This cohort observational study was conducted in the COVID departments of the University Hospital of Sassari (Infectious and Tropical Disease, Pneumology, Onco-COVID and Neuro-COVID operative units) between January 10 and February 1, 2021.
To be enrolled in the study, patients had to meet the following inclusion criteria: adults over 18 years of age, rhino-pharyngeal swab positive for SARS-CoV-2 infection, COVID-19 symptoms present for less than 10 days, patient acceptance for participation in the study. On the contrary, the study exclusion criteria were: uncooperative patients, assisted ventilation, psychiatric or neurological disorders, previous surgery or radiotherapy in the oral and nasal cavities, pre-existing self-reported smell and taste alterations, history of head trauma, allergic rhinitis, chronic rhinosinusitis.
All patients provided informed consent for participation in the study. The study protocol was approved by University Hospital of Cagliari Ethical Committee (PG/2021/5471).
Some clinical and epidemiological information was collected for all patients: age, gender and COVID-19 symptoms. All patients were followed up clinically until the nasopharyngeal swab was negative. The overall clinical severity of COVID-19 was classified according to Tian et al. [21] in mild, moderate, severe and critical.
Psychophysical olfactory evaluation was performed with the Connecticut Chemosensory Clinical Research Center test (CCCRC). The CCCRC is a validated, widely used and easy to perform psychophysical test. The methodology, the scoring system and its application in COVID-19 patients have been extensively described in previous studies [22–25]. The CCCRC includes the assessment of the olfactory threshold using solutions with increasing concentration of N-butyl acid and an identification task for common odorants. The olfactory score thus obtained allows to clinically classify the olfactory function in five categories: normal (scores 90 and 100), mild (scores 70 and 80), moderate (scores 50 and 60) or severe hyposmia (scores 20, 30 and 40) and anosmia (scores 0 and 10).
Within 24 hours after the olfactory test, plasma levels of IL-6 (reference value < 5.9 pg/mL) were determined on a peripheral blood sample taken from each patient by means of a fully automated Elecsys system on a cobas e801 platform (Roche Diagnostics, Basel, Switzerland) as previously described [18].
The statistical analysis was performed with SPSS 26.0 (IBM, Armonk, NY, USA). Categorical variables are reported in numerals and percentages of the total. Descriptive statistics for quantitative variables are given as the mean ± standard deviation (SD) or median (interquartile range – IQR). The Kruskal-Wallis Test was performed to evaluate the statistical significance of differences in olfactory scores between clinical severity groups. Post-hoc analysis with Mann-Whitney U test was used to define the different relationships of the olfactory severity score and IL-6 blood levels with each of the COVID-19 severity subgroups. The correlation between olfactory scores and IL-6 levels was assessed with the Spearman rank correlation coefficient. The level of statistical significance was set at p < 0.05 with a 95% confidence interval.