Relationship between nasal SARS-CoV-2 viral load and endemic
coronavirus antibody levels
To explore the potential basis for the higher antibody response to
SARS-CoV-2 in patients with undetectable or lower SARS-CoV-2 viral load,
the levels of antibodies to the S protein of endemic coronaviruses were
measured (Figure 3 ). First, we observed that anosmic and
normosmic patients had similar levels of nasal and serum IgG and IgA to
the S protein of 229E, OC43, HKU1 and NL63 viruses, except for serum
levels of IgG to 229E that were slightly lower among anosmic patients(Figure 3a) . We then observed that antibody levels to the four
endemic coronaviruses were comparable in SARS-CoV-2 PCR positive and
negative patients, whether anosmic or normosmic (Figure 3b) . A
moderate negative correlation was observed between SARS-CoV-2 viral load
and nasal levels of IgG to OC43 and HKU1 but no other correlations were
observed (Figure 3c) . Together these data indicate that overall
antibody levels to endemic coronaviruses are not associated with nasal
SARS-CoV-2 viral load in our study population. Immunity to endemic
coronaviruses can therefore not explain the association between
SARS-CoV-2 viral load and SARS-CoV-2-specific antibodies. However, the
fact that OC43 and HKU1 have the closest homology with SARS-CoV-2 among
endemic coronaviruses suggests that the moderate negative correlation
observed between SARS-CoV-2 viral load and serum levels of IgG to these
two coronaviruses may indicate some role for cross-reactive immunity in
the control of SARS-CoV-2 replication in anosmic patients.
To the best of our knowledge, this is the first study showing an inverse
association between nasal SARS-CoV-2 viral load and the levels of
antibodies. The specificity of this observation in patients with
COVID-19 OD suggests an interaction with other immune components
involved in the pathogenesis of the olfactive disorder. The data
suggests that boosting local immunity to SARS-CoV-2 may be beneficial to
patients with OD and may reduce the duration of symptoms. Systemic
vaccination with currently available vaccines provides limited mucosal
immunity. The development of mucosal vaccines may offer opportunities
for the prevention of local symptoms, in addition to the reduction of
SARS-CoV-2 shedding and transmission20 .
The relatively large number of patients and the prospective design are
the main strengths of the study. Moreover, patients were recruited and
followed-up within relatively narrow time windows, increasing the
likelihood of measuring dynamic virological and immunological events at
similar times between patients. Some limitations can be mentioned as
well. Measurements were performed at a single time point, preventing
analysis of the dynamics of the relationship between viral replication
and antibody responses. As explained above, the study was conducted from
October to November 2020 (second wave of SARS-CoV-2 in Europe) when the
dominant strain of SARS-CoV-2 was the Wuhan strain. The interactions
between variants of concern and antibodies at the mucosal level could be
significantly different, limiting the potential extrapolation of our
study results to the current stage of the pandemic. The lack of fully
objective methods to assess the olfactory dysfunction is another
limitation. The use of Identification Sniffin’Sticks Test (16 items) and
not the complete TDI test was made according to the quarantine
restrictions of physician-patient contact in the first waves of the
pandemic. We are however well aware that this identification test is
less effective in the objective analysis of smell disorders.