Discussion
Among 396 residents from 7 NHs facing a VOC-α outbreak over 14 days
after the end of a BNT162b2/Pfizer vaccination campaign, 103 had a
positive RT-PCR test. After two vaccine doses, the risk of incident
VOC-α infection was reduced by 48% when compared to non-vaccinated
residents, and by 26% in residents with one dose. In RT-PCR-positive
residents, two vaccine doses reduced the risk of severe symptoms by 56%
(from 47.6% to 21.1%), and Covid-19 death by 82.4% (from 23.8% to
4.2%). Post-vaccine RBD-IgG levels under 1,050 AU/mL were associated
with (i) an increased risk of incident VOC-α infection, (ii) a low serum
neutralizing effect against SARS-CoV-2 wild type and VOC-α, and (iii)
high levels of N-Ag that were associated with a higher risk of severe
Covid-19 (severe symptoms, high C-reactive protein, low glomerular
filtration rate).
The 48% reduction of SARS-CoV-2 infection after two vaccine doses found
in the present study is consistent with NH studies reporting a VOC-α
outbreak, even if the percentage of infected residents differed among
the vaccinated and non-vaccinated. 2,4,9 The reduction
in Covid-19 risk was estimated at 65% after a single BNT162b2/Pfizer
vaccine dose in a national data study in England. 29The strong reduction of severe symptoms and death found in vaccinated
residents was also reported. 4,9
In contrast to two previous studies, 2,30 we did not
find any difference in viral load, estimated by the mean Ct. Because Ct
values, vaccine regimen, and Covid-19 severity strongly differed between
the three studies, further investigations are needed to determine the
reduction of the viral load in infected residents after vaccination.
This information is crucial to minimize the duration and consequences of
isolation in vaccinated infected residents.
A novel result of the present study is that post-vaccine RBD-IgG levels
can partly predict the efficacy of the vaccine in to prevent incident
SARS-CoV-2 and severe symptoms. This is consistent with This result is
also consistent with he lack of neutralizing effect observed in the
serum against SARS-CoV-2 in vitro under a threshold of 1,050
AU/mL and the association between RBD-IgG levels and serum
neutralization activity found above this threshold. In addition, lower
RBD-IgG levels were significantly associated with higher N-Ag levels
which were associated with a higher risk of Covid-19 severity (more
severe symptoms, higher C-Reactive Protein levels and lower glomerular
filtration rate - two biological markers of Covid-19 severity)18,19 which is in line with previous studies conducted
in the general population. 31 Our results are
consistent with studies in the general population showing a correlation
between RBD-IgG and serum neutralization, 32,33 These
studies combine to suggest that (i) low RBD-IgG levels following
vaccination may not necessarily possess the key footprints required to
block viral infection, and (ii) a minimal post-vaccine RBD-IgG level,
possibly over 1,050 AU/mL, may be required to block VOC-α infection
and/or prevent severe symptoms.
The strengths of this study include the sample size, and all studied NHs
followed the same IPC guidance, making it possible to compare the
results.21,22
This study also has several limitations: (i) RBD-IgG levels were
measured using an immunoassay and results expressed in arbitrary units.
However, the assay used in our study can probably be considered as a
quantitative assay (<3.5% imprecision). 34(ii) RBD-IgG levels were measured within five days after the diagnosis
of the first RT-PCR-positive resident of the NH. Even if this delay was
as short as possible, RDB-IgG levels may also reflect a possible rapid
anamnestic response to infection. This bias tends however to reinforce
our results, since we found a relationship between low levels of RBD-IgG
and a higher risk of SARS-CoV-2. (iii) Although the NH residents of the
present study were comparable to the French NH population in terms of
mean age, gender, and comorbidity status, our results obtained in
residents exposed to a high risk of infection may not be extrapolated to
all NH residents. (iv) Our results are only valuable for NHs facing a
VOC-α outbreak. RBD-IgG produced by vaccinated residents seems less
effective for binding and neutralizing in vitro β, δ, κ and ε
variants 13 14-17,35 than the
SARS-CoV-2 “wild type”. 14-17,35,36 (v) The results
obtained are restricted to the BNT162b2/Pfizer vaccination in NH
residents. Further studies conducted in NH residents facing other
variants and different vaccines are therefore necessary. In this study,
8.7% of residents with RBD-IgG levels of over 4,160 AU/mL developed a
positive RT-PCR. This suggests that vaccinated residents, even with high
levels of S-protein IgG after two vaccine doses, may participate in
SARS-CoV-2 transmission while most often being asymptomatic or
pauci-symptomatic. These results suggest that vaccinated residents
should be included in the wide-facility testing strategy when a resident
is infected.