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.