Olfactory Dysfunction in Coronavirus Disease 2019 Patients: Observational Cohort Study and Systematic Review

Abstract

Background Olfactory dysfunction (OD) has been reported in coronavirus disease 2019 (COVID-19). However, there are knowledge gaps about the severity, prevalence, etiology, and duration of OD in COVID-19 patients. Methods Olfactory function was assessed in all participants using questionnaires and the butanol threshold test (BTT). Patients with COVID-19 and abnormal olfaction were further evaluated using the smell identification test (SIT), sinus imaging, and nasoendoscopy. Selected patients received nasal biopsies. Systematic review was performed according to PRISMA guidelines. PubMed items from January 1, 2020 to April 23, 2020 were searched. Studies that reported clinical data on olfactory disturbances in COVID-19 patients were analyzed. Results We included 18 COVID-19 patients and 18 controls. Among COVID-19 patients, 12 of 18 (67%) reported olfactory symptoms and OD was confirmed in 6 patients by BTT and SIT. Olfactory dysfunction was the only symptom in 2 patients. Mean BTT score of patients was worse than controls (P = .004, difference in means = 1.8; 95% confidence interval, 0.6–2.9). Sinusitis and olfactory cleft obstruction were absent in most patients. Immunohistochemical analysis of nasal biopsy revealed the presence of infiltrative CD68+ macrophages harboring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen in the stroma. Olfactory dysfunction persisted in 2 patients despite clinical recovery. Systematic review showed that the prevalence of olfactory disturbances in COVID-19 ranged from 5% to 98%. Most studies did not assess olfaction quantitatively. Conclusions Olfactory dysfunction is common in COVID-19 and may be the only symptom. Coronavirus disease 2019-related OD can be severe and prolonged. Mucosal infiltration by CD68+ macrophages expressing SARS-CoV-2 viral antigen may contribute to COVID-19-related OD.

Olfactory taste disorder as a presenting symptom of COVID-19: a large single-center Singapore study

“…However, we note that these symptoms of blocked nose and runny nose were only present in up to 30% of our patients with OTD, suggesting that whilst blocked nose can contribute to OTD, the majority of our patients’ OTD symptoms must be due to other non-obstructive causes. Chung et al’s [ 15 ] study demonstrated that half of their patients with OTD had patent olfactory clefts on imaging and this lends further support to non-obstructive causes of OTD.…”

“…In their study, they found that elevated levels of inflammatory cytokines were associated with reduced olfactory identification scores in patients with chronic rhinosinusitis. However, Chung et al [ 15 ] again found that only 17% of their patients with OTD had rhinorrhea or nasal congestion and minimal inflammatory infiltrates as seen in their nasal biopsy specimens. This would suggest that local inflammation is at best a contributing factor but not the sole factor.…”

A Systematic Review and Meta-analysis Protocol Examining the Clinical Characteristics and Epidemiological Features of Olfactory Dysfunction in Coronavirus Disease 2019 (COVID-19)

“…For the systematic review, our group had recently conducted a review, [6] which searched PubMed articles published from 1st January 2020 to 22nd April 2020, using the keywords "SARS-CoV-2", "COVID-19", "2019-nCoV", "novel coronavirus" and "coronavirus disease". As an extension to this recent publication, another search will be performed for articles published on PubMed from 23rd April 2020 to 10th June 2020, which will include the same search terms.…”

“…[3][4][5] In addition, COVID-19 was shown to be associated with olfactory disturbances, which has since been recognised as a common and important neurosensory impairment in COVID-19 infection. [6][7][8] Recent systematic reviews and meta-analyses regarding COVID-19-related olfactory dysfunction (OD) have found signi cant discordance between subjective reporting of smell changes and objective quantitation of olfaction, [9,10] suggesting that validated tools for the assessment of olfactory function, such as the butanol threshold test [11] and smell identi cation test [12], may be more sensitive in identifying smell disturbances in COVID-19 patients. Interestingly, one of the articles suggested that the prevalence of COVID-19-related OD is inversely related to the patients' age, implying that young patients are more prone to experience smell disturbances in SARS-CoV-2 infection.…”

A systematic review and meta-analysis protocol examining the clinical characteristics and epidemiological features of olfactory dysfunction (OD) in coronavirus disease 2019 (COVID-19)

“…[6][7][8] In addition, COVID-19 was shown to be associated with olfactory dysfunction (OD), which has since been recognised as a common and important neurosensory impairment in COVID-19. [9][10][11] Recent systematic reviews and meta-analyses regarding COVID-19-related OD have found signi cant discordance between subjective reporting of smell changes and objective quantitation of olfaction, [12][13][14] suggesting that validated tools for the quantitative assessment of olfactory function, such as butanol threshold test (BTT) [15] and smell identi cation test (SIT), [16] may be more sensitive in identifying smell disturbances in COVID-19 patients. Interestingly, one article suggested that the prevalence of COVID-19related OD was inversely related to the patients' age, implying that young patients were more prone to experience smell disturbances in SARS-CoV-2 infection.…”