Distorted chemosensory perception and female sex associate with persistent smell and/or taste loss in people with SARS-CoV-2 antibodies: a community based cohort study investigating clinical course and resolution of acute smell and/or taste loss in people with and without SARS-CoV-2 antibodies in London, UK

Janine Makaronidis, Chloe Firman, Cormac G Magee, Jessica Mok, Nyaladzi Balogun, Matt Lechner, Alisia Carnemolla, Rachel L Batterham, Janine Makaronidis, Chloe Firman, Cormac G Magee, Jessica Mok, Nyaladzi Balogun, Matt Lechner, Alisia Carnemolla, Rachel L Batterham

Abstract

Background: Loss of smell and/or taste are cardinal symptoms of COVID-19. 'Long-COVID', persistence of symptoms, affects around one fifth of people. However, data regarding the clinical resolution of loss of smell and/or taste are lacking. In this study we assess smell and taste loss resolution at 4-6 week follow-up, aim to identify risk factors for persistent smell loss and describe smell loss as a feature of long-COVID in a community cohort in London with known SARS-CoV-2 IgG/IgM antibody status. We also compare subjective and objective smell assessments in a subset of participants.

Methods: Four hundred sixty-seven participants with acute loss of smell and/or taste who had undergone SARS-CoV-2 IgG/IgM antibody testing 4-6 weeks earlier completed a follow-up questionnaire about resolution of their symptoms. A subsample of 50 participants completed an objective olfactory test and results were compared to subjective smell evaluations.

Results: People with SARS-CoV-2 antibodies with an acute loss of sense of smell and taste were significantly less likely to recover their sense of smell/taste than people who were seronegative (smell recovery: 57.7% vs. 72.1%, p = 0.027. taste recovery 66.2% vs. 80.3%, p = 0.017). In SARS-CoV-2 positive participants, a higher percentage of male participants reported full resolution of smell loss (72.8% vs. 51.4%; p < 0.001) compared to female participants, who were almost 2.5-times more likely to have ongoing smell loss after 4-6 weeks (OR 2.46, 95%CI 1.47-4.13, p = 0.001). Female participants with SARS-CoV-2 antibodies and unresolved smell loss and unresolved taste loss were significantly older (> 40 years) than those who reported full resolution. Participants who experienced parosmia reported lower smell recovery rates and participants with distorted taste perception lower taste recovery rates. Parosmia had a significant association to unresolved smell loss (OR 2.47, 95%CI 1.54-4.00, p < 0.001).

Conclusion: Although smell and/or taste loss are often transient manifestations of COVID-19, 42% of participants had ongoing loss of smell, 34% loss of taste and 36% loss of smell and taste at 4-6 weeks follow-up, which constitute symptoms of 'long-COVID'. Females (particularly > 40 years) and people with a distorted perception of their sense of smell/taste are likely to benefit from prioritised early therapeutic interventions.

Trials registration: ClinicalTrials.gov NCT04377815 Date of registration: 23/04/2020.

Keywords: COVID-19; Long COVID-19; SARS-CoV-2 IgG/IgM; Smell loss; Smell recovery; Taste loss; Taste recovery.

Conflict of interest statement

The authors declare no competing interests.

References

    1. WHO. Coronavirus disease (COVID-19) pandemic 2020 [cited 2020 22 June]. Available from: .
    1. Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, et al. Real-time tracking of self-reported symptoms to predict potential COVID-19. Nat Med. 2020.
    1. Hopkins C, Surda P, Kumar N. Presentation of new onset anosmia during the COVID-19 pandemic. Rhinology. 2020.
    1. Makaronidis J, Mok J, Balogun N, Magee CG, Omar RZ, Carnemolla A, et al. Seroprevalence of SARS-CoV-2 antibodies in people with an acute loss in their sense of smell and/or taste in a community-based population in London, UK: an observational cohort study. PLoS Med. 2020;17(10):e1003358. doi: 10.1371/journal.pmed.1003358.
    1. Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, et al. Attributes and predictors of Long-COVID: analysis of COVID cases and their symptoms collected by the Covid Symptoms Study App. medRxiv. 2020;2020:10.19.20214494.
    1. Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020;370:m3026. doi: 10.1136/bmj.m3026.
    1. NICE. COVID-19 rapid guideline: managing the long-term effects of COVID-19 : NICE Guidance; 2021 [Available from: .
    1. ONS. Office for National Statistics. The prevalence of long COVID symptoms and COVID-19 complications. 2020 [Available from: .
    1. Soler ZM, Patel ZM, Turner JH, Holbrook EH. A primer on viral-associated olfactory loss in the era of COVID-19. Int Forum Allergy Rhinol. 2020;10(7):814–820. doi: 10.1002/alr.22578.
    1. Suzuki M, Saito K, Min WP, Vladau C, Toida K, Itoh H, et al. Identification of viruses in patients with postviral olfactory dysfunction. Laryngoscope. 2007;117(2):272–277. doi: 10.1097/01.mlg.0000249922.37381.1e.
    1. Boscolo-Rizzo P, Borsetto D, Fabbris C, Spinato G, Frezza D, Menegaldo A, et al. Evolution of altered sense of smell or taste in patients with mildly symptomatic COVID-19. JAMA Otolaryngol Head Neck Surg. 2020.
    1. Chary E, Carsuzaa F, Trijolet JP, Capitaine AL, Roncato-Saberan M, Fouet K, et al. Prevalence and recovery from olfactory and gustatory dysfunctions in Covid-19 infection: a prospective multicenter study. Am J Rhinol Allergy. 2020;34(5):686–693. doi: 10.1177/1945892420930954.
    1. Otte MS, Klussmann JP, Luers JC. Persisting olfactory dysfunction in patients after recovering from COVID-19. J Inf Secur. 2020;81(3):e58.
    1. Whitcroft KL, Hummel T. Olfactory dysfunction in COVID-19: diagnosis and management. JAMA. 2020.
    1. . Coronavirus Smell Therapy for Anosmia Recovery 2021 [Available from: .
    1. Croy I, Nordin S, Hummel T. Olfactory disorders and quality of life--an updated review. Chem Senses. 2014;39(3):185–194. doi: 10.1093/chemse/bjt072.
    1. Elabscience. COVID-19 IgG and IgM [Available from: .
    1. Doty RL, Shaman P, Kimmelman CP, Dann MS. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope. 1984;94(2 Pt 1):176–178. doi: 10.1288/00005537-198402000-00004.
    1. Wajnberg A, Amanat F, Firpo A, Altman DR, Bailey MJ, Mansour M, et al. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science (New York, NY) 2020;370(6521):1227. doi: 10.1126/science.abd7728.
    1. Rodda LB, Netland J, Shehata L, Pruner KB, Morawski PA, Thouvenel CD, et al. Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19. Cell. 2021;184(1):169–183. doi: 10.1016/j.cell.2020.11.029.
    1. Meini S, Suardi LR, Busoni M, Roberts AT, Fortini A. Olfactory and gustatory dysfunctions in 100 patients hospitalized for COVID-19: sex differences and recovery time in real-life. Eur Arch Otorhinolaryngol. 2020;277(12):3519–3523. doi: 10.1007/s00405-020-06102-8.
    1. Dell'Era V, Farri F, Garzaro G, Gatto M, Aluffi Valletti P, Garzaro M. Smell and taste disorders during COVID-19 outbreak: cross-sectional study on 355 patients. Head Neck. 2020;42(7):1591–1596. doi: 10.1002/hed.26288.
    1. Vaira LA, Hopkins C, Petrocelli M, Lechien JR, Chiesa-Estomba CM, Salzano G, et al. Smell and taste recovery in coronavirus disease 2019 patients: a 60-day objective and prospective study. J Laryngol Otol. 2020;134(8):703–709. doi: 10.1017/S0022215120001826.
    1. Lechien JR, Journe F, Hans S, Chiesa-Estomba CM, Mustin V, Beckers E, et al. Severity of Anosmia as an Early Symptom of COVID-19 Infection May Predict Lasting Loss of Smell. Front Med (Lausanne) 2020;7:582802. doi: 10.3389/fmed.2020.582802.
    1. Beltrán-Corbellini Á, Chico-García JL, Martínez-Poles J, Rodríguez-Jorge F, Natera-Villalba E, Gómez-Corral J, et al. Acute-onset smell and taste disorders in the context of COVID-19: a pilot multicentre polymerase chain reaction based case-control study. Eur J Neurol. 2020;27(9):1738–1741. doi: 10.1111/ene.14273.
    1. Reden J, Maroldt H, Fritz A, Zahnert T, Hummel T. A study on the prognostic significance of qualitative olfactory dysfunction. Eur Arch Otorhinolaryngol. 2007;264(2):139–144. doi: 10.1007/s00405-006-0157-0.
    1. Leopold DA, Loehrl TA, Schwob JE. Long-term follow-up of surgically treated phantosmia. Arch Otolaryngol Head Neck Surg. 2002;128(6):642–647. doi: 10.1001/archotol.128.6.642.
    1. Liu DT, Sabha M, Damm M, Philpott C, Oleszkiewicz A, Hähner A, et al. Parosmia is Associated with Relevant Olfactory Recovery After Olfactory Training. The Laryngoscope. 2020.
    1. Lee Y, Min P, Lee S, Kim SW. Prevalence and duration of acute loss of smell or taste in COVID-19 patients. J Korean Med Sci. 2020;35(18):e174. doi: 10.3346/jkms.2020.35.e174.
    1. Dhong HJ, Chung SK, Doty RL. Estrogen protects against 3-methylindole-induced olfactory loss. Brain Res. 1999;824(2):312–315. doi: 10.1016/S0006-8993(99)01241-X.
    1. Nathan BP, Tonsor M, Struble RG. Acute responses to estradiol replacement in the olfactory system of apoE-deficient and wild-type mice. Brain Res. 2010;1343:66–74. doi: 10.1016/j.brainres.2010.04.070.
    1. Yan CH, Prajapati DP, Ritter ML, DeConde AS. Persistent smell loss following undetectable SARS-CoV-2. Otolaryngol Head Neck Surg. 2020;163(5):923–925. doi: 10.1177/0194599820934769.
    1. Cavazzana A, Larsson M, Münch M, Hähner A, Hummel T. Postinfectious olfactory loss: a retrospective study on 791 patients. Laryngoscope. 2018;128(1):10–15. doi: 10.1002/lary.26606.
    1. Hwang CS. Olfactory neuropathy in severe acute respiratory syndrome: report of a case. Acta Neurol Taiwanica. 2006;15(1):26–28.
    1. Erskine SE, Philpott CM. An unmet need: patients with smell and taste disorders. Clin Otolaryngol. 2020;45(2):197–203. doi: 10.1111/coa.13484.
    1. Hopkins C, Lechien JR, Saussez S. More that ACE2? NRP1 may play a central role in the underlying pathophysiological mechanism of olfactory dysfunction in COVID-19 and its association with enhanced survival. Med Hypotheses. 2020;110406.
    1. Bryche B, St Albin A, Murri S, Lacôte S, Pulido C, Ar Gouilh M, et al. Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters. Brain Behav Immun. 2020;89:579–586. doi: 10.1016/j.bbi.2020.06.032.
    1. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271–280. doi: 10.1016/j.cell.2020.02.052.
    1. Prajapati DP, Shahrvini B, MacDonald BV, Crawford KL, Lechner M, DeConde AS, et al. Association of subjective olfactory dysfunction and 12-item odor identification testing in ambulatory COVID-19 patients. Int Forum Allergy Rhinol. 2020.

Source: PubMed

3
订阅