Smell loss is a prognostic factor for lower severity of coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) can present with a myriad of symptoms. Guidelines from the People's Republic of China, the United Kingdom, and Italy had focused screening efforts on patients with fever and cough, excluding anosmia from similar scrutiny. However, the screening of individuals with reported anosmia and dysgeusia has been associated with a greater likelihood of a positive COVID-19 result than other indicators of an upper respiratory tract infection.2, 3, 4 The relative predictive value of presenting COVID-19 symptoms is under current investigation.3, 4, 5, 6 This study seeks to ascertain the role of smell loss in risk stratification and predicting COVID-19 patients’ prognosis.

Adult patients with COVID-19 who were evaluated at a university medical center between February 1, 2020 and April 3, 2020 were identified by an electronic medical records query and included in our initial series. Complete data on demographic variables, clinical characteristics, COVID-19 symptoms, COVID-19 treatments, and clinical evaluations were retrieved. Through a predesigned screening questionnaire for COVID-19, the patients were evaluated through telemedicine, in-person, or at the emergency department and were asked about their symptoms during the history taking, including whether they had acute smell loss. Patients with incomplete clinical data or whose smell loss was not recorded were excluded.

The retrieved information included the following: (1) demographics; (2) body mass index (BMI); (3) comorbid conditions (asthma, allergic rhinitis, chronic rhinosinusitis, eczema, food allergy); (4) preexisting smell dysfunction; (5) COVID-19–related inflammatory laboratory values (complete blood cell counts, C-reactive protein, albumin, creatinine, ferritin, and erythrocyte subdimension rate); (6) COVID-19 outcomes (need for hospitalization, intensive care unit admission, intubation); and (7) development of acute respiratory disease syndrome. To identify and confirm comorbidities and other clinical variables, all charts were reviewed by 2 independent trained researchers, and 20% of the charts were randomly checked by the principal investigator. Data points with a lack of concordant information were reviewed again by an independent investigator, and if needed, were excluded from the analysis.

The Statistical Product and Service Solutions version 23 (SPSS Inc, Chicago, Illinois) was used for all analyses. Results with continuous variables were presented as mean plus or minus SD unless otherwise specified and were compared using parametric analysis if normally distributed (Student's t test). The χ2 test was performed to analyze the correlation among the categorical parameters. Logistic regression was conducted to calculate the odds ratio (OR) of smell loss in association with nominal dependent variables such as preexisting comorbidities and COVID-19 outcome was adjusted for possible confounders (demographics and BMI). The adjusted ORs were presented with their 95% confidence intervals (CIs). Analysis of covariance was conducted to compare the adjusted means of continuous variables such as laboratory values in association with smell loss, adjustment for demographics, and BMI. This research study was approved by the institutional review board.

The initial series consisted of 1013 patients who were evaluated and received positive test results for COVID-19. Sufficient data on smell loss, demographic variables, comorbidities, and outcomes were available for 949 patients (93.7%), who were included for the analysis. The cohort consisted of 55.2% of women with a mean (SD) age of 48.42 (±15.67) years. In this series, 54.3% of patients were Black, 25.0% were non-Latino White, 22.9% were Latino, and 14.3% were identified as other race or ethnicity.

Overall, 198 (20.9%) patients reported smell loss during their initial evaluation for COVID-19. Smell loss was significantly associated with younger age, female sex, and higher BMI: the mean age was 46 vs 49 years in those with and without smell loss, respectively (P = .02); 64.7% of patients with smell loss vs 52.8% of those without smell loss were women (P = .003); and the mean BMI was 33.6 vs 31.5 in those with and without anosmia, respectively (P = .001). There was a significant association between smell loss and history of preexisting smell dysfunction (OR, 4.66; 95% CI, 2.07-10.46, P < .001), allergic rhinitis (OR, 1.79; 95% CI, 1.12-2.87, P = .02), and chronic rhinosinusitis (OR, 3.70; 95% CI, 1.29-10.67, P = .02) compared with patients without smell loss.

Sufficient data on laboratory markers was available for 419 (41.8%) patients. Compared with patients without smell loss, patients with smell loss exhibited less lymphopenia (the mean ± SD of lymphocyte count was 1.84 ± 3.69 vs 1.11 ± 0.81 in those with and without smell loss, respectively; P = .001) and higher albumin counts (3.02 ± 0.83 vs 2.77 ± 0.83, P = .02). Other laboratory values and inflammatory markers were not associated with smell loss among patients with COVID-19. These results did not change after adjusting for demographics and BMI.

Smell loss was also significantly associated with decreased hospitalization (OR, 0.69; 95% CI, 0.47-0.99, P = .04), intensive care unit admission (OR, 0.38; 95% CI 0.20-0.70, P = .002), intubation (OR, 0.43; 95% CI, 0.21-0.89, P = .02), and acute respiratory distress syndrome (OR, 0.45; 95% CI, 0.23-0.89, P = .02) after adjustment for demographics and BMI (Table 1 ). These results remained significant after further adjustment for allergic rhinitis and chronic rhinosinusitis.

Table 1

Preexisting Conditions and COVID-19–related Outcomes in 949 COVID-19 Patients in Association With Smell Loss

Conditions	Number of cases with condition among the series	Odds ratio (95% CI) of having smell loss in patients with the condition compared with those without the condition	Adjusted P valuea
History of smell dysfunction	27	4.66 (2.07-10.46)	<.001b
Allergic rhinitis	101	1.79 (1.12-2.87)	.02c
Food allergy	71	1.64 (0.95- 2.83)	.08
Atopic dermatitis (eczema)	42	1.22 (0.59-2.50)	.60
Asthma	243	1.18 (0.82-1.70)	.36
Chronic rhinosinusitis	15	3.70 (1.29-10.67)	.02c
GERD	60	0.67 (0.29-1.58)	.36
Diabetes	243	0.86 (0.57-1.29)	.46
Hypertension	391	1.14 (0.77-1.68)	.52
Emergency department visit for COVID-19	520	0.83 (0.59-1.16)	.28
Hospitalized	311	0.69 (0.47-0.99)	.04c
ICU-admitted	131	0.38 (0.20-0.70)	.002c
Intubated	86	0.43 (0.21-0.89)	.02c
ARDS	93	0.45 (0.23-0.89)	.02c

Abbreviations: ARDS, acute respiratory distress syndrome; BMI, body mass index; COVID-19, coronavirus disease 2019; GERD, gastroesophageal reflux disease; ICU, intensive care unit.

Odds ratios and adjusted P values are calculated by logistic regression adjusting for age, sex, and BMI.

P value less than .001.

P value less than .05.

Our data implicate smell loss as an independent positive prognostic factor of a less severe COVID-19 infection. It was significantly associated with decreased hospitalization, intensive care unit admission, intubation, and acute respiratory distress syndrome rates compared with the lack of smell loss (Table 1). In further support, smaller studies of 169 and 34 patients who received a positive COVID-19 diagnosis found an association between anosmia with outpatient care as opposed to hospitalization. Our data aligns with these findings. In addition, smell loss was associated with less lymphopenia and higher levels of albumin, suggesting a less severe reaction to COVID-19 in patients with smell loss than those with an intact smell.

A history of preexisting smell dysfunction, allergic rhinitis, or chronic rhinosinusitis was associated with a greater chance of acute smell loss in patients with COVID-19. However, because most patients who experience smell loss in the setting of COVID-19 report a return of smell with clinical resolution of illness, and an initial neuroimaging study seemed to indicate an absence of acute visible size changes to the neural olfactory system, COVID-19 is not associated with permanent anosmia. Positive and negative predictive values could not be calculated because the basal rates of hyposmia and anosmia, the prevalence of COVID infection, and the individual phases of illness of each infected patient were not established for the studied population; however, they have been evaluated in further detail elsewhere. Female sex, lower age, higher BMI, history of previous smell loss, and preexisting allergic rhinitis and chronic rhinosinusitis appeared as important predictors of smell loss in the setting of COVID-19 infection. The main limitations of our study were its retrospective nature, subjective nature of smell loss, and focused nature of the data collection that did not include the patients' current medications.