Telemedicine allows quantitative measuring of olfactory dysfunction in COVID‐19

Abstract

To the Editor, Evidence is accumulating that olfactory dysfunction is common in COVID-19. New-onset anosmia 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 noninfected 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, 24-32 years) who went to a 3-day holidays to Austria with 7 developing COVID-19 with mild symptoms (cough ± fever, no dyspnoea) after return. Due to a singular social event, the time of infection could be confirmed 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 (Table S2) and Pearson/point biserial correlation were performed, and wellness-of-fit analysis revealed good regression fit. A P-value of <.05 was considered statistically significant. See Appendix S1 for full data table. Functional anosmia was measurable in all patients for 14 days in threshold, discrimination and identification (Figure 1) and differed significantly from normosmic controls (P < .05). Multiple independent variables for TDI score were identified in regression analysis (Table S2). Four patients self-reported smell loss, while 3 others did not notice and 1 reported anosmia without any other complaints for 6 days after infection. Self-reporting did not detect quantitatively impaired patients (P > .05) in the first 3 days. Olfaction recovered in 6 patients within 4 weeks (P = .65). Olfactory impairment occurred without symptoms of rhinitis (Table S1). 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 angiotensin-converting enzyme receptor-2 (ACE2) for intracellular invasion.6 Our data suggest (a) functional anosmia in COVID-19 is more frequent using psychophysical olfaction tests than self-evaluations, (b) telemedicine allows early detection and monitoring a full disease course, (c) smell function is largely affected, and (d) olfactory function in mildly symptomatic outpatients recovers without specific therapy in most, but not all patients within 4 weeks. Telemedicine not only can be valuable for patient monitoring of SARS-CoV-2 infection, but may be a helpful tool for ongoing COVID-19 olfaction research. We would like to formally acknowledge our study assistants and nurses, which included a team of Center for Rhinology and Allergology, Mainz University Hospital and Allergiezentrum Rheinland-Pfalz and Corona Test Center house staff and would like to thank Prof. van Ewijk and Fabienne Pradella for their statistical consulting and Dr Lise Leclercq for editing. Dr Klimek, Dr Hagemann, Dr Alali, Dr Spielhaupter, Dr Huppertz, Dr Hörmann, Dr Stielow, Dr Freudelsperger and Dr Matthias have nothing to disclose. This work was supported by a grant from the Hessische Stiftung für Prävention, Wiesbaden, Germany (HSP 2020/03-1). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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