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

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 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article 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UK Janine Makaronidis, Chloe Firman, Cormac Magee, Jessica Mok, Nyaladzi Balogun, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-156677/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Feb, 2021 Read the published version in BMC Infectious Diseases → Version 1 posted 6 You are reading this latest preprint version 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. We assessed COVID-19 symptoms in a community cohort in London 4-6 weeks after they initially reported acute loss of their sense of smell and/or taste, 78% of whom had SARS-CoV-2 IgG/IgM antibodies. In addition, to assess whether self-reported change in sense of smell was reliable, we compared subjective and objective smell assessments in a subset of participants. Methods: 467 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 Infectious Diseases COVID-19 Long COVID-19 SARS-CoV-2 IgG/IgM Smell loss Taste loss Smell recovery Taste recovery Figures Figure 1 Figure 2 Introduction Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which results in coronavirus disease 2019 (COVID-19), emerged in 2019 resulting in a global pandemic with over 85 million cases and 1.8 million deaths reported worldwide[ 1 ]. The association between COVID-19 and smell and taste loss was established in March 2020 and has since been identified among the most specific symptoms of COVID-19, with implications for case identification, isolation and tracing[ 2 , 3 ]. We previously reported seroprevalence of SARS-CoV-2 IgG/IgM antibodies of 78% in a community cohort in London, UK who developed an acute loss of their sense of smell and/or taste during the peak of the first local wave of the pandemic[ 4 ]. We also showed that seropositivity for SARS-CoV-2 antibodies was three times more likely for people with smell loss compared to taste loss. With the ongoing spread of SARS-CoV-2 globally, COVID-19 and its complications are continuing to affect millions globally. Despite the development of vaccinations resulting in optimism that the pandemic will be contained, healthcare providers worldwide will continue to face the challenge of an unprecedented incidence of COVID-19 related morbidity. It is now evident that symptoms can persist beyond resolution of the acute systemic viral infection and cause a chronic condition, termed ‘long-COVID’, in up to a quarter of cases[ 5 ]. ‘Long covid’ (> 4 weeks) as well as ‘post-acute covid’ (> 3 weeks) and ‘chronic covid’ (> 12 weeks) have been used to describe ongoing symptoms of the disease[ 6 , 7 ]. Symptoms persisting longer than 5 weeks are estimated to occur in 1 in 5 and symptoms and lasting longer than 12 weeks in 1 in 10 people, according to data published by the UK Office for National Statistics (ONS)[ 8 ]. Identifying the people most at risk of long-term symptoms will be key to guide monitoring in order to deliver follow-up care and therapeutic interventions to patients with long COVID-19 disease. Despite the recognition of loss of smell and/or taste as key symptoms of COVID-19 there remains a paucity of data within the literature regarding the clinical course, recovery rates and demographic risk factors for long-lasting symptoms. Post-viral smell loss from other respiratory pathogens is typically a short-lived phenomenon and recovery usually coincides with resolution of other viral symptoms[ 9 , 10 ]. In contrast, current data from COVID-19 patients, suggest a wide range of recovery times, from a few days to several months[ 11 – 13 ]. This observation raises concerns of unresolved smell loss as a manifestation of long-COVID. Therefore, identifying risk factors for persistent smell loss will be key to guide therapeutic interventions, such as olfactory rehabilitation and use of corticosteroids, once these are widely available[ 14 , 15 ]. Furthermore, given the negative impact of these symptoms on quality of life and safety, research on prognostic information is warranted to inform patients, their carers, as well as treatment algorithms[ 16 ]. In this follow-up study, we aim to describe and compare the temporal resolution patterns of loss of smell and/or taste in a community cohort with acute smell and/or taste loss with and without SARS-CoV-2 antibodies. This study will focus on smell loss resolution and aim to identify risk factors for persistent smell loss, as well as describe smell loss as a feature of long-COVID. Finally, to address the original study’s limitations of reliance on self-reported symptoms, we will correlate self-reported smell function with objective olfactory testing. Methods The study was conducted in London, UK, at a time when loss of smell and taste were not recognised as symptoms of COVID-19. People with an acute loss of their sense of smell and/or taste were invited to participate through text messages, sent via primary care centres in London, UK. Recruitment took place over a 4-week period between 23 April and 14 May 2020, during the local first wave of the pandemic. Participants were recruited via an online platform, as previously described[ 4 ]. Inclusion criteria were age > 18 years, proficiency in written and spoken English and access to video calling. Exclusion criteria were any pre-existing loss of the sense of smell or taste of longer than one month’s duration. Participation was voluntary and written informed consent was obtained electronically. Enrolled participants completed an online questionnaire (see Additional File 1), capturing their sex, age, ethnicity, smoking status, questions about their smell and taste loss, as well as other symptoms of COVID-19. SARS-CoV-2 immunoglobulin G (IgG)/ immunoglobulin M (IgM) antibody testing was carried out via a telemedicine consultation as described previously described[ 17 ], using a lateral flow immunoassay detecting IgM and IgG antibodies to SARS-CoV-2 (Wuhan UNscience Biotechnology Co., Ltd. COVID-19 Antibody IgM/IgG) with a relative sensitivity of 98.8% (95% CI 97.3–99.6%) and a relative specificity of 98.0% (95% CI 97.15–98.7%)[ 18 ]. A link to a follow-up questionnaire was sent to participants’ registered email addresses 4 weeks after they completed their original questionnaire. The follow up questionnaire (see Additional File 1) contained questions about resolution of their smell and taste loss, as well as resolution of the other symptoms of COVID-19 and admission to hospital. Reminders were sent to participants who did not complete the original questionnaire at 72 hours and 7 days and the platform remained open for questionnaire completion for a further 4 weeks (22 May to 20 July 2020). In order to correlate participants’ questionnaire responses about their loss of smell with objective olfactory testing, a subsample of 50 participants were recruited for objective smell testing. Participants received a separate information sheet and informed consent was obtained electronically using a separate consent form. The University of Pennsylvania Smell Identification Test (UPSIT), a 40-item smell test which is validated to be self-administered, was used[ 19 ]. UPSIT kits were sent to recruited participants together with instructions on completing the test. Photographs of the booklet were obtained and the tests were scored by a healthcare professional, who then explained the results to participants. The study received ethical approval from the National Health Service Queen’s Square Research Ethics Committee (IRAS Project ID 282668, ClinicalTrials.gov: NCT04377815) and was conducted in line with the declaration of Helsinki and Good Clinical Practice. Statistical analysis A sample size calculation was undertaken in order to determine the study’s recruitment target, using the information on reported symptoms from the web-based COVID symptom study app developed by King’s College London and symptom reporting between the 24–29 March 2020. To calculate an estimate of 50% (95% CI 45–55%) as the proportion who would test positive amongst those who reported a change in smell or taste, we needed 385 participants in the study [ 17 ]. Assuming a 15% attrition, the number increased to 453 participants in the study. The recruitment target was set to 500 participants and was exceeded to allow for larger attrition and increase accuracy. Data were analyzed using GraphPad Prism version 8 ( https://www.graphpad.com/scientific-software/prism/ ) and SPSS version 26 ( https://www.ibm.com/uk-en/products/spss-statistics ). Descriptive analyses included the calculation of means (plus standard deviation [SD]) for continuous variables and numbers ( n , with percentages) for categorical variables. Chi-squared tests were performed on categorical data. When performing multiple comparisons, the significance level was adjusted by applying a Bonferroni correction. Parametric and non-parametric tests were used as appropriate on continuous data. Logistic regression analysis was performed to estimate the association between smell loss resolution and additional factors including participant’s age, sex, ethnicity, smoking status and smell loss pattern. A Spearman Rank correlation analysis was performed to investigate the association between participants’ perceived smell function and an objective assessment of their olfactory function. Results Study population A total of 467 out of the 569 participants who enrolled and underwent a SARS-CoV-2 antibody test completed the follow-up questionnaire, yielding a follow-up rate of 82.1%. The demographics of the entire study cohort can be seen in Additional File 2. Out of the cohort of 467 who completed the follow-up questionnaire, participants with positive and negative SARS-CoV-2 antibodies were comparable in terms of age, gender, smoking status and ethnicity (Table 1). Admission to hospital was reported by 1.6% (n=7) of participants in the antibody positive group vs. 3.1% (n=4) in the antibody negative group (p=0.097). Table 1: Demographics of participants followed up after 4-6 weeks with positive and negative SARS-CoV-2 antibodies Demographics SARS-CoV-2 IgG/IgM positive (n=381) SARS-CoV-2 IgG/IgM negative (n=86) p -value (0.05) Gender Female 70.9% (n=270) 66.3% (n=57) 0.382 Male 28.8% (n=110) 33.7% (n=29) Other 0.3% (n=1) 0 0.450 Age (years) 39.67±12.12 40.25±12.33 0.689 Ethnicity * White 83.7% (n=319) 81.4% (n=70) 0.600 Mixed/Multiple Ethnicities 5.5% (n=21) 4.7% (n=4) 0.749 Asian/Asian British 5% (n=19) 4.7% (n=4) 0.897 Black/African/Caribbean/Black British 1.6% (n=6) 2.3% (n=2) 0.628 ‘Other’ 3.7% (n=14) 3.5% (n=3) 0.933 Smoking status Current/ Ex-smoker 42% (n=160) 44.2% (n=38) 0.710 Never smoked 58% (n=221) 55.8% (n=48) Figures presented as % with total number (n). SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. *5 participants opted not to disclose their ethnicity. Smell and taste loss and resolution at 4 -6 weeks follow-up The frequency of reported smell and/or taste loss at baseline can be seen in Table 2. Table 2: Loss of smell and/or taste in SARS-CoV-2 IgG/IgM positive and negative participants SARS-CoV-2 IgG/IgM positive (n=443) SARS-CoV-2 IgG/IgM negative (n=126) p -value (0.05) Sense of smell Loss of sense of smell (complete and partial) 93.5% (n=414) 79.4% (n=100) <0.001 Partial loss of smell 24.4% (n=108) 39.7% (n=50) <0.001 Complete loss of smell 69.1% (n=306) 39.7% (n=50) Parosmia (distorted sense of taste) 30% (n=133) 21.4% (n=27) 0.245 Sense of taste Loss of sense of taste (complete and partial) 90.1% (n=399) 88.9% (n=112) 0.700 Partial loss of taste 42.7% (n=189) 61.9% (n=78) <0.001 Complete loss of taste 47.4% (n=210) 27% (n=34) Dysgeusia (distorted sense of taste) 44.7% (n=198) 42.9% (n=54) 0.856 Experience of taste without eating/drinking 21.4% (n=95) 24.6% (n=31) 0.374 Only loss of smell 9.9% (n=43) 11.1% (n=14) 0.643 Only loss of taste 6.5% (n=28) 20.6% (n=27) <0.001 Loss of sense of smell and taste (partial and complete) 83.6% (n=371) 68.3% (n=86) <0.001 Out of 467 patients followed up at 4-6 weeks, 57.7% (n=206) of participants with positive SARS-CoV-2 antibodies reported full resolution of their smell loss, compared to 72.1% (n=49) of participants with a negative antibody test (p=0.027). Out of the participants with positive SARS-CoV-2 antibodies, 38.4% (n=137) reported partial and 3.9% (n=14) reported no resolution of their smell loss at the time of follow-up. Out of participants with negative SARS-CoV-2 antibodies 25.0% (n=17) reported partial and 2.9% (n=2) no resolution of their smell loss. Figure 1 shows the resolution of smell and taste loss reported at the time of follow-up. Full resolution of taste loss was reported by 66.2% (n=227) of participants with SARS-CoV-2 antibodies and 80.3% (n=61) of participants with negative SARS-CoV-2 antibodies (p=0.017). Out of participants with positive SARS-CoV-2 antibodies, 31.2% (n=107) reported partial and 2.6% (n=9) no resolution of their taste loss at the time of follow up. Out of participants with negative SARS-CoV-2 antibodies, 19.7% (n=15) reported partial resolution of their taste loss (0 participants reported ‘no resolution’ of taste loss). Out of participants with positive SARS-CoV-2 antibodies, only 24 experienced a loss of their sense of taste in the absence of a loss of smell. The demographics were comparable to those of the entire SARS-CoV-2 positive cohort, with a mean age of 38.4 ±14.21 years and 70.8% (n=17) of participants of female sex. For subsequent analyses participants with partial and no resolution were grouped together in order to enable comparison between participants who achieved full resolution versus those who had ongoing smell and/or taste impairment at the time of follow-up. Table 3 shows results regarding resolution vs. no resolution of smell loss, taste loss and combined smell/taste loss in participants with positive and negative SARS-CoV-2 antibodies. A higher percentage of participants without SARS-CoV-2 antibodies fully recovered their sense of smell (72.1% vs 57.7%. p=0.027), their sense of taste (80.3% vs 66.2%, p=0.017) and both their senses of smell and taste (79.6% vs 64.0%, p=0.026). Table 3: Smell and/or taste loss resolution in SARS-CoV-2 IgG/IgM positive and negative participants Pattern of resolution SARS-CoV-2 IgG/IgM positive SARS-CoV-2 IgG/IgM negative p -Value (0.05) Smell loss Total (n=357) Total (n=68) No/partial resolution 42.3% (n=151) 27.9% (n=19) 0.027 Full resolution 57.7% (n=206) 72.1% (n=49) Taste loss Total (n=343) Total (n=76) No/partial resolution 33.8% (n=116) 19.7% (n=15) 0.017 Full resolution 66.2% (n=227) (80.3%) (n=61) Combined smell and taste loss Total (n=261) Total (n=54) No/partial resolution 36.0% (n=94) 20.4% (n=11) 0.026 Full resolution 64.0% (n=167) 79.6% (n=43) In participants with SARS-CoV-2 antibodies who reported full resolution of their smell loss, a full recovery of the sense of smell was reported to have occurred within one week in 11.7%, within 1-2 weeks in 26%, within 2-4 weeks in 26.5% and within >4 weeks in 35.8%. The effects of smell loss pattern and presence of parosmia on recovery of the sense of smell in participants with SARS-CoV-2 IgG/IgM antibodies The effect of complete vs. partial smell loss and the presence of parosmia on smell recovery in participants with positive SARS-CoV-2 antibodies was investigated. In participants who experienced complete loss of their sense of smell, full sense of smell recovery was reported by 54.5% compared to 67.4% in participants who reported a partial loss of their sense of smell (54.5% vs 67.4%, p=0.032). Out of participants who reported parosmia at the time of their smell loss, full recovery was reported by 41.4% compared to 65% in participants with smell loss who did not experience parosmia (41.4% vs. 65%, p<0.001). The effects of taste loss pattern and presence of dysgeusia on recovery of the sense of taste in participants with SARS-CoV-2 IgG/IgM antibodies The effect of complete vs. partial taste loss and the presence of dysgeusia on smell recovery in participants with positive SARS-CoV-2 antibodies was investigated. There was no significant difference in the reported rates of recovery of taste loss in participant who reported complete vs. partial loss of their sense of taste (64.7% vs. 67.9%, p=0.525). Out of participants who experienced dysgeusia at time of their loss of taste, a significantly lower proportion reported full resolution of their taste loss, compared to participants who did not experience dysgeusia (60.7% vs. 71.4%, p=0.036). Participants who experienced taste sensations in the absence of eating or drinking reported lower resolution rates compared to participants who did not (51.2% vs 71.0%, p=0.001). The effect of sex and age on the recovery of the sense of smell and taste in participants with SARS-CoV-2 IgG/IgM antibodies Full recovery of sense of smell was more prevalent among males compared to females (72.8% in males vs. 51.4% in females, p<0.001). Similarly, full taste loss resolution was more common in males vs. females (80.8% vs. 60.1%, p<0.001) as was full resolution of combined smell/taste loss (69.6% vs. 4.1%, p<0.001); Table 4. Table 4: Resolution of loss of smell, loss of taste and combined loss of smell and taste in female vs. male participants with SARS-CoV-2 IgG/IgM antibodies. Female Male p-value (0.05) Smell loss resolution Full resolution 51.4% (n=130) 72.8% (n=75) <0.001 No/partial resolution 48.6% (n=123) 27.1% (n=28) Taste loss resolution Full resolution 60.1% (n=146) 80.8% (n=80) <0.001 No/partial resolution 39.9% (n=97) 19.2% (n=19) Combined smell and taste loss resolution Full resolution 45.1% (n=102) 69.6% (n=64) <0.001 No/partial resolution 54.9% (n=124) 30.4% (n=28) The effect of age on resolution of smell and taste loss was evaluated. Mean age of male and female participants was comparable for participants who experienced full resolution of the loss in their sense of smell (40.4 ± 13.2 years in males vs. 38.1 ± 11.3 in females, p=0.333), their sense of taste (40.3 ±13.4 vs .37.1 ± 10.7 p=0.153) and combined loss of smell and taste (40.0 ± 12.6 vs. 37.1 ± 11.0, p=0.122). In participants with loss of their sense of taste that did not resolve at the time of follow-up, mean age was significantly higher in females compared to males (42.7 ± 12.5 years vs. 37.6 ± 12.6 years, p=0.030). Mean age was also significantly higher in female participants with unresolved combined loss of smell and taste loss compared to male participants (42.8 ± 12.5 vs. 34.6 ± 10.4, p=0.001). Mean age of female participants with unresolved smell loss was 41.6 ± 11.7 years compared to 37.4 ± 12.7 years in male participants, however this borderline difference did not reach statistical significance (p=0.053) (Figure 2). In light of the above findings, we further evaluated the effect of age on smell and/or taste loss resolution in female participants. A significantly higher age was observed in female participants without resolution compared to those with full resolution of the loss of their sense of smell (41.6 ± 11.7 yrs vs. 38.1 ± 11.3 yrs, p=0.010), their sense of taste (42.7 ± 12.5 yrs vs. 37.1 ± 10.7 yrs, p<0.001) and combined smell and taste (42.8 ± 12.5 yrs vs. 37.1 ± 11.0 yrs, p<0.001). Predictors of persisting smell loss in a community population with SARS-CoV-2 antibodies and acute loss of their sense of smell Logistic regression was used to explore the relative importance of participant’s age, sex, ethnicity, smoking status, presence of parosmia and smell loss pattern as risk factors for persistent smell loss at >4 weeks from onset. Female participants were almost 2.5 times more likely to have ongoing smell loss after 4 weeks compared to participants of male sex (OR 2.46, 95% CI 1.47 to 4.13, p=0.001). Parosmia was also shown to have a significant association with unresolved smell loss at 4-6 week follow-up (OR 2.47, 95%CI 1.54 to 4.00, p<0.001), in a model adjusting for the age, ethnicity, patterns of smell loss (complete vs partial) and smoking; Table 5. Table 5: Logistic regression exploring the association between age, sex, ethnicity, smoking status, presence of parosmia and smell loss pattern (complete vs partial) and no resolution of smell loss at 4 weeks follow up. Variable B OR 95% CI (lower) 95% CI (upper) p value Age 0.13 1.013 .994 1.032 0.172 Ethnicity 0.96 1.101 .595 2.034 0.760 Complete anosmia 0.529 1.697 0.998 2.884 0.051 Parosmia 0.904 2.470 1.539 3.966 <0.001 Sex (Female) 0.901 2.461 1.468 4.126 0.001 Smoking 0.303 1.355 0.604 3.038 0.462 Persistent smell and/or taste loss as a manifestation of long COVID. At the end of the 4-6 week follow-up period 42.3% (n=151) of participants with positive SARS-CoV-2 antibodies had ongoing smell loss, 33.8% experienced ongoing taste loss and 36% had ongoing taste and smell loss. We also evaluated the resolution of other symptoms of COVID-19 at the end of the follow-up period in participants positive for SARS-CoV-2 antibodies. Out of 134 participants with unresolved smell loss who reported additional COVID-19 symptoms on their original questionnaire, 29.1% (n=39) had at least 1 additional unresolved symptom at the time they completed their follow-up questionnaire, compared to 19.9% (n=35) of participants with full resolution of their smell loss (29.1% vs 19.9%, p=0.059). The most commonly reported unresolved symptoms were shortness of breath, chest pain and muscle/joint pains. Objective smell testing in a subsample of participants and correlation with perceived smell function A subsample of 50 participants underwent objective olfactory testing using the UPSIT. 84% were female (n=42) and 16% (n=8) male. The mean age was 39.6 ±13.5 years and mean duration of test date from the onset of symptoms was 21.6 ±4.7 weeks. 76% (n=38) participants had complete loss of their sense of smell at the time of the original questionnaire and 24% (n=12) partial loss of smell. At the time of the follow-up questionnaire 16% (n=8) reported their smell loss ‘did not resolve’, 42% (n=21) reported their smell loss ‘resolved partially’ and 42% (n=21) reported their smell loss ‘resolved fully’. The mean UPSIT test score was 29.1 ±7.5 points. In view of the time elapsed between the completion of the follow-up questionnaire and the UPSIT testing, prior to testing, participants were asked how they perceived their smell function. Their answers were grouped into: ‘No or minimal sense of smell’, ‘Sense of smell improved but not fully recovered’ or ‘Sense of smell fully recovered’. Table 6 illustrates a comparison of participants’ perceived smell function and their UPSIT test result, by test result category. A Spearman rank correlation analysis found a significant correlation between perceived smell function and UPSIT test result category (r=0.84 ± 0.71 to 0.90, p<0.001). Table 6: Comparison between UPSIT test result and perceived smell function in a study subgroup of 50 participants Minimal/no sense of smell (n=11) Improved sense of smell, not fully recovered (n=9) Fully recovered (n=30) Total anosmia 45.5% (5) 0% 0% Severe microsmia 45.5% (5) 0% 0% Moderate microsmia 9.0% (1) 77.8% (7) 0% Mild microsmia 0% 11.1% (1) 16.7% (n=5) Normosmia 0% 11.1% (1) 83.3% (n=25) Spearman r 0.95 -0.63 -0.89 Discussion We report longitudinal data from a community cohort with a new loss in their sense of smell and/or taste and resolution of these symptoms both in people with positive and negative SARS-CoV-2 IgG/IgM antibodies. Our data come from an entirely community based cohort with a low hospital admission rate where loss of taste and/or smell are the predominant symptoms. 77.9% of our cohort had positive SARS-CoV-2 antibodies and the study had a follow-up completion rate of 82.2%. We report a higher rate of recovery of smell loss (72.1% vs. 57.7%; p = 0.027), taste loss (80.3% vs. 66.2%; p = 0.017) and combined smell and taste loss (79.6% vs. 64%; p = 0.026) in participants who tested negative compared to participants who tested positive for SARS-CoV-2 antibodies. Importantly, our study highlights the high percentage of patients with ongoing smell loss (42.3%), ongoing taste loss (33.8%) and combined smell and taste loss (36.0%). The observed smell loss resolution rate of 57.7% in participants with SARS-CoV-2 antibodies within 4–6 weeks in our study is in line with existing literature[ 12 , 20 ]. Dell’Era et al. similarly reported that in 355 participants with COVID-19, 70% reported either smell loss and/or taste loss during infection[ 21 ]. 49.5% of participants reported full resolution of both sense of smell/taste after 14 days since the onset of symptoms, increasing to 62.9% at time of interview (23 days median, range 15-31), with a median recovery time of 10 days. In contrast to our community-based study, their findings come from a hospitalised patient cohort. Resolution rates in the literature currently range from 29-92.8%[ 11 , 12 , 22 ]. Discrepancies are likely due to differences in study populations, sample size, location and duration of follow up since onset of symptoms. Furthermore, we report higher rates of smell loss resolution in participants with partial compared to complete smell loss (67.4% vs. 54.5%, p = 0.032). This is compatible with Kosugi et al. [ 14 ] who reported that the full resolution from ‘partial loss of smell’ in COVID-19 positive patients takes place more frequently than that from ‘complete loss of smell’. Supportively, using an objective approach, Lechien et al. also found that higher baseline severity of smell loss, measured by ‘Sniffin-Sticks’ was strongly predictive of persistent smell loss[ 23 ]. Beltrán-Corbellini et al. compared smell loss recovery in 70 COVID-19 and 40 influenza participants[ 24 ]. 40% of COVID-19 positive participants reported full resolution after 7.4 ± 2.3 days and 16.7% reported partial resolution after 9.1 ± 3.6 days, whereas 100% of influenza participants fully recovered their sense of smell. The fact that participants with SARS-CoV-2 antibodies also had higher rates of complete anosmia, suggests a more severe spectrum of COVID-19 related smell loss compared to post-viral smell loss from other respiratory pathogens. Interestingly, one of our key findings shows that parosmia was more common in the group of participants with unresolved smell loss and was also a predictor of non-remission in the logistic regression analysis, which is novel in COVID-19. Parosmia has been associated with post-viral smell loss prior to the COVID-19 pandemic[ 25 ]. A potential explanation for our finding may be that parosmia has been associated with decreased number and disordered regrowth of olfactory axons into existing neural circuits and a preponderance of immature neurons[ 26 ]. Comparatively, Liu et al. found that in 153 participants with post-infectious smell loss the presence of parosmia was associated with clinically significant recovery in suprathreshold olfactory function discrimination in patients receiving olfactory training[ 27 ]. Parosmia in the context of post-viral smell loss is associated with ongoing smell impairment, and although has been viewed as a sign of recovery, its role as a prognostic marker remains largely unclear. However, our data suggest that parosmia is a marker of poor prognosis in COVID-19. Similarly, our finding show that dysgeusia and experiencing taste sensations in the absence of eating and drinking were associated with lower reported taste loss resolution rates. Together, these findings suggest that distorted chemosensory perception is a risk factor for prolonged smell and/or taste loss and long-COVID. With regard to full resolution of smell and/or taste loss, a significant sex difference was evident. Females had a lower full resolution rate of smell loss (51.4% vs. 72.8%; p < 0.001), taste loss (60.1% vs. 80.8%; p < 0.001) and combined smell and taste loss (45.1% vs. 69.6%; p < 0.001), compared to males, respectively. These findings are supported by several studies who also report the recovery of sense of smell was longer in females[ 10 , 21 ]. Although Meini et al. found that the recovery rate did not differ significantly between males and females, they however, the mean recovery time from smell loss or taste loss was significantly longer for females than for males (26 vs. 14 days, p = 0.009), even though the mean age of males was significantly higher than that of females (66 vs. 57 years, p = 0.04)[ 20 ]. Notably, in our study, female participants who reported no/partial resolution of smell loss were significantly older (41.6 ± 11.7 years) than female participants who reported full resolution of smell loss (38.1 ± 11.3 years, p = 0.010). The same was also found to be true for taste loss (42.7 ± 12.5 vs. 37.1 ± 10.7, (p < 0.001) and combined smell and taste loss (42.8 ± 12.5 vs. 37.1 ± 11.0, p < 0.001). In contrast, Lee et al. reported that young age, particularly the age group of 20–39 years, showed a tendency to be associated with a longer persistence of anosmia[ 28 ]. Interestingly, oestradiol has been shown to increase olfactory epithelial cell density and to have a protective role against olfactory function decline[ 29 ]. Additionally, in animal models of neurogenerative diseases oestradiol replacement prevents olfactory dysfunction[ 30 ]. This study was not powered to estimate the effect of menopause-driven differences in this subgroup. Nevertheless, a link between prolonged or reduced recovery of smell function and a post-menopausal state appears plausible. Loss of smell and taste have been demonstrated to persist beyond resolution of the infectious phase of COVID-19[ 31 ]. In light of evidence from the clinical course of smell loss from other viruses, smell loss after COVID-19 could persist for two or more years[ 32 , 33 ]. Arguably, our study follow-up window still only represents a relatively short-term observation and it is reasonable to predict that a number of participants will have further recovered their sense of smell and taste over additional weeks. Nevertheless, loss of smell and taste undoubtedly constitute a manifestation of long-COVID, which may result in significant psychological morbidity and adversely impact quality of life of the subset of patients with long-term unresolved smell and taste loss[ 8 , 16 , 34 ]. Given the limitations in accuracy and accessibility to testing during particularly the earlier phases of the pandemic, further patient populations may present with olfactory and gustatory impairment and features of long-COVID, indicative of previous COVID-19 infections. Of note, current proposed diagnostic criteria for long-COVID or chronic COVID-19 do not necessitate a positive test at time of symptom onset. The magnitude of the pandemic and the potential for SARS-CoV-2 to cause long-term smell and/or taste loss in relatively small cohorts therefore suggest that the overall prevalence of long-COVID with smell loss within the general population will be considerable[ 5 , 9 ]. It will be vital to develop a better understanding of the pathophysiology causing smell loss as well as the physiological processes driving smell recovery, in order to facilitate development of effective treatments for smell loss. Angiotensin-converting enzyme-2 receptors (ACE-2) present on olfactory epithelial cells and neuropilin-1 receptors (NRP1), abundant on all olfactory cell lines, are known entry routes for SARS-CoV-2 and damage to these cells have been proposed as potential mechanisms for smell loss[ 35 – 37 ]. Viral entry via NRP1 could result in direct damage to olfactory sensory neurons[ 35 ]. Furthermore, the distribution of these two receptors may form a plausible explanation for the spectrum of smell loss, with mild and typically short-lived smell loss from ACE-2 invasion versus more longstanding smell loss via NRP1 mediated sensory neuronal damage, following COVID-19. Therapeutic strategies including olfactory rehabilitation and corticosteroids are already in use to aid recovery of smell function following COVID-19, with further therapeutic strategies in clinical trials [ 14 , 15 ]. With emerging treatments for COVID-19 related anosmia and the high predicted prevalence of long covid with long-standing smell loss, identifying those at risk of long-COVID with smell loss will be key. We highlight female sex (and increasing age within female cohorts) as well as the presence of parosmia as key risk factors for a prolonged clinical course of COVID-19 related smell loss. Finally, in this study, we addressed the limitation of using subjective assessment of smell by recruiting a subset of participants who underwent objective UPSIT testing. Our results show that objectively assessed smell function using UPSIT correlates well with perceived smell function in this population, which highlights the reliability of our subjective patient-reported data on smell function following COVID-19. This finding is in line with a study conducted in ambulatory COVID-19 patients using the 12-item Brief Smell Identification Test (BSIT) which also concluded that self-reported olfactory loss is a strong predictor of abnormal olfactory function[ 38 ]. Furthermore, this highlights that in this subsample, tested 21.6 ±4.7 weeks since the onset of their symptoms, 20% of participants had ongoing loss of their sense of smell, who would meet diagnostic criteria for both long-COVID and chronic COVID-19. Limitations The main limitation of this study remains the lack of a general population control group without loss of smell/taste. Our selection criteria enabled us to study acute smell and taste loss as presentations of COVID-19 as well as their resolution in people both with and without SARS-CoV-2 antibodies. Coupled with the web-based delivery of the study, this leads to susceptibility to a degree of selection and age bias, which required proficiency with computers and smartphones and may have resulted in under-representation of older adults. Furthermore, the majority of our participants were female; this may reflect previous findings that females are more likely to engage in research and also have a higher frequency of loss of smell and/or taste with COVID-19 than males. Through recruiting a subset of participants for objective testing we addressed the previous limitation of lack of objective testing, and demonstrated a strong correlation between perceived and assessed smell function. Conclusions We followed up a community cohort of people who had reported acute loss of their sense of smell and/or taste and had undergone SARS-CoV-2 IgG/IgM antibody testing 4–6 weeks earlier in order to investigate the clinical course of smell and/or taste loss. We also aimed to identify factors that were associated with persistent smell loss at 4–6 weeks of follow-up. In line with existing literature, we can offer reassurance that smell and/or taste loss is a transient phenomenon in most SARS-CoV-2 cases. However, persistent smell and taste loss constitute a feature of long-COVID. The population of patients with longstanding smell and/or taste loss as a manifestation of long-COVID will continue to grow during and following the pandemic; given the impact of these symptoms on quality of life and safety, it will be imperative to devise support and treatment pathways. We identified the presence of parosmia and female sex as risk factors for persistent smell loss, as well as increasing age within the female sub-cohort. Similarly, female sex and increasing age as well as distorted taste perception were associated with persistent taste loss. Our findings highlight that female patients over the age of 40, who experience with a distorted perception of their sense of smell and/or taste are likely to benefit from therapeutic interventions to prevent persistent smell and/or taste loss and should be prioritized when targeted therapies for post-covid smell and taste loss become available. Abbreviations Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus disease 2019 (COVID-19) Immunoglobulin G (IgG) Immunoglobulin M (IgM) University of Pennsylvania Smell Identification Test (UPSIT) Angiotensin-converting enzyme-2 receptors (ACE-2) Neuropilin-1 receptors (NRP1) Brief Smell Identification Test (BSIT) Declarations Ethics approval and consent to participate The study received ethical approval from the National Health Service Queen’s Square Research Ethics Committee (IRAS Project ID 282668, ClinicalTrials.gov: NCT04377815) and was conducted in line with the declaration of Helsinki and Good Clinical Practice. Consent for publication Not applicable Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare no competing interests. Funding This work was funded by the National Institute for Health Research (BRC751). https://www.nihr.ac.uk/ RLB, CGM, JM, and AC are funded by National Institute for Health Research grant RP-2015-06-005 (https://www.nihr.ac.uk/). RLB, NB, and JM are funded by the Sir Jules Thorn Trust Biomedical Research Award (https://julesthorntrust.org.uk/programmes/medical-research/the-sir-jules-thorn-award-for-biomedical-research/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Authors' contributions JM: Conceptualization, Data curation, Participant recruitment, Formal analysis, Investigation, Validation, Writing CF: Data curation, Formal analysis, Investigation, Writing CM: Investigation, Methodology, Writing JMok: Investigation, Methodology, Writing NB: Data curation, Investigation, Writing ML: Investigation, Writing AC: Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Writing RLB: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Writing All authors read and approved the final manuscript. Acknowledgements We thank Professor Valerie Lund for her advice and collaboration. We thank the Hampstead Group Practice, The Northern Medical Centre, the James Wigg Practice, and the Queen’s Crescent Practice for their collaboration in sending out the invitation text messages to their registered patients. References WHO. Coronavirus disease (COVID-19) pandemic 2020 [cited 2020 22 June]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019. 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. Nature medicine. 2020. Hopkins C, Surda P, Kumar N. Presentation of new onset anosmia during the COVID-19 pandemic. Rhinology. 2020. 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 medicine. 2020;17(10):e1003358. 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. Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020;370:m3026. NICE. COVID-19 rapid guideline: managing the long-term effects of COVID-19 nice.org.uk: NICE Guidance; 2021 [Available from: https://www.nice.org.uk/guidance/NG188. ONS. Office for National Statistics. The prevalence of long COVID symptoms and COVID-19 complications. 2020 [Available from: https://www.ons.gov.uk/news/statementsandletters/theprevalenceoflongcovidsymptomsandcovid19complications. 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. Suzuki M, Saito K, Min WP, Vladau C, Toida K, Itoh H, et al. Identification of viruses in patients with postviral olfactory dysfunction. The Laryngoscope. 2007;117(2):272-7. 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. 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. Otte MS, Klussmann JP, Luers JC. Persisting olfactory dysfunction in patients after recovering from COVID-19. J Infect. 2020;81(3):e58. Whitcroft KL, Hummel T. Olfactory Dysfunction in COVID-19: Diagnosis and Management. JAMA. 2020. ClinicalTrials.gov. Coronavirus Smell Therapy for Anosmia Recovery 2021 [Available from: https://www.clinicaltrials.gov/ct2/show/NCT04422275. Croy I, Nordin S, Hummel T. Olfactory disorders and quality of life--an updated review. Chem Senses. 2014;39(3):185-94. 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 medicine. 2020;17(10):e1003358. Elabscience. COVID-19 IgG and IgM [Available from: https://www.elabscience.com/p-covid_19_igg_igm_rapid_test-375335.html. Doty RL, Shaman P, Kimmelman CP, Dann MS. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. The Laryngoscope. 1984;94(2 Pt 1):176-8. 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. 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. 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. 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. 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. 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):139-44. Leopold DA, Loehrl TA, Schwob JE. Long-term follow-up of surgically treated phantosmia. Arch Otolaryngol Head Neck Surg. 2002;128(6):642-7. 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. 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. Dhong HJ, Chung SK, Doty RL. Estrogen protects against 3-methylindole-induced olfactory loss. Brain Res. 1999;824(2):312-5. 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. 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. Cavazzana A, Larsson M, Münch M, Hähner A, Hummel T. Postinfectious olfactory loss: A retrospective study on 791 patients. The Laryngoscope. 2018;128(1):10-15. Hwang CS. Olfactory neuropathy in severe acute respiratory syndrome: report of A case. Acta neurologica Taiwanica. 2006;15(1):26-8. Erskine SE, Philpott CM. An unmet need: Patients with smell and taste disorders. Clin Otolaryngol. 2020;45(2):197-203. 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. 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. 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.e8. 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. Supplementary Files AdditionalFile1.docx AdditionalFile2.docx Cite Share Download PDF Status: Published Journal Publication published 25 Feb, 2021 Read the published version in BMC Infectious Diseases → Version 1 posted Reviewer # 1 agreed at journal 25 Jan, 2021 Editor assigned by journal 24 Jan, 2021 Reviewers invited by journal 24 Jan, 2021 Submission checks completed at journal 24 Jan, 2021 Editor invited by journal 24 Jan, 2021 First submitted to journal 16 Jan, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-156677","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":9112268,"identity":"dd348d8f-3a4b-4928-b0ac-7ebe01d3b369","order_by":0,"name":"Janine Makaronidis","email":"","orcid":"","institution":"University College London","correspondingAuthor":false,"prefix":"","firstName":"Janine","middleName":"","lastName":"Makaronidis","suffix":""},{"id":9112269,"identity":"49872d19-8b6b-4a17-b83a-3f0d8fe9a9c9","order_by":1,"name":"Chloe Firman","email":"","orcid":"","institution":"University College London","correspondingAuthor":false,"prefix":"","firstName":"Chloe","middleName":"","lastName":"Firman","suffix":""},{"id":9112270,"identity":"9c9752e1-b3fa-43bd-9b75-dde7fc22e0a8","order_by":2,"name":"Cormac Magee","email":"","orcid":"","institution":"University College London","correspondingAuthor":false,"prefix":"","firstName":"Cormac","middleName":"","lastName":"Magee","suffix":""},{"id":9112271,"identity":"32fc7fa2-672c-4b0f-8a99-9abebdd03b1d","order_by":3,"name":"Jessica Mok","email":"","orcid":"","institution":"University College London","correspondingAuthor":false,"prefix":"","firstName":"Jessica","middleName":"","lastName":"Mok","suffix":""},{"id":9112272,"identity":"527d05f3-e057-498e-8d11-c60c452390d9","order_by":4,"name":"Nyaladzi Balogun","email":"","orcid":"","institution":"University College London","correspondingAuthor":false,"prefix":"","firstName":"Nyaladzi","middleName":"","lastName":"Balogun","suffix":""},{"id":9112273,"identity":"1280fde1-1dd0-4606-ba11-8a47b95e5e02","order_by":5,"name":"Matt Lechner","email":"","orcid":"","institution":"University College London Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Matt","middleName":"","lastName":"Lechner","suffix":""},{"id":9112274,"identity":"3bc6829b-6e6f-4791-9977-571166760754","order_by":6,"name":"Alisia Carnemolla","email":"","orcid":"","institution":"University College London","correspondingAuthor":false,"prefix":"","firstName":"Alisia","middleName":"","lastName":"Carnemolla","suffix":""},{"id":9112275,"identity":"fc2dbf06-d484-46ac-a58c-9a28b624bda3","order_by":7,"name":"Rachel Batterham","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIiWNgGAWjYFACHghlwMDA+ICBwQLMYWwgpOVAAlgLMxBLkKaFTYIoLeYNvAc/f/xhk2/OfjqtmqdGgoG//QCb5Aw8WmQO8CVLHEhIs9zZk7vtNs8xCQaJMwlskhvwaJFg4DEAajlsYHAAqIW3AeiwGwxskg/wazH+cSDhv4HB+bfbikFa5InQYga05YCBwY3cbcwgLQYgLXgdxsyXZnEmLRmo5e1myTnHJHgMzyQ2W+LzvgR77+EbFTZ2QIflbvzwpsZGTu744YM3e/BoYWBG4/MQjMhRMApGwSgYBYQBAJbSR5eeYs2DAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-5477-8585","institution":"University College London","correspondingAuthor":true,"prefix":"","firstName":"Rachel","middleName":"","lastName":"Batterham","suffix":""}],"badges":[],"createdAt":"2021-01-27 12:02:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-156677/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-156677/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-021-05927-w","type":"published","date":"2021-02-25T15:00:28+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":5457648,"identity":"43a7424e-b744-4412-bb10-5fe195dd505a","added_by":"auto","created_at":"2021-01-29 22:48:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":14899,"visible":true,"origin":"","legend":"Resolution of smell (A) and taste loss (B) in participants seropositive and seronegative for SARS-CoV-2 IgG/IgM antibodies.\nBar graph comparing resolution of smell and taste loss in participants with SARS-Cov-2 positive vs negative antibodies at a 4 week-follow up. A significantly greater percentage of participants without SARS-CoV-2 antibodies reported full resolution of their sense of smell (72.1% vs 57.7%, p=0.027) and sense of taste (80.3% vs 66.2% = 0.017) compared to participants with SARS-CoV-2 antibodies.\n","description":"","filename":"BMCFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-156677/v1/9c58ed9ec31c77491816e80a.png"},{"id":5457817,"identity":"84dfb83e-62b0-40e6-805e-94f5b3b6e95d","added_by":"auto","created_at":"2021-01-29 22:51:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":13769,"visible":true,"origin":"","legend":"Age differences in females vs males with and without full smell and/or taste loss resolution.\nBar graph comparing the mean age of female and male participants with SARS-CoV-2 antibodies and resolution of smell and/or taste loss at 4 weeks follow up. The mean age was significantly higher in females compared to males who reported unresolved taste loss (42.7 ± 12.5 years vs. 37.6 ± 12.6 years, p=0.030) and unresolved combined smell and taste loss (42.8 ± 12.5 vs. 34.6 ± 10.4, p=0.001). (*) = statistically significant association.\n","description":"","filename":"BMCFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-156677/v1/5b39bedc4b5d475f844733d5.png"},{"id":13654649,"identity":"822ca5f3-758d-42d4-b7e4-e9b49e3368b9","added_by":"auto","created_at":"2021-09-17 09:58:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1000780,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-156677/v1/6215555d-1320-4d17-b2de-741d3847db02.pdf"},{"id":5457818,"identity":"8835720f-3e02-46d4-9676-e54893a43742","added_by":"auto","created_at":"2021-01-29 22:51:11","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":20966,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-156677/v1/f85780e591fd168c9cf884db.docx"},{"id":5457932,"identity":"97e2e6f2-8e49-455c-9757-359dcfe3b05e","added_by":"auto","created_at":"2021-01-29 22:54:11","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":15079,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile2.docx","url":"https://assets-eu.researchsquare.com/files/rs-156677/v1/3df8c1832d77f2994010e14f.docx"}],"financialInterests":"","formattedTitle":"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","fulltext":[{"header":"Introduction","content":" \u003cp\u003eSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which results in coronavirus disease 2019 (COVID-19), emerged in 2019 resulting in a global pandemic with over 85\u0026nbsp;million cases and 1.8\u0026nbsp;million deaths reported worldwide[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The association between COVID-19 and smell and taste loss was established in March 2020 and has since been identified among the most specific symptoms of COVID-19, with implications for case identification, isolation and tracing[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. We previously reported seroprevalence of SARS-CoV-2 IgG/IgM antibodies of 78% in a community cohort in London, UK who developed an acute loss of their sense of smell and/or taste during the peak of the first local wave of the pandemic[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. We also showed that seropositivity for SARS-CoV-2 antibodies was three times more likely for people with smell loss compared to taste loss.\u003c/p\u003e \u003cp\u003eWith the ongoing spread of SARS-CoV-2 globally, COVID-19 and its complications are continuing to affect millions globally. Despite the development of vaccinations resulting in optimism that the pandemic will be contained, healthcare providers worldwide will continue to face the challenge of an unprecedented incidence of COVID-19 related morbidity. It is now evident that symptoms can persist beyond resolution of the acute systemic viral infection and cause a chronic condition, termed \u0026lsquo;long-COVID\u0026rsquo;, in up to a quarter of cases[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. \u0026lsquo;Long covid\u0026rsquo; (\u0026gt;\u0026thinsp;4 weeks) as well as \u0026lsquo;post-acute covid\u0026rsquo; (\u0026gt;\u0026thinsp;3 weeks) and \u0026lsquo;chronic covid\u0026rsquo; (\u0026gt;\u0026thinsp;12 weeks) have been used to describe ongoing symptoms of the disease[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Symptoms persisting longer than 5 weeks are estimated to occur in 1 in 5 and symptoms and lasting longer than 12 weeks in 1 in 10 people, according to data published by the UK Office for National Statistics (ONS)[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Identifying the people most at risk of long-term symptoms will be key to guide monitoring in order to deliver follow-up care and therapeutic interventions to patients with long COVID-19 disease.\u003c/p\u003e \u003cp\u003eDespite the recognition of loss of smell and/or taste as key symptoms of COVID-19 there remains a paucity of data within the literature regarding the clinical course, recovery rates and demographic risk factors for long-lasting symptoms. Post-viral smell loss from other respiratory pathogens is typically a short-lived phenomenon and recovery usually coincides with resolution of other viral symptoms[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In contrast, current data from COVID-19 patients, suggest a wide range of recovery times, from a few days to several months[\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This observation raises concerns of unresolved smell loss as a manifestation of long-COVID. Therefore, identifying risk factors for persistent smell loss will be key to guide therapeutic interventions, such as olfactory rehabilitation and use of corticosteroids, once these are widely available[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Furthermore, given the negative impact of these symptoms on quality of life and safety, research on prognostic information is warranted to inform patients, their carers, as well as treatment algorithms[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In this follow-up study, we aim to describe and compare the temporal resolution patterns of loss of smell and/or taste in a community cohort with acute smell and/or taste loss with and without SARS-CoV-2 antibodies. This study will focus on smell loss resolution and aim to identify risk factors for persistent smell loss, as well as describe smell loss as a feature of long-COVID. Finally, to address the original study\u0026rsquo;s limitations of reliance on self-reported symptoms, we will correlate self-reported smell function with objective olfactory testing.\u003c/p\u003e "},{"header":"Methods","content":" \u003cp\u003eThe study was conducted in London, UK, at a time when loss of smell and taste were not recognised as symptoms of COVID-19. People with an acute loss of their sense of smell and/or taste were invited to participate through text messages, sent via primary care centres in London, UK. Recruitment took place over a 4-week period between 23 April and 14 May 2020, during the local first wave of the pandemic. Participants were recruited via an online platform, as previously described[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eInclusion criteria were age\u0026thinsp;\u0026gt;\u0026thinsp;18 years, proficiency in written and spoken English and access to video calling. Exclusion criteria were any pre-existing loss of the sense of smell or taste of longer than one month\u0026rsquo;s duration. Participation was voluntary and written informed consent was obtained electronically. Enrolled participants completed an online questionnaire (see Additional File 1), capturing their sex, age, ethnicity, smoking status, questions about their smell and taste loss, as well as other symptoms of COVID-19. SARS-CoV-2 immunoglobulin G (IgG)/ immunoglobulin M (IgM) antibody testing was carried out via a telemedicine consultation as described previously described[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], using a lateral flow immunoassay detecting IgM and IgG antibodies to SARS-CoV-2 (Wuhan UNscience Biotechnology Co., Ltd. COVID-19 Antibody IgM/IgG) with a relative sensitivity of 98.8% (95% CI 97.3\u0026ndash;99.6%) and a relative specificity of 98.0% (95% CI 97.15\u0026ndash;98.7%)[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A link to a follow-up questionnaire was sent to participants\u0026rsquo; registered email addresses 4 weeks after they completed their original questionnaire. The follow up questionnaire (see Additional File 1) contained questions about resolution of their smell and taste loss, as well as resolution of the other symptoms of COVID-19 and admission to hospital. Reminders were sent to participants who did not complete the original questionnaire at 72 hours and 7\u0026nbsp;days and the platform remained open for questionnaire completion for a further 4 weeks (22 May to 20 July 2020).\u003c/p\u003e \u003cp\u003eIn order to correlate participants\u0026rsquo; questionnaire responses about their loss of smell with objective olfactory testing, a subsample of 50 participants were recruited for objective smell testing. Participants received a separate information sheet and informed consent was obtained electronically using a separate consent form. The University of Pennsylvania Smell Identification Test (UPSIT), a 40-item smell test which is validated to be self-administered, was used[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. UPSIT kits were sent to recruited participants together with instructions on completing the test. Photographs of the booklet were obtained and the tests were scored by a healthcare professional, who then explained the results to participants.\u003c/p\u003e \u003cp\u003eThe study received ethical approval from the National Health Service Queen\u0026rsquo;s Square Research Ethics Committee (IRAS Project ID 282668, ClinicalTrials.gov: NCT04377815) and was conducted in line with the declaration of Helsinki and Good Clinical Practice.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eA sample size calculation was undertaken in order to determine the study\u0026rsquo;s recruitment target, using the information on reported symptoms from the web-based COVID symptom study app developed by King\u0026rsquo;s College London and symptom reporting between the 24\u0026ndash;29 March 2020. To calculate an estimate of 50% (95% CI 45\u0026ndash;55%) as the proportion who would test positive amongst those who reported a change in smell or taste, we needed 385 participants in the study [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Assuming a 15% attrition, the number increased to 453 participants in the study. The recruitment target was set to 500 participants and was exceeded to allow for larger attrition and increase accuracy.\u003c/p\u003e \u003cp\u003eData were analyzed using GraphPad Prism version 8 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.graphpad.com/scientific-software/prism/\u003c/span\u003e\u003c/span\u003e) and SPSS version 26 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ibm.com/uk-en/products/spss-statistics\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDescriptive analyses included the calculation of means (plus standard deviation [SD]) for continuous variables and numbers (\u003cem\u003en\u003c/em\u003e, with percentages) for categorical variables. Chi-squared tests were performed on categorical data. When performing multiple comparisons, the significance level was adjusted by applying a Bonferroni correction. Parametric and non-parametric tests were used as appropriate on continuous data. Logistic regression analysis was performed to estimate the association between smell loss resolution and additional factors including participant\u0026rsquo;s age, sex, ethnicity, smoking status and smell loss pattern. A Spearman Rank correlation analysis was performed to investigate the association between participants\u0026rsquo; perceived smell function and an objective assessment of their olfactory function.\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 467 out of the 569 participants who enrolled and underwent a SARS-CoV-2 antibody test completed the follow-up questionnaire, yielding a follow-up rate of 82.1%. The demographics of the entire study cohort can be seen in Additional File 2. Out of the cohort of 467 who completed the follow-up questionnaire, participants with positive and negative SARS-CoV-2 antibodies were comparable in terms of age, gender, smoking status and ethnicity (Table 1). Admission to hospital was reported by 1.6% (n=7) of participants in the antibody positive group vs. 3.1% (n=4) in the antibody negative group (p=0.097).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: Demographics of participants followed up after 4-6 weeks with positive and negative SARS-CoV-2 antibodies\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eDemographics\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"125\"\u003e\n\u003cp\u003e\u003cstrong\u003eSARS-CoV-2 IgG/IgM positive \u003cbr /\u003e (n=381)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e\u003cstrong\u003eSARS-CoV-2 IgG/IgM negative \u003cbr /\u003e (n=86)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003cstrong\u003e-value \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(0.05)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" width=\"519\"\u003e\n\u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"125\"\u003e\n\u003cp\u003e70.9% \u003cbr /\u003e (n=270)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e66.3%\u003cbr /\u003e (n=57)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"66\"\u003e\n\u003cp\u003e\u003cem\u003e0.382\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"125\"\u003e\n\u003cp\u003e28.8%\u003cbr /\u003e (n=110)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e33.7% \u003cbr /\u003e (n=29)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003eOther\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"125\"\u003e\n\u003cp\u003e0.3%\u003c/p\u003e\n\u003cp\u003e(n=1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e\u003cem\u003e0.450\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"125\"\u003e\n\u003cp\u003e39.67\u0026plusmn;12.12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e40.25\u0026plusmn;12.33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e\u003cem\u003e0.689\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eEthnicity *\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" width=\"322\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003eWhite\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"125\"\u003e\n\u003cp\u003e83.7%\u003cbr /\u003e (n=319)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e81.4%\u003cbr /\u003e (n=70)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e\u003cem\u003e0.600\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003eMixed/Multiple Ethnicities\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"125\"\u003e\n\u003cp\u003e5.5%\u003cbr /\u003e (n=21)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e4.7%\u003cbr /\u003e (n=4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e\u003cem\u003e0.749\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003eAsian/Asian British\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"125\"\u003e\n\u003cp\u003e5%\u003cbr /\u003e (n=19)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e4.7%\u003cbr /\u003e (n=4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e\u003cem\u003e0.897\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003eBlack/African/Caribbean/Black British\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"125\"\u003e\n\u003cp\u003e1.6%\u003cbr /\u003e (n=6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e2.3%\u003cbr /\u003e (n=2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e\u003cem\u003e0.628\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026lsquo;Other\u0026rsquo;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"125\"\u003e\n\u003cp\u003e3.7%\u003cbr /\u003e (n=14)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e3.5%\u003cbr /\u003e (n=3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e\u003cem\u003e0.933\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eSmoking status\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" width=\"322\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003eCurrent/ Ex-smoker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"125\"\u003e\n\u003cp\u003e42%\u003cbr /\u003e (n=160)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e44.2%\u003cbr /\u003e (n=38)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"66\"\u003e\n\u003cp\u003e\u003cem\u003e0.710\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003eNever smoked\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"125\"\u003e\n\u003cp\u003e58%\u003cbr /\u003e (n=221)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"131\"\u003e\n\u003cp\u003e55.8%\u003cbr /\u003e (n=48)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eFigures presented as % with total number (n). SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.\u003cbr /\u003e *5 participants opted not to disclose their ethnicity.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSmell and taste loss and resolution at 4 -6 weeks follow-up\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe frequency of reported smell and/or taste loss at baseline can be seen in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2:\u003c/strong\u003e \u003cstrong\u003eLoss of smell and/or taste in SARS-CoV-2 IgG/IgM positive and negative participants\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003eSARS-CoV-2 IgG/IgM positive (n=443)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003eSARS-CoV-2 IgG/IgM negative (n=126)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value (0.05)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eSense of smell \u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eLoss of sense of smell (complete and partial) \u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e93.5%\u003c/p\u003e\n\u003cp\u003e(n=414)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e79.4%\u003c/p\u003e\n\u003cp\u003e(n=100)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026lt;0.001\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; Partial loss of smell\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e24.4%\u003c/p\u003e\n\u003cp\u003e(n=108)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e39.7%\u003c/p\u003e\n\u003cp\u003e(n=50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026lt;0.001\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; Complete loss of smell\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e69.1%\u003c/p\u003e\n\u003cp\u003e(n=306)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e39.7%\u003c/p\u003e\n\u003cp\u003e(n=50)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eParosmia \u003c/strong\u003e(distorted sense of taste)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e30%\u003c/p\u003e\n\u003cp\u003e(n=133)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e21.4%\u003c/p\u003e\n\u003cp\u003e(n=27)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003e0.245\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eSense of taste\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eLoss of sense of taste (complete and partial)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e90.1%\u003c/p\u003e\n\u003cp\u003e(n=399)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e88.9%\u003c/p\u003e\n\u003cp\u003e(n=112)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003e0.700\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Partial loss of taste\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e42.7%\u003c/p\u003e\n\u003cp\u003e(n=189)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e61.9%\u003c/p\u003e\n\u003cp\u003e(n=78)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026lt;0.001\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Complete loss of taste\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e47.4%\u003c/p\u003e\n\u003cp\u003e(n=210)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e27%\u003c/p\u003e\n\u003cp\u003e(n=34)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eDysgeusia \u003c/strong\u003e(distorted sense of taste)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e44.7%\u003c/p\u003e\n\u003cp\u003e(n=198)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e42.9%\u003c/p\u003e\n\u003cp\u003e(n=54)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003e0.856\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eExperience of taste without eating/drinking\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e21.4%\u003c/p\u003e\n\u003cp\u003e(n=95)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e24.6%\u003c/p\u003e\n\u003cp\u003e(n=31)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003e0.374\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eOnly loss of smell\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e9.9%\u003c/p\u003e\n\u003cp\u003e(n=43)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e11.1%\u003c/p\u003e\n\u003cp\u003e(n=14)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003e0.643\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eOnly loss of taste\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6.5%\u003c/p\u003e\n\u003cp\u003e(n=28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e20.6%\u003c/p\u003e\n\u003cp\u003e(n=27)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026lt;0.001\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eLoss of sense of smell and taste (partial and complete)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e83.6%\u003c/p\u003e\n\u003cp\u003e(n=371)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e68.3%\u003c/p\u003e\n\u003cp\u003e(n=86)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026lt;0.001\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eOut of 467 patients followed up at 4-6 weeks, 57.7% (n=206) of participants with positive SARS-CoV-2 antibodies reported full resolution of their smell loss, compared to 72.1% (n=49) of participants with a negative antibody test (p=0.027). Out of the participants with positive SARS-CoV-2 antibodies, 38.4% (n=137) reported partial and 3.9% (n=14) reported no resolution of their smell loss at the time of follow-up. Out of participants with negative SARS-CoV-2 antibodies 25.0% (n=17) reported partial and 2.9% (n=2) no resolution of their smell loss. Figure 1 shows the resolution of smell and taste loss reported at the time of \u0026nbsp;follow-up.\u003c/p\u003e\n\u003cp\u003eFull resolution of taste loss was reported by 66.2% (n=227) of participants with SARS-CoV-2 antibodies and 80.3% (n=61) of participants with negative SARS-CoV-2 antibodies (p=0.017). Out of participants with positive SARS-CoV-2 antibodies, 31.2% (n=107) reported partial and 2.6% (n=9) no resolution of their taste loss at the time of follow up. Out of participants with negative SARS-CoV-2 antibodies, 19.7% (n=15) reported partial resolution of their taste loss (0 participants reported \u0026lsquo;no resolution\u0026rsquo; of taste loss). Out of participants with positive SARS-CoV-2 antibodies,\u0026nbsp; only 24 experienced a loss of their sense of taste in the absence of a loss of smell. The demographics were comparable to those of the entire SARS-CoV-2 positive cohort, with a mean age of 38.4 \u0026plusmn;14.21 years and 70.8% (n=17) of participants of female sex.\u003c/p\u003e\n\u003cp\u003eFor subsequent analyses participants with partial and no resolution were grouped together in order to enable comparison between participants who achieved full resolution versus those who had ongoing smell and/or taste impairment at the time of follow-up. Table 3 shows results regarding resolution vs. no resolution of smell loss, taste loss and combined smell/taste loss in participants with positive and negative SARS-CoV-2 antibodies. A higher percentage of participants without SARS-CoV-2 antibodies fully recovered their sense of smell (72.1% vs 57.7%. p=0.027), their sense of taste (80.3% vs 66.2%, p=0.017) and both their senses of smell and taste (79.6% vs 64.0%, p=0.026).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Smell and/or taste loss resolution in SARS-CoV-2 IgG/IgM positive and negative participants\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003e\u003cstrong\u003ePattern of resolution\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eSARS-CoV-2 IgG/IgM positive \u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eSARS-CoV-2 IgG/IgM negative\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-Value (0.05)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003e\u003cstrong\u003eSmell loss \u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal (n=357)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal (n=68)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eNo/partial resolution\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e42.3%\u003c/p\u003e\n\u003cp\u003e(n=151)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e27.9%\u003c/p\u003e\n\u003cp\u003e(n=19)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"94\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.027\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eFull resolution\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e57.7%\u003c/p\u003e\n\u003cp\u003e(n=206)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e72.1%\u003c/p\u003e\n\u003cp\u003e(n=49)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003e\u003cstrong\u003eTaste loss \u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal (n=343)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal (n=76)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eNo/partial resolution\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e33.8%\u003c/p\u003e\n\u003cp\u003e(n=116)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e19.7%\u003c/p\u003e\n\u003cp\u003e(n=15)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"94\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.017\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eFull resolution\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e66.2%\u003c/p\u003e\n\u003cp\u003e(n=227)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e(80.3%)\u003c/p\u003e\n\u003cp\u003e(n=61)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003e\u003cstrong\u003eCombined smell and taste loss \u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal (n=261)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal (n=54)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eNo/partial resolution\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e36.0%\u003c/p\u003e\n\u003cp\u003e(n=94)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u0026nbsp;20.4%\u003c/p\u003e\n\u003cp\u003e(n=11)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"94\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.026\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eFull resolution\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e64.0%\u003c/p\u003e\n\u003cp\u003e(n=167)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e79.6%\u003c/p\u003e\n\u003cp\u003e(n=43)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIn participants with SARS-CoV-2 antibodies who reported full resolution of their smell loss, a full recovery of the sense of smell was reported to have occurred within one week in 11.7%, within 1-2 weeks in 26%, within 2-4 weeks in 26.5% and within \u0026gt;4 weeks in 35.8%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe effects of smell loss pattern and presence of parosmia on recovery of the sense of smell in participants with \u003c/strong\u003e\u003cstrong\u003eSARS-CoV-2 IgG/IgM antibodies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe effect of complete vs. partial smell loss and the presence of parosmia on smell recovery in participants with positive SARS-CoV-2 antibodies was investigated. In participants who experienced complete loss of their sense of smell, full sense of smell recovery was reported by 54.5% compared to 67.4% in participants who reported a partial loss of their sense of smell (54.5% vs 67.4%, p=0.032).\u003c/p\u003e\n\u003cp\u003eOut of participants who reported parosmia at the time of their smell loss, full recovery was reported by 41.4% compared to 65% in participants with smell loss who did not experience parosmia (41.4% vs. 65%, p\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe effects of taste loss pattern and presence of dysgeusia on recovery of the sense of taste in participants with \u003c/strong\u003e\u003cstrong\u003eSARS-CoV-2 IgG/IgM antibodies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe effect of complete vs. partial taste loss and the presence of dysgeusia on smell recovery in participants with positive SARS-CoV-2 antibodies was investigated. There was no significant difference in the reported rates of recovery of taste loss in participant who reported complete vs. partial loss of their sense of taste (64.7% vs. 67.9%, p=0.525).\u003c/p\u003e\n\u003cp\u003eOut of participants who experienced dysgeusia at time of their loss of taste, a significantly lower proportion reported full resolution of their taste loss, compared to participants who did not experience dysgeusia (60.7% vs. 71.4%, p=0.036).\u003c/p\u003e\n\u003cp\u003eParticipants who experienced taste sensations in the absence of eating or drinking reported lower resolution rates compared to participants who did not (51.2% vs 71.0%, p=0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe effect of sex and age on the recovery of the sense of smell and taste in\u003c/strong\u003e \u003cstrong\u003eparticipants with \u003c/strong\u003e\u003cstrong\u003eSARS-CoV-2 IgG/IgM antibodies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFull recovery of sense of smell was more prevalent among males compared to females (72.8% in males vs. 51.4% in females, p\u0026lt;0.001). Similarly, full taste loss resolution was more common in males vs. females (80.8% vs. 60.1%, p\u0026lt;0.001) as was full resolution of combined smell/taste loss (69.6% vs. 4.1%, p\u0026lt;0.001); Table 4.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4: Resolution of loss of smell, loss of taste and combined loss of smell and taste in female vs. male participants with SARS-CoV-2 IgG/IgM antibodies.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"217\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"161\"\u003e\n\u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"82\"\u003e\n\u003cp\u003e\u003cstrong\u003ep-value (0.05)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" width=\"601\"\u003e\n\u003cp\u003e\u003cstrong\u003eSmell loss resolution\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"217\"\u003e\n\u003cp\u003e\u003cstrong\u003eFull resolution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003e51.4%\u003cbr /\u003e (n=130)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"161\"\u003e\n\u003cp\u003e72.8%\u003c/p\u003e\n\u003cp\u003e(n=75)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"82\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026lt;0.001\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"217\"\u003e\n\u003cp\u003e\u003cstrong\u003eNo/partial resolution\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003e48.6%\u003c/p\u003e\n\u003cp\u003e(n=123)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"161\"\u003e\n\u003cp\u003e27.1%\u003c/p\u003e\n\u003cp\u003e(n=28)\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" width=\"601\"\u003e\n\u003cp\u003e\u003cstrong\u003eTaste loss resolution\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"217\"\u003e\n\u003cp\u003e\u003cstrong\u003eFull resolution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003e60.1%\u003c/p\u003e\n\u003cp\u003e(n=146)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"161\"\u003e\n\u003cp\u003e80.8%\u003c/p\u003e\n\u003cp\u003e(n=80)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"82\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026lt;0.001\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"217\"\u003e\n\u003cp\u003e\u003cstrong\u003eNo/partial resolution\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003e39.9%\u003c/p\u003e\n\u003cp\u003e(n=97)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"161\"\u003e\n\u003cp\u003e19.2%\u003c/p\u003e\n\u003cp\u003e(n=19)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" width=\"601\"\u003e\n\u003cp\u003e\u003cstrong\u003eCombined smell and taste loss resolution\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"217\"\u003e\n\u003cp\u003e\u003cstrong\u003eFull resolution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003e45.1%\u003c/p\u003e\n\u003cp\u003e(n=102)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"161\"\u003e\n\u003cp\u003e69.6%\u003c/p\u003e\n\u003cp\u003e(n=64)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"82\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026lt;0.001\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"217\"\u003e\n\u003cp\u003e\u003cstrong\u003eNo/partial resolution\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003e54.9%\u003c/p\u003e\n\u003cp\u003e(n=124)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"161\"\u003e\n\u003cp\u003e30.4%\u003c/p\u003e\n\u003cp\u003e(n=28)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe effect of age on resolution of smell and taste loss was evaluated. Mean age of male and female participants was comparable for participants who experienced full resolution of the loss in their sense of smell (40.4 \u0026plusmn; 13.2 years in males vs. 38.1 \u0026plusmn; 11.3 in females, p=0.333), their sense of taste (40.3 \u0026plusmn;13.4 vs .37.1 \u0026plusmn; 10.7 p=0.153) and combined loss of smell and taste (40.0 \u0026plusmn; 12.6 vs. 37.1 \u0026plusmn; 11.0, p=0.122). In participants with loss of their sense of taste that did not resolve at the time of follow-up, mean age was significantly higher in females compared to males (42.7 \u0026plusmn; 12.5 years vs. 37.6 \u0026plusmn; 12.6 years, p=0.030). Mean age was also significantly higher in female participants with unresolved combined loss of smell and taste loss compared to male participants (42.8 \u0026plusmn; 12.5 vs. 34.6 \u0026plusmn; 10.4, p=0.001). Mean age of female participants with unresolved smell loss was 41.6 \u0026plusmn; 11.7 years compared to 37.4 \u0026plusmn; 12.7 years in male participants, however this borderline difference did not reach statistical significance (p=0.053) (Figure 2).\u003c/p\u003e\n\u003cp\u003eIn light of the above findings, we further evaluated the effect of age on smell and/or taste loss resolution in female participants. A significantly higher age was observed in female participants without resolution compared to those with full resolution of the loss of their sense of smell (41.6 \u0026plusmn; 11.7 yrs vs. 38.1 \u0026plusmn; 11.3 yrs, p=0.010), their sense of taste (42.7 \u0026plusmn; 12.5 yrs vs. 37.1 \u0026plusmn; 10.7 yrs, p\u0026lt;0.001) and combined smell and taste (42.8 \u0026plusmn; 12.5 yrs vs. 37.1 \u0026plusmn; 11.0 yrs, p\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePredictors of persisting smell loss in a community population with SARS-CoV-2 antibodies and acute loss of their sense of smell\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLogistic regression was used to explore the relative importance of participant\u0026rsquo;s age, sex, ethnicity, smoking status, presence of parosmia and smell loss pattern as risk factors for persistent smell loss at \u0026gt;4 weeks from onset.\u003c/p\u003e\n\u003cp\u003eFemale participants were almost 2.5 times more likely to have ongoing smell loss after 4 weeks compared to participants of male sex (OR 2.46, 95% CI 1.47 to 4.13, p=0.001). Parosmia was also shown to have a significant association with unresolved smell loss at 4-6 week follow-up (OR 2.47, 95%CI 1.54 to 4.00, p\u0026lt;0.001), in a model adjusting for the age, ethnicity, patterns of smell loss (complete vs partial) and smoking; Table 5.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5: Logistic regression exploring the association between age, sex, ethnicity, smoking status, presence of parosmia and smell loss pattern (complete vs partial) and no resolution of smell loss at 4 weeks follow up.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"141\"\u003e\n\u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003eB\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e\u003cstrong\u003e95% CI (lower)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"107\"\u003e\n\u003cp\u003e\u003cstrong\u003e95% CI (upper)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"91\"\u003e\n\u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"141\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e0.13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e1.013\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e.994\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"107\"\u003e\n\u003cp\u003e1.032\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"91\"\u003e\n\u003cp\u003e\u003cem\u003e0.172\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"141\"\u003e\n\u003cp\u003e\u003cstrong\u003eEthnicity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e0.96\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e1.101\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e.595\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"107\"\u003e\n\u003cp\u003e2.034\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"91\"\u003e\n\u003cp\u003e\u003cem\u003e0.760\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"141\"\u003e\n\u003cp\u003e\u003cstrong\u003eComplete anosmia\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e0.529\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e1.697\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e0.998\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"107\"\u003e\n\u003cp\u003e2.884\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"91\"\u003e\n\u003cp\u003e\u003cem\u003e0.051\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"141\"\u003e\n\u003cp\u003e\u003cstrong\u003eParosmia\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e0.904\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e2.470\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e1.539\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"107\"\u003e\n\u003cp\u003e3.966\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"91\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026lt;0.001\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"141\"\u003e\n\u003cp\u003e\u003cstrong\u003eSex (Female)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e0.901\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e2.461\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e1.468\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"107\"\u003e\n\u003cp\u003e4.126\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"91\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.001\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"141\"\u003e\n\u003cp\u003e\u003cstrong\u003eSmoking\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e0.303\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"66\"\u003e\n\u003cp\u003e1.355\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"110\"\u003e\n\u003cp\u003e0.604\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"107\"\u003e\n\u003cp\u003e3.038\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"91\"\u003e\n\u003cp\u003e\u003cem\u003e0.462\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003ePersistent smell and/or taste loss as a manifestation of long COVID.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt the end of the 4-6 week follow-up period 42.3% (n=151) of participants with positive SARS-CoV-2 antibodies had ongoing smell loss, 33.8% experienced ongoing taste loss and 36% had ongoing taste and smell loss. We also evaluated the resolution of other symptoms of COVID-19 at the end of the follow-up period in participants positive for SARS-CoV-2 antibodies. Out of 134 participants with unresolved smell loss who reported additional COVID-19 symptoms on their original questionnaire, 29.1% (n=39) had at least 1 additional unresolved symptom at the time they completed their follow-up questionnaire, compared to 19.9% (n=35) of participants with full resolution of their smell loss (29.1% vs 19.9%, p=0.059). The most commonly reported unresolved symptoms were shortness of breath, chest pain and muscle/joint pains.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective smell testing in a subsample of participants and correlation with perceived smell function\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA subsample of 50 participants underwent objective olfactory testing using the UPSIT. 84% were female (n=42) and 16% (n=8) male. The mean age was 39.6 \u0026plusmn;13.5 years and mean duration of test date from the onset of symptoms was 21.6 \u0026plusmn;4.7 weeks. 76% (n=38) participants had complete loss of their sense of smell at the time of the original questionnaire and 24% (n=12) partial loss of smell. At the time of the follow-up questionnaire 16% (n=8) reported their smell loss \u0026lsquo;did not resolve\u0026rsquo;, 42% (n=21) reported their smell loss \u0026lsquo;resolved partially\u0026rsquo; and 42% (n=21) reported their smell loss \u0026lsquo;resolved fully\u0026rsquo;.\u003c/p\u003e\n\u003cp\u003eThe mean UPSIT test score was 29.1 \u0026plusmn;7.5 points. In view of the time elapsed between the completion of the follow-up questionnaire and the UPSIT testing, prior to testing, participants were asked how they perceived their smell function. Their answers were grouped into: \u0026lsquo;No or minimal sense of smell\u0026rsquo;, \u0026lsquo;Sense of smell improved but not fully recovered\u0026rsquo; or \u0026lsquo;Sense of smell fully recovered\u0026rsquo;. Table 6 illustrates a comparison of participants\u0026rsquo; perceived smell function and their UPSIT test result, by test result category. A Spearman rank correlation analysis found a significant correlation between perceived smell function and UPSIT test result category (r=0.84 \u0026plusmn; 0.71 to 0.90, p\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6: Comparison between UPSIT test result and perceived smell function in a study subgroup of 50 participants\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"140\"\u003e\n\u003cp\u003e\u003cstrong\u003eMinimal/no sense of smell\u003cbr /\u003e (n=11)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u003cstrong\u003eImproved sense of smell, not fully recovered (n=9)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u003cstrong\u003eFully recovered\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(n=30)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003eTotal anosmia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"140\"\u003e\n\u003cp\u003e45.5% (5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003eSevere microsmia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"140\"\u003e\n\u003cp\u003e45.5% (5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003eModerate microsmia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"140\"\u003e\n\u003cp\u003e9.0% (1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e77.8% (7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003eMild microsmia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"140\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e11.1% (1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e16.7% (n=5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003eNormosmia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"140\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e11.1% (1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e83.3% (n=25)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e\u003cstrong\u003eSpearman r\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"140\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.95\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u003cstrong\u003e-0.63\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u003cstrong\u003e-0.89\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":" \u003cp\u003eWe report longitudinal data from a community cohort with a new loss in their sense of smell and/or taste and resolution of these symptoms both in people with positive and negative SARS-CoV-2 IgG/IgM antibodies. Our data come from an entirely community based cohort with a low hospital admission rate where loss of taste and/or smell are the predominant symptoms. 77.9% of our cohort had positive SARS-CoV-2 antibodies and the study had a follow-up completion rate of 82.2%. We report a higher rate of recovery of smell loss (72.1% vs. 57.7%; p\u0026thinsp;=\u0026thinsp;0.027), taste loss (80.3% vs. 66.2%; p\u0026thinsp;=\u0026thinsp;0.017) and combined smell and taste loss (79.6% vs. 64%; p\u0026thinsp;=\u0026thinsp;0.026) in participants who tested negative compared to participants who tested positive for SARS-CoV-2 antibodies.\u003c/p\u003e \u003cp\u003eImportantly, our study highlights the high percentage of patients with ongoing smell loss (42.3%), ongoing taste loss (33.8%) and combined smell and taste loss (36.0%). The observed smell loss resolution rate of 57.7% in participants with SARS-CoV-2 antibodies within 4\u0026ndash;6 weeks in our study is in line with existing literature[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Dell\u0026rsquo;Era \u003cem\u003eet al.\u003c/em\u003e similarly reported that in 355 participants with COVID-19, 70% reported either smell loss and/or taste loss during infection[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. 49.5% of participants reported full resolution of both sense of smell/taste after 14 days since the onset of symptoms, increasing to 62.9% at time of interview (23 days median, range 15-31), with a median recovery time of 10 days. In contrast to our community-based study, their findings come from a hospitalised patient cohort. Resolution rates in the literature currently range from 29-92.8%[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Discrepancies are likely due to differences in study populations, sample size, location and duration of follow up since onset of symptoms.\u003c/p\u003e \u003cp\u003eFurthermore, we report higher rates of smell loss resolution in participants with partial compared to complete smell loss (67.4% vs. 54.5%, p\u0026thinsp;=\u0026thinsp;0.032). This is compatible with Kosugi et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] who reported that the full resolution from \u0026lsquo;partial loss of smell\u0026rsquo; in COVID-19 positive patients takes place more frequently than that from \u0026lsquo;complete loss of smell\u0026rsquo;. Supportively, using an objective approach, Lechien \u003cem\u003eet al.\u003c/em\u003e also found that higher baseline severity of smell loss, measured by \u0026lsquo;Sniffin-Sticks\u0026rsquo; was strongly predictive of persistent smell loss[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Beltr\u0026aacute;n-Corbellini \u003cem\u003eet al.\u003c/em\u003e compared smell loss recovery in 70 COVID-19 and 40 influenza participants[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. 40% of COVID-19 positive participants reported full resolution after 7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3 days and 16.7% reported partial resolution after 9.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6 days, whereas 100% of influenza participants fully recovered their sense of smell. The fact that participants with SARS-CoV-2 antibodies also had higher rates of complete anosmia, suggests a more severe spectrum of COVID-19 related smell loss compared to post-viral smell loss from other respiratory pathogens.\u003c/p\u003e \u003cp\u003eInterestingly, one of our key findings shows that parosmia was more common in the group of participants with unresolved smell loss and was also a predictor of non-remission in the logistic regression analysis, which is novel in COVID-19. Parosmia has been associated with post-viral smell loss prior to the COVID-19 pandemic[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. A potential explanation for our finding may be that parosmia has been associated with decreased number and disordered regrowth of olfactory axons into existing neural circuits and a preponderance of immature neurons[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Comparatively, Liu \u003cem\u003eet al.\u003c/em\u003e found that in 153 participants with post-infectious smell loss the presence of parosmia was associated with clinically significant recovery in suprathreshold olfactory function discrimination in patients receiving olfactory training[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Parosmia in the context of post-viral smell loss is associated with ongoing smell impairment, and although has been viewed as a sign of recovery, its role as a prognostic marker remains largely unclear. However, our data suggest that parosmia is a marker of poor prognosis in COVID-19. Similarly, our finding show that dysgeusia and experiencing taste sensations in the absence of eating and drinking were associated with lower reported taste loss resolution rates. Together, these findings suggest that distorted chemosensory perception is a risk factor for prolonged smell and/or taste loss and long-COVID.\u003c/p\u003e \u003cp\u003eWith regard to full resolution of smell and/or taste loss, a significant sex difference was evident. Females had a lower full resolution rate of smell loss (51.4% vs. 72.8%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), taste loss (60.1% vs. 80.8%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and combined smell and taste loss (45.1% vs. 69.6%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), compared to males, respectively. These findings are supported by several studies who also report the recovery of sense of smell was longer in females[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Although Meini \u003cem\u003eet al.\u003c/em\u003e found that the recovery rate did not differ significantly between males and females, they however, the mean recovery time from smell loss or taste loss was significantly longer for females than for males (26 vs. 14 days, p\u0026thinsp;=\u0026thinsp;0.009), even though the mean age of males was significantly higher than that of females (66 vs. 57 years, p\u0026thinsp;=\u0026thinsp;0.04)[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNotably, in our study, female participants who reported no/partial resolution of smell loss were significantly older (41.6\u0026thinsp;\u0026plusmn;\u0026thinsp;11.7\u0026nbsp;years) than female participants who reported full resolution of smell loss (38.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3 years, p\u0026thinsp;=\u0026thinsp;0.010). The same was also found to be true for taste loss (42.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5 vs. 37.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7, (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and combined smell and taste loss (42.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5 vs. 37.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.0, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In contrast, Lee \u003cem\u003eet al.\u003c/em\u003e reported that young age, particularly the age group of 20\u0026ndash;39 years, showed a tendency to be associated with a longer persistence of anosmia[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Interestingly, oestradiol has been shown to increase olfactory epithelial cell density and to have a protective role against olfactory function decline[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Additionally, in animal models of neurogenerative diseases oestradiol replacement prevents olfactory dysfunction[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. This study was not powered to estimate the effect of menopause-driven differences in this subgroup. Nevertheless, a link between prolonged or reduced recovery of smell function and a post-menopausal state appears plausible.\u003c/p\u003e \u003cp\u003eLoss of smell and taste have been demonstrated to persist beyond resolution of the infectious phase of COVID-19[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In light of evidence from the clinical course of smell loss from other viruses, smell loss after COVID-19 could persist for two or more years[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Arguably, our study follow-up window still only represents a relatively short-term observation and it is reasonable to predict that a number of participants will have further recovered their sense of smell and taste over additional weeks. Nevertheless, loss of smell and taste undoubtedly constitute a manifestation of long-COVID, which may result in significant psychological morbidity and adversely impact quality of life of the subset of patients with long-term unresolved smell and taste loss[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Given the limitations in accuracy and accessibility to testing during particularly the earlier phases of the pandemic, further patient populations may present with olfactory and gustatory impairment and features of long-COVID, indicative of previous COVID-19 infections. Of note, current proposed diagnostic criteria for long-COVID or chronic COVID-19 do not necessitate a positive test at time of symptom onset. The magnitude of the pandemic and the potential for SARS-CoV-2 to cause long-term smell and/or taste loss in relatively small cohorts therefore suggest that the overall prevalence of long-COVID with smell loss within the general population will be considerable[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIt will be vital to develop a better understanding of the pathophysiology causing smell loss as well as the physiological processes driving smell recovery, in order to facilitate development of effective treatments for smell loss. Angiotensin-converting enzyme-2 receptors (ACE-2) present on olfactory epithelial cells and neuropilin-1 receptors (NRP1), abundant on all olfactory cell lines, are known entry routes for SARS-CoV-2 and damage to these cells have been proposed as potential mechanisms for smell loss[\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Viral entry via NRP1 could result in direct damage to olfactory sensory neurons[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Furthermore, the distribution of these two receptors may form a plausible explanation for the spectrum of smell loss, with mild and typically short-lived smell loss from ACE-2 invasion versus more longstanding smell loss via NRP1 mediated sensory neuronal damage, following COVID-19. Therapeutic strategies including olfactory rehabilitation and corticosteroids are already in use to aid recovery of smell function following COVID-19, with further therapeutic strategies in clinical trials [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. With emerging treatments for COVID-19 related anosmia and the high predicted prevalence of long covid with long-standing smell loss, identifying those at risk of long-COVID with smell loss will be key. We highlight female sex (and increasing age within female cohorts) as well as the presence of parosmia as key risk factors for a prolonged clinical course of COVID-19 related smell loss.\u003c/p\u003e \u003cp\u003eFinally, in this study, we addressed the limitation of using subjective assessment of smell by recruiting a subset of participants who underwent objective UPSIT testing. Our results show that objectively assessed smell function using UPSIT correlates well with perceived smell function in this population, which highlights the reliability of our subjective patient-reported data on smell function following COVID-19. This finding is in line with a study conducted in ambulatory COVID-19 patients using the 12-item Brief Smell Identification Test (BSIT) which also concluded that self-reported olfactory loss is a strong predictor of abnormal olfactory function[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Furthermore, this highlights that in this subsample, tested 21.6 \u0026plusmn;4.7 weeks since the onset of their symptoms, 20% of participants had ongoing loss of their sense of smell, who would meet diagnostic criteria for both long-COVID and chronic COVID-19.\u003c/p\u003e "},{"header":"Limitations","content":" \u003cp\u003eThe main limitation of this study remains the lack of a general population control group without loss of smell/taste. Our selection criteria enabled us to study acute smell and taste loss as presentations of COVID-19 as well as their resolution in people both with and without SARS-CoV-2 antibodies. Coupled with the web-based delivery of the study, this leads to susceptibility to a degree of selection and age bias, which required proficiency with computers and smartphones and may have resulted in under-representation of older adults. Furthermore, the majority of our participants were female; this may reflect previous findings that females are more likely to engage in research and also have a higher frequency of loss of smell and/or taste with COVID-19 than males. Through recruiting a subset of participants for objective testing we addressed the previous limitation of lack of objective testing, and demonstrated a strong correlation between perceived and assessed smell function.\u003c/p\u003e "},{"header":"Conclusions","content":" \u003cp\u003eWe followed up a community cohort of people who had reported acute loss of their sense of smell and/or taste and had undergone SARS-CoV-2 IgG/IgM antibody testing 4\u0026ndash;6 weeks earlier in order to investigate the clinical course of smell and/or taste loss. We also aimed to identify factors that were associated with persistent smell loss at 4\u0026ndash;6 weeks of follow-up. In line with existing literature, we can offer reassurance that smell and/or taste loss is a transient phenomenon in most SARS-CoV-2 cases. However, persistent smell and taste loss constitute a feature of long-COVID. The population of patients with longstanding smell and/or taste loss as a manifestation of long-COVID will continue to grow during and following the pandemic; given the impact of these symptoms on quality of life and safety, it will be imperative to devise support and treatment pathways. We identified the presence of parosmia and female sex as risk factors for persistent smell loss, as well as increasing age within the female sub-cohort. Similarly, female sex and increasing age as well as distorted taste perception were associated with persistent taste loss. Our findings highlight that female patients over the age of 40, who experience with a distorted perception of their sense of smell and/or taste are likely to benefit from therapeutic interventions to prevent persistent smell and/or taste loss and should be prioritized when targeted therapies for post-covid smell and taste loss become available.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)\u003c/p\u003e \u003cp\u003eCoronavirus disease 2019 (COVID-19)\u003c/p\u003e \u003cp\u003eImmunoglobulin G (IgG)\u003c/p\u003e \u003cp\u003eImmunoglobulin M (IgM)\u003c/p\u003e \u003cp\u003eUniversity of Pennsylvania Smell Identification Test (UPSIT)\u003c/p\u003e \u003cp\u003eAngiotensin-converting enzyme-2 receptors (ACE-2)\u003c/p\u003e \u003cp\u003eNeuropilin-1 receptors (NRP1)\u003c/p\u003e \u003cp\u003eBrief Smell Identification Test (BSIT)\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study received ethical approval from the National Health Service Queen\u0026rsquo;s Square Research Ethics Committee (IRAS Project ID 282668, ClinicalTrials.gov: NCT04377815) and was conducted in line with the declaration of Helsinki and Good Clinical Practice.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was funded by the National Institute for Health Research (BRC751).\u0026nbsp;https://www.nihr.ac.uk/\u0026nbsp;RLB, CGM, JM, and AC are funded by National Institute for Health Research grant RP-2015-06-005 (https://www.nihr.ac.uk/). RLB, NB, and JM are funded by the Sir Jules Thorn Trust Biomedical Research Award (https://julesthorntrust.org.uk/programmes/medical-research/the-sir-jules-thorn-award-for-biomedical-research/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJM: Conceptualization, Data curation, Participant recruitment, Formal analysis, Investigation, Validation, Writing\u003c/p\u003e\n\u003cp\u003eCF: Data curation, Formal analysis, Investigation, Writing\u003c/p\u003e\n\u003cp\u003eCM: Investigation, Methodology, Writing\u003c/p\u003e\n\u003cp\u003eJMok: Investigation, Methodology, Writing\u003c/p\u003e\n\u003cp\u003eNB: Data curation, Investigation, Writing\u003c/p\u003e\n\u003cp\u003eML: Investigation, Writing\u003c/p\u003e\n\u003cp\u003eAC: Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Writing\u003c/p\u003e\n\u003cp\u003eRLB: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Writing\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Professor Valerie Lund for her advice and collaboration. We thank the Hampstead Group Practice, The Northern Medical Centre, the James Wigg Practice, and the Queen\u0026rsquo;s Crescent Practice for their collaboration in sending out the invitation text messages to their registered patients.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWHO. Coronavirus disease (COVID-19) pandemic 2020 [cited 2020 22 June]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019.\u003c/li\u003e\n\u003cli\u003eMenni 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. Nature medicine. 2020.\u003c/li\u003e\n\u003cli\u003eHopkins C, Surda P, Kumar N. Presentation of new onset anosmia during the COVID-19 pandemic. Rhinology. 2020.\u003c/li\u003e\n\u003cli\u003eMakaronidis J, Mok J, Balogun N, Magee CG, Omar RZ, Carnemolla A, et al. 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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.\u003c/li\u003e\n\u003cli\u003eOtte MS, Klussmann JP, Luers JC. Persisting olfactory dysfunction in patients after recovering from COVID-19. J Infect. 2020;81(3):e58.\u003c/li\u003e\n\u003cli\u003eWhitcroft KL, Hummel T. Olfactory Dysfunction in COVID-19: Diagnosis and Management. JAMA. 2020.\u003c/li\u003e\n\u003cli\u003eClinicalTrials.gov. Coronavirus Smell Therapy for Anosmia Recovery 2021 [Available from: https://www.clinicaltrials.gov/ct2/show/NCT04422275.\u003c/li\u003e\n\u003cli\u003eCroy I, Nordin S, Hummel T. Olfactory disorders and quality of life--an updated review. Chem Senses. 2014;39(3):185-94.\u003c/li\u003e\n\u003cli\u003eMakaronidis 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 medicine. 2020;17(10):e1003358.\u003c/li\u003e\n\u003cli\u003eElabscience. COVID-19 IgG and IgM [Available from: https://www.elabscience.com/p-covid_19_igg_igm_rapid_test-375335.html.\u003c/li\u003e\n\u003cli\u003eDoty RL, Shaman P, Kimmelman CP, Dann MS. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. The Laryngoscope. 1984;94(2 Pt 1):176-8.\u003c/li\u003e\n\u003cli\u003eMeini 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.\u003c/li\u003e\n\u003cli\u003eDell'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.\u003c/li\u003e\n\u003cli\u003eVaira 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.\u003c/li\u003e\n\u003cli\u003eLechien 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.\u003c/li\u003e\n\u003cli\u003eBeltr\u0026aacute;n-Corbellini \u0026Aacute;, Chico-Garc\u0026iacute;a JL, Mart\u0026iacute;nez-Poles J, Rodr\u0026iacute;guez-Jorge F, Natera-Villalba E, G\u0026oacute;mez-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.\u003c/li\u003e\n\u003cli\u003eReden 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):139-44.\u003c/li\u003e\n\u003cli\u003eLeopold DA, Loehrl TA, Schwob JE. Long-term follow-up of surgically treated phantosmia. Arch Otolaryngol Head Neck Surg. 2002;128(6):642-7.\u003c/li\u003e\n\u003cli\u003eLiu DT, Sabha M, Damm M, Philpott C, Oleszkiewicz A, H\u0026auml;hner A, et al. Parosmia is Associated with Relevant Olfactory Recovery After Olfactory Training. The Laryngoscope. 2020.\u003c/li\u003e\n\u003cli\u003eLee 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.\u003c/li\u003e\n\u003cli\u003eDhong HJ, Chung SK, Doty RL. Estrogen protects against 3-methylindole-induced olfactory loss. Brain Res. 1999;824(2):312-5.\u003c/li\u003e\n\u003cli\u003eNathan 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.\u003c/li\u003e\n\u003cli\u003eYan CH, Prajapati DP, Ritter ML, DeConde AS. Persistent Smell Loss Following Undetectable SARS-CoV-2. Otolaryngol Head Neck Surg. 2020;163(5):923-925.\u003c/li\u003e\n\u003cli\u003eCavazzana A, Larsson M, M\u0026uuml;nch M, H\u0026auml;hner A, Hummel T. Postinfectious olfactory loss: A retrospective study on 791 patients. The Laryngoscope. 2018;128(1):10-15.\u003c/li\u003e\n\u003cli\u003eHwang CS. Olfactory neuropathy in severe acute respiratory syndrome: report of A case. Acta neurologica Taiwanica. 2006;15(1):26-8.\u003c/li\u003e\n\u003cli\u003eErskine SE, Philpott CM. An unmet need: Patients with smell and taste disorders. Clin Otolaryngol. 2020;45(2):197-203.\u003c/li\u003e\n\u003cli\u003eHopkins 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.\u003c/li\u003e\n\u003cli\u003eBryche B, St Albin A, Murri S, Lac\u0026ocirc;te 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.\u003c/li\u003e\n\u003cli\u003eHoffmann M, Kleine-Weber H, Schroeder S, Kr\u0026uuml;ger 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.e8.\u003c/li\u003e\n\u003cli\u003ePrajapati 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.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, Long COVID-19, SARS-CoV-2 IgG/IgM, Smell loss, Taste loss, Smell recovery, Taste recovery","lastPublishedDoi":"10.21203/rs.3.rs-156677/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-156677/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eLoss 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. We assessed COVID-19 symptoms in a community cohort in London 4-6 weeks after they initially reported acute loss of their sense of smell and/or taste, 78% of whom had SARS-CoV-2 IgG/IgM antibodies. In addition, to assess whether self-reported change in sense of smell was reliable, we compared subjective and objective smell assessments in a subset of participants.\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003e467 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.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003ePeople 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\u0026lt;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 (\u0026gt;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\u0026lt;0.001). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eAlthough 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 \u0026gt;40 years) and people with a distorted perception of their sense of smell/taste are likely to benefit from prioritised early therapeutic interventions. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTrials registration:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eClinicalTrials.gov\u0026nbsp;\u003ca href=\"https://clinicaltrials.gov/ct2/show/NCT04377815\" rel=\"noopener noreferrer\" target=\"_blank\"\u003eNCT04377815\u003c/a\u003e\u003c/p\u003e","manuscriptTitle":"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","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-01-29 22:48:09","doi":"10.21203/rs.3.rs-156677/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2021-01-26T00:00:00+00:00","index":1,"fulltext":""},{"type":"editorAssigned","content":"","date":"2021-01-25T00:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-01-25T00:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-01-24T23:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-01-24T23:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2021-01-17T00:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4bedee79-049d-4fd3-82e8-c1c26137d577","owner":[],"postedDate":"January 29th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":2124088,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2021-02-28T15:00:36+00:00","versionOfRecord":{"articleIdentity":"rs-156677","link":"https://doi.org/10.1186/s12879-021-05927-w","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2021-02-25 15:00:28","publishedOnDateReadable":"February 25th, 2021"},"versionCreatedAt":"2021-01-29 22:48:09","video":"","vorDoi":"10.1186/s12879-021-05927-w","vorDoiUrl":"https://doi.org/10.1186/s12879-021-05927-w","workflowStages":[]},"version":"v1","identity":"rs-156677","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-156677","identity":"rs-156677","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}