\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[T2A]{fontenc}
\usepackage[polish,ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Incidence of SARS-CoV-2 infection among healthcare workers before and
after COVID-19 vaccination in a tertiary paediatric hospital in Warsaw:
a retrospective cohort study}



\author[1]{Kasztelewicz Beata}%
\author[1]{Skrok Katarzyna}%
\author[1]{Burzyńska Julia}%
\author[1]{Migdał Marek}%
\author[1]{Katarzyna Dzierzanowska-Fangrat}%
\affil[1]{Children’s Memorial Health Institute}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
A retrospective observational study was conducted among healthcare
workers (HCWs) in a tertiary paediatric hospital. The study covered the
period before and after implementation of the vaccination programme and
evaluated the incidence of new SARS-CoV-2 infections in both periods.
Risk factors of the new SARS-CoV-2 infection and COVID-19 vaccine
effectiveness was also assessed in a real-world setting. The overall
incidence of SARS-CoV-2 infections among HCWs in the study period was
19.4\% with a high proportion of asymptomatic individuals (45.1\%). The
incidence before vaccination was 16.6\% and nurses had a higher risk of
infection, while physicians had a reduced risk (OR 1.80, 95\% CI
1.29--2.52; and OR 0.45, 95\% CI 0.30--0.68). Within two months of
implementation, the programme achieved a high (88.9\%) vaccination
coverage in our cohort, although some disparities in vaccination rates
were observed. In particular, older individuals, physicians, those
working in clinical settings, and those previously uninfected were more
likely to be vaccinated. The overall incidence of SARS-CoV-2 infection
after vaccination deployment was 6.3\% (40.0\% in unvaccinated
individuals and 3.2\% in individuals vaccinated with at least one dose).
The estimated vaccine efficacy was high (95.0\%) in fully vaccinated
HCWs and similar to those observed previously in clinical trials and
real-world settings.%
\end{abstract}%



\sloppy


\textbf{Incidence of SARS-CoV-2 infection among healthcare workers
before and after COVID-19 vaccination in a tertiary paediatric hospital
in Warsaw: a retrospective cohort study}

Kasztelewicz Beata\textsuperscript{1}, Skrok
Katarzyna\textsuperscript{1}, Burzy\selectlanguage{polish}ń\selectlanguage{english}ska Julia\textsuperscript{1}, Migda\selectlanguage{polish}ł
\selectlanguage{english}Marek\textsuperscript{2}, Dzier\selectlanguage{polish}ż\selectlanguage{english}anowska-Fangrat
Katarzyna\textsuperscript{1}

\textsuperscript{\textbf{1}} Department of Clinical Microbiology and
Immunology, The Children's Memorial Health Institute, Warsaw, Poland.

\textsuperscript{\textbf{2}} The Children's Memorial Health Institute,
Warsaw, Poland, CEO of the CMHI.

\textbf{Correspondence:}

Kasztelewicz B, Department of Clinical Microbiology and Immunology, The
Children's Memorial Health Institute, Warsaw, Poland.

Email: b.kasztelewicz@ipczd.pl

\textbf{Abstract:}

A retrospective observational study was conducted among healthcare
workers (HCWs) in a tertiary paediatric hospital. The study covered the
period before and after implementation of the vaccination programme and
evaluated the incidence of new SARS-CoV-2 infections in both periods.
Risk factors of the new SARS-CoV-2 infection and COVID-19 vaccine
effectiveness was also assessed in a real-world setting. The overall
incidence of SARS-CoV-2 infections among HCWs in the study period was
19.4\% with a high proportion of asymptomatic individuals (45.1\%). The
incidence before vaccination was 16.6\% and nurses had a higher risk of
infection, while physicians had a reduced risk (OR 1.80, 95\% CI
1.29--2.52; and OR 0.45, 95\% CI 0.30--0.68). Within two months of
implementation, the programme achieved a high (88.9\%) vaccination
coverage in our cohort, although some disparities in vaccination rates
were observed. In particular, older individuals, physicians, those
working in clinical settings, and those previously uninfected were more
likely to be vaccinated. The overall incidence of SARS-CoV-2 infection
after vaccination deployment was 6.3\% (40.0\% in unvaccinated
individuals and 3.2\% in individuals vaccinated with at least one dose).
The estimated vaccine efficacy was high (95.0\%) in fully vaccinated
HCWs and similar to those observed previously in clinical trials and
real-world settings.

\textbf{Key words:}

SARS-CoV-2, healthcare workers, COVID-19 vaccine

\textbf{INTRODUCTION}

The ongoing pandemic of the coronavirus disease 2019 (COVID-19) caused
by the novel severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) has had significant impact worldwide. Healthcare workers
(HCWs) are considered to be at high risk of exposure to SARS-CoV-2 both
in the community and in the workplace and may play a critical role,
especially when asymptomatic, in the transmission of the infection
within the workplace (both to their patients and co-workers) as well as
in the community\textsuperscript{1}.

Preventing SARS-CoV-2 infection among HCWs is critical to ensure safety
for both patients and HCWs, to contain the ongoing pandemic, and to
maintain a functioning healthcare system.

Many preventive measures have been implemented throughout the pandemic
to contain the spread of the SARS-CoV-2 infection in healthcare
settings, including universal masking, enhanced hand hygiene and
personal protective equipment (PPE) training, symptom screening, and
self-isolation of HCWs if symptomatic or in the case of close contact
with an infected person. Notably, there has been a paradigm shift in the
infection control practices against respiratory infections, which
includes widespread testing of patients and HCWs, including asymptomatic
individuals\textsuperscript{2,3}.

Universal testing of HCWs enabled the prompt identification of
asymptomatic and presymptomatic individuals, determined the
effectiveness of control measures, and helped prevent transmission to
patients and co-workers\textsuperscript{1,4,5}.

Furthermore, COVID-19 vaccines were developed to overcome the pandemic.

Following the implementation of COVID-19 vaccines, HCWs were among the
first prioritised for vaccination in many countries, including Poland.
Data from the placebo-controlled randomized phase 3 clinical trial of
the Pfizer-BioNTech BNT162b2 vaccine showed 95\% efficiency in
preventing symptomatic SARS-CoV-2 infection\textsuperscript{6}. Benefits
similar to those observed in clinical trials were also observed in
real-world conditions\textsuperscript{7}.

There is limited data on the incidence of SARS-CoV-2 infection among
HCWs beyond the second wave of the pandemic, and limited data on the
incidence of infection before and after the implementation of the
vaccination programme, especially for European
countries\textsuperscript{8}. So far, most studies performed in Poland
were voluntary seroprevalence studies in small cohorts of HCWs, so the
representativeness of the results obtained may be
limited\textsuperscript{9,10}.

Knowing the factors associated with SARS-CoV-2 infection in HCWs informs
preventive measures and improves the protection of HCWs and patients.

To further explore factors associated with SARS-CoV-2 infection, we
retrospectively analysed the large real-world testing database obtained
between October 20, 2020, and August 31, 2021, at The Children's
Memorial Health Institute (CMHI), a tertiary paediatric hospital in
Warsaw. In this setting, 2,332 HCWs participated in the universal
screening programme for early identification of the SARS-CoV-2
infection. The aim of the study was to analyse the incidence of new
SARS-CoV-2 infections among HCWs (before and after vaccination with
BNT162b2) and to explore the demographics and work-related factors
associated with SARS-CoV-2 infection. We also attempted to assess the
vaccine effectiveness in a real-world setting.

\textbf{METHODS:}

\textbf{Study design, setting, and participants}

This was a cohort, retrospective study with secondary data, conducted
with the Strengthening the Reporting of Observational Studies in
Epidemiology (STROBE) guidelines for reporting observational
studies\textsuperscript{11}, performed among HCWs at the CMHI in Warsaw
(see \textbf{Supplementary Material} ).

The CMHI is the largest tertiary paediatric hospital and research
institute in Poland, with nearly 600 beds and approximately 2,430 HCWs,
including employees and trainees. As previously
described\textsuperscript{12}, beginning on March 9, 2020, a set of
infection prevention and control measures were implemented at the CMHI
to contain the spread of SARS-CoV-2 within the hospital.

The SARS-CoV-2 RT-PCR testing for symptomatic personnel, coupled with
contact tracing, was implemented starting from March 17, 2020. In
addition, since October 20, 2020 (the beginning of the second wave of
the COVID-19 epidemic in Poland), a universal SARS-CoV-2 screening
programme was deployed at the CMHI for all HCWs using a RT-PCR assay of
nasopharyngeal swabs. Up to May 6, 2021 (corresponding to the end of the
third pandemic wave), there were seven rounds of screening which made it
possible to identify and isolate asymptomatic and presymptomatic HCWs.
The HCW vaccination programme with the Pfizer-BioNTech BNT162b2 vaccine
began on January 4, 2021, and up to February 28, 2021, approximately
80\% of HCWs received at least one dose of the vaccine. All HCWs
(clinical and non-clinical) who had at least one PCR test performed as
part of the universal screening were included in the study.

Demographic, occupational, epidemiological (if applicable), and
laboratory data were collected for each participant up to August 31,
2021. All data were analysed anonymously in April 2023. Details on the
data sources are provided in the \textbf{Supplementary Material} .

\textbf{Fig. 1} illustrates the study timeline. The study population and
definition of the follow-up period for the incidence of SARS-CoV-2
infection in HCWs before vaccination (study phase 1) and after
vaccination (study phase 2) are presented in \textbf{Table 1} .

\textbf{Statistical analysis:}

The main outcomes were the incidence of new SARS-CoV-2 infection in HCWs
before and after vaccination, and the vaccine effectiveness (VE) against
any SARS-CoV-2 infection. The outcomes were analysed for predefined
subgroups according to age, gender, profession, workplace, and
vaccination status. Data were presented as a median with interquartile
range (IQR) of continuous variables and proportions of dichotomous
variables. Univariable and multivariable logistic regression models were
used to assess factors associated with the primary outcomes of
SARS-CoV-2 infection. Details on statistical analysis including sample
size calculations are presented in the \textbf{Supplementary Material} .
Statistical analyses were performed using the Statistica data analysis
software system (TIBCO Software Inc.), version 13. Two-side tests with a
p-value of \textless{} 0.05 were considered statistically significant.

\textbf{Sensitivity analysis}

Sensitivity analysis was performed to examine the robustness of the
results. Complete case analysis was performed (i.e. after inclusion of
previously infected HCWs, those with missing vaccination status, or no
follow-up data) to cover more possible events and to investigate
influences of missing data on the study results (results of the
sensitivity analysis are presented in the \textbf{Supplementary
Material} ).

\textbf{RESULTS}

Of the 2,332 HCWs who participated in the universal screening programme,
1,967 (84.3\%) were female. The median age was 46.9 (IQR: 36.4--55.4)
years. Approximately one third (32\%) were nurses. One hundred and
eighty-four (7.9\%) HCWs worked in the COVID-19 area (\textbf{Table 2}
).

Beginning on March 17, 2020 (the first case of a SARS-CoV-2 infected HCW
identified at the CMHI) and up to October 19, 2020 (the start of
universal screening of HCWs), we identified 86 HCWs with SARS-CoV-2
infection from the 2,332 HCWs, which corresponds to a baseline
prevalence of 3.7\%.

In total, 11,797 samples from 2,332 HCWs were tested as part of the
universal screening programme between October 20, 2020, to May 6, 2021.
After excluding 199 (1.7\%) invalid test results, the median number of
tests per person was 6 (IQR: 3--7). In addition, 1,298 PCR test results
performed outside the screening and up to August 31, 2021, were
available for 934 (40.1\%) of the 2,332 HCWs (median 1 sample per
person, IQR: 1--2).

Overall, 457 (19.6\%) of the 2,332 HCWs had positive SARS-CoV-2 PCR test
results within the study period, including 452 new infections (19.4\%)
and 8 (0.2\%) reinfections. Almost half (45.1\%) of the infections were
asymptomatic and 48.6\% were identified during the universal screening
programme. Among 281 HCWs with laboratory confirmed SARS-CoV-2
infection, for whom data on the probable source of infection were
available, the most common source of infection was the community
(44.1\%), followed by the household (32.7\%), while the rate of
infection at the workplace was only 14.2\%.

\textbf{Fig. 2} shows the incidence of SARS-CoV-2 infection among HCWs
at the CMHI and in the general population in the Mazovian voivodeship
and \textbf{Fig. S1} reports the new weekly cases of SARS-CoV-2
infection among HCWs at the CMHI by testing mode. The weekly incidence
of new cases among HCWs at the CMHI fluctuated during the study period,
corresponding to the dynamic of SARS-CoV-2 transmission in the
community. In particular, most of the cases were identified between
epidemiological (epi) week 43 and 49, 2020, which encompassed the peak
of the second epidemic wave in Poland. The incidences among the HCWs
decreased during the first three months of the vaccination programme and
then increased again and peaked at epi week 13, 2021, which corresponded
to the peak of the third wave in Poland, caused by variant Alpha
(B.1.1.7; \textbf{Fig. S2} ). This later peak of incidence was
relatively lower among HCWs than in the community.

Study phase 1: incidence of new SARS-CoV-2 infection acquired before
vaccination rollout

After exclusion of 185 HCWs with previous SARS-CoV-2 infection (n = 86)
and those with the first PCR test performed after the implementation of
the vaccination programme (n = 99), the study phase 1 consisted of 2,147
HCWs (\textbf{Fig. 3;} Study flow chart). During the 18-week period, 357
nurses acquired SARS-CoV-2 infection, which corresponds to a cumulative
incidence of 16.6\%.

More than half of the infected HCWs were asymptomatic (51\%). The HCWs
who tested positive for SARS-CoV-2 were similar in age and gender. The
lowest percentage of SARS-CoV-2 infections was found among physicians
(10\%) and the highest among nurses (20\%; p \textless{} 0.001). There
was no significant difference in infection rates among HCWs working in
wards involved and not involved in the treatment of COVID-19 patients or
clinical and non-clinical areas, as well as across wards (\textbf{Table
3} ).

Each HCW had 4 PCR tests performed as a median (IQR: 3--5 tests), with a
higher number of tests performed for uninfected HCWs (p \textless{}
0.001).

Following adjustment for age, gender, and number of tests per person,
there remained significant differences in the incidence of new
SARS-CoV-2 infection across professional categories. Most notably, the
odds of being infected were greater for nurses and lesser for physicians
relative to the `other without patient contact' category (OR 1.80, 95\%
CI 1.29--2.52, p = 0.001 and OR 0.45, 95\% CI 0.30--0.68, p \textless{}
0.001, respectively; \textbf{Table S2} ).

Vaccine coverage among HCWs at study phase 2

One thousand nine hundred and sixty (84.0\%) HCWs of the 2,332 HCWs had
known vaccination status, among them 1,743 (88.9\%) HCWs had received at
least one dose of the BNT162b2 vaccine by the end of February, 2021
(1,717 received two doses with a median time of 20 days between dose 1
and 2). The characteristics of the HCWs by vaccination status are
presented in \textbf{Table S3} .

Unvaccinated HCWs were significantly younger than vaccinated (median
age: 45.9 vs 48.2 years; p = 0.002). Physicians were significantly more
likely to be vaccinated than other professional groups (p \textless{}
0.001). The HCWs in non-clinical areas were less vaccinated than those
working in clinical locations (85.7\% vs 90.2\%, p = 0.005). There were
differences in the vaccination status between the wards, with HCWs
working on the surgical wards being the most frequently vaccinated group
(92.6\%, p = 0.04). There were no significant differences in vaccination
status between HCWs working in wards involved and not involved in the
treatment of COVID-19 patients. The HCWs most likely to have received at
least one dose of the vaccine were previously uninfected with SARS-CoV-2
(p \textless{} 0.001). Before the implementation of the vaccination
programme, 352 HCWs (285 vaccinated and 67 unvaccinated) had laboratory
confirmed SARS-CoV-2 infection. Unvaccinated HCWs had a shorter time
period from previous infections when compared with vaccinated HCWs
(median 20 vs 61 days; p \textless{} 0.001).

Study phase 2: incidence of new SARS-CoV-2 infections after
implementation of the vaccination programme

The incidence of SARS-CoV-2 infections was determined for vaccinated
(partially and fully) and unvaccinated HCWs. HCWs with unknown
vaccination status, previous SARS-CoV-2 infection, and/or without
follow-up data were excluded from the incidence analysis
(\textbf{Fig.3;} study flowchart). After applying the exclusion
criteria, the incidence analysis included 1,461 HCWs with a median
follow-up of 79 (IQR: 70--86) days.

In total, 93 of 1,461 (6.4\%) HCWs tested positive for SARS-CoV-2 by the
end of August, 2021.

There was no significant difference between infected and uninfected HCWs
across demographic and occupational categories (\textbf{Table S5} ). The
cumulative incidence of SARS-CoV-2 infection was significantly higher
among unvaccinated HCWs than in vaccinated HCWs (40.0\% vs 3.2\%; p
\textless{} 0.001). When vaccination groups were considered, the
cumulative incidence of new SARS-CoV-2 cases was 12.2\% and 2.9\% in
partially and fully vaccinated HCWs, respectively (\textbf{Fig. 4} ).
The median interval from the first vaccine dose to SARS-CoV-2 infection
was 28 (IQR: 21--31, range: 18--73) days in partially vaccinated HCWs,
while in the fully vaccinated group, the median interval between the
second vaccine dose and infection was 62 (IQR: 49--76, range: 25--200)
days.

In a multivariate logistic regression model with confirmed SARS-CoV-2
cases as a response variable, vaccination status was the only
significant predictor for SARS-CoV-2 infection after adjusting for age,
gender, and number of PCR tests per HCWs (\textbf{Table S7} ).

Vaccine effectiveness in preventing any SARS-CoV-2 infection was 79\%
(95\% CI 46--92\%) and 95\% (95\% CI 91--97\%) in partially and fully
vaccinated HCWs, respectively.

Vaccine effectiveness (VE) by age group and professional categories is
presented in \textbf{Table 4} . VE for fully vaccinated HCWs did not
vary by age (age group \textless{} 50 years: adjusted VE (aVE) = 95\%,
95\% CI 90--97\%; 50+ years: aVE = 95\%, 95\% CI 87--98\%) and was
slightly lower for the other without direct patient contact category
(aVE = 89\%, 95\% CI 73--96\%) when compared with physicians (aVE =
96\%, 95\% CI 84--99\%) and nurses (aVE = 98\%, 95\% CI 92--99\%).

\textbf{DISCUSSION}

By using longitudinal data, our study provides robust data on the
incidence of new SARS-CoV-2 infection among HCWs in a paediatric
hospital during the pre- and post-vaccinations periods, encompassing the
second and third wave of the COVID-19 pandemic in Poland.

During the ten months of the study period, approximately one fifth
(19.4\%) of the HCWs susceptible to primary infection became infected
with SARS-CoV-2.

It is worth noting that almost half of the HCWs who had laboratory
confirmed SARS-CoV-2 infection in our study did not report symptoms,
suggesting that without the implementation of proactive universal
screening a significant proportion of infection among HCWs would have
remained undetected and that they would likely have continued working
while unaware of their status, therefore presenting a risk of
transmission to patients and co-workers. Although this study was not
designed to address the issue of nosocomial transmission reduction
through asymptomatic testing, we assume that the universal screening
programme of HCWs applied in our hospital (as part of a bundle of
intensified infection control measures) reduced the number of SARS-CoV-2
infections by early identification and isolation of SARS-CoV-2--positive
individuals. There are also some issues associated with massive
asymptomatic testing that must be underlined. First, it requires
additional operational and testing costs and a large laboratory capacity
to provide rapid turnaround for testing. Second, the results of the
PCR-based screening are valid only for the day of the test, which can
cause a false sense of confidence\textsuperscript{13}. Furthermore, the
resources required to identify a single asymptomatic case are
substantial and may not be cost-effective during a low prevalence
period\textsuperscript{14}. Thus, testing strategies should be
implemented after careful consideration of resources, infrastructure
capacity, and logistical issues\textsuperscript{15}. In addition, the
testing strategy must be guided by the local epidemiology, vaccination
coverage, and efficacy among HCWs and in the community.

In line with some other studies conducted after the first wave of the
pandemic, the changes in the incidence rate of SARS-CoV-2 infection
among HCWs in our cohort were closely followed by community infection
rates\textsuperscript{8,16,17}. Especially in the period before
vaccination (study phase 1), both the dynamic and the magnitude of new
SARS-CoV-2 infections were similar. On the other hand, after deployment
of the HCW vaccination programme, a reduction in the weekly incidence of
new cases among HCWs was observed. This downward trend initially was in
parallel with the incidence decline in the community but persisted up to
epi week 11, 2021, while in the general population a rapid increase in
SARS-CoV-2 incidence was observed attributed to the SARS-CoV-2 Alpha
variant domination (corresponding to the third pandemic wave). The
incidence rate among HCWs also increased afterwards, but the observed
peak was relatively lower. This finding is consistent with the
anticipated protective effect of the COVID-19 vaccine.

When considering the two phases of the present study, the cumulative
incidence of new SARS-CoV-2 infections decreased from 16.6\% before
vaccination to 6.3\% after the implementation of the vaccination
programme at the CMHI (study phase 2).

Due to the observational design of our study, we were unable to assess
the extent to which HCW vaccination contributed to the observed
reduction in the incidence of HCW SARS-CoV-2 infections. However, as the
uptake of vaccination among HCWs at the CMHI was high (88.9\%), we
hypothesise that this impact could be significant, especially when the
short-term effect is considered.

In addition, this hypothesis was supported by the high vaccine
effectiveness observed in our cohort. Our findings indicate that the
effectiveness of the vaccine was 95\% and 79\% in fully and partially
vaccinated HCWs, respectively. These results are comparable to previous
reports including those from clinical trials and other real-world
studies\textsuperscript{6,7,18}. In line with a previous study conducted
among HCWs, we did not observe significant differences in vaccine
effectiveness by age or occupational groups\textsuperscript{7,18},
although we observed slightly lower vaccine efficacy among HCWs in the
`other without direct patient contact' group. This finding could reflect
lower awareness, behaviour change, and a misbelief that vaccination
allows infection control measures to be relaxed.

However, despite high vaccine efficacy and high vaccination coverage, we
still observed new SARS-CoV-2 infections among HCWs at a rate from 2.9\%
in the fully vaccinated to 39.7\% in those unvaccinated.

These numbers are higher than those reported previously. In a systematic
review of eighteen studies, the pooled proportion of SARS-CoV-2
infection was 1.3\%, 2.3\%, and 10.1\% among fully vaccinated, partially
vaccinated, and unvaccinated HCWs, respectively\textsuperscript{19}.

Variability in demographic and occupational factors, as well as case
definitions, could explain this difference. Furthermore, the fact that
we excluded HCWs with a previous SARS-CoV-2 infection from our analysis
may have affected the higher infection rates observed in our cohort (the
absence of the protective effect of post-infection immunity).

Although rare, these infections might diminish HCWs' belief in
vaccination effectiveness, especially in those becoming infected with
SARS-CoV-2 after initial vaccination. It is worth noting that, at the
time of manuscript preparation, we faced a low rate (approximately 5\%)
of second booster dose uptake among HCWs at the CMHI. This led to
concerns when considering waning vaccine immunity over time and the
emergence of new variants of concern (VOC).

A systematic review by Biswas et al. revealed that vaccine acceptance
varied widely between countries and ranged from 4.3\% to
72\%\textsuperscript{20}. Individuals who were men, older, physicians,
or well educated had a lower hesitancy to receive the COVID-19 vaccine.
Other factors associated with higher vaccine acceptance were: higher
income, medical risk, chronic disease history, not being infected with
SARS-CoV-2 in the past, knowledge of COVID-19, and a belief that
vaccines may protect friends, family, and community
members\textsuperscript{20}. Although the present study was not designed
to assess the attitude to vaccination, these findings are consistent
with our study. We observed that older individuals, physicians, those
working in clinical settings, and those previously uninfected were more
likely to be vaccinated. These observations might inform tailored
communication strategies to be implemented to increase the uptake rate
of COVID-19 vaccines among HCWs.

Reliable data on risk factors, SARS-CoV-2 incidence, and the proportion
of HCWs who remain na\selectlanguage{ngerman}ïve (had no history of SARS-CoV-2 infection and/or
unvaccinated) are crucial to inform infection control strategies.
Previous studies reported widely varying estimates of incidence and risk
factors for infection among HCW\textsuperscript{21}, and only a few
studies assessed HCW infection and risk
longitudinally\textsuperscript{17}.

When considering potential risk factors of SARS-CoV-2 infection among
HCWs in our study, we did not find a significant difference in the
infection rates among HCWs working in wards involved and not involved in
the treatment of COVID-19 patients, clinical or non-clinical areas, or
across different wards and these findings applied to both phases of the
study. Our findings are in contrast to some previous studies, especially
those studies performed during the early pandemic
stage\textsuperscript{22}, which reported higher infection rates among
HCWs working in COVID-19 wards with direct patient contact, but our
findings are in line with the emerging literature pointing out that,
except for breaches in PPE, the main risks to HCWs come from outside of
work factors (in the community and
household)\textsuperscript{17,23--26}. In our cohort, before
implementation of the vaccination programme (study phase 1), nurses had
the highest adjusted likelihood of being infected, while physicians had
a lower likelihood. Surprisingly, in the post-vaccination study period,
we did not find any association between risk of SARS-CoV-2 infection and
professional category. The only factor significantly associated with
SARS-CoV-2 infection in the multivariate analysis was vaccination
status. The increased risk of SARS-CoV-2 infection for nurses was
previously reported in many observational
studies\textsuperscript{27--29}. The higher risk among nursing staff has
been consistently explained by their more frequent contact with and
longer contact times with COVID-19 patients when compared with
physicians\textsuperscript{28,30,31}. However, in our study we did not
observe an increase in the number of cases on the wards involved in the
treatment of patients with COVID-19. Furthermore, only a small
percentage of HCWs (with available data on the possible source of
exposure) reported exposure at work, and even fewer had high-risk
contact with a COVID-19 patient. A recent case-control study from
Ireland, investigating the impact of demographic and work-related
factors on the risk of SARS-CoV-2 infection after in-work exposure to a
confirmed case of COVID-19, revealed that male sex, Eastern European
nationality, exposure location, PPE use, and vaccination status all
impact the likelihood of SARS-CoV-2 infection throughout the first,
second, and third pandemic waves\textsuperscript{32}. In this study, no
individual job role was determined to have a consistently higher risk of
infection after documented nosocomial exposure. It is likely that the
increased risk of SARS-CoV-2 infection among nurses observed in our and
other studies may be an indication of the cumulative risk of certain
nursing staff roles, which have an increased intensity of contact with
patients and other HCWs over time, and this increases the probability of
infection. In addition, nurses make up a significant proportion of the
total hospital staff (approximately one-third in our cohort), thus
resulting in over-representation, which may influence the interpretation
of risk\textsuperscript{32}.

Together, these observations highlight the need for awareness of
non-patient care exposure risk that contributes to infection in HCWs and
should be considered in infection control measures (i.e. universal
masking, reinforcement of hand hygiene, and distancing).

The limitations of our data should be borne in mind. First, the
retrospective and observational design of the study is subject to
missing and incomplete data and thus to unmeasured confounding bias.
Second, although our study cohort was stratified by different
occupational categories, there may still be different exposure risks
within the categories. Third, we were unable to adjust our analysis for
other potential confounders that may affect the risk of infection (such
as comorbidities, contact time with COVID-19 cases, movement of HCWs
between high- and low-risk wards, compliance with PPE, household size)
due to data limitations, and therefore the results may not generalise to
other settings with different characteristics. Fourth, the clinical data
regarding symptoms for each HCW were retrieved from an unstandardized
database generated by the ICP team for epidemiological purposes and were
not consistently available. In addition, we relied on self-reported
symptoms and community/household exposures. Exposures in the workplace
were revealed through epidemiological investigations, including contact
tracing, but are still subject to recall bias. Data on exposure was
missing for almost 40\% of the HCWs, therefore it was unknown whether
SARS-CoV-2 PCR positive cases resulted from infections in the workplace
or were acquired in the community or household. On the other hand, the
exact source and direction of infection may only be inferred from
epidemiological data combined with viral genomic data, otherwise
assessing the source is often subjective. Fifth, the lack of detailed
information on SARS-CoV-2 exposure and the use of PPE, prevented us from
analysing the association of adherence to PPE over time and across
different occupational categories with the risk of infection. Six, we
attempted to include only new cases of SARS-CoV-2 infection, excluding
HCWs with records of a positive test by PCR or anti-nucleocapsid IgG.
However, as systematic testing by PCR was not performed before the study
period and not all HCWs had participated in a previous serology
screening programme, we cannot rule out that we included some previous
positive cases in our incidence analysis. Seventh, testing in study
phase 2 was less dense as the universal screening programme ended on May
6, 2021, thus HCWs with asymptomatic SARS-CoV-2 infection might be
underrepresented. Eight, although our estimated vaccine effectiveness
aligns with the results provided in other reports, this estimate is
based on a relatively short follow-up period. Finally, our study took
place prior to the emergence of the Delta variant of SARS-CoV-2, thus it
might not be generalizable to an epidemic situation with a domination of
another VOC (variant of concern), however, the evidence from the early
period of the pandemic may inform the infection control policy in a
vulnerable population with regard to other respiratory viruses.

To our knowledge, this is the only study of the SARS-CoV-2 infection
among HCWs in Poland and one of the few studies based on robust data
obtained mainly from proactive universal screening PCR testing. The size
and diversity of the cohort (all HCWs, including nurses, physicians, and
other personnel providing direct and indirect patient care, as well as
non-clinical staff) together with longitudinal data collected in the
period before and after vaccination implementation in HCWs, meant that
it was possible to examine risk factors of the new SARS-CoV-2 infection
by demographic, occupational, and vaccination status (which was
determined based on vaccination records instead of self-reporting, to
mitigate recall bias).

In summary, our analysis provides information on the incidence of
SARS-CoV-2 infection in the pre- and post-vaccination periods. We found
that after the implementation of vaccination, the risk of infection
among HCWs remained relatively high despite the high coverage of
vaccination and the high effectiveness of the vaccine. Although rare,
breakthrough infections are challenging, as they may pose a risk to the
vulnerable population. Furthermore, there are concerns about the
decrease in vaccine effectiveness over time and during the emergence of
new VOCs.

Thus, continued efforts to promote infection control measures and
vaccination (including booster vaccine doses) and distancing remain
necessary during the ongoing COVID-19 pandemic.

\textbf{CONFLICT OF INTEREST}

The authors declare no conflict of interest.

\textbf{FUNDING}

No funds, grants, or other support was received.

\textbf{AUTHOR CONTRIBUTIONS}

KB, MM, and DFK were involved in study concept and design. KB, SK, and
BJ were involved in acquisition of data and performing RT-PCR SARS-CoV-2
testing. KB was involved in statistical analysis and interpretation of
results. BK, SK, and BJ drafted the manuscript. MM and DFK were involved
in data curation and supervision of the study. All authors were involved
in the critical revision of the manuscript for important intellectual
content and final approval of the manuscript.

\textbf{ETHICAL STATEMENT}

The study was reviewed and approved by the Institutional Review Board of
The Children's Memorial Health Institute in Warsaw (Ref. no. 42/KBE/2020
with later revision on March 31, 2021), and granted a waiver of consent
since the data were retrospective and were deidentified prior to review
and statistical analysis. Data were accessed between April 2021 and
September 2022.

\textbf{DATA AVAILABILITY STATEMENT}

The data that support the findings of this study are available from the
corresponding author upon reasonable request.

\textbf{ORCID ID:}

Kasztelewicz Beata: https://orcid.org/0000-0003-1504-5589

Skrok Katarzyna: https://orcid.org/0009-0007-6701-7105

Julia Burzy\selectlanguage{polish}ń\selectlanguage{english}ska https://orcid.org/0000-0003-2654-5984

Migda\selectlanguage{polish}ł \selectlanguage{english}Marek https://orcid.org/0000-0001-6686-5988

Dzier\selectlanguage{polish}ż\selectlanguage{english}anowska-Fangrat Katarzyna https://orcid.org/0000-0003-4684-0630

\textbf{SUPPLEMENTAL MATERIAL}

Supplementary materials are available at the Journal of Medical Virology
online.

\textbf{References:}

1. Bielicki, J. A. \emph{et al.} Monitoring approaches for health-care
workers during the COVID-19 pandemic. \emph{The Lancet Infectious
Diseases} vol. 20 (2020).

2. Abbas, M. \emph{et al.} Nosocomial transmission and outbreaks of
coronavirus disease 2019: the need to protect both patients and
healthcare workers. \emph{Antimicrobial Resistance and Infection
Control} vol. 10 (2021).

3. Gandhi, M., Yokoe, D. S. \& Havlir, D. V. Asymptomatic Transmission,
the Achilles' Heel of Current Strategies to Control Covid-19. \emph{N.
Engl. J. Med.} \textbf{382} , (2020).

4. Rivett, L. \emph{et al.} Screening of healthcare workers for
SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19
transmission. \emph{Elife} \textbf{9} , (2020).

5. Jabs, J. M. \emph{et al.} The role of routine SARS-CoV-2 screening of
healthcare-workers in acute care hospitals in 2020: a systematic review
and meta-analysis. \emph{BMC Infect. Dis.} \textbf{22} , (2022).

6. Polack, F. P. \emph{et al.} Safety and Efficacy of the BNT162b2 mRNA
Covid-19 Vaccine. \emph{N. Engl. J. Med.} \textbf{383} , (2020).

7. Thompson, M. G. \emph{et al.} Prevention and Attenuation of Covid-19
with the BNT162b2 and mRNA-1273 Vaccines. \emph{N. Engl. J.
Med.}\textbf{385} , (2021).

8. Larese Filon, F., Rui, F., Ronchese, F., De Michieli, P. \& Negro, C.
Incidence of COVID-19 infection in hospital workers from March 1, 2020
to May 31, 2021 routinely tested, before and after vaccination with
BNT162B2. \emph{Sci. Rep.} \textbf{12} , (2022).

9. Rosi\selectlanguage{polish}ń\selectlanguage{english}ska, M. \emph{et al.} HEALTHCARE WORKERS HIGHLY AFFECTED DURING
THE COVID-19 EPIDEMIC WAVE IN POLAND PRIOR TO VACCINATION AVAILABILITY:
SEROPREVALENCE STUDY. \emph{Med. Pr.} \textbf{73} , (2022).

10. Owsianka, I. \emph{et al.} SARS-CoV-2 antibody response after mRNA
vaccination in healthcare workers with and without previous COVID-19, a
follow-up study from a university hospital in Poland during 6 months
2021. \emph{Front. Immunol.} \textbf{13} , 7898 (2023).

11. von Elm, E. \emph{et al.} The strengthening the reporting of
observational studies in epidemiology (STROBE) statement: Guidelines for
reporting observational studies. \emph{Int. J. Surg.} \textbf{12} ,
(2014).

12. Kasztelewicz Id, B. \emph{et al.} Prevalence of IgG antibodies
against SARS-CoV-2 among healthcare workers in a tertiary pediatric
hospital in Poland. \emph{PLoS One} \textbf{16} , e0249550 (2021).

13. Oster, Y. \emph{et al.} Proactive screening approach for SARS-CoV-2
among healthcare workers. \emph{Clinical Microbiology and Infection}vol.
27 (2021).

14. Azamgarhi, T., Maynard-Smith, L., Bysouth, H. \& Warren, S.
Coronavirus disease 2019 (COVID-19) polymerase chain reaction (PCR)
screening of asymptomatic healthcare workers in a low-prevalence
setting: A single-center UK cohort study. \emph{Antimicrob. Steward.
Healthc. Epidemiol.} \textbf{2} , (2022).

15. Carrara, E. \emph{et al.} ESCMID guidelines on testing for
SARS-CoV-2 in asymptomatic individuals to prevent transmission in the
health care setting. \emph{Clinical Microbiology and Infection} vol. 28
(2022).

16. Wack, M. \emph{et al.} No SARS-CoV-2 reinfection among staff
health-care workers: Prospective hospital-wide screening during the
first and second waves in Paris. \emph{J. Clin. Virol.} \textbf{145} ,
104999 (2021).

17. Doernberg, S. B. \emph{et al.} Incidence and Prevalence of
Coronavirus Disease 2019 Within a Healthcare Worker Cohort During the
First Year of the Severe Acute Respiratory Syndrome Coronavirus 2
Pandemic. \emph{Clin. Infect. Dis.} \textbf{75} , 1573--1584 (2022).

18. El Adam, S. \emph{et al.} SARS-CoV-2 mRNA Vaccine Effectiveness in
Health Care Workers by Dosing Interval and Time Since Vaccination:
Test-Negative Design, British Columbia, Canada. \emph{Open Forum Infect.
Dis.} \textbf{9} , (2022).

19. Chandan, S. \emph{et al.} Postvaccination SARS-CoV-2 infection among
healthcare workers: A systematic review and meta-analysis. \emph{J. Med.
Virol.} \textbf{94} , (2022).

20. Biswas, N., Mustapha, T., Khubchandani, J. \& Price, J. H. The
Nature and Extent of COVID-19 Vaccination Hesitancy in Healthcare
Workers. \emph{J. Community Health} \textbf{46} , 1244--1251 (2021).

21. Hausfater, P. \emph{et al.} Cumulative incidence of SARS-CoV-2
infection and associated risk factors among frontline health care
workers in Paris: the SEROCOV cohort study. \emph{Sci. Rep.}\textbf{12}
, (2022).

22. Galanis, P., Vraka, I., Fragkou, D., Bilali, A. \& Kaitelidou, D.
Seroprevalence of SARS-CoV-2 antibodies and associated factors in
healthcare workers: a systematic review and meta-analysis. \emph{J.
Hosp. Infect.} \textbf{108} , 120--134 (2021).

23. Fell, A. \emph{et al.} SARS-CoV-2 Exposure and Infection Among
Health Care Personnel - Minnesota, March 6-July 11, 2020. \emph{MMWR.
Morb. Mortal. Wkly. Rep.} \textbf{69} , 1605--1610 (2020).

24. Lentz, R. J. \emph{et al.} Assessing coronavirus disease 2019
(COVID-19) transmission to healthcare personnel: The global ACT-HCP
case-control study. \emph{Infect. Control Hosp. Epidemiol.} \textbf{42}
, 1 (2021).

25. Elgersma, I. H., Telle, K., Elstr\selectlanguage{ngerman}øm, P., Skagseth, H. \& Kacelnik,
O. Transmission of severe acute respiratory coronavirus virus 2
(SARS-CoV-2) between hospital workers and members of their household:
Nationwide, registry-based, cohort study from Norway. \emph{Infect.
Control Hosp. Epidemiol.} (2022) doi:10.1017/ICE.2022.108.

26. Ganz-Lord, F. A., Segal, K. R., Gendlina, I., Rinke, M. L. \&
Weston, G. SARS-CoV-2 exposures among healthcare workers in New York
City. \emph{Occup. Med. (Chic. Ill).} \textbf{72} , (2022).

27. Hanrath, A. T. \emph{et al.} SARS-CoV-2 Testing of 11,884 Healthcare
Workers at an Acute NHS Hospital Trust in England: A Retrospective
Analysis. \emph{Front. Med.} \textbf{8} , 239 (2021).

28. Barrett, E. S. \emph{et al.} Risk Factors for Severe Acute
Respiratory Syndrome Coronavirus 2 Infection in Hospital Workers:
Results From a Screening Study in New Jersey, United States in Spring
2020. \emph{Open Forum Infect. Dis.} \textbf{7} , (2020).

29. Zheng, C. \emph{et al.} Characteristics and transmission dynamics of
COVID-19 in healthcare workers at a London teaching hospital. \emph{J.
Hosp. Infect.} \textbf{106} , 325--329 (2020).

30. Poletti, P. \emph{et al.} Seroprevalence of and Risk Factors
Associated With SARS-CoV-2 Infection in Health Care Workers During the
Early COVID-19 Pandemic in Italy. \emph{JAMA Netw. Open} \textbf{4} ,
e2115699 (2021).

31. Bahrs, C. \emph{et al.} Non-patient-related SARS-CoV-2 exposure from
colleagues and household members poses the highest infection risk for
hospital employees in a German university hospital: follow-up of the
prospective Co-HCW seroprevalence study. \emph{Infection} (2023)
doi:10.1007/S15010-023-01995-Z.

32. McGrath, J. \emph{et al.} Risk factors for SARS-CoV-2 infection in
healthcare workers following an identified nosocomial COVID-19 exposure
during waves 1-3 of the pandemic in Ireland. \emph{Epidemiol.
Infect.}\textbf{150} , (2022).

\textbf{SUPPORTING INFORMATION:}

Additional supporting information may be found in the online version of
the article at the publisher's website.

\textbf{Hosted file}

\verb`Figures_art_06.07.23.docx`  available at \url{https://authorea.com/users/636646/articles/653426-incidence-of-sars-cov-2-infection-among-healthcare-workers-before-and-after-covid-19-vaccination-in-a-tertiary-paediatric-hospital-in-warsaw-a-retrospective-cohort-study}

\textbf{Hosted file}

\verb`Tables_06.07.23.docx`  available at \url{https://authorea.com/users/636646/articles/653426-incidence-of-sars-cov-2-infection-among-healthcare-workers-before-and-after-covid-19-vaccination-in-a-tertiary-paediatric-hospital-in-warsaw-a-retrospective-cohort-study}

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

