Discussion:
Olfactory disorder is undoubtedly a key symptom of mild COVID-19 patients, affecting more than 70% of patients.4,5 However, its prevalence remains uninvestigated in severe forms of the disease. In this study, we found that 38.3% of patients with severe disease experience SLS. Among them, 38.9% had abnormal objective tests 1-month after the onset of the infection. Irrespective to the method used to evaluate the prevalence of SLS (patient-reported outcome questionnaireversus objective tests), these data indicate that SLS could be more prevalent in mild-to-moderate forms of the infection.
According to a previous study conducted in the same population and with the same methods, self-reported SLS concerned more than 70% of mild COVID-19 patients and, among them, 62% had abnormal objective evaluations.3 The higher incidence of SLS in mild forms of COVID-19 suggests a relative compartmentalization of the disease. Such compartmentalization may involve differences in immune responses to SARS-CoV-2 at the level of nasal and olfactory mucosa. In patients with potent mucosal immune responses, viral replication and dissemination to the lower respiratory tract may be better controlled and this could be at the expense of local inflammation and symptoms involving nasal and bulb regions. In patients with less potent mucosal immune responses, viral replication could spread to the lower respiratory tract and lead to systemic immune response and inflammation. This hypothesis is supported by our observation that nasal burning was inversely correlated with SARS-CoV-2 serum IgG whereas severe forms of the disease have been positively correlated with SARS-CoV-2 IgG responses.7 Further studies are needed to test this hypothesis. Both age and diabetes could be favoring factors in the development of SLS, which is well known in other olfactory diseases.8,9
The main limitations of the present study are the low number of patients and the performance of olfactory tests one month after the onset of symptoms. Performing the tests during hospitalization was difficult due to the sanitary situation, the patient clinical state, and the difficulties to correctly sense the pens with transnasal oxygenation. Although this possibility is not supported by patient-reported symptoms, the delay between the onset of symptoms and the objective olfactory testing may underestimate the incidence of olfactory dysfunction.