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1.
Lancet Neurol ; 20(9): 753-761, 2021 09.
Article in English | MEDLINE | ID: covidwho-1599333

ABSTRACT

BACKGROUND: 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. RECENT DEVELOPMENTS: 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. WHERE NEXT?: 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.


Subject(s)
COVID-19/complications , COVID-19/diagnostic imaging , Olfaction Disorders/diagnostic imaging , Olfaction Disorders/etiology , Olfactory Mucosa/diagnostic imaging , Brain/diagnostic imaging , Brain/physiopathology , Brain/virology , COVID-19/physiopathology , Humans , Neurodegenerative Diseases/diagnostic imaging , Neurodegenerative Diseases/etiology , Neurodegenerative Diseases/physiopathology , Olfaction Disorders/physiopathology , Olfaction Disorders/virology , Olfactory Mucosa/physiopathology , Olfactory Mucosa/virology , Prospective Studies , Smell/physiology
2.
PLoS One ; 16(11): e0259321, 2021.
Article in English | MEDLINE | ID: covidwho-1506148

ABSTRACT

Olfactory loss has been identified as one of the common symptoms related to COVID-19 infection. Although olfactory loss is recognized, our understanding of both the extent of loss and time to olfactory recovery following infection is less well known. Similarly, knowledge of potential impactful patient factors and therapies that influence olfactory recovery is desirable but is not overtly clear in the literature. Our systematic review sought to fill this knowledge gap. We included studies that: involved either an observational or an interventional design that reported data on patients with olfactory dysfunction due to Reverse Transcription Polymerase Chain Reaction (RT-PCR) diagnosed COVID-19 infection; and reported data regarding olfactory recovery measured by an objective olfactory test, Likert scale and/or visual analog scale (VAS). The study methods were determined a priori and registered in PROSPERO (Registration Number CRD42020204354). An information specialist searched Medline, Embase, LitCovid and the Cochrane Register of Controlled Trials up to March 2021, and two reviewers were involved in all aspects of study selection and data collection. After screening 2788 citations, a total of 44 studies of assorted observational designs were included. Patients had undergone objective COVID-19 testing, and most were adult patients with mild to moderate COVID-19. Olfactory recovery was found to occur as early as 7 days, with most patients recovering olfaction within 30 days. Few studies included prolonged follow-up to 6 months or longer duration. Poor olfaction at initial presentation was associated with poor recovery rates. Only a small number of studies assessed olfactory retraining and steroid therapy. Additional trials are underway.


Subject(s)
COVID-19/complications , Olfaction Disorders/etiology , Olfaction Disorders/virology , Smell/physiology , COVID-19/virology , Humans , SARS-CoV-2/pathogenicity , Visual Analog Scale
3.
Dev Psychobiol ; 63(7): e22201, 2021 11.
Article in English | MEDLINE | ID: covidwho-1482123

ABSTRACT

Fetuses are able to process olfactory stimuli present in the womb and continue to show a preference for these odors for months after birth. Despite the accumulated knowledge about their early ability to perceive odors, there is a lack of validated scales for odor response in newborns. The evaluation of reactions of the olfactory system to environmental stimuli in infants has been defined by methodological theoretical approaches of experimental and clinical assessment tools. These approaches are mainly based on psychophysical approaches and predominantly use behavioral and physiological measures. Examples can be found in studies describing early abilities of newborn babies for behaviors or heart rate variability showing memory of maternal food preferences or mother's breast milk. This systematic review aimed to determine whether validated odor assessment tools can be feasibly used in studies. Particularly in light of the current COVID-19 pandemic and evidence of associated olfactory impairment resulting from SARS-COV-2 infection, the study is also motivated by the need for tools to assess olfactory function in neonates.


Subject(s)
Infant, Newborn/physiology , Smell , Anosmia/diagnosis , COVID-19/diagnosis , COVID-19/physiopathology , Humans , Infant, Newborn, Diseases/diagnosis , Odorants , Smell/physiology
4.
J Med Virol ; 93(10): 5924-5930, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1432426

ABSTRACT

The introduction of trained sniffer dogs for COVID-19 detection could be an opportunity, as previously described for other diseases. Dogs could be trained to detect volatile organic compounds (VOCs), the whiff of COVID-19. Dogs involved in the study were three, one male and two females from different breeds, Black German Shepherd, German Shepherd, and Dutch Shepherd. The training was performed using sweat samples from SARS-CoV2 positive patients and from SARS-Cov2 free patients admitted at the University Hospital Campus Bio-medico of Rome. Gauze with sweat was collected in a glass jar with a metal top and put in metal boxes used for dog training. The dog training protocol was performed in two phases: the olfactory conditioning and the olfactory discrimination research. The training planning was focused on the switch moment for the sniffer dog, the moment when the dog was able to identify VOCs specific for COVID-19. At this time, the dog was able to identify VOCs specific for COVID-19 with significant reliability, in terms of the number of correct versus incorrect (p < 0.0001) reporting. In conclusion, this protocol could provide a useful tool for sniffer dogs' training and their introduction in a mass screening context. It could be cheaper and faster than a conventional testing method.


Subject(s)
COVID-19/diagnosis , Learning/physiology , Smell/physiology , Working Dogs/physiology , Animals , COVID-19/pathology , Dogs , Female , Humans , Male , Middle Aged , Reproducibility of Results , SARS-CoV-2/isolation & purification , Sweat/chemistry , Volatile Organic Compounds/analysis , Volatile Organic Compounds/isolation & purification
5.
Eur Rev Med Pharmacol Sci ; 25(11): 4156-4162, 2021 06.
Article in English | MEDLINE | ID: covidwho-1281021

ABSTRACT

OBJECTIVE: Approximately 30% of patients with confirmed COVID-19 report persistent smell or taste disorders as long-term sequalae of infection. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with inflammatory changes to the olfactory bulb, and treatments with anti-inflammatory properties are hypothesized to attenuate viral injury and promote recovery of olfaction after infection. Our study investigated the efficacy of a supplement with Palmitoylethanolamide (PEA) and Luteolin to support recovery of olfaction in COVID-19 patients. PATIENTS AND METHODS: We conducted a randomized-controlled pilot study in outpatients with history of confirmed COVID-19 with post-infection olfactory impairment that persisted ≥ 90 days after SARS-CoV-2 negative testing. Patients were randomized to two times a day olfactory rehabilitation alone or weekly olfactory rehabilitation plus daily oral supplement with PEA and Luteolin. Subjects with preexisting olfactory disorders were excluded. Sniffin' Sticks assessments were performed at baseline and 30 days after treatment.  Data on gender, age, and time since infection were collected. Kruskal-Wallis (KW) test was used to compare variances of Sniff scores between groups over time, and Spearman's correlation coefficients were calculated to assess for correlations between Sniff Score and gender or duration of infection. RESULTS: Among 12 patients enrolled (n=7, supplement; n=5, controls), patients receiving supplement had greater improvement in olfactory threshold, discrimination, and identification score versus controls (p=0.01). Time since infection was negatively correlated with Sniff Score, and there was no correlation between gender. CONCLUSIONS: Treatment combining olfactory rehabilitation with oral supplementation with PEA and Luteolin was associated with improved recovery of olfactory function, most marked in those patients with longstanding olfactory dysfunction. Further studies are necessary to replicate these findings and to determine whether early intervention including olfactory rehabilitation and PEA+Luteolin oral supplement might prevent SARS-CoV-2 associated olfactory impairment.


Subject(s)
Amides/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Antiviral Agents/administration & dosage , COVID-19/drug therapy , Ethanolamines/administration & dosage , Luteolin/administration & dosage , Olfaction Disorders/drug therapy , Palmitic Acids/administration & dosage , Adult , COVID-19/complications , COVID-19/diagnosis , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Olfaction Disorders/diagnosis , Olfaction Disorders/etiology , Pilot Projects , Single-Blind Method , Smell/drug effects , Smell/physiology
6.
J Med Virol ; 93(10): 5924-5930, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1274731

ABSTRACT

The introduction of trained sniffer dogs for COVID-19 detection could be an opportunity, as previously described for other diseases. Dogs could be trained to detect volatile organic compounds (VOCs), the whiff of COVID-19. Dogs involved in the study were three, one male and two females from different breeds, Black German Shepherd, German Shepherd, and Dutch Shepherd. The training was performed using sweat samples from SARS-CoV2 positive patients and from SARS-Cov2 free patients admitted at the University Hospital Campus Bio-medico of Rome. Gauze with sweat was collected in a glass jar with a metal top and put in metal boxes used for dog training. The dog training protocol was performed in two phases: the olfactory conditioning and the olfactory discrimination research. The training planning was focused on the switch moment for the sniffer dog, the moment when the dog was able to identify VOCs specific for COVID-19. At this time, the dog was able to identify VOCs specific for COVID-19 with significant reliability, in terms of the number of correct versus incorrect (p < 0.0001) reporting. In conclusion, this protocol could provide a useful tool for sniffer dogs' training and their introduction in a mass screening context. It could be cheaper and faster than a conventional testing method.


Subject(s)
COVID-19/diagnosis , Learning/physiology , Smell/physiology , Working Dogs/physiology , Animals , COVID-19/pathology , Dogs , Female , Humans , Male , Middle Aged , Reproducibility of Results , SARS-CoV-2/isolation & purification , Sweat/chemistry , Volatile Organic Compounds/analysis , Volatile Organic Compounds/isolation & purification
7.
J Med Internet Res ; 23(5): e29583, 2021 05 27.
Article in English | MEDLINE | ID: covidwho-1232515

ABSTRACT

BACKGROUND: Persistent olfactory dysfunction is a significant complication of SARS-CoV-2 infection. Olfactory training involving aromatic oils has been recommended to improve olfactory recovery, but quantitative data are missing. OBJECTIVE: We aimed to quantify the benefit of olfactory training and visual stimulation assisted by a dedicated web application for patients who experienced olfactory dysfunction for ≥1 month. METHODS: We performed an observational, real-life, data-based study on a cohort of patients who experienced at least 1 month of persistent olfactory dysfunction between January 30 and March 26, 2021. An analysis was performed after a mean olfactory training time of 4 weeks, and at least 500 patients were assessable for primary outcome assessment. Participants exposed themselves twice daily to odors from 4 high-concentration oils and visual stimulation assisted by a dedicated web application. Improvement was defined as a 2-point increase on a 10-point, self-assessed olfactory visual analogue scale. RESULTS: In total, 548 patients were assessable for primary outcome assessment. The mean baseline, self-assessed olfactory score was 1.9 (SD 1.7), and this increased to 4.6 (SD 2.8) after a mean olfactory training time of 27.7 days (SD 17.2). Olfactory training was associated with at least a 2-point increase in 64.2% (352/548) of patients. The rate of patients' olfactory improvement was higher for patients who trained for more than 28 days than that rate for patients who trained for less than 28 days (73.3% vs 59%; P=.002). The time to olfactory improvement was 8 days faster for patients with hyposmia compared to the time to improvement for patients with anosmia (P<.001). This benefit was observed regardless of the duration of the olfactory dysfunction. CONCLUSIONS: Olfactory training and visual stimulation assisted by a dedicated web application was associated with significant improvement in olfaction, especially after 28 days of olfactory training.


Subject(s)
COVID-19/complications , Internet-Based Intervention , Olfaction Disorders/complications , Olfaction Disorders/rehabilitation , Anosmia/complications , Anosmia/rehabilitation , Anosmia/therapy , Cohort Studies , Female , Humans , Male , Olfaction Disorders/therapy , Photic Stimulation , SARS-CoV-2/pathogenicity , Smell/physiology
8.
Am J Otolaryngol ; 42(6): 103068, 2021.
Article in English | MEDLINE | ID: covidwho-1210791

ABSTRACT

The effects of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) exist on a spectrum. Clinical symptoms of smell and taste dysfunction are prominent features of COVID-19. The objective of this study was to elucidate the factors associated with smell and taste dysfunction amongst hospitalized COVID-19 patients. A retrospective review of a multi-hospital health network's COVID-19 database between March and June 2020 was performed. Patients with self-reported smell or taste loss were included. Demographic information, patient comorbidities, and mortality data was obtained. There were 2892 patients included in this analysis and 117 reported smell or taste loss (4.0%, 95% confidence interval [CI]: 3.4%-4.8%). The proportion of females with smell or taste loss was significantly higher than males (6.3% vs. 2.5%, P < 0.001), whereas no differences existed between ethnicity or smoking status. When compared with age of 30-40 years, the age group of 10-20 years were most likely to present with smell or taste dysfunction (odds ratio [OR] 6.59, 95% CI 1.32-26.12; P = 0.01). The majority of specific comorbidities were not associated with increased incidence of smell or taste dysfunction. Outpatient healthcare workers were more likely to present with smell or taste loss (OR 3.2, CI 1.8-5.47; P < 0.001). The mortality rate among COVID-19 patients with smell or taste dysfunction was significantly lower than those without (0% vs. 20.3%; P < 0.001). Smell or taste loss is more prevalent in women, younger age groups, and healthier individuals. It may be associated with lower mortality and a milder disease trajectory compared to the overall cohort.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Hospitalization , Olfaction Disorders/etiology , Olfaction Disorders/physiopathology , Smell/physiology , Taste Disorders/etiology , Taste Disorders/physiopathology , Taste/physiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/mortality , Child , Female , Humans , Male , Middle Aged , Olfaction Disorders/epidemiology , Olfaction Disorders/mortality , Retrospective Studies , Sex Factors , Taste Disorders/epidemiology , Taste Disorders/mortality , Young Adult
9.
J Laryngol Otol ; 135(5): 436-441, 2021 May.
Article in English | MEDLINE | ID: covidwho-1199243

ABSTRACT

BACKGROUND: The long-term recovery rate for coronavirus disease 2019 related chemosensory disturbances has not yet been clarified. METHODS: Olfactory and gustatory functions were assessed with psychophysical tests in patients in the first seven days from coronavirus disease 2019 onset and one, two, three and six months after the first evaluation. RESULTS: A total of 300 patients completed the study. The improvement in olfactory function was significant at the two-month follow up. At the end of the observation period, 27 per cent of the patients still experienced a persistent olfactory disturbance, including anosmia in 5 per cent of cases. As for taste, the improvement in the psychophysical scores was significant only between the baseline and the 30-day control. At the 6-month evaluation, 10 per cent of the patients presented with a persistent gustatory disturbance with an incidence of complete ageusia of 1 per cent. CONCLUSION: Six months after the onset of coronavirus disease 2019, about 6 per cent of patients still had a severe persistent olfactory or gustatory disturbance.


Subject(s)
COVID-19/complications , Olfaction Disorders/etiology , Psychophysics/methods , Recovery of Function/physiology , Taste Disorders/etiology , Adult , Ageusia/epidemiology , Anosmia/epidemiology , COVID-19/diagnosis , COVID-19/psychology , COVID-19/virology , Female , Follow-Up Studies , Humans , Incidence , Italy/epidemiology , Male , Middle Aged , Olfaction Disorders/diagnosis , Prospective Studies , SARS-CoV-2/isolation & purification , Smell/physiology , Taste/physiology , Taste Disorders/diagnosis
10.
Neurosci Lett ; 748: 135694, 2021 03 23.
Article in English | MEDLINE | ID: covidwho-1188917

ABSTRACT

Patients with COVID-19 often complain of smell and taste disorders (STD). STD emerge early in the course of the disease, seem to be more common in SARS-CoV-2 infection than in other upper respiratory tract infections, and could in some cases persist for long after resolution of respiratory symptoms. Current evidence suggests that STD probably result from a loss of function of olfactory sensory neurons and taste buds, mainly caused by infection, inflammation, and subsequent dysfunction of supporting non-neuronal cells in the mucosa. However, the possible occurrence of other mechanisms leading to chemosensory dysfunction has also been hypothesized, and contrasting data have been reported regarding the direct infection of sensory neurons by SARS-CoV-2. In this mini-review, we summarize the currently available literature on pathogenesis, clinical manifestations, diagnosis, and outcomes of STD in COVID-19 and discuss possible future directions of research on this topic.


Subject(s)
COVID-19/complications , Olfaction Disorders/etiology , SARS-CoV-2/pathogenicity , Taste Disorders/etiology , COVID-19/immunology , COVID-19/virology , Humans , Mouth Mucosa/immunology , Mouth Mucosa/pathology , Olfaction Disorders/diagnosis , Olfaction Disorders/epidemiology , Olfaction Disorders/physiopathology , Olfactory Mucosa/immunology , Olfactory Mucosa/pathology , Olfactory Receptor Neurons/immunology , Olfactory Receptor Neurons/pathology , SARS-CoV-2/immunology , Smell/physiology , Taste/physiology , Taste Buds/immunology , Taste Buds/pathology , Taste Disorders/diagnosis , Taste Disorders/epidemiology , Taste Disorders/physiopathology
12.
J Neurosci Nurs ; 53(3): 123-128, 2021 Jun 01.
Article in English | MEDLINE | ID: covidwho-1158037

ABSTRACT

ABSTRACT: BACKGROUND: Alteration in olfaction, the sense of smell, can lead to a surprisingly high level of functional disability. Effects can range from mild changes in nutrient intake to a significant decrease in quality of life. Olfactory dysfunction can follow clinical problems such as trauma to the brain and nose. During recent months, in the setting of the current worldwide pandemic of coronavirus disease 2019 (COVID-19), the infection caused by severe acute respiratory syndrome coronavirus 2, it has become clear that olfaction can also be damaged by viruses that enter the body through the nose. METHODS: To learn more about this important clinical problem, we reviewed the current literature about smell sensation and the contextual application of altered olfaction in the setting of COVID-19. Knowledge about this topic, along with other clinical aspects of COVID-19, is expanding quickly. CONCLUSION: Nurses perform assessments, assist with implementing treatment interventions, and provide vital education to patients and their families. These interventions help patients with olfactory dysfunction achieve the best possible functional outcome.


Subject(s)
COVID-19/complications , Nursing Care/methods , Smell/physiology , COVID-19/physiopathology , Humans , Nurse-Patient Relations , Nursing Care/trends , Pandemics/statistics & numerical data , Quality of Life/psychology
14.
Rev Med Inst Mex Seguro Soc ; 59(1): 4-6, 2021 Feb 02.
Article in Spanish | MEDLINE | ID: covidwho-1119707

ABSTRACT

Some reports have been recently published on olfactory loss in people with severe COVID-19. It is suggested to take into consideration the recommendations of the American Academy of Otolaryngology and the British Association of Otorhinolaryngology to include olfactory loss as an early clinical symptom of COVID-19 and consider sudden olfactory loss, as a high index of suspicion of SARS-CoV-2 infection. It can be established that the majority of patients with olfactory loss due to COVID-19, present hyposmia and not anosmia. Patients with olfactory loss, who had SARS-CoV-2 infection, should be classified as loss secondary to viral infection.


En fechas recientes se han publicado algunos informes sobre la pérdida olfatoria en personas con COVID-19. Se sugiere tomar en consideración las recomendaciones de la American Academy of Otolaryngology y la British Association of Otorhinolaryngology para agregar la pérdida olfatoria como síntoma clínico temprano de COVID-19, y considerar la pérdida súbita olfatoria como alto índice de sospecha de infección por SARS-CoV-2. Se puede establecer que la mayoría de los pacientes con pérdida olfatoria por COVID-19 presentan hiposmia y no anosmia. Los pacientes con pérdida olfatoria que cursaron con infección por SARS-CoV-2 deben ser clasificados como pérdida secundaria a infección viral.


Subject(s)
Anosmia/etiology , COVID-19 , Olfaction Disorders/diagnosis , Olfaction Disorders/virology , Humans , Olfaction Disorders/etiology , Pandemics , SARS-CoV-2 , Smell/physiology
15.
PLoS One ; 16(3): e0248025, 2021.
Article in English | MEDLINE | ID: covidwho-1115309

ABSTRACT

INTRODUCTION: Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals. In this study we sought to determine if tracking smell sensitivity and loss using an at-home assessment could identify SARS-CoV-2 infection in HCW. METHODS AND FINDINGS: We performed a prospective cohort study tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, behavioral at-home assessment of olfaction with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and real-time quantitative polymerase chain reaction testing to identify SARS-CoV-2 infection. Our main measures were the prevalence of smell loss in SARS-CoV-2-positive HCW versus SARS-CoV-2-negative HCW, and timing of smell loss relative to SARS-CoV-2 test positivity. SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. HCW with SARS-CoV-2 infection were more likely to report smell loss than SARS-CoV-2-negative HCW on both the at-home assessment and the screening questionnaire (9/17, 53% vs 105/456, 23%, P < .01). 6/9 (67%) of SARS-CoV-2-positive HCW reporting smell loss reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among SARS-CoV-2-positive HCW who reported smell loss compared to those without smell loss (9/9, 100% vs 3/8, 38%, P < .01). CONCLUSIONS: In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of SARS-CoV-2 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms.


Subject(s)
Anosmia/epidemiology , COVID-19/diagnosis , Health Personnel/trends , Adult , Anosmia/diagnosis , Anosmia/virology , Asymptomatic Infections/epidemiology , COVID-19/epidemiology , Female , Health Personnel/statistics & numerical data , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2/pathogenicity , Self Report , Smell/physiology , United States/epidemiology
16.
Eur Rev Med Pharmacol Sci ; 25(2): 1114-1134, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1082737

ABSTRACT

OBJECTIVE: The novel coronavirus disease-19 (COVID-19) pandemic had intense social and economic effects. Patients infected with COVID-19 may present with a series of conditions. A considerable number of patients express taste and smell disturbances as a prodromal, coexistent, or as the only manifestation of COVID-19 infection. The objective of the present review is to review the hypothetical mechanisms of action and etiopathogenesis of dysgeusia in COVID-19 patients. MATERIALS AND METHODS: Multiple scientific databases were explored, including PubMed, Medline, Scopus, Cochrane-library, LILACS, Livivo and OpenGrey. All types of articles that discussed the pathogenesis of dysgeusia were included, while articles that described dysgeusia without detail about its mode of action were excluded. RESULTS: A total of 47 articles, with different designs, were included in this review. These articles suggested direct viral neural invasion to olfactory and gustatory nerves, viral cytotoxicity to taste buds, angiotensin II imbalance, augmented pro-inflammatory cytokines, and disturbances in salivary glands and sialic acid. COVID-19 induced-dysgeusia was also associated with systemic diseases, medications, zinc, chemicals, and disinfectants. CONCLUSIONS: The most likely cause of transient dysgeusia in COVID-19 is peripheral neurotropism and direct toxicity to taste buds or olfactory epithelium. Other factors may also play a contributory role in dysgeusia, such as a defect in the quality and quantity of saliva, pro-inflammatory cytokines, angiotensin II accumulation, systemic diseases, hypozincemia, and excessive use of chemicals.


Subject(s)
COVID-19/complications , COVID-19/metabolism , Dysgeusia/etiology , Dysgeusia/metabolism , Ageusia/diagnosis , Ageusia/etiology , Ageusia/metabolism , COVID-19/diagnosis , Dysgeusia/diagnosis , Humans , Olfaction Disorders/diagnosis , Olfaction Disorders/etiology , Olfaction Disorders/metabolism , Prospective Studies , Renin-Angiotensin System/physiology , Retrospective Studies , Smell/physiology , Taste/physiology
17.
Eur Arch Otorhinolaryngol ; 278(1): 101-108, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1064481

ABSTRACT

PURPOSE: To evaluate the evolution of chemosensation via extended psychophysical testing in patients who suffered from sudden chemosensory loss due to coronavirus disease 2019 (COVID-19). Additionally, this study sought to determine whether odor threshold testing provided additional information on olfactory loss due to COVID-19 compared to the more common odor identification testing. METHODS: Prospective cohort study of patients with sudden chemosensory loss since February 2020 and confirmed COVID-19 infection via RT-PCR or serology testing. Olfactory function was tested extensively using the "Sniffin Sticks" test battery. In addition, we screened gustatory perception and nasal cooling sensations using psychophysical tests. RESULTS: Seventy-two patients completed the study. After a mean of 37 days, 37% of patients showed olfactory dysfunction, 7% were dysgeusic, and 48% showed signs of low sensitivity for cooling sensation. A longer duration of anosmia before smell improvement was correlated with lower olfactory function at 5 weeks. Odor threshold detection was more affected by COVID-19 compared to odor identification. CONCLUSION: Five weeks after developing sudden chemosensory loss due to COVID-19, a high proportion of patients were dysosmic and showed signs of low nasal cooling sensitivity, whereas most of them had normal taste function. SARS-CoV-2 affected mainly odor thresholds, possibly suggesting that the major cause of loss of smell lies at the level of the olfactory neuroepithelium, rather than in the central nervous system.


Subject(s)
Anosmia/etiology , COVID-19/diagnosis , COVID-19/psychology , Olfaction Disorders/etiology , Smell/physiology , Adult , Anosmia/psychology , COVID-19/complications , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Odorants , Prospective Studies , SARS-CoV-2 , Symptom Assessment/methods
18.
Am J Med Sci ; 361(2): 216-225, 2021 02.
Article in English | MEDLINE | ID: covidwho-1064781

ABSTRACT

BACKGROUND: The presence of olfactory dysfunction or "loss of smell" has been reported as an atypical symptom in patients with coronavirus disease 2019 (COVID-19). We performed a systematic review and meta-analysis of the available literature to evaluate the prevalence of "loss of smell" in COVID-19 as well as its utility for prognosticating the disease severity. METHODS: An exhaustive search of the PubMed/Medline, Embase, Web of Science, Cochrane Library, LitCovid NIH, and WHO COVID-19 database was conducted through August 6th, 2020. All studies reporting the prevalence of "loss of smell" (anosmia and/or hyposmia/microsmia) in laboratory-confirmed COVID-19 patients were included. Pooled prevalence for cases (positive COVID-19 through reverse transcriptase (RT-PCR) and/or serology IgG/IgM) and controls (negative RT-PCR and/or serology) was compared, and the odds ratio (OR), 95% confidence interval (CI) and the p-value were calculated. A p-value of <0.05 was considered statistically significant. RESULTS: A total of 51 studies with 11074 confirmed COVID-19 patients were included. Of these, 21 studies used a control group with 3425 patients. The symptom of "loss of smell" (OR: 14.7, CI: 8.9-24.3) was significantly higher in the COVID-19 group when compared to the control group. Seven studies comparing severe COVID-19 patients with- and without "loss of smell" demonstrated favorable prognosis for patients with "loss of smell" (OR: 0.36, CI 0.27-0.48). CONCLUSIONS: Olfactory dysfunction or "loss of smell" is a prevalent symptom in COVID-19 patients. Moreover, COVID-19 patients with "loss of smell" appear to have a milder course of the disease.


Subject(s)
Anosmia/diagnosis , Anosmia/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , Humans , Smell/physiology
20.
Nat Neurosci ; 24(2): 168-175, 2021 02.
Article in English | MEDLINE | ID: covidwho-1060446

ABSTRACT

The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.


Subject(s)
Brain/virology , COVID-19/virology , Olfactory Mucosa/virology , SARS-CoV-2/pathogenicity , Central Nervous System , Humans , RNA, Viral/genetics , Smell/physiology , Virus Internalization
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