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

Abstract

Background Loss of smell and/or taste are cardinal symptoms of COVID-19. ‘Long-COVID’, persistence of symptoms, affects around one fifth of people. However, data regarding the clinical resolution of loss of smell and/or taste are lacking. In this study we assess smell and taste loss resolution at 4–6 week follow-up, aim to identify risk factors for persistent smell loss and describe smell loss as a feature of long-COVID in a community cohort in London with known SARS-CoV-2 IgG/IgM antibody status. We also compare subjective and objective smell assessments in a subset of participants. Methods Four hundred sixty-seven participants with acute loss of smell and/or taste who had undergone SARS-CoV-2 IgG/IgM antibody testing 4–6 weeks earlier completed a follow-up questionnaire about resolution of their symptoms. A subsample of 50 participants completed an objective olfactory test and results were compared to subjective smell evaluations. Results People with SARS-CoV-2 antibodies with an acute loss of sense of smell and taste were significantly less likely to recover their sense of smell/taste than people who were seronegative (smell recovery: 57.7% vs. 72.1%, p = 0.027. taste recovery 66.2% vs. 80.3%, p = 0.017). In SARS-CoV-2 positive participants, a higher percentage of male participants reported full resolution of smell loss (72.8% vs. 51.4%; p < 0.001) compared to female participants, who were almost 2.5-times more likely to have ongoing smell loss after 4–6 weeks (OR 2.46, 95%CI 1.47–4.13, p = 0.001). Female participants with SARS-CoV-2 antibodies and unresolved smell loss and unresolved taste loss were significantly older (> 40 years) than those who reported full resolution. Participants who experienced parosmia reported lower smell recovery rates and participants with distorted taste perception lower taste recovery rates. Parosmia had a significant association to unresolved smell loss (OR 2.47, 95%CI 1.54–4.00, p < 0.001). Conclusion Although smell and/or taste loss are often transient manifestations of COVID-19, 42% of participants had ongoing loss of smell, 34% loss of taste and 36% loss of smell and taste at 4–6 weeks follow-up, which constitute symptoms of ‘long-COVID’. Females (particularly > 40 years) and people with a distorted perception of their sense of smell/taste are likely to benefit from prioritised early therapeutic interventions. Trials registration ClinicalTrials.govNCT04377815 Date of registration: 23/04/2020.

Risk factors for long COVID: analyses of 10 longitudinal studies and electronic health records in the UK

“…This decline in older age has been observed in other studies, 4,17,18 and may be spurious due to selective competing risk of mortality, non-response bias, lower symptom reporting in older adults, misattribution of long COVID to other illness, or a combination of these factors. The findings that long COVID was 50% higher in women than men is consistent with reports from most 4,17,19–22 but not all previous studies. 4,18 We found some evidence of higher long COVID reporting among individuals of white ethnicity and of higher educational attainment, which was unexpected given the common associations of these characteristics with lower morbidity more generally.…”

Predictors of smell recovery in a nationwide prospective cohort of patients with COVID-19

“…In addition they also found no association between recovery of smell function and viral load on nasopharyngeal swab testing or COVID-19 severity. Contrarily, Makaronidis et al found in their study of 380 patients (270 female, 110 male) recruited online from a community-based cohort that men were more likely than women (72.8% vs. 51.4%) to fully recover their sense of smell [24] . Age, race, and smoking status were not associated with improved rates of recovery at 4 weeks.…”

“…Despite numerous reports describing rates of smell recovery, very little information exists regarding the factors associated with recovery vs. non-recovery. Few have investigated this phenomenon, and to date almost no clinical, epidemiological, or laboratory markers have been identified [22] , [23] , [24] , [25] . In their study of prospectively recruited patients from 3 European centers, Saussez and colleagues examined patterns of recovery among 288 patients within 60 days of onset of olfactory dysfunction [23] .…”

Neurological sequelae of COVID-19: a review

“…Olfactory dysfunction has been reported with other coronavirus infections and epidemics, including the SARS-CoV virus [ 53 ], providing precedence for the OD caused by SARS-CoV-2. What’s more, two studies found COVID-19 patients had a longer duration (10 vs. 15 days, p < 0.006) and lower recovery (57.7% vs. 72.1%, p = 0.027) than COVID-19 seronegative patients with olfactory dysfunction, suggesting that OD in COVID-19 has a unique etiology (although false negatives could complicate these results) [ 54 , 55 ]. Therefore, while the exact etiology is unclear, it is likely that SARS-CoV-2 produces sensory impairment irrespective of other upper respiratory symptoms.…”

“…Sex and age differences have been reported, with some studies observing a higher incidence ( p < 0.011) [ 50 ] and longer duration (26 vs. 14 days, p = 0.009) of OD in females than males, including higher persistence at 4–6-week follow-up (OR 2.46, 95% CI 1.46–4.13, p = 0.001) [ 49 , 55 ]. Conversely, Amer and colleagues noted that females had better recovery at 1 month from COVID-19 onset (83.9% vs. 62.5%, p < 0.005), proposing elevated androgens in males that enhance transcription of TMPRSS2 [ 56 ].…”