The presumed mechanism and diagnosis of olfactory dysfunction related to COVID-19 are described. Olfactory training and adjuvant medication treatments are among the proposed assessment and management ...strategies to address the dysfunction.
To estimate the prevalence of olfactory and gustatory dysfunctions (OGDs) among patients infected with novel coronavirus disease 2019 (COVID-19).
A systematic review was conducted by searching ...MEDLINE, EMBASE, and the preprint server MedRxiv from their inception until May 11, 2020, using the terms anosmia or hyposmia or dysosmia or olfactory dysfunction or olfaction disorder or smell dysfunction or ageusia or hypogeusia or dysgeusia or taste dysfunction or gustatory dysfunction or neurological and COVID-19 or 2019 novel coronavirus or 2019-nCoV or SARS-CoV-2. The references of included studies were also manually screened. Only studies involving patients with diagnostic-confirmed COVID-19 infection were included. Random-effects meta-analysis was performed.
Twenty-four studies with data from 8438 patients with test-confirmed COVID-19 infection from 13 countries were included. The pooled proportions of patients presenting with olfactory dysfunction and gustatory dysfunction were 41.0% (95% CI, 28.5% to 53.9%) and 38.2% (95% CI, 24.0% to 53.6%), respectively. Increasing mean age correlated with lower prevalence of olfactory (coefficient = -0.076; P=.02) and gustatory (coefficient = -0.073; P=.03) dysfunctions. There was a higher prevalence of olfactory dysfunctions with the use of objective measurements compared with self-reports (coefficient = 2.33; P=.01). No significant moderation of the prevalence of OGDs by sex was observed.
There is a high prevalence of OGDs among patients infected with COVID-19. Routine screening for these conditions could contribute to improved case detection in the ongoing COVID-19 pandemic. However, to better inform population screening measures, further studies are needed to establish causality.
Olfactory disorders are common and affect about one-fifth of the general population. The main causes of olfactory loss are post viral upper respiratory infection, nasal/sinus disease, and head trauma ...and are therefore very frequent among patients in ear, nose, and throat clinics. We have systematically reviewed the impact of quantitative, qualitative, and congenital olfactory disorders on daily life domains as well as on general quality of life and depression. From the extensive body of literature, it can be concluded that loss of the sense of smell leads to disturbances in important areas, mainly in food enjoyment, detecting harmful food and smoke, and to some extent in social situations and working life. Most patients seem to deal well and manage those restrictions. However, a smaller proportion has considerable problems and expresses a noticeable reduction in general quality of life and enhanced depression. The impact of coping strategies is discussed.
Objectives/Hypothesis
Olfactory dysfunction has been observed as one of the clinical manifestations in COVID‐19 patients. We aimed to conduct a systematic review and meta‐analysis to estimate the ...overall pooled prevalence of olfactory dysfunction in COVID‐19 patients.
Study Design
Systematic review and meta‐analyses.
Methods
PubMed, Scopus, Web of Science, Embase, and Google Scholar databases were searched to identify studies published between 1 December 2019 and 23 July 2020. We used random‐effects model to estimate the pooled prevalence with 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic and Cochran's Q test. Robustness of the pooled estimates was checked by different subgroup and sensitivity analyses This study is registered with PROSPERO (CRD42020183768).
Results
We identified 1162 studies, of which 83 studies (n = 27492, 61.4% female) were included in the meta‐analysis. Overall, the pooled prevalence of olfactory dysfunction in COVID‐19 patients was 47.85% 95% CI: 41.20–54.50. We observed olfactory dysfunction in 54.40% European, 51.11% North American, 31.39% Asian, and 10.71% Australian COVID‐19 patients. Anosmia, hyposmia, and dysosmia were observed in 35.39%, 36.15%, and 2.53% of the patients, respectively. There were discrepancies in the results of studies with objective (higher prevalence) versus subjective (lower prevalence) evaluations. The discrepancy might be due to false‐negative reporting observed in self‐reported health measures.
Conclusions
The prevalence of olfactory dysfunction in COVID‐19 patients was found to be 47.85% based on high‐quality evidence. Due to the subjective measures of most studies pooled in the analysis, further studies with objective measures are advocated to confirm the finding.
Level of Evidence
2 Laryngoscope, 131:865–878, 2021
Neurologic sequelae can be devastating complications of respiratory viral infections. We report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at ...postmortem examination from a patient infected with severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). Our observations of virus in neural tissue, in conjunction with clinical correlates of worsening neurologic symptoms, pave the way to a closer understanding of the pathogenic mechanisms underlying central nervous system involvement by SARS‐CoV‐2.
Highlights
The clinical spectrum of COVID-19 has expanded to include neurologic manifestations such as anosmia, ageusia, ataxia and seizures, suggesting that SARS-CoV-2 may also be neurotropic.
Ultrastructural analysis of tissue from this case revealed the presence of viral-like particles in brain and capillary endothelium, which was further confirmed by molecular testing for SARS-CoV-2.
This case provides first evidence for the potential direct propagation and presence of SARS-CoV-2 in human brain tissue.
These findings have direct implications for neurologic clinical practice and should raise awareness amongst physicians managing SARS-CoV-2-infected patients with CNS symptoms.
Rapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of ...identifying early or subclinical symptoms of coronavirus disease 2019 (COVID-19) infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in COVID-19 may help facilitate screening and early isolation of cases.
A single-institution, cross-sectional study evaluating patient-reported symptoms with a focus on smell and taste was conducted using an internet-based platform on adult subjects who underwent testing for COVID-19. Logistic regression was employed to identify symptoms associated with COVID-19 positivity.
A total of 1480 patients with influenza-like symptoms underwent COVID-19 testing between March 3, 2020, and March 29, 2020. Our study captured 59 of 102 (58%) COVID-19-positive patients and 203 of 1378 (15%) COVID-19-negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of COVID-19-positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of COVID-19-negative patients (p < 0.001). Smell and taste impairment were independently and strongly associated with COVID-19 positivity (anosmia: adjusted odds ratio aOR 10.9; 95% CI, 5.08-23.5; ageusia: aOR 10.2; 95% CI, 4.74-22.1), whereas sore throat was associated with COVID-19 negativity (aOR 0.23; 95% CI, 0.11-0.50). Of patients who reported COVID-19-associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness.
In ambulatory individuals with influenza-like symptoms, chemosensory dysfunction was strongly associated with COVID-19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks, paralleling resolution of other disease-related symptoms.
The pandemic of Coronavirus Disease 2019 (COVID-19) has caused a vast disaster throughout the world. There is increasing evidence that olfactory dysfunction can present in COVID-19 patients. Anosmia ...can occur alone or can be accompanied by other symptoms of COVID-19, such as a dry cough. However, the pathogenic mechanism of olfactory dysfunction and its clinical characteristics in patients with COVID-19 remains unclear. Multiple cross-sectional studies have demonstrated that the incidence rate of olfactory dysfunction in COVID-19 patients varies from 33.9–68% with female dominance. Anosmia and dysgeusia are often comorbid in COVID-19 patients. Otolaryngologists should be mindful of the symptom of anosmia in outpatients so as not to delay the diagnosis of COVID-19. In this paper, we have reviewed the relevant knowledge based on up-to-date literature.
The mechanisms by which any upper respiratory virus, including SARS-CoV-2, impairs chemosensory function are not known. COVID-19 is frequently associated with olfactory dysfunction after viral ...infection, which provides a research opportunity to evaluate the natural course of this neurological finding. Clinical trials and prospective and histological studies of new-onset post-viral olfactory dysfunction have been limited by small sample sizes and a paucity of advanced neuroimaging data and neuropathological samples. Although data from neuropathological specimens are now available, neuroimaging of the olfactory system during the acute phase of infection is still rare due to infection control concerns and critical illness and represents a substantial gap in knowledge.
The active replication of SARS-CoV-2 within the brain parenchyma (ie, in neurons and glia) has not been proven. Nevertheless, post-viral olfactory dysfunction can be viewed as a focal neurological deficit in patients with COVID-19. Evidence is also sparse for a direct causal relation between SARS-CoV-2 infection and abnormal brain findings at autopsy, and for trans-synaptic spread of the virus from the olfactory epithelium to the olfactory bulb. Taken together, clinical, radiological, histological, ultrastructural, and molecular data implicate inflammation, with or without infection, in either the olfactory epithelium, the olfactory bulb, or both. This inflammation leads to persistent olfactory deficits in a subset of people who have recovered from COVID-19. Neuroimaging has revealed localised inflammation in intracranial olfactory structures. To date, histopathological, ultrastructural, and molecular evidence does not suggest that SARS-CoV-2 is an obligate neuropathogen.
The prevalence of CNS and olfactory bulb pathosis in patients with COVID-19 is not known. We postulate that, in people who have recovered from COVID-19, a chronic, recrudescent, or permanent olfactory deficit could be prognostic for an increased likelihood of neurological sequelae or neurodegenerative disorders in the long term. An inflammatory stimulus from the nasal olfactory epithelium to the olfactory bulbs and connected brain regions might accelerate pathological processes and symptomatic progression of neurodegenerative disease. Persistent olfactory impairment with or without perceptual distortions (ie, parosmias or phantosmias) after SARS-CoV-2 infection could, therefore, serve as a marker to identify people with an increased long-term risk of neurological disease.
Olfactory dysfunction (OD) in old age is associated with poor health outcomes. Interrelationships among different correlates of OD can offer insights into the underlying mechanisms, but to date ...remain understudied.
Odor identification performance and self-reported olfactory functioning were studied in 2,234 people aged 60-90 years, who were free of neurodegenerative disease and enrolled in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) study, Stockholm, Sweden. OD was defined as the inability to identify more than 10 out of 16 odors (free or cued identification) in a standardized odor identification task. OD prevalence was estimated, and associations with demographic, genetic, vascular, clinical, and behavioral factors, as well as their interactions were examined using multiple logistic regression analyses.
Overall prevalence of OD was 24.8% (CI: 23.1; 26.6). Self-reports were characterized by low sensitivity (35%), but high specificity (87%). Advancing age (OR = 15.50, CI = 9.40; 26.10 between the first and last age group), and history of coronary heart disease (OR = 1.35, 95% CI = 1.04; 1.75) were the principal factors associated with an increased probability of OD, whereas female gender (OR = 0.53, 95% CI = 0.43; 0.66) and more years of education (OR = 0.97, CI 0.94; 0.99) were linked to a lower probability. Exploratory interaction analyses indicated that prevalence of OD was particularly elevated among Apolipropotein E (APOE) ε4 allele carriers who were also obese, and that being physically active counteracted the negative impact of cerebrovascular disease on OD.
Demographic and genetic factors, but also prior and current health insults, are linked to OD in old age. Modulatory effects of behavioral factors highlight their value as possible prevention targets.
Objective
The objective of this study was to determine the burden of depressed mood and anxiety in COVID‐19, and associated disease characteristics.
Materials and Methods
This is a prospective, ...cross‐sectional study of 114 COVID‐19 positive patients diagnosed using RT‐PCR‐based testing over a 6‐week period. The two‐item Patient Health Questionnaire (PHQ‐2) and the two‐item Generalized Anxiety Disorder questionnaire (GAD‐2) were used to measure depressed mood and anxiety level, respectively, at enrollment and for participants' baseline, pre‐COVID‐19 state. Severity of smell loss, loss of taste, nasal obstruction, rhinorrhea/mucus production, fever, cough, and shortness of breath (SOB) during COVID‐19 were assessed.
Results
PHQ‐2 and GAD‐2 significantly (P < .001) increased from baseline to enrollment. PHQ‐2 was associated with smell loss (adjusted incidence rate ratio aIRR = 1.40, 95% CI, 1.10–1.78, P = .006), age (aIRR = 1.02, 95% CI, 1.01–1.04, P = .006), and baseline PHQ‐2 score (aIRR = 1.39, 95% CI, 1.09–1.76, P = .007). GAD‐2 score was associated with smell loss (aIRR = 1.29, 95% CI, 1.02–1.62, P = .035), age (aIRR = 1.02, 95% CI, 1.01–1.04, P = .025) and baseline GAD‐2 score (aIRR = 1.55, 95% CI, 1.24–1.93, P < .001). Loss of taste also exhibited similar associations with PHQ‐2 and GAD‐2. PHQ‐2 and GAD‐2 scores were not associated with severities of any other symptoms during the COVID‐19 course.
Conclusions
Despite the occurrence of symptoms—such as SOB—associated with severe manifestations of COVID‐19, only the severities of smell and taste loss were associated with depressed mood and anxiety. These results may raise the novel possibility of emotional disturbance as a CNS manifestation of COVID‐19 given trans‐olfactory tract penetration of the central nervous system (CNS) by coronaviruses.
Level of Evidence
3 Laryngoscope, 130:2520–2525, 2020
PDF
