus and Google Scholar were screened by searching articles on audiovestibular symptoms and olfactory/gustatory dysfunction after SARS-CoV-2 infection. The keywords used were hearing loss, tinnitus, vertigo, smell disorders, parosmia, anosmia, hyposmia, dysgeusia combined with COVID-19 or SARS-CoV-2. Results: 1100 articles were identified. After removal of duplicates (382), 702 articles were excluded, and 16 were included in the systematic review. All articles included identified an association between SARS-CoV-2 infection and persistent hearing or chemosensory impairment. The studies were published over a period of 2 years, between 2019 and 2021. Conclusions: The likelihood of patients with persistent audiovestibular symptoms related to COVID-19 was different among the articles; however, olfactory and gustatory disturbances were more consistently reported. Studies with longer follow-up are required to fully evaluate the long-term impact of these conditions.

Olfactory dysfunction and coronavirus disease 2019 severity: a prospective cohort study.

OBJECTIVE: The primary goal of this study was to evaluate the association between olfactory dysfunction or taste impairment and disease severity and radiological findings in coronavirus disease-2019. The secondary goal was to assess the prevalence, severity and course of olfactory dysfunction or taste impairment in patients with coronavirus disease 2019. METHOD: This prospective observational cohort study evaluated patients hospitalised with coronavirus disease 2019 between April 1 and 1 May 2020. Olfactory dysfunction and taste impairment were evaluated by two questionnaires. Chest computed tomography findings and coronavirus disease-2019 severity were assessed. RESULTS: Among 133 patients, 23.3 per cent and 30.8 per cent experienced olfactory dysfunction and taste impairment, respectively, and 17.2 per cent experienced both. The mean age was 56.03 years, and 64.7 per cent were male and 35.3 per cent were female. No statistically significant association was found between olfactory dysfunction (p = 0.706) and taste impairment (p = 0.35) with either disease severity or chest computed tomography grading. CONCLUSION: Olfactory dysfunction or taste impairment does not have prognostic importance in patients with coronavirus disease 2019.

Patterns and clinical outcomes of olfactory and gustatory disorders in six months: Prospective study of 1031 COVID-19 patients.

OBJECTIVE: This study aims to comprehensively evaluate olfactory and gustatory dysfunctions during the COVID-19 pandemic regarding onset, course, associated symptoms, prognosis and relation to patients' demographics, treatment received and other symptoms. PATIENTS& METHODS: This is a prospective study conducted on patients proven to be infected with COVID-19 and with olfactory/gustatory dysfunction symptoms. Detailed history was taken from each patient about the onset of this dysfunction, associated symptoms. Then follow-up survey was done after 6 months to evaluate the prognosis. RESULTS: 1031 patients were included in the study, aged 18 to 69 years old, with 31.8% were male. Olfactory/gustatory dysfunctions occurred after other COVID-19 symptoms in 43.5% of cases, occurred suddenly in 80.4% and gradually in 19.6%. These dysfunctions were anosmia & ageusia in 50.2%, hyposmia & hypogeusia in 23.3%, anosmia alone in 17.7%, phantosmia in 18%, Parosmia in 28.4%. In terms of recovery 6-month follow up, 680 patients (66%) recovered completely, 22.1% recovered partially while 11.9% did not recover. Most improvement occurred in the first two weeks. Headache, malaise, nasal obstruction and rhinorrhea were the commonest COVID-19 symptoms associated. CONCLUSION: Most recovery of olfactory/gustatory dysfunction in COVID-19 infection occurs at the first two weeks and is unrelated to patient demographics, treatment or olfactory training. Parosmia is an independent predictor for complete recovery, while phantosmia is significantly associated with lower probability of complete recovery.

Clinical, virological and immunological evolution of the olfactory and gustatory dysfunction in COVID-19.

PURPOSE: New-onset olfactory and gustatory dysfunction (OGD) represents a well-acknowledged COVID-19 red flag. Nevertheless, its clinical, virological and serological features are still a matter of debate. MATERIALS AND METHODS: For this cohort study, 170 consecutive subjects with new-onset OGD were consecutively recruited. Otolaryngological examination, OGD subjective grading, nasopharyngeal swabs (NS) for SARS-CoV-2 RNA detection and serum samples (SS) collection for SARS-CoV-2 IgG quantification were conducted at baseline and after one (T1), two (T2) and four weeks (T3). RESULTS: SARS-CoV-2 infection was confirmed in 79% of patients. Specifically, 43% of positive patients were detected only by SS analysis. The OGD was the only clinical complaint in 10% of cases. Concurrent sinonasal symptoms were reported by 45% of patients. Subjective improvement at T3 was reported by 97% of patients, with 40% recovering completely. Hormonal disorders and RNA detectability in NS were the only variables associated with OGD severity. Recovery rate was higher in case of seasonal influenza vaccination, lower in patients with systemic involvement and severe OGD. Not RNA levels nor IgG titers were correlated with recovery. CONCLUSION: Clinical, virological and serological features of COVID-19 related OGD were monitored longitudinally, offering valuable hints for future research on the relationship between host characteristics and chemosensory dysfunctions.

Virus load and incidence of olfactory, gustatory, respiratory, gastrointestinal disorders in COVID-19 patients: A retrospective cohort study.

OBJECTIVES: This study investigated the relationship between viral load and the incidence of olfactory and gustatory dysfunction (OD and GD), the incidence of respiratory and gastrointestinal symptoms and the recovery of OD and GD in COVID-19 patients. DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: This study was conducted on 599 outpatients' cases in Golestan province between February and June 2020. MAIN OUTCOME MEASURES: The incidence, severity (complete or partial) and recovery time of OD and GD and their associations with cycle threshold (CT) values of SARS-CoV-2 polymerase chain reaction were assessed. RESULTS: The mean age of patients was 38.27 ± 13.62 years. The incidence of general symptoms included myalgia 70.1%, headache 51.8%, fever 47.7% and dyspnoea 21.4%. 41.9% of patients had gastrointestinal symptoms, including abdominal pain 26.5%, diarrhoea 25.2%, nausea 20.5% and vomiting 12.9%. 12.2% of patients had comorbidity. The trimester recovery rates of OD and GD were 93.94% and 94.74% respectively. The mean recovery time of OD and GD was 14.56 ± 13.37 and 13.8 ± 3.77 days respectively. The mean CT value in all patients was 27.45 ± 4.55. There were significant associations between the mean of CT value with headache (p = 0.04), GD (p = 0.002) and OD (p = 0.001). CONCLUSIONS: The finding of this study indicates a possible association between viral load with incidence of OD and GD in COVID-19 patient's cases and assures the recovery of OD/GD in these patients.

Presence of gustatory and olfactory dysfunction in the time of the COVID-19 pandemic.

BACKGROUND: The unexpected outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused more than 49 million cases and an estimated 2,000,000 associated deaths worldwide. In Germany, there are currently more than 2,000,000 laboratory-confirmed coronavirus disease 2019 (COVID-19) cases including 51,800 deaths. However, regional differences also became apparent and with the second wave of infections, the detailed characterization of COVID-19 patients is crucial to early diagnosis and disruption of chains of infections. METHODS: Handing out detailed questionnaires to all individuals tested for COVID-19, we evaluated the clinical characteristics of negative and positive tested individuals. Expression of symptoms, symptom duration and association between predictor variables (i.e. age, gender) and a binary outcome (olfactory and gustatory dysfunction) were assessed. RESULTS: Overall, the most common symptoms among individuals who tested positive for SARS-CoV-2 were fatigue, headache, and cough. Olfactory and gustatory dysfunction were also reported by many SARS-CoV-2 negative individuals, more than 20% of SARS-CoV-2 negative tested individuals in our study reported olfactory and gustatory dysfunction. Independent of SARS-CoV-2 status, more females displayed symptoms of gustatory (29.8%, p = 0.0041) and olfactory dysfunction (22.9%, p = 0.0174) compared to men. CONCLUSIONS: Bringing early SARS-CoV-2 tests to the populations at risk must be a main focus for the upcoming months. The reliability of olfactory and gustatory dysfunction in COVID-19 negative tested individuals requires deeper investigation in the future.

Oral manifestations of Covid-19-A literature review.

Initially, it was reported that coronavirus 2019 disease (Covid-19) affects respiratory, gastrointestinal and neurological systems, but the oral, olfactory and integumentary systems are also involved. This review discusses various oral manifestations of Covid-19 reported in the literature along with possible underlying mechanisms. The reported manifestations include taste impairment, oral mucosal changes (petechiae, ulcers, plaque-like lesions, reactivation of herpes simplex virus 1(HSV1), geographical tongue and desquamative gingivitis) and dry mouth. The prominent location for mucosal lesions are tongue, palate and labial mucosa. The exact pathogenesis of these oral symptoms is not known. Angiotensin-converting enzyme 2 (ACE2) cell receptors are expressed in abundance on oral mucosa allowing severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) to infect them. Gustatory impairment along with olfactory changes is now listed as a symptom of Covid-19 by the World Health Organization, but further research is needed to confirm a link between reported additional oral symptoms and Covid-19. Dental professionals may encounter individuals with Covid-19 and be called upon to identify various oral manifestations of this disease.

A structural equation model to examine the clinical features of mild-to-moderate COVID-19: A multicenter Italian study.

The purpose of this study was to evaluate the clinical features of mild-to-moderate coronavirus disease 2019 (COVID-19) in a sample of Italian patients and to investigate the occurrence of smell and taste disorders. Infected individuals with suspected (clinical diagnosis) or laboratory-confirmed COVID-19 infection were recruited. Patients completed a survey-based questionnaire with the aim of assessing their epidemiological and clinical characteristics, general otorhinolaryngological symptoms, and smell and taste disorders. A total of 294 patients with mild-to-moderate COVID-19 completed the survey (147 females). The most prevalent general symptoms included fever, myalgia, cough, and headache. A total of 70.4% and 59.2% of patients reported smell and taste disorders, respectively. A significant association between the two above-mentioned disorders was found (rs: 0.412; P < .001). Smell disorders occurred before the other symptoms in 11.6% of patients and was not significantly associated with nasal obstruction or rhinorrhea. Interestingly, our statistical analysis did not show any significant difference, either for general symptoms or otorhinolaryngological features, between the clinical diagnosis group and the laboratory-confirmed diagnosis (polymerase chain reaction) group. The structural equation model confirmed significant standardized paths (P < .05) between general symptoms, comorbidities, and general otorhinolaryngological complaints in the absence of a significant correlation between these elements and smell and taste alterations. The prevalence of smell and taste disorders in mild-to-moderate Italian COVID-19 patients is significant both in suspected and laboratory-confirmed cases and reveals a strong correlation between these clinical signs regardless of the presence of general or otorhinolaryngological symptoms, such as nasal obstruction or rhinorrhea.

Eight-month follow-up of olfactory and gustatory dysfunctions in recovered COVID-19 patients.

PURPOSE: To investigate the recovery of loss of smell and taste among recovered COVID-19 patients. MATERIALS AND METHODS: This cross-sectional follow-up study is a sequel to a study by Biadsee et al. Among the previous study population of 128 non-hospitalized patients, positive for COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR), 97 patients participated in a survey designed for this study. Information and data regarding loss of smell and taste, rate of recovery, xerostomia, and additional symptoms; (Cough, Myalgia, Weakness, Rhinorrhea, Nasal congestion) were collected. RESULTS: A total of 43 men and 54 women were included. Mean age was 37.5 years (range 19-74). Mean follow-up was 229 days (range 191-253). Sixty-five patients reported gustatory dysfunction during the disease of which 61.5% reported full recovery, 38.5% partial recovery. Of 65 patients who reported olfactory impairment during the disease, 52% had full recovery and 48% reported partial recovery of olfactory function. Complete recovery of olfactory function was positively associated with full recovery of gustatory function (p = 0.01). Gender did not significantly affect the recovery of OD and GD (p = 0.45, p = 0.90, respectively). Patients who experienced olfactory dysfunction as an initial symptom had lower rates of olfactory complete recovery (p = 0.043). CONCLUSION: After a mean follow-up of 229 days, complete recovery of smell and taste functions occurred in 52% and 61.5%, respectively. However, dysfunction persisted in 48%-38.5% of patients.

Olfactory and Gustatory Dysfunction in Coronavirus Disease 2019 (COVID-19).

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide. Given scarce resources, nonlaboratory diagnostics are crucial. In this cross-sectional study, two-thirds of European patients with confirmed COVID-19 reported olfactory and gustatory dysfunction, indicating the significance of these symptoms in early diagnostics.

Otolaryngology manifestations of COVID-19 in pediatric patients.

BACKGROUND: The coronavirus disease 2019 pandemic has affected millions of people since its outbreak in December 2019. Limited data exist on otolaryngology manifestations of COVID-19 in pediatrics. This study aims to discuss the clinical features of COVID-19 in pediatrics, with an emphasis on otolaryngology manifestations. METHODS: The study included 660 COVID-19 laboratory-confirmed positive pediatric patients (aged 3-15 years) diagnosed at King Abdullah Specialist Children Hospital, Riyadh, Saudi Arabia. Data were retrospectively retrieved from January to July 2020 from electronic medical records and included patients' epidemiological and clinical features. Patients were then followed-up via phone calls to document any symptoms encountered after the first visit. Patients were categorized into three main groups according to age (3-6 years, 7-10 years, 11-15 years). RESULTS: Nearly half of the patients (43.6%) had asymptomatic infections. Fever and cough were the most commonly reported manifestations accounting for 39.2% and 19.8%, respectively. The most frequently reported otolaryngology symptoms were sore throat (17.3%) and rhinorrhea (14.4%). Moreover, 10.4% and 13.1% of children aged 7-15 years old experienced smell and taste disturbances, respectively. Older children (11-15 years) were more likely to report taste disturbances when compared to the younger children (17.2% vs 9.8%, p-value 0.02). Children aged between 3 and 6 years had significantly higher rates of admission (13.7%) and mortality (0.9%) when compared to the older groups (p-value 0.00). CONCLUSION: COVID-19 in pediatrics has a milder disease course and a better prognosis than adults. Multiple otolaryngology symptoms were reported in pediatric patients with COVID-19, which can help identify the suspected cases before the test result.

SARS-CoV-2 infection of the oral cavity and saliva.

Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.

COVID-19-related smell and taste disorders: A guide for nurses.

ABSTRACT: Olfactory impairment is recognized as a hallmark of COVID-19. This article highlights dysfunction of smell and taste associated with COVID-19 and discusses implications for nursing practice.

Quality of life and safety impact of COVID-19 associated smell and taste disturbances.

OBJECTIVE: The association between COVID-19 and chemosensory loss has garnered substantial attention, however to date little is known about the real-life consequences of impairment in this unique patient population. The aim of this study is to evaluate the quality of life (QOL) and personal safety deficits experienced by patients with COVID-19 infection. STUDY DESIGN: Prospective, longitudinal questionnaires. SETTING: National survey. METHODS: A longitudinal web-based nationwide survey of adults with COVID-19 and/or a sudden change in smell and taste was launched April 10, 2020. Previously published questions on chemosensory-related QOL and safety events were asked at the 6-month follow-up survey. RESULTS: As of February 10, 2021, 480 eligible respondents took the 6-month questionnaire, of whom 322 were COVID-19 positive. Impact on QOL was substantial with 96% of subjects reporting at least one of the defined deficits, and over 75% reporting at least 3 of these. "Reduced enjoyment of food" was the most common complaint (87%), while 43% of subjects self-reported depression. The prevalence of safety-related issues was common in this population, with over 57% reporting at least one, and 36% reporting 2 or more events. Of the events asked, the inability to smell smoke that others could perceive was the most common at 45%. CONCLUSIONS: COVID-19 associated chemosensory losses have a real and substantial impact on both quality of life and safety, beyond mere inconvenience. The high prevalence of these issues despite a relatively short period of olfactory deficit should alert clinicians to the serious risks to an already vulnerable patient population.

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.