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\begin{document}

\title{RBD-IgG levels correlate with protection in Residents Facing SARS-CoV-2
B.1.1.7 Outbreaks}



\author[1]{Hubert Blain}%
\author[1]{Edouard Tuaillon}%
\author[1]{Lucie Gamon}%
\author[1]{Amandine Pisoni}%
\author[1]{Stephanie Miot}%
\author[1]{Valentin Delpui}%
\author[1]{Nejm Si-Mohamed}%
\author[1]{Clémence Niel}%
\author[2]{Yves Rolland}%
\author[1]{Brigitte Montes}%
\author[1]{Soraya Groc}%
\author[1]{Sophia Rafasse}%
\author[1]{Anne-Marie Dupuy}%
\author[1]{Nathalie Gros}%
\author[1]{Delphine Muriaux}%
\author[1]{Marie-Christine Picot}%
\author[3]{Jean Bousquet}%
\affil[1]{Montpellier Universite d'Excellence}%
\affil[2]{Centre Hospitalier Universitaire de Toulouse}%
\affil[3]{Charite Universitatsmedizin Berlin}%


\vspace{-1em}



  
  \date{May 17, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
\textbf{Background} Limited information exists on nursing home (NH)
residents regarding BNT162b2/Pfizer vaccine efficacy in preventing
SARS-CoV-2 and severe Covid-19, and its association with post-vaccine
humoral response. \textbf{Methods} 396 residents from seven NHs
suffering a SARS-CoV-2 B.1.1.7 (VOC-\selectlanguage{greek}α\selectlanguage{english}) outbreak at least 14 days after a
vaccine campaign were repeatedly tested using SARS-CoV-2 real-time
reverse-transcriptase polymerase chain reaction on nasopharyngeal swab
test (RT-PCR). SARS-CoV-2 Receptor-Binding Domain (RBD) of the S1
subunit (RBD-IgG) was measured in all residents. Nucleocapsid
antigenemia (N-Ag) was measured in RT-PCR-positive residents, and serum
neutralizing antibodies in vaccinated residents from one NH.
\textbf{Results} The incidence of positive RT-PCR was lower in residents
vaccinated by two doses (22.7\%) vs one dose (32.3\%) or non-vaccinated
residents (43.7\%)(p\textless{}0.01). Covid-19-induced deaths were
observed in 10.4\% of the non-vaccinated residents, in 6.4\% of those
who had received one dose, and in 0.9\% with two doses (p=0.0007).
Severe symptoms were more common in infected non-vaccinated (21.0\%) vs
vaccinated residents (47.6\%, p=0.002). Higher levels of RBD-IgG (n=325)
were associated with a lower SARS-CoV-2 incidence. No in vitro serum
neutralization activity was found for RBD-IgG levels below 1,050 AU/mL.
RBD-IgG levels were inversely associated with N-Ag levels, found as a
risk factor of severe Covid-19. \textbf{Conclusions} Two BNT162b2/Pfizer
doses are associated with a 48\% reduction of SARS-CoV-2 incidence and a
91.3\% reduction of death risk in residents from NHs facing a VOC-\selectlanguage{greek}α
\selectlanguage{english}outbreak. BNT162b2/Pfizer efficacy was partly predicted by post-vaccine
RBD-IgG levels.%
\end{abstract}%



\sloppy


\textbf{RBD-IgG levels correlate with protection in Residents Facing
SARS-CoV-2 B.1.1.7 Outbreaks}

H. Blain*, E. Tuaillon*, L. Gamon, A. Pisoni, S. Miot, V. Delpui, N.
Si-Mohamed, C. Niel, Y. Rolland, B. Montes, S. Groc, S. Rafasse, A.M.
Dupuy, N. Gros, D. Muriaux, M.C. Picot, J. Bousquet

* Both authors contributed equally to the manuscript

Authors' full names, academic degrees, and affiliations: Hubert Blain,
MD, PhD,\textsuperscript{1} Edouard Tuaillon MD,
PhD,\textsuperscript{2}Lucie Gamon,\textsuperscript{3} Amandine Pisoni
PhD,\textsuperscript{2}St\selectlanguage{ngerman}éphanie Miot MD, PhD,\textsuperscript{1}
Valentin Delpui,\textsuperscript{1} Nejm Si-Mohamed, \textsuperscript{1}
Clémence Niel,\textsuperscript{2} Yves Rolland MD,
PhD,\textsuperscript{4} Brigitte Montes PharmD, PhD\textsuperscript{2},
Soraya Groc\textsuperscript{2}, Sophia Rafasse,\textsuperscript{5}
Anne-Marie Dupuy MD, PhD,\textsuperscript{6} Nathalie Gros PhD,
\textsuperscript{5} Delphine Muriaux PhD,\textsuperscript{5}
Marie-Christine Picot MD, PhD,\textsuperscript{3} Jean Bousquet MD,
PhD\textsuperscript{7}

\begin{enumerate}
\tightlist
\item
  Department of Internal Medicine and Geriatrics, MUSE University,
  Montpellier, France.
\item
  Laboratory of Virology, INSERM U 1058/EFS, University hospital,
  Montpellier, France.
\item
  Clinical research and epidemiology unit, University hospital,
  Montpellier, France.
\item
  Gérontopôle de Toulouse, INSERM 1027; Toulouse, France.
\item
  CEMIPAI, University of Montpellier, UAR3725 CNRS, Montpellier, France,
  and Institute of Research in Infectiology of Montpellier (IRIM),
  University of Montpellier, UMR9004 CNRS, Montpellier, France.
\item
  Biochemistry and hormonology laboratory, University hospital,
  Montpellier, France
\item
  Department of Dermatology and Allergy, Universitätsmedizin, Berlin,
  Germany and University hospital, Montpellier, France.
\end{enumerate}

\textbf{Running head:} Antibodies and BNT162b2 Effectiveness

\textbf{Corresponding author:}

Prof. Hubert BLAIN, Department of Geriatrics, Montpellier University
Hospital, Montpellier University, France. Full postal address: Centre
Antonin Balmes, Pôle de Gérontologie du Centre Hospitalier Universitaire
de Montpellier , 39 avenue Charles Flahault, 34295 Montpellier Cedex 5,
France.

e-mail:~h-blain@chu-montpellier.fr; tel: +33 467339957; Fax: +33
467330948

This work was not supported by a grant.

\textbf{ABSTRACT}

\textbf{Background}

Limited information exists on nursing home (NH) residents regarding
BNT162b2/Pfizer vaccine efficacy in preventing SARS-CoV-2 and severe
Covid-19, and its association with post-vaccine humoral response.

\textbf{Methods}

396 residents from seven NHs suffering a SARS-CoV-2 B.1.1.7 (VOC-\selectlanguage{greek}α\selectlanguage{english})
outbreak at least 14 days after a vaccine campaign were repeatedly
tested using SARS-CoV-2 real-time reverse-transcriptase polymerase chain
reaction on nasopharyngeal swab test (RT-PCR). SARS-CoV-2
Receptor-Binding Domain (RBD) of the S1 subunit (RBD-IgG) was measured
in all residents. Nucleocapsid antigenemia (N-Ag) was measured in
RT-PCR-positive residents, and serum neutralizing antibodies in
vaccinated residents from one NH.

\textbf{Results}

The incidence of positive RT-PCR was lower in residents vaccinated by
two doses (22.7\%) vs one dose (32.3\%) or non-vaccinated residents
(43.7\%)(p\textless{}0.01). Covid-19-induced deaths were observed in
10.4\% of the non-vaccinated residents, in 6.4\% of those who had
received one dose, and in 0.9\% with two doses (p=0.0007). Severe
symptoms were more common in infected non-vaccinated (21.0\%) vs
vaccinated residents (47.6\%, p=0.002). Higher levels of RBD-IgG (n=325)
were associated with a lower SARS-CoV-2 incidence. No in vitro serum
neutralization activity was found for RBD-IgG levels below 1,050 AU/mL.
RBD-IgG levels were inversely associated with N-Ag levels, found as a
risk factor of severe Covid-19.

\textbf{Conclusions}

Two BNT162b2/Pfizer doses are associated with a 48\% reduction of
SARS-CoV-2 incidence and a 91.3\% reduction of death risk in residents
from NHs facing a VOC-\selectlanguage{greek}α \selectlanguage{english}outbreak. BNT162b2/Pfizer efficacy was partly
predicted by post-vaccine RBD-IgG levels.

\textbf{Key words:} SARS-CoV-2; Covid-19; symptoms; nursing homes;
residents; BNT162b2/Pfizer vaccine; efficacy; antibody response;
nucleocapsid antigenemia; neutralizing antibodies

\textbf{INTRODUCTION}

Nursing Home (NH) residents are at high risk of serious illness and
death from coronavirus disease 2019 (Covid-19) \textsuperscript{1}.
Vaccination is safe and effective in adults, but less documented in NH
residents. \textsuperscript{2-4} Vaccine monitoring is partly based on
post-vaccine IgG response against SARS-CoV-2 Receptor-Binding Domain
(RBD) of the S1 subunit (RBD-IgG). \textsuperscript{5} Based on RBD-IgG
levels, \textsuperscript{6-8} it is recommended in France to administer
one mRNA vaccine dose in adults with prior Covid-19 and a third dose in
immunocompromized patients. The interest of a third vaccine dose also
arises in NH residents without prior
Covid-19.\textsuperscript{2,9,10,11} It remains however unclear as to
whether blood levels are predictive of SARS-CoV-2 infection and Covid-19
severe symptoms.

The recent emergence of SARS-CoV-2 `variants of concern' (VOC) has
transformed the epidemic, \textsuperscript{12} possibly because RBD-IgG
produced by vaccinated individuals is less effective in binding and
neutralizing \emph{in vitro} VOCs than the ``wild type''
SARS-CoV-2.\textsuperscript{13,14-17}

Between January and March 2021, all French NH residents, including those
of the Occitanie region, were offered two BNT162b2/Pfizer doses at a
three-week interval. Between March and April 2021, 7 NHs of the
Montpellier area (Occitanie) faced a SARS-CoV-2 B.1.1.7 (VOC-\selectlanguage{greek}α\selectlanguage{english}) outbreak
after the vaccine campaign.

The primary aim of this study was to assess the incidence of positive
SARS-CoV-2 real-time reverse-transcriptase polymerase chain reaction
(RT-PCR) results according to the vaccination status. Secondary aims
were to compare Covid-19-related deaths and RBD-IgG levels according to
the vaccination status. Other secondary aims were to assess the links in
RT-PCR-positive residents between symptom severity, blood RBD-IgG levels
and SARS-CoV-2 nucleocapsid antigenemia (N-Ag). Exploratory objectives
were to analyze the link between RBD-IgG levels and serum neutralization
activity against VOC-\selectlanguage{greek}α \selectlanguage{english}and SARS-CoV-2 wild-type in one NH, and the links
between biological markers with Covid-19 severity in RT-PCR-positive
residents (N-Ag, C-reactive protein, and glomerular filtration
rate).\textsuperscript{18,19}



\textbf{Methods}

\textbf{Design of the study}

Between March and April 2021, among the 122 NHs (6 241 residents)
followed by the Montpellier Covid-19 support platform after
vaccination,\textsuperscript{20} 13 had at least one RT-PCR-positive
resident (747 residents; 124 positive RT-PCR residents). Among these 13
NH, a prospective cohort study was carried out in all seven NHs with
more than five RT-PCR-positive residents tested at least 14 days after
the end of the vaccination campaign, considering that the exposure risk
of residents should be sufficient to study the effect of the vaccination
on Covid-19 incidence. Clinical characteristics of all residents present
at the time of the first positive RT-PCR were studied, regardless of the
date of their arrival in the NH. As for other Occitanie NHs, when a
first RT-PCR-positive resident was diagnosed, the same infection
prevention and control (IPC) measures were implemented and no new
resident entry was permitted until the end of the outbreak (Online
supplement 1) \textsuperscript{21,22}. Blood was drawn on the day of
positive RT-PCR testing in the first infected residents and within the 5
following days in all the others. Blood collection within this delay was
possible in 6/7 NHs. Blood sample allowed to measure IgG-RBD and
nucleoprotein IgG levels and, in RT-PCR-positive residents, N-Ag. Serum
neutralizing antibodies were assessed in a subsample of 36 vaccinated
residents from the first NH facing a SARS-CoV-2 outbreak, chosen to have
a wide range of IgG-RBD values.

\textbf{Participants}

When a first resident had a positive RT-PCR, residents and their family
or legal representative were informed of the possibility to assess
RDB-IgG and nucleocapsid IgG in order to assess humoral immunity.

All residents of the 6 NH in which the blood sample was offered were
tested, except those in palliative medical situation and those for whom
informed consent for the blood collection and the use of anonymized data
was not obtained. History of previous RT-PCR testing and the Charlson
comorbidity index were determined based on residents' medical
files.\textsuperscript{23}

The study was approved by the Montpellier University Hospital
institutional review board (IRB-MTP\_2020\_06\_202000534 and IRB-MTP

\textbf{Outcomes}

\textbf{Main outcome: Incidence of SARS-CoV-2 infection}

The diagnosis of SARS-CoV-2 infection was performed using RT-PCR on
nasopharyngeal swab (Allplex 2019-nCoV assay, Seegene) (Online
supplement 2). \textsuperscript{24} An RT-PCR multiple variant assay was
used for the detection of \selectlanguage{greek}α \selectlanguage{english}and \selectlanguage{greek}β/γ \selectlanguage{english}variants (ID SARS-CoV-2/UK/SA
Variant Triplex (id Solutions) and for genome sequencing.

\textbf{Secondary outcomes}

\textbf{Covid-19 severity:} Symptoms were those recorded in residents'
files by NH staff between 7 days before and 14 days after RT-PCR
testing, according to previous studies \textsuperscript{21,25} (Online
supplement 3). Covid-19 was considered to be severe when residents had
either (i) respiratory symptoms including shortness of breath,
respiratory rate \textgreater{} 24/min, oxygen saturation \textless{}
90\% or when oxygen therapy was used, or (ii) when they displayed other
symptoms whose intensity was considered by the NH coordinating
practitioner as sufficient to justify an hospitalization or an
examination by the resident's General Practitioner. Other symptomatic
residents had mild symptoms.

\textbf{SARS-CoV-2 RBD and Nucleoprotein immunoglobulin levels:} RBD-IgG
levels were measured using the SARS-CoV-2 IgG II Quant assay (Abbott
Diagnostics). Results were expressed as arbitrary units per mL (AU/mL;
positive threshold: 50 AU/mL; upper limit: 40,000 AU/mL). According to
the manufacturer and to previous studies, a first threshold [?] 1,050
AU/mL was considered as a significant response, \textsuperscript{26} and
a second one [?] 4,160 AU/mL indicated a high neutralizing
effect.\textsuperscript{27} Nucleoprotein IgG (N-IgG) levels were
measured using the SARS-CoV-2 IgG assay (Abbott Diagnostics) (Online
supplement 4).

\textbf{Nucleocapsid antigenemia}

N-Ag was quantified in all RT-PCR-positive residents seronegative for
N-IgG, using the COV-QUANTO\selectlanguage{ngerman}® kit (AAZ, France), a CE-IVD marked
immunoassay. \textsuperscript{28}

\textbf{Exploratory outcomes}

\textbf{Neutralizing antibodies} : Micro-neutralization assays were
performed in 36 residents (online supplement 5). \textsuperscript{27}

\textbf{Inflammatory and kidney markers:} C-reactive protein (hsCRP) and
creatinine levels were measured (online supplement 6).



\textbf{Statistical analysis}

In NH 4 (Table S1), blood sampling was not possible, and residents' data
were used only to assess the link between vaccination status and
SARS-CoV-2 infection and severe Covid-19 incidence. Due to the very low
number of missing data in the 6 NHs in which blood was collected, and to
the fact that residents who did ou did not contribute to blood
collection did not differ for age, gender, and comorbidity status, no
assumptions were made for missing data et missing data were not
replaced.

Categorical variables were described with frequency and proportions for
each category. The description of continuous variables was performed
using mean and standard deviation and/or median, with interquartiles,
according to the distribution.

The statistical analysis plan was pre-specified according to previous
studies from our group. \textsuperscript{6,7}, with the following
primary, secondary, and exploratory outcomes

The primary outcome (incidence of positive RT-PCR) was estimated in the
entire cohort with 95\% confidence interval (CI), and compared according
to the residents' vaccination status (non-vaccinated, one vaccine dose,
or two vaccine doses) using the Chi-2 test. Death was not considered as
a competing risk as all deaths were related to Covid-19 during the study
period. Covid-19-related deaths were considered as incident cases.

Secondary outcomes were compared in the whole cohort according to the
vaccination status using the Fisher exact test for deaths and the
Kruskal-Wallis (KW) test for RBD-IgG levels.

Other secondary outcomes according to the vaccination status were
analyzed in RT-PCR-positive residents: Covid-19 symptom severity using
the Fisher exact test, RBD-IgG and N-Ag using the KW test. The
relationship between levels of RBD-IgG and risk of incident SARS-CoV-2
was analyzed using the Fisher exact test.

Exploratory analyzes on the relationship between RBD IgG levels and
serum neutralization in RT-PCR-positive residents of one NH were
performed using Fisher's exact test. Wilcoxon--Mann--Whitney 2-sided
tests were used to compare N-Ag in asymptomatic, mild, and severe
Covid-19 residents.

Holm's correction was applied for the post-hoc comparisons for each
outcome. The statistical significance threshold was set at 5\%.

We displayed the positive predicted values (PPVs) and negative
predictive values (NPVs) of a positive RT-PCR testing for the accepted
thresholds of IgG-RBD values (positive threshold set at 50 AU/mL,
significant threshold set at 1,050 AU/mL, and 4,160 AU/mL, indication a
high neutralizing effect). \textsuperscript{26,27}

Analyses were performed and illustrated using SAS Enterprise Guide, v7.3
(SAS Institute Inc) and GraphPad Prism 9.1.1 (GraphPad Software, Inc.,
San Diego, CA).

\textbf{Results}

\textbf{characteristics of the residents}

In the seven NHs, non-vaccinated residents ranged from 3.9\% to 32.6\%,
and RT-PCR-positive residents from 9.8\% to 54.9\%. Residents'
vaccination coverage was not significantly different across the NH sites
(Table S 1). A total of 396 residents (57 to 103 years, mean ± sd: 87.33
± 9.17 years), with 312 females (78.8\%), were included. The Charlson
comorbidity index ranged from 2 to 15 (median, percentiles: 6.0,
5.0-7.0). Fifty-one residents had prior-Covid-19, determined by a
positive RT-PCR in 2020 or 2021, and only residents without prior
positive RT-PCR had detectable N-protein-IgG in the blood collected for
this study. There were 48 (12.2\%) non-vaccinated residents, 31 (7.8\%)
with one vaccine dose, and 317 (80.0\%) with two doses. Age, sex,
Charlson co-morbidity index, or previous RT-PCR results were comparable
in the groups (Table 1).

Blood sampling could not be performed in residents from NH number 4
(Table 1, Table S1, and Figure 1). In the 6 NHs in which a blood sample
was offered, residents who were (N = 325) or were not (N = 25) sampled
were similar in age, gender, and Charlson index (data not shown).

\textbf{Covid-19 incidence depending on vaccination status}

RT-PCR was positive in 103 residents with an incidence of 26\% (95\% CI:
21.7\%-30.3\%). RT-PCR cycle thresholds (Ct) were comparable in
vaccinated and non-vaccinated residents (Table 1). The VOC-\selectlanguage{greek}α \selectlanguage{english}variant was
found in all NHs. Positive RT-PCR results were obtained in 22.7\% of
residents with two vaccine doses, 32.3\% with one dose, and 43.7\% in
non-vaccinated subjects.

\textbf{Covid-19-related deaths depending on vaccination status}

Incident deaths, all due to Covid-19, were higher in non-vaccinated
(10.4\%) than in vaccinated residents (6.4\% and 0.9\% for those
vaccinated with one or two doses, Table 1). In RT-PCR-positive
residents, the non-vaccinated ones died more frequently (25\% vs
4.3\%)(Table 2). Two non-vaccinated residents received monoclonal
antibodies and recovered completely.

\textbf{Covid-19-related symptoms depending on vaccination status}

In RT-PCR-positive residents, the non-vaccinated developed significantly
more severe symptoms than the vaccinated (47.6\% vs 21.1\%) (Table 2).

\textbf{Clinical outcomes depending on RBD IgG levels}

Serum samples were available for 325/350 residents from 6 NHs in which
the blood collected could be organized (92.9\%). Causes of missing data
are displayed in Figure 1.

By comparison with residents who received two vaccine doses, the RBD-IgG
level was lower in non-vaccinated residents and in those with one dose
(Table 1).

Residents with higher levels of RBD-IgG had a lower risk of developing
SARS-CoV-2 during the outbreak (Table 3). PPV and NPV of a positive
RT-PCR by RBD-IgG levels over 1,050 AU/mL (significant
response\textsuperscript{26}) were 0.86 and 0.24, respectively, with a
sensitivity and specificity of 0.63 and 0.54 (Table S2).

Among the 48 RT-PCR-positive vaccinated residents with blood results,
RBD-IgG levels tended to be higher in asymptomatic residents than in
those with mild or severe symptoms (median (IQR){[}range{]} 1249 AU/mL
(337 ; 3027) {[}11.00 ; 25,453.00{]} vs 517 AU/mL (150 ; 1,289) {[}3 ;
14,631{]} vs 358 AU/mL (128 ; 1,339) {[}93 ; 5,824{]}, respectively).

No \emph{in vitro} serum neutralization activity was found for RBD-IgG
levels under 1,050 AU/mL for both SARS-CoV-2 and VOC-\selectlanguage{greek}α. \selectlanguage{english}Above this
threshold, the RBD-IgG levels were associated with serum neutralization
activity (Figure 2).

\textbf{nucleocapside antigenemia}

Among the 49 RT-PCR-positive residents with N-Ag measurement, median
N-Ag levels were higher in non-vaccinated residents than in those having
received 2 vaccine doses (Table 2), and higher in residents with severe
symptoms (Fig. S1A). RBD-IgG level was predictive of N-Ag in
SARS-CoV-2-infected residents (Fig. S1B).

\textbf{INFLAMMATORY AND KIDNEY BIOMARKERS}

RT-PCR-positive residents with elevated CRP (\textgreater{}10 mg/L, S1C)
or reduced glomerular filtration rates (GFR) (\textless{}60
ml/min/1.73m2) had higher N-Ag levels (Fig.S1D).

\textbf{Discussion}

Among 396 residents from 7 NHs facing a VOC-\selectlanguage{greek}α \selectlanguage{english}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-\selectlanguage{greek}α \selectlanguage{english}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-\selectlanguage{greek}α \selectlanguage{english}infection, (ii) a low serum
neutralizing effect against SARS-CoV-2 wild type and VOC-\selectlanguage{greek}α, \selectlanguage{english}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-\selectlanguage{greek}α
\selectlanguage{english}outbreak, even if the percentage of infected residents differed among
the vaccinated and non-vaccinated. \textsuperscript{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.
\textsuperscript{29}The strong reduction of severe symptoms and death
found in vaccinated residents was also reported. \textsuperscript{4,9}

In contrast to two previous studies, \textsuperscript{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 \emph{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)\textsuperscript{18,19} which is in line with previous studies
conducted in the general population. \textsuperscript{31} Our results
are consistent with studies in the general population showing a
correlation between RBD-IgG and serum neutralization,
\textsuperscript{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-\selectlanguage{greek}α \selectlanguage{english}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.\textsuperscript{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 (\textless{}3.5\% imprecision).
\textsuperscript{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-\selectlanguage{greek}α \selectlanguage{english}outbreak. RBD-IgG produced by
vaccinated residents seems less effective for binding and neutralizing
\emph{in vitro} \selectlanguage{greek}β, δ, κ \selectlanguage{english}and \selectlanguage{greek}ε \selectlanguage{english}variants \textsuperscript{13}
\textsuperscript{14-17,35} than the SARS-CoV-2 ``wild type''.~
\textsuperscript{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.

\textbf{Conclusions}

These results confirm the effectiveness of two BNT162b2/Pfizer doses to
reduce significantly the incidence and the severity of Covid-19 in NH
residents facing a VOC-\selectlanguage{greek}α \selectlanguage{english}outbreak. They tend to validate the
quantification of the vaccine antibody response as an estimate of
SARS-CoV-2 prevention efficacy.



\textbf{Acknowledgements}

We thank (i) Drs. Vincent Foulongue and Monsef Benkirane (Montpellier)
for providing the SARS-CoV-2/CHU Montpellier/France strain, and (ii)
Drs. Olivier Terrier, Andres Pizzorno and Manuel Rosa-Calatrava (CIRI,
Centre International de Recherche en Infectiologie, Team VirPath,
Inserm, U1111, Universit\selectlanguage{ngerman}é Claude Bernard Lyon 1, CNRS, UMR5308, ENS de
Lyon, Lyon) for providing the Gisaid UK (B.1.1.7): EPI\_ISL\_900512
strain, referred to as hCoV-19/France/ARA-SC2118/2020.

The authors would also like to thank Anna Bedbrook, Fabienne Portejoie
(MACVIA France), and Eva Pons (Master Métiers de l'Enseignement, de
l'Education et de la Formation; éducation nationale française, Lyon) for
their editorial assistance, Joy Martin, Isabelle Bussereau, and
Marie-Suzanne Léglise, Secours Infirmiers (Department of Geriatrics,
Montpellier University Hospital), Véronique Vera and Florence Biblocque
(admission office, Montpellier University Hospital) for material
support, Xavier Basagaña for his methodological support, as well as the
residents and staff members of the nursing homes involved in the study.
None of these contributors received any compensation for their help in
carrying out the study.

\textbf{Conflicts of Interest:}

The authors declare no conflicts of interest/competing interests.



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Bas du formulaire

\textbf{Table 1. Characteristics of the residents depending on their
vaccination status}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Non-vaccinated (a) (n=48)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Vaccinated\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Vaccinated\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
P value\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 vaccine dose (b) (n=31)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 vaccine doses (c) (n=317)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Age, mean (SD), yr*\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
87.2 (9.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
85.1 (9.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
87.6 (9.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.22\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Sex, n (\%)** Female Male\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
35 (72.9) 13 (27.1)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
25 (80.7) 6 (19.3)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
252 (79.5) 65 (20.5)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.56\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Charlson index (median, IGR) {[}range{]} *\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
6.0 (5.0-7.0) 2-15\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
6.0 (5.0-8.0) 3-15\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
6.0 (5.0-7.0) 2-15\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.41\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Prior SARS-CoV-2 positive RT-PCR, n (\%)**\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (10.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (9.7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
43 (13.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.82\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Positive RT-PCR during outbreak, n (\%)**\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
21 (43.7)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
10 (32.3)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
72 (22.7)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.0059 0.005 (a vs c)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N-protein IgG \textgreater{} 0.8 signal to cutoff ratio, n (\%)***\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (20.0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (17.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
38 (14.0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.57\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
RBD-IgG level, AU/mL, median (IQR) *\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
n = 26 2 (1-415)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
n =28 534.00 (201.50 ; 2166.50)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
n =271 1522.00 (444.00 ; 5389.00)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.000001 0.001 (a vs b) 0.01 (a vs c) 0.08: (b vs c)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Covid-19-related deaths, n (\%)***\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
5 (10.4)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
2 (6.4)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
3 (0.9)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.0007 0.004 (a vs c)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

*Analysis using Kruskal-Wallis test; ** Analysis using chi-2 test;
***Analysis using Fisher test

\textbf{Table 2. Characteristics of the residents with RT-PCR positive
results}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Non-vaccinated (a) (n =21)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Vaccinated\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Vaccinated\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
P value\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 vaccine dose (b) (n =10)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 vaccine doses (c) (n =72)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Age, mean (SD), yr**\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
90.3 (7.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
83.8 (8.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
89.1 (7.8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.06\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Sex, n (\%)**** Female Male\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
15 (71.4) 6 (28.6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
8 (80.0) 2 (20.0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
56 (77.8) 16 (22.2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.87\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Charlson index (median, IQR) {[}range{]} **\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
6 (6.0-8.0) {[}4-15{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
7.0 (5.0-8.0) 5-9\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
7.0 (6.0-8.0) 3-15\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.96\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Prior SARS-CoV-2-positive RT-PCR, n (\%)***\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (4.8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (4.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.00\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
First positive RT-PCR cycle threshold, median (IQR) ****\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
26.0 (23.0-32.0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
24.85 (20.4 ; 28.0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
24.00 (19.2 ; 28.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.74\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Cycle threshold of the second RT-PCR*, median (IQR) ****\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
30.3 (27-35.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
30.7 (23.1 ; 34.5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
27.00 (21.0 ; 31.7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.21\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Symptoms, n (\%)*** Asymptomatic Mild Severe\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (9.5) 4 (19.1) 10 (47.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6 (60.0) 2 (20.0) 0\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
31 (43.7) 23 (31.0) 15 (21.1)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.002 0.01 (a vs b), 0.002 (a vs c) 0.09 (b vs c)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Deaths, n (\%)***\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (23.8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (20.0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (4.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.002 (a vs c)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
SARS-CoV-2 IgG levels - N-protein IgG \textgreater{} 0.8 signal to
cutoff ratio, n (\%)** - SARS-RBD-IgG (AU/mL) ***** \textless{}50
51-1,050 1,051-4,160 \textgreater{}4,160\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
n =10 2 (20.0) 6 (60.0) 3 (30.0) 0 (0) 1 (10)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
n =7 1 (14.3) 1 (14.3) 5 (71.4) 1 (14.3) 0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
n =49 4 (8) 5 (10.2) 22 (44.9) 15 (30.6) 7 (14.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.29 0.010.01 (a vs c)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Nucleocapide antigenaemia titer **, median (IQR){[}range{]} ******\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
n = 7 43.0 (2.9-150.2) {[}0.7-555.2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
n =5 1.8 (0.5-3.0) {[}0.2-12.5{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
n =37 1.5 (-0.4-16-6) {[}-1.5-328-4{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.03 0.004 (a vs c)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

* The second RT-PCR was performed 7 days after the first positive RT-PCR
result in 47 residents; **Analysis using Kruskal-Wallis test; ***
Analysis using Fisher test; ****Analysis using ANOVA; *****Analysis
using Mann-Whitney test; ****** level of detection of the assay is 2.95
ng/mL. Samples with Nucleocapside Ag level over 180 pg/mL were diluted.
Titer is the number of dilution possible, still reaching the detection
threshold. According to the manufacturer of the SARS-CoV-2 IgG II Quant
assay (Abbott Diagnostics), the positive threshold is of 50 AU/mL
RBD-IgG levels. Based on previous studies, an RBD-IgG level [?] 1,050
AU/mL is considered as a significant antibody response to the
vaccine,\textsuperscript{26} and a level [?] 4,160 AU/mL indicates a high
neutralizing effect against SARS-CoV-2 \textsuperscript{27}.



\textbf{Table 3. Incidence rate of positive RT-PCR testing and serum
neutralizing activity depending on SARS-CoV-2 RBD IgG levels}\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
SARS-CoV-2 RBD IgG levels, AU/mL*\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
SARS-CoV-2 RBD IgG levels, AU/mL*\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
SARS-CoV-2 RBD IgG levels, AU/mL*\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
SARS-CoV-2 RBD IgG levels, AU/mL*\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{} 50\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
51-1,050\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1,051-4,160\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textgreater{} 4,160\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
P value\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
RT-PCR testing result, n (\%) Positive Negative\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
n = 12 5 (41.67) 7 (58.33)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
n = 97 22 (22.68) 75 (77.32)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
n = 82 15 (18.29) 67 (81.71)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
n = 80 7 (8.75) 73 (91.25)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Serum micro-neutralization titer against SARS-CoV-2 wild type, median
(IQR){[}range{]}**\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
n = 3 0 (0-0) {[}0-0{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
n = 10 0 (0-0) {[}0-0{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
n = 10 10.0 (0-10) {[}0-20{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
n = 5 160 (40-320) {[}20-640{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0.005\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Serum neutralization against SARS-CoV-2 B.1.1.7 (VOC \selectlanguage{greek}α\selectlanguage{english}), median
(IQR){[}range{]}**\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
n = 3 0 (0-0) {[}0-0{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
n = 10 0 (0-0) {[}0-0{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
n = 10 10.0 (10-20) {[}0-40{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
n = 5 320 (80-640) {[}40-640{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0.005\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

* Analysis using the Fisher test; ** Analysis using the Kruskal-Wallis
test; Micro-neutralization titers are expressed as the serial dilution
for which 50\% neutralization is obtained.

\textbf{Figure 1. Flow Diagram of the sample of residents having faced a
COVID-19 outbreak at least 14 days after a BNT162b2/Pfizer vaccination
campaign.}

\textbf{Hosted file}

\verb`image1.emf`  available at \url{https://authorea.com/users/343419/articles/538850-rbd-igg-levels-correlate-with-protection-in-residents-facing-sars-cov-2-b-1-1-7-outbreaks}



\textbf{Figure 2. SARS-CoV-2-specific neutralizing antibody levels
against SARS-CoV-2 wild type (WT) and VOV-alpha depending on RBD-IgG
levels in 36 residents.}

Legend. Micro-neutralization titers are expressed as the serial dilution
for which 50\% neutralization is measured.

\textbf{Figure S1. Levels of nucleocapsid antigenemia (N-Ag) in 49
vaccinated residents with SARS-CoV-2 confirmed infection. A) N-Ag levels
according to Covid-19 severity, green circles: asymptomatic; yellow
circles: mild forms; red circles: severe forms. B) ROC evaluating
RBD-IgG levels to predict undetectable N-Ag at the thresholds of 2.97
pg/mL, AUC: 0.70; 12.5 pg/mL, AUC: 0.76; 50 pg/mL, AUC: 0.83. C).}

\textbf{N-Ag levels according to C-reactive protein (CRP) level; green
circles: CRP [?] 10 mg/L; red circle CRP \textgreater{} 10 mg/L. D) N-Ag
levels according to glomerular filtration rates; green circles: GFR [?] 60
ml/min); red circles: GFR \textless{} 60 ml/min.}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

Legend. Covid-19 residents were considered as having severe symptoms
when they had either (i) respiratory symptoms including shortness of
breath, respiratory rate \textgreater{} 24/min, oxygen saturation
\textless{} 90\% or when oxygen therapy was used, or (ii) when they
displayed other symptoms whose intensity was sufficient to lead to
hospitalization or to justify medical examination. Residents with mild
symptoms had no severe symptoms.

\selectlanguage{english}
\FloatBarrier
\end{document}

