key: cord-0891040-hgmwmrtq
authors: Hornuss, D.; Lange, B.; Schroeter, N.; Rieg, S.; Kern, W. V.; Wagner, D.
title: Anosmia in COVID-19 patients
date: 2020-05-03
journal: nan
DOI: 10.1101/2020.04.28.20083311
sha: 28443d9be13bac78a7967681c26c3337e5b531a0
doc_id: 891040
cord_uid: hgmwmrtq

Objectives: Coronaviruses (CoVs) have a neuroinvasive propensity, and the frequently reported symptoms of smelling and taste dysfunction in many COVID-19 patients may be related to the respective capability of SARS-CoV2, the cause of the current pandemic. In this study we objecti-fied and quantified the magnitude and underreporting of the smelling dysfunction caused by COVID-19 using a standardized test. Methods: We conducted a prospective cross-sectional study comparing the proportion of anos-mia using Sniffin-sticks in those reporting a loss of smell, in those who did not as well as in unin-fected controls. The outcome of anosmic versus not anosmic patients were recorded during hospital stay and at day 15 on a six-category ordinal scale. The study was approved by the insti-tutional review board, all participants consented to the study. Results: 40% of 45 consecutive hospitalized COVID-19 patients and 0% of 45 uninfected con-trols consenting were diagnosed with anosmia. 44% of anosmic and 50% of hyposmic patients did not report having smelling problems. Anosmia or hyposmia was not predictive of a severe COVID-19 manifestation. Conclusions: The majority of COVID-19 patients have an objective anosmia and hyposmia, which often occurs unnoticed. These symptoms may be related to the neuroinvasive propensity of SARS-COV-2 and the unusual presentation of COVID-19 disease manifestations.

3 Anosmia in COVID-19 patients -Manuscript -DW Introduction: Coronaviruses (CoVs) including SARS-CoV-2, the cause of the current pandemic 47 of coronavirus disease 2019 , have a neuroinvasive propensity [1, 2] , with the olfacto-48 rial neurons being currently discussed as portal of entry for neuroinvasion [3] and a spread of 49 CoVs after infection of neural cells from CNS to the periphery via a transneural route [1] . A rele-50 vant proportion of admitted COVID-19 patients report the disturbances of taste or smelling [4] , 51 without any other obvious cause like nasal obstruction or rhinorrhea, which may be related to 52 this capability. In this study we objectified the magnitude of the smelling disorder caused by 53 SARS-CoV-2.

Methods: Burghart-Sniffin'-Sticks®, a widely used screening test for smelling disorders, was 56 used; according to the manufacturers specifications anosmia, hyposmia and normosmia, were 57 defined as correctly identifying 1-6, 7-10, and 11-12 odors, respectively [5,6] . We conducted a 58 prospective cross-sectional study at the Medical Center -University of Freiburg, Germany in 59 April 2020 comparing the proportion of anosmia in patients with positive PCR result for SARS-60 CoV-2 in nasopharyngeal swaps or sputum using Sniffin-sticks in those reporting a loss of smell, 61 in those who did not as well as in uninfected patients and health care workers as controls. Pa-62 tients younger than 18 years, with known smelling disorder or who did not consent to the study 63 were excluded. Assuming a prevalence of anosmia of 5% in the uninfected control group [6], the 64 sample size was calculated to test the null hypothesis that anosmia in COVID-19 is the same as 65 in controls and to find a significant difference using the chi square test with a power of >90%. To (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 3, 2020. .

The study was approved by the University hospital ethical committee (No. 184/20) , written in-73 formed consent was obtained from all participants in the study. Study protocol and data set are 74 available from the corresponding author upon request.

Results: We tested 45 consecutive hospitalized COVID-19 patients and 45 uninfected controls 77 (age (median years ± STD) 56 ± 16.9 and 54 ± 18.3, respectively) consenting to the study (ta-78 ble). The controls correctly identified a median of 11 out of 12 odors of Sniffin' Sticks, none was 79 anosmic, 12/45 (27%, 95%CI 14-41%, age (median years ± STD) 63 ± 19.6) were hyposmic, 80 and 33 (73%, 95%CI 58-85%, age (median years ± STD) 49 ± 10.2) were normosmic. A higher been reported using the same test; however the 12-stick-test is not able to distinguish properly 98 between hyposmia and normosmia [6], thus the high percentage of 44 % of our COVID-19 pa-99 tients with hyposmia needs to be interpreted carefully. Patients were not tested after having 100 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 3, 2020. . Anosmia in COVID-19 patients -Manuscript -DW been discharged, but telephone interviews even with patients with mild to moderate COVID-19 101 showed that not all patients had returned to normal smelling 15 days after start of first symptoms 102 although no other symptoms persisted. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 3, 2020. . 

Neurologic Alterations Due to Respiratory

COVID-19 patients diagnosed with Sniffin' sticks as normosmic, hyposmic or anosmic (e.g. correctly identifying 11-12, 7-10, and 0-6 odors of Sniffin' sticks, respectively) are shown. n, number; %, percentage; STD

95%CI, 95% confidence interval

PCR, polymerase chain reaction

NIV = noninvasive ventilation

IMV, invasive mechanical ventilation

# Linear regression analysis adjusted for age and sex show that COVID-19 patients on average smell 4 sticks less than uninfected controls. ¶ at the day of testing. ‡ the worst outcome was recorded. † n = 41. *p< 0,001, chi square test with null hypothesis that anosmia in COVID-19 is the same as in controls. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder

Report of impaired smelling (n, %, 95CI) ¶ yes 22 (49%) 10 (45%, 24-68%) 10 (45%, 24-68%) 2 (10%, 1-29%) no 23 (51%) 8 (34%, 16-57%) 10 (43%, 23-65%) 5 (21%, 7-43%) Time course (days; median ± STD) first symptom to first positive PCR result 2 ± 4.2 2 ± 4.1 1.5 ± 3.7 2 ± 4 first symptom to reported impaired smelling 5 ± 3.04 6.5 ± 3 2.5 ± 2.7 5.5 ± 2.5 first symptoms to Sniffin test 10 ± 5.1 11 ± 4 8.5 ± 4.5 12 ± 7.5 first positive PCR result to Sniffin test 4 ± 4.6 3.5 ± 3.9 4 ± 4.4 5 ± 6.3 Clinical course during hospital stay (n, %) ‡ Discharged 23 (51%) 11 (48%) 9 (39%) 3 (13%) No oxygen 27 (68%) 8 (30%) 13 (48%) 6 (22%) Supplemental oxygen 15 (33%) 7 (47%) 7 (47%) 1 (7%) NIV or high flow oxygen 2 (4%) 2 (100%) 0 0 IMV or ECMO 0 0 0 0 Death 1 (2%) 1 (100%) 0 0Outcome at day 15 (n, %) † Discharged 17 (41%) 7 (41%) 6 (35%) 4 (24%) No oxygen 14 (32%) 3 (21%) 8 (57%) 3 (21%) Supplemental oxygen 9 (22%) 7 (78%) 2 (22%) 0 NIV or high flow oxygen 0 0 0 0 IMV or ECMO 0 0 0 0 Death 1 (2%) 1 (100%) 0 0