key: cord-0855866-x6f8p8e3 authors: VANDERSTEEN, C.; PAYNE, M.; DUMAS, L. E.; PLONKA, A.; D'ANDREA, G.; CHIRIO, D.; DEMONCHY, E.; RISSO, K.; ASKENAZY, F. G.; GUEVARA, N.; CASTILLO, L.; MANERA, V.; GROS, A. title: WHAT ABOUT USING SNIFFIN STICKS 12 SCREENING TEST TO IDENTIFY POST-COVID-19 OLFACTORY DISORDERS? date: 2021-06-09 journal: nan DOI: 10.1101/2021.06.06.21258430 sha: f98ecbb18ed8f845644db11453aa756429d4ea93 doc_id: 855866 cord_uid: x6f8p8e3 Background: Olfactory impairment is a major sequela of SARS CoV 2 infection and has a negative impact on daily life quality. Olfactory loss can be assessed in many ways but seems to be little realized in a daily clinical practice. The sniffin Sticks test12 items (SST12) can be used in quick olfactory disorders screening. Its use in a post-covid19 situation was the main objective of this work. Methodology: Consecutive patients consulting to the ENT department with post-Covid-19 olfactory loss were included. The clinical examination included an analog scale for the self-assessment of olfactory recovery (VAS), self-reported salt and sugar intake, a nasofibroscopy, the complete Sniffin Stick Test (SST) and the SST12. Results: Among the 54 patients included, based on the SST12, 14,8% (n=8) of the patients could be classified as normosmic (SST12[≥]11), 48,1% (n=26) as hyposmic (6< SST12<10) and 37% (n=20) as functional anosmic (SST12[≤]6). We report excellent and significant correlations between SST12 and SST or VAS assessments. Salt and Sugar increased intake seems significantly related to SST12 results. Conclusions: SST12 is a reliable way to screen post COVID 19 olfactory disorders could be used in a daily clinical practice and might be used to prevent bad diet habits and so cardiovascular risk. The study was approved by the institutional review board of the Nice University 83 Hospital (CNIL number: 412). This study is part of a large work registered under a 84 ClinicalTrials.gov number (ID: NCT04799977). Since March 2020, we retroprospectively 85 recruited at ENT department of Nice University Hospital all patients infected by COVID-19 with 86 persistent olfactory disorders from two to nine months. Patients where self-referred or 87 referred by colleagues, general practitioners or advised by the infectiology department that 88 managed all COVID-19 declared patients (city guidelines). Patients had either an olfactory 89 complaint for over 6 weeks and a molecular-proven SARS-CoV-2 diagnosis or a CT-proven 90 SARS-CoV-2 diagnosis secondarily confirmed by serology. We retrospectively extracted 91 patients' demographic data, and clinical characteristics including nasofibroscopy, visual 92 analogue scale (VAS) for the subjective assessment of olfactory recovery (ranging from 0% to 93 100%), subjective taste impairment, over intake of salt and sugar, and SST (26, 29, 30) total and 94 subdomains results which were systematically assessed. SST-12 results were extrapolated 95 from SST results. 96 97 Olfaction diseases SST-12 test has been validated in 2001 by Hummel et al. (31) . This 4 99 min screening psychophysical test is an odor identification test based on 12 from the 16 odors 100 being sniffed during the identification subdomain part of the original SST. 101 The original SST identification odors set include peppermint, orange, fish, leather, rose, 102 cloves, coffee, pineapple, licorice, anise, lemon, banana, cinnamon, apple, turpentine and 103 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint garlic. During the identification SST test, subjects were blindfolded. Sixteen odorant sticks 104 were presented once, separated by an interval of at least 20 seconds to prevent olfactory 105 desensitization. Each stick presentation was accompanied by a written list containing the 106 correct odorant and 3 semantic distractors. Retrospectively, results from all odors set but 107 apple, turpentine, garlic and anise were summed up to the SST-12 global score, as previously 108 described (31) . We defined a normosmia (SST-12≥11), an hyposmia (10>SST-12>6) or an 109 anosmia (SST-12≤6) based on normative values assessed from more than 1200 patients 110 assessed with SST and olfactive evoked potential for anosmic and hyposmic ones (31) . Apple, 111 turpentine and garlic have been removed from the SST-12 because identified by less than 55% 112 of its normosmic validation cohort (31) . Anise was removed too because of being too similar to 113 liquorice. With a reproducibility kappa coefficient of 0,77, the diagnosis agreement can be 114 considered as "good" (Altman, 1991). Although olfactory abilities decreased at extreme ages, 115 SST-12 can be used before the age of 10 and after the age of 80. 116 117 Data are presented as mean (SD) for quantitative variables and as frequency and 119 percentage for qualitative variables. The degree of accordance between the SST and the SST-120 12 in patients' categorization was calculated using Cohen's Kappa coefficient. Sensitivity and 121 specificity of the SST-12 compared to the SST in classifying patients as anosmic, was also 122 reported. To verify whether patients that increased their consumption of salt and sugar had 123 lower SST and SST-12 scores compared to those who did not, we employed Mann-Whitney U 124 tests. Chi2 tests were employed to explore links between self-reported taste disorders and 125 the presence of an increased salt and sugar consumption. To investigate correlations between 126 subjective reports (VAS), and odor identification disorders (based on the SST and SST-12) we 127 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint performed bivariate correlation analyses. As data were not normally distributed (as suggested 128 by Kolmogorov-Smirnov test), non-parametric Spearman's correlations were employed. 129 130 131 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint (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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint (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 June 9, 2021. 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint patients that increased their consummation of salt showed lower SST (U=112.5, p=0.003) and 231 SST-12 (U=121, p=0.005) scored compared to the patients that did not increase salt usage 232 (20.0±8.8 vs. 27.9±7.7, and 5.7±3.5 vs. 8.5±2.2, respectively). The same result was found for 233 patients who increased their consummation of sugar, that showed lower SST (U=73. the SST score, is reported in Table 3 and suggests that a score of 6 is the cut-off that maximize 246 the combination between specificity (100%) and sensitivity (81%) in detecting anosmic 247 patients. The presence of taste disorders did not affect the type of errors of the SST-12 248 compared to the SST. 249 250 Correlations between self-reported olfactory recovery, SST and SST-12 score 251 VAS scores were 45±24% (range 5%-70%), 38±25% (range 1%-90%), and 13±16% (range 252 0%-50%) for respectively normosmic, hyposmic and anosmic patients, based on the SST. Based 253 on the SST-12, VAS scores were 52±26%, 42±22%, and 16±19% for respectively normosmic, 254 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint hyposmic and anosmic patients. An almost perfect correlation between scores at the SST and 255 SST-12 was found (rho(52)=0.98, p<0.001), confirming that the SST-12 can assess odor 256 identification as well as the SST. Correlations between subjective reports (VAS) and the SST 257 and SST-12 scores suggested a significant, positive correlation between percentage of 258 subjective olfactory recovery (VAS) and the identifications scores for both the SST 259 (rho(52)=0.47, p< 0.001) and the SST-12 scores (rho(52)=0.49, p< 0.001), testifying that the two 260 scales were equally correlated to self-reported disorders. These results are reported in Figure 261 1. 262 263 264 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint This is the first study that evaluates quantitatively the efficiency of the SST-12 to screen 266 for post-COVID-19 olfactory disorders, and specially to identify post COVID-19 anosmics 267 patients. 268 Screening for olfactory disorders is important because, in addition to allowing to set 269 up appropriate care for patients, it helps prevent the occurrence of consequences of long-270 term anosmia like an alteration in the quality of life (5) , psychiatric disorders such as 271 depression (6,7) , anxiety, anorexia (8) and its nutritional consequences (9) , social interaction 272 disorders (10,11) or cognitive impairment (10, 12, 13) . Although a subjective olfactory complaint (80% 273 anosmia, 20% hyposmia) is now a very frequent symptom of a COVID-19 infection (2) affecting 274 70 to 85% of patients (32, 33) , only 21% of clinicians use psychophysical olfactory tests to 275 characterize this olfactory complaint (20) . Odor disorder is also the only symptom in 16-20% of 276 cases (3, 34) . The other differences in scores between the SST-12 and the SST do not modify the purpose of 287 the screening, which is to perform or have performed complete olfactory tests in the event of 288 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint an abnormality detected. In this way, all but 4 patients (92%) would have been correctly 289 screened using the SST-12. All the anosmics patients at the SST were correctly screened by the 290 SST-12 as evidenced by the "good" correlation coefficient (0,61≤Kappa≤0,80 -Altman 1991). 291 Other screening test do exist. The Q-stick test (35, 36) is another olfactory screening test validated 292 on 196 people from the SST. It allows, after the age of 12, to assess the identification of three 293 smells (coffee, cloves and rose) contained again in olfactory markers. On the other hand, its 294 reliability coefficient is less good than the SST-12 (Kappa between 0.2 and 0.33 at most) (36) . 295 Also, it does not detect 8% of anosmics according to its authors (36) . Others are more used in 296 Asia or the American continent (Cross Cultural Smell Identification Test (CC-SIT) (27) , Q-SIT (28) ) 297 but they are based on single-use "scratch and sniff". Others are less used (17) (Kremer olfactory 298 Test, Le Nez du Vin, Smell Diskettes). They require additional specific equipment (Jet Stream 299 Olfactometer) or have been validated outside of Europe (different scents) or on small cohorts, 300 and never in the context of COVID-19. 301 The total SST-12, as SST, was significantly correlated (p <0.001) with odor complaint 302 (VAS -figure 1) which reflects persistent post-COVID-19 olfactory impairment, i.e. 303 identification disorder (5) . Unlike the SST, the SST-12 only assesses the identification of odors 304 and thus seems more suited to detect an identification disorder than the SST, which adds to 305 the identification score, a score for discrimination and perception of the odor threshold. As 306 we have shown in previous studies (5) , the SST interpretation can conclude to a global 307 normosmia when one of its subdomains is altered. The SST should therefore not be used as a 308 gold standard in the post-COVID-19 odor evaluation given that some patients, early (37) and at 309 a distance (5) from SARS-COV-2 infection, may be incorrectly classified as normosmic on SST 310 despite odor loss (5) . In this study we found that olfactory complain (VAS) was significantly 311 linked to an SST or SST12 impairment, justifying the no need to a psychophysical screening 312 Recent Smell Loss Is the Best Predictor of 353 COVID-19 Among Individuals With Recent Respiratory Symptoms Isolated Sudden Onset Anosmia in COVID-19 Infection. A 356 Novel Syndrome? Anosmia and dysgeusia in COVID-19: A 358 systematic review Smell 360 and taste dysfunction in patients with SARS-CoV-2 infection: A review of 361 epidemiology, pathogenesis, prognosis, and treatment options COVID-19: a new interpretation of the psychophysical olfactory scores Association of alterations in smell and taste 367 with depression in older adults Olfaction and Depression: A Systematic Review Olfactory disorders and quality of life-an updated review Sensory perception of food and ageing The Impact of Olfactory 375 Obstruction and Septal Deviation Sadness might isolate you in a non-smelling world: olfactory 378 perception and depression Complaints of olfactory disorders: epidemiology, assessment 380 and clinical implications Post-traumatic brain injury olfactory 382 dysfunction: factors influencing quality of life Six month follow-up of self-reported loss of smell 385 during the COVID-19 pandemic Changes and Factors of Increase in Caloric/Salty Food Intake, Screen Use Substance Use During the Early COVID-19 Containment Phase in the General 389 Self -reported smell and taste recovery in 391 coronavirus disease 2019 patients : a one -year prospective study Office Procedures for Quantitative Assessment of Olfactory Function Clinical Implications of Psychophysical Olfactory Testing Dysfunction in Patients With COVID-19: A Systematic Review and Meta-analysis Updated Sniffin' Sticks 404 normative data based on an extended sample of 9139 subjects Changes of olfactory abilities in relation 407 to age: odor identification in more than 1400 people aged 4 to 80 years Patterns of olfactory impairment 410 reflect underlying disease etiology Clinical significance of results 412 from olfactory testing Qualitative and Quantitative Assessment of 414 Taste and Smell Changes in Patients Undergoing Chemotherapy for Breast Cancer or 415 Performance Assessed by the Combined Testing of Odour Identification, Odor 418 Discrimination and Olfactory Threshold Development of the 12-Item Cross-Cultural Smell 420 Identification Test(CC-SIT) Utility of a Three-Item Smell Identification Test in Detecting 422 Smell and Taste Disorders Comment tester l'olfaction avec le Sniffin' Sticks 426 test®. Ann françaises d'Oto-rhino-laryngologie Pathol Cervico-faciale Screening of Olfactory Function with 429 a Four-Minute Odor Identification Test: Reliability, Normative Data, and Investigations 430 in Patients with Olfactory Loss Clinical and epidemiological 432 characteristics of 1420 European patients with mild-to-moderate coronavirus disease 433 2019 Objective olfactory evaluation of 435 self-reported loss of smell in a case series of 86 COVID-19 patients Sniffing out the evidence; It's now time for public 438 health bodies recognize the link between COVID-19 and smell and taste disturbance A short olfactory test based on the identification of 441 three odors Olfactory Function Using the Q-Sticks Test Detection of COVID-19 in Patients With Sudden Onset Olfactory Dysfunction: A 446 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint test to take social distancing and barrier measures in case of acute olfactory disorders in 313 COVID-19 pandemic times. Even if SST-12 has been recently evaluated in a single-use "filter 314 paper" manner (38) , 7% of hyposmic patients could be missed with such a test. This is especially 315 true since such a screening test poses a contamination risk to the examiner. However, at a 316 distance from acute infection, SST-12 could be helpful to screen post COVID-19 olfactory 317 disorders. In case of a complaining person, as our results suggest, a complete psychophysical 318 olfactory test might be directly performed as an olfactory complain is highly correlated with 319 an impaired SST and SST-12. But in case of a non-complaining, or olfactory impairment 320 unaware, post-COVID-19 patient, SST-12 could avoid negative consequences of unknown 321 olfactory disorders, especially quality of life (5,39-41) and metabolic impairments. Indeed, 45,5 322 and 20,5% (n=44) of post COVID-19 patients increased respectively their daily diet salt and 323 sugar intake. As previously published, salt and sugar intake increase concerned near 30% of 324 COVID-19 patients (15) , especially young women. Our results suggest that theses bad diet habits 325 could concerned in fact olfactory impaired post-COVID-19 patients, specifically anosmics ones 326 (SST-12≤6) being deprived of their original food tastes and trying to enhance it whatever the 327 way. Interestingly, there is no significant relation, otherwise only with the SST-12 score, 328 between the risk of bad diet habits and subjective olfactory complain, underlining the benefits 329 of using SST-12. The sugar intake is also concerned as COVID-19 could basically raise blood 330 glucose and HbA1c levels (42) which has to be monitored after hospital discharge. It's a major 331 public health concern as post-COVID-19 olfaction disorders recovery time is still uncertain and 332 long term salt and sugar intake could increase respectively blood pressure (43) and type 2 333 diabetes (44) onset and so, cardiovascular risk. In case of SST-12 screened anosmia, a not to 334 change daily use of salt and sugar advice must be added to the patient consultation. 335 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint Despite these interesting results, this study suffers from some limitations. The main 336 limitation concerns the small cohort of 54 patients, with no follow up reported, who 337 spontaneously consulted our university hospital, which represents the risk of a recruitment 338bias. The small sample size may have contributed to a limited strength of correlations (rho(32) 339 MAX = 0,49), and therefore our results cannot be directly generalized to all patients with a 340 post-covid olfactory disorder and could be verified in a larger prospective cohort study. 341 342 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 June 9, 2021. (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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint 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. (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 June 9, 2021. ; https://doi.org/10.1101/2021.06.06.21258430 doi: medRxiv preprint