key: cord-0732763-9x4n8mdr authors: Klimek, Ludger; Hagemann, Jan; Alali, Ali; Spielhaupter, Magdalena; Huppertz, Tilman; Hörmann, Karl; Stielow, Sabine; Freudelsperger, Laura; Matthias, Christoph title: Telemedicine allows quantitative measuring of olfactory dysfunction in COVID‐19 date: 2020-06-22 journal: Allergy DOI: 10.1111/all.14467 sha: da16f8288074b015a4ceba8b27506db726135a9e doc_id: 732763 cord_uid: 9x4n8mdr nan has been considered as early marker for SARS CoV-2 infection 1-3 , but until now, all studies rely on self-evaluations of patients without objectified and quantitative measures. Moreover, no longitudinal measures of olfaction in COVID-19 are available and no data on recovery of olfaction in surviving patients. We report on the unique situation that olfaction could be quantitatively measured in a cohort of skiers from day 2 of infection over 4 weeks versus 2 non-infected controls in the same quarantine situation using telemedicine. The study was performed according to the Declaration of Helsinki and approved by the regional Ethics Committee (LÄK RLP, No. 2020-14337). All participants gave written informed consent after detailed explanation of all study-related measures. COVID-19 was defined if positive to SARS-CoV-2 RNA by polymerase chain reaction (PCR) in both of 2 swabs taken from nasopharynx and throat in presence of clinical symptoms such as cough or fever. Inclusion criteria were verified SARS-CoV-2 infection or ski group member travelling together and present at time of infection leading to identical obligation to quarantine, missing other disease that may interfere with olfaction, willingness to participate, being adult (> 18 years), being intellectually and clinically able to self-perform a full Sniffin´Sticks, visual-analogue-scales (VAS) and questionnaires. The cohort consisted of 9 otherwise healthy skiers (5 female, 24 to 32 years) who went to a three-day holidays to Austria with 7 developing COVID-19 with mild symptoms (cough ±fever, no dyspnea) after return. Due to a singular social event, the time of infection could be confirmed This article is protected by copyright. All rights reserved with high certainty. Over the following 4 weeks, psychophysical olfactory function tests (Sniffin´Sticks) were performed via telemedicine consultation daily from day 2 after infection during entire quarantine (14 resp. 21 days) and weekly, thereafter. After 14 days quarantine, individuals were retested again with negative PCR results in 5 out of 7, while 1 couple stayed positive and needed to prolong quarantine with negative PCR at day 21. Instructions in use of Sniffin`Sticks were given in video conferences (4 couples living together were trained and contacted together), with remote consultation every morning before breakfast, thus preventing missing any data. Statistical analysis tested for differences in outcome parameters between patients vs. controls during the quarantine days 1 to 14 and on days 21 and 28 (Robust error variance, Mann-Whitney-U t-test). Multiple regression analysis (Suppl. Table 2 ) and Pearson/point biserial correlation were performed and wellness-of-fit analysis revealed good regression fit. A p-value of <0.05 was considered statistically significant. See Online supplement for full data table. Results Functional anosmia was measurable in all patients for 14 days in threshold, discrimination and identification ( Figure 1 ) and differed significantly from normosmic controls (p<0.05). Multiple independent variables for TDI score were identified in regression analysis (Suppl. Table 2 ). Four patients self-reported smell loss, while 3 others didn´t notice and 1 reported anosmia without any other complaints for 6 days after infection. Self-reporting did not detect quantitatively impaired patients (p>0.05) in the first three days. Olfaction recovered in 6 patients within 4 weeks (p=0.65). Olfactory impairment occurred without symptoms of rhinitis (Suppl. Table 1 ). Discussion For the first time, quantitative psychophysical analyses of olfaction were performed over a full course of COVID-19 in this homogenous cohort of relatively young adults, while previous studies used self-ratings, only 1,2,4 . It is well accepted that self-ratings largely underestimate olfactory dysfunction 5 . Usually required face-to-face contact seems to cause this systematic error, while telemedicine consultations allows safe testing for patients and staff. The comprehensive impairment without nasal symptoms supports the suggestion of a neurotropic and neuro-invasive virus that is site-specific for the olfactory system using angiotensinconverting-enzyme-receptor-2 (ACE2) for intracellular invasion 6 . Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies Association of chemosensory dysfunction and Covid-19 in patients presenting with influenza-like symptoms. International forum of allergy & rhinology Anosmia and Ageusia: Common Findings in COVID-19 Patients. The Laryngoscope Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection Ratings of overall olfactory function. Chemical senses SARS-CoV-2: Olfaction, Brain Infection, and the Urgent Need for Clinical Samples Allowing Earlier Virus Detection This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved