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

Boscolo‐Rizzo, Paolo; Menegaldo, Anna; Fabbris, Cristoforo; Spinato, Giacomo; Borsetto, Daniele; Vaira, Luigi Angelo; Calvanese, Leonardo; Pettorelli, Andrea; Sonego, Massimo; Frezza, Daniele; Bertolin, Andy; Cestaro, Walter; Rigoli, Roberto; D’Alessandro, Andrea; Tirelli, Giancarlo; Mosto, Maria Cristina Da; Menini, Anna; Polesel, Jerry; Hopkins, Claire

doi:10.1093/chemse/bjab006

Cited by 116 publications

(139 citation statements)

References 36 publications

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“… 96 , 97 Although a definitive link between chronic or permanent olfactory impairment and future neurological vulnerability cannot yet be made, some studies suggest an association. 40 , 41 , 42 , 54 , 55 , 98 , 99 …”

Section: Discussionmentioning

confidence: 99%

Post-viral effects of COVID-19 in the olfactory system and their implications

Xydakis

Albers

Holbrook

et al. 2021

The Lancet Neurology

156

153

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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.

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Section: Discussionmentioning

confidence: 99%

Post-viral effects of COVID-19 in the olfactory system and their implications

Xydakis

Albers

Holbrook

et al. 2021

The Lancet Neurology

156

153

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“…In our study, patients were evaluated within the first 10 days of symptom onset, when olfactory dysfunction should not yet have begun to recover [ 29 , 30 ]. At this early stage of COVID-19, 74.3% of patients had olfactory dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Correlations between IL-6 serum level and olfactory dysfunction severity in COVID-19 patients: a preliminary study

Vaira

Vito

Deiana

et al. 2021

Eur Arch Otorhinolaryngol

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Background Interleukin 6 (IL-6) is a proinflammatory cytokine that is secreted by cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is widely recognized as a negative prognostic factor. The purpose of this study was to analyze the correlations between the olfactory scores determined by psychophysical tests and the serum levels of IL-6 in patients affected by coronavirus disease 2019 (COVID-19) Methods Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and IL-6 plasma level determination within 10 days of the clinical onset of COVID-19. Results Seventy-four COVID-19 patients were included in this study. COVID-19 staged as mild in 34 patients, moderate in 26 and severe in 14 cases. There were no significant differences in olfactory scores across the different COVID-19 severity groups. In the patient series, the median plasma level of IL-6 was 7.7 pg/mL (IQR 3.7–18.8). The concentration of IL-6 was found to be significantly correlated with the severity of COVID-19 with a directly proportional relationship. The correlation between IL-6 plasma concentrations and olfactory scores was weak (rs = 0.182) and not significant (p = 0.12). Conclusions In COVID-19 patients, psychophysical olfactory scores did not show significant correlations with the plasma levels of a well-recognized negative prognostic factor such as IL-6. This observation casts some shadows on the positive prognostic value of olfactory dysfunctions.

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“…We analysed 202 patients with positive COVID-19 swabs and showed that 65% reported smell and taste alterations in addition to the other ENT symptoms reported above 23 . These patients were reviewed 4 weeks after onset of their sensory changes: 50% m recovered completely, 40% had improvement and 10% had unchanged or worsened symptoms [24][25][26] . Reports from a different study on household members with positive COV-ID-19 swabs found that 38% showed typical COVID-19 symptoms and 22% had these symptoms in association with altered sense of smell and taste, while 4% only had alteration of smell and taste as an isolated symptom 27 .…”

Section: Discussionmentioning

confidence: 99%

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

Spinato

Costantini

Fabbris

et al. 2021

Acta Otorhinolaryngol Ital

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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.

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

Cited by 116 publications

References 36 publications

Post-viral effects of COVID-19 in the olfactory system and their implications

Post-viral effects of COVID-19 in the olfactory system and their implications

Correlations between IL-6 serum level and olfactory dysfunction severity in COVID-19 patients: a preliminary study

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

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