a pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly from Wuhan, Hubei Province, China, to all over the world. 1 As of April 20, 2020, SARS-CoV-2 has been responsible for 2 414 595 infections and 165 174 deaths worldwide, with Italy accounting for 178 972 cases and 23 660 deaths. 2 The clinical spectrum of COVID-19 ranges from an asymptomatic or mild flu-like illness to a severe pneumonia and systemic disease requiring critical care. Main symptoms are fever, dry or productive cough, and dyspnea. 3 Human strains of coronavirus have been demonstrated to invade the central nervous system through the olfactory neu-roepithelium and propagate from within the olfactory bulb. 4 Furthermore, nasal epithelial cells display the highest expression of the SARS-CoV-2 receptor, angiotensin converting enzyme 2, in the respiratory tree. 5 Smell impairment was first observed among other neurologic manifestations of COVID-19 in hospitalized patients, 6 and subsequently has been reported to be a common symptom reported in patients with mild disease. 7,8 Recently, we reported the prevalence of altered smell or taste to be 64% among a case series of 202 mildly symptomatic home-isolated patients with confirmed SARS-CoV-2 infection. 8 The aim of this study was to evaluate the evolu-IMPORTANCE An altered sense of smell and taste has been reported to be associated with coronavirus disease 2019 (COVID-19). To understand the evolution of these symptoms during the course of the disease is important to identify patients with persistent loss of smell or taste and estimate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the burden of olfactory and gustative dysfunctions.OBJECTIVE To evaluate the evolution of the loss of sense of smell and taste in a case series of mildly symptomatic patients with SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTSThis cross-sectional survey-based study included 202 mildly symptomatic adults (Ն18 years) consecutively assessed at Treviso Regional Hospital, Italy, between March 19 and March 22, 2020, who tested positive for SARS-CoV-2 RNA by polymerase chain reaction on nasopharyngeal and throat swabs. MAIN OUTCOMES AND MEASURESPrevalence of altered sense of smell and taste at follow-up and their variation from baseline. RESULTSOf 202 patients completing the survey at baseline, 187 (92.6%) also completed the follow-up survey (103 [55.1%] women; median age, 56 years). The evaluation of the evolution of altered sense of smell or taste in the 113 patients reporting sudden onset of these symptoms at baseline showed that 55 patients (48.7%; 95% CI, 39.2-58.3) reported complete resolution of smell or taste impairment, 46 (40.7%; 95% CI, 31.6-50.4) reported an improvement in the severity, and only 12 (10.6%; 95% CI, 5.6-17.8) reported the symptom was unchanged or worse. Persistent loss of smell or taste was not associated with persistent SARS-CoV-2 infection.CONCLUSIONS AND RELEVANCE At 4 wee...

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Background: Using an age and gender matched-pair case-control study, we aimed to estimate the long-term prevalence of psychophysical olfactory, gustatory , and chemesthesis impairment at least one year after SARS-CoV-2 infection considering the background of chemosensory dysfunction in non-COVID-19 population. Methodology: This case-controlled study included 100 patients who were home-isolated for mildly symptomatic COVID-19 between March and April 2020. One control regularly tested for SARS-CoV-2 infection and always tested negative was matched to each case according to gender and age. Chemosensory function was investigated by a comprehensive psychophysical evaluation including ortho- and retronasal olfaction and an extensive assessment of gustatory function. Differences in chemosensory parameters were evaluated through either Fisher’s exact test or Kruskal-Wallis test. Results: The psychophysical assessment of chemosensory function took place after a median of 401 days from the first SARS-CoV-2 positive swab. The evaluation of orthonasal smell identified 46% and 10% of cases and controls, respectively, having olfactory dysfunction, with 7% of COVID-19 cases being functionally anosmic. Testing of gustatory function revealed a 27% of cases versus 10% of controls showing a gustatory impairment. Nasal trigeminal sensitivity was significantly lower in cases compared to controls. Persistent chemosensory impairment was associated with emotional distress and depression. Conclusion: More than one year after the onset of COVID-19, cases exhibited an excess of olfactory, gustatory , and chemesthesis disturbances compared to matched-pair controls with these symptoms being associated to emotional distress and depression.

This study prospectively assessed the six-month prevalence of self-reported and psychophysically measured olfactory dysfunction in subjects with mild-to-moderate COVID-19. Self-reported smell or taste impairment was prospectively evaluated by SNOT-22 at diagnosis, 4-week, 8-week, and 6-month. At 6 months from the diagnosis, psychophysical evaluation of olfactory function was also performed using the 34-item culturally adapted University of Pennsylvania Smell Identification Test (CA-UPSIT). 145 completed both the 6-month subjective and psychophysical olfactory evaluation. According to CA-UPSIT, 87 subjects (60.0%) exhibited some smell dysfunction, with 10 patients being anosmic (6.9%) and 7 being severely microsmic (4.8%). At the time CA-UPSIT was administered, a weak correlation was observed between the self-reported alteration of sense of smell or taste and olfactory test scores (Spearman’s r=-0.26). Among 112 patients who self-reported normal sense of smell at last follow-up, CA-UPSIT revealed normal smell in 46 (41.1%), mild microsmia in 46 (41.1%), moderate microsmia in 11 (9.8%), severe microsmia in 3 (2.3%), and anosmia in 6 (5.4%) patients; however, of those patients self-reporting normal smell but who were found to have hypofunction on testing, 62 out of 66 had self-reported reduction in sense of smell or taste at an earlier time point. Despite most patients report a subjectively normal sense of smell, we observed a high percentage of persistent smell dysfunction at 6 months from the diagnosis of SARS-CoV-2 infection, with 11.7% of patients being anosmic or severely microsmic. These data highlight a significant long-term rate of smell alteration in patients with previous SARS-COV-2 infection.