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COVID-19 in health-care workers in three hospitals in the south of the Netherlands: a cross-sectional study

Authors:
  • Microvida

Abstract and Figures

Background 10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of infection in health-care workers. Methods We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms (fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through structured interviews with health-care workers and combined this information with data from whole-genome sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients. Findings Between March 2 and March 12, 2020, 1796 (15%) of 12 022 health-care workers were screened, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals through community-acquired infections and local amplification in the community. Interpretation Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread nosocomial transmission as the source of infection in patients or health-care workers. Funding EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
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www.thelancet.com/infection Published online July 2, 2020 https://doi.org/10.1016/S1473-3099(20)30527-2
1
Articles
Lancet Infect Dis 2020
Published Online
July 2, 2020
https://doi.org/10.1016/
S1473-3099(20)30527-2
*Contributed equally
Viroscience, Erasmus MC,
Rotterdam, Netherlands
(R S Sikkema DVM,
D F Nieuwenhuijse MSc,
A van der Linden BSc,
I Chestakova MSc,
C Schapendonk BSc,
M Pronk BSc, P Lexmond BSc,
T Bestebroer BSc,
R J Overmars MSc,
S van Nieuwkoop BSc,
A van der Eijk MD,
R Molenkamp PhD,
B B Oude Munnink PhD,
M P G Koopmans PhD); Julius
Center for Health Sciences and
Primary Care, University
Medical Center Utrecht,
Utrecht, Netherlands
(J A J W Kluytmans MD,
M F Q Kluytmans van den Bergh MD);
Microvida Laboratory for
Microbiology, Bravis Hospital,
Roosendaal, Netherlands
(S D Pas PhD, B M Diederen MD,
A M C Bergmans PhD);
University of Edinburgh,
Edinburgh, UK (Á O’Toole MSc,
A Rambaut PhD); Laboratory for
Medical Microbiology and
Immunology (J Verweij PhD,
A G M Buiting MD), and
Department of Infection
Control (A G M Buiting,
A J G van Oudheusden MSc),
Elisabeth-TweeSteden
Hospital, Tilburg, Netherlands;
Microvida Laboratory for
Microbiology (S D Pas,
W van den Bijllaardt MD,
R G Bentvelsen MD,
M M L van Rijen PhD,
J A J W Kluytmans,
M F Q Kluytmans van den Bergh),
and Department of Infection
Control (J A J W Kluytmans,
M F Q Kluytmans van den Bergh),
Amphia Hospital, Breda,
Netherlands; Department of
Medical Microbiology, Leiden
COVID-19 in health-care workers in three hospitals in the
south of the Netherlands: a cross-sectional study
Reina S Sikkema*, Suzan D Pas*, David F Nieuwenhuijse, Áine O’Toole, Jaco Verweij, Anne van der Linden, Irina Chestakova, Claudia Schapendonk,
Mark Pronk, Pascal Lexmond, Theo Bestebroer, Ronald J Overmars, Stefan van Nieuwkoop, Wouter van den Bijllaardt, Robbert G Bentvelsen,
Miranda M L van Rijen, Anton G M Buiting, Anne J G van Oudheusden, Bram M Diederen, Anneke M C Bergmans, Annemiek van der Eijk,
Richard Molenkamp, Andrew Rambaut, Aura Timen, Jan A J W Kluytmans, Bas B Oude Munnink, Marjolein F Q Kluytmans van den Bergh*,
Marion P G Koopmans*
Summary
Background 10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the
south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of
infection in health-care workers.
Methods We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We
screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms
(fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through
structured interviews with health-care workers and combined this information with data from whole-genome
sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth
analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients.
Findings Between March 2 and March 12, 2020, 1796 (15%) of 12 022 health-care workers were screened, of whom
96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-
care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local
circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals
through community-acquired infections and local amplification in the community.
Interpretation Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread
nosocomial transmission as the source of infection in patients or health-care workers.
Funding EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the
National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND
4.0 license.
Introduction
In January, 2020, a cluster of patients with pneumonia
of unknown cause was reported in Wuhan, China;1
the disease was subsequently named COVID-19, caused
by severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2). The clinical spectrum of COVID-19 varies
from asymptomatic or mild symp tomatic infections to
severe respiratory symptoms and death, with older age
groups generally presenting with more severe disease and
higher death rates.2,3 Since its identification, SARS-CoV-2
has rapidly spread across the globe. On June 22, 2020,
177 countries had reported cases of COVID-19, adding up
to more than 8·9 million reported cases and 468 000 deaths
worldwide.4
Health-care workers are at increased risk of being
exposed to SARS-CoV-2 and could potentially have a
role in hospital transmission. Nosocomial outbreaks of
severe acute respiratory syndrome coronavirus and Middle
East respiratory syndrome coronavirus (MERS-CoV) are
thought to have played a crucial part in the amplifi cation
and spread of these viruses. For MERS-CoV, hospital
outbreaks caused approximately 50% of confirmed cases,
of which around 40% were in health-care workers.5
Currently, the extent of SARS-CoV-2 transmission and risk
factors associated with infection in health-care settings
are unclear. During the WHO–China Joint Mission on
COVID-19,3 2055 laboratory confirmed cases were reported
in health-care workers from 476 hospitals in China, mostly
(88%) from Hubei province. Most health-care workers were
thought to have been infected within household settings
rather than in a health-care setting, although conclusive
evidence was scant.3
On Feb 27, 2020, the first patient in the Netherlands
tested positive for SARS-CoV-2 RNA after returning from
a holiday to Lombardy, Italy.6 In the following week, the
number of infections in the country grew to 128, with an
increasing proportion of cases without a known source of
infection. These cases included nine health-care workers
Articles
2
www.thelancet.com/infection Published online July 2, 2020 https://doi.org/10.1016/S1473-3099(20)30527-2
University Medical Center,
Leiden, Netherlands
(R G Bentvelsen); Landelijke
Coördinatie
Infectieziektebestrijding,
Rijksinstituut voor
Volksgezondheid en Milieu,
Bilthoven, Netherlands
(A Timen MD); and VU
University Amsterdam,
Amsterdam, Netherlands
(A Timen)
Correspondence to:
Dr Reina S Sikkema, Viroscience,
Erasmus MC, 3015 CA Rotterdam,
Netherlands
r.sikkema@erasmusmc.nl
from two hospitals in the province of North Brabant, in
the south of the Netherlands.7,8 The Dutch national
outbreak manage ment team advised to extend screening
of health-care workers to other hospitals in North
Brabant, to assess possible community transmission.
From March 6 to March 8, 2020, 1097 employees of nine
hospitals were tested, of whom 45 (4%) were positive for
SARS-CoV-2.8 A follow-up study was done at three
hospitals to assess the clinical presentations of COVID-19
of these health-care workers.7 The impending shortage of
personal protective equipment (PPE) and the proposed
changes in its use in later phases of the outbreak
response also triggered a debate on possible risks to
health-care workers.9
To understand sources and modes of transmission of
SARS-CoV-2 in health-care workers and patients in the
same hospitals, we did an in-depth analysis combining
epidemiological data with whole-genome sequencing
(WGS) of SARS-CoV-2 from clinical samples obtained
from health-care workers and patients in three dierent
hospitals
Methods
Study design and participants
We did a cross-sectional study at two teaching hospitals
(Amphia Hospital, Breda, Netherlands [700 beds], and
Elisabeth-TweeSteden Hospital, Tilburg, Netherlands
[800 beds]) and one regional hospital (Bravis Hospital,
Roosendaal and Bergen op Zoom, Netherlands [600 beds]),
at which 12 022 health-care workers in total were employed.
PPE was used according to national guidelines that applied
during this period of the outbreak.10,11 Patients with
suspected COVID-19 were nursed under strict isolation
precautions and health-care workers applied additional
PPE (gowns, gloves, goggles, hair cover, and type IIR
surgical masks) on entering the isolation room. When
aerosol-generating procedures were done, an FFP2 mask
was used.
All health-care workers at these three hospitals who had
fever or mild respiratory symptoms in the 10 days before
screening for SARS-CoV-2 infection were eligible for
testing, which was voluntary. All patients testing positive
for SARS-CoV-2 and who had been admitted 2 days or
more before the last date of onset of symptoms of health-
care workers per hospital were included. All health-care
workers with confirmed SARS-CoV-2 infection underwent
a structured interview to obtain epidemiological data and
to record any history of foreign travel and attendance at
public events with more than 50 people, such as the yearly
carnival in February, 2020 (appendix 1 p 1).
Ethics approval was obtained from the Medical Ethics
Committee Brabant, with a waiver of written informed
consent (METC Brabant/20.134/NW2020-26). Verbal
informed consent was obtained from all health-care
workers for SARS-CoV-2 testing, sequencing, and data
collection. Data were deidentified before analysis. For
patients, location and sequence data were obtained as
part of the routine infection control policy in outbreak
situations. All patients are notified of this policy on
hospital admission and can actively dissent (opt out).
Procedures
We tested for SARS-CoV-2 infection using oropharyngeal
or naso pharyn geal swabs in universal transport medium
Research in context
Evidence before this study
We searched Google Scholar on April 27, 2020, for articles
published since 2020, with the keywords “SARS-CoV-2” AND
“healthcare workers” AND “whole genome sequencing”.
We did not restrict our search to a publication language.
Our search retrieved 13 results. Two reports presented original
research of severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2); no reports were of the role of health-care
workers in SARS-CoV-2 transmission or used whole-genome
sequencing (WGS). Hospital transmission had an important
role in previous outbreaks of Middle East respiratory
syndrome and severe acute respiratory syndrome. The scarcity
of personal protective equipment led to changes in policy
during the initial phases of the SARS-CoV-2 outbreak
response, also triggering a debate on possible risks to
health-care workers. Up to now, possible SARS-CoV-2
outbreaks in health-care facilities have only been described
using traditional molecular diagnostic tools combined with
epidemiological data. However, previous studies
implementing WGS have shown that hypotheses on virus
transmission routes can be incorrect based solely on these
data. Moreover, screening of health-care workers can be used
to assess the level of local community transmission, but this
can only be done if patient-to-health-care worker
transmission can be reliably excluded.
Added value of this study
Our study aimed to gain insight in possible sources of infection
of health-care workers at three hospitals in the Netherlands.
All health-care workers with respiratory symptoms or fever in
the previous 10 days were screened for SARS-CoV-2 infection.
WGS was done of samples obtained from health-care workers
and patients at these hospitals and this information was
combined with epidemiological data.
Implications of all the available evidence
At the beginning of the SARS-CoV-2 outbreak in the
Netherlands, health-care workers were probably infected in the
community rather than at the hospitals. Possible nosocomial
outbreaks should be carefully investigated using both
epidemiological data and WGS to exclude or confirm
transmission in health-care facilities.
See Online for appendix 1
Articles
www.thelancet.com/infection Published online July 2, 2020 https://doi.org/10.1016/S1473-3099(20)30527-2
3
(Copan, Brescia, Italy) or E-swab medium (Amies;
Copan), following local infection control policy during
outbreaks. At Amphia Hospital and Bravis Hospital, total
nucleic acids were extracted for RT-PCR after an external
lysis step (1:1 with lysis binding buer; Roche Diagnostics,
Almere, Netherlands), using MagnaPure96 (Roche) with
an input volume of 500 µL and output volume of 100 µL.
The extraction was internally controlled by addition of a
known concentration of phocine distemper virus (PDV).12
Subsequently, 10 μL extracted nucleic acids was amplified
in three singleplex reactions in 25 μL final volume, using
TaqMan Fast Virus 1-Step Master Mix (Thermofisher,
Nieuwerkerk aan den IJssel, Netherlands), and 1 μL of
primers and probe mixture for envelope (E) gene, RNA-
dependent RNA-polymerase gene, and PDV.13 Amplifi-
cation was done in a 7500SDS (Thermofisher) with a
cycling profile of 5 min at 50°C, 20 s at 95°C, 45 cycles of
3 s at 95°C, and 30 s at 58°C. At Elisabeth-TweeSteden
Hospital, total nucleic acids were extracted, with a known
concentration of PDV as internal control, using the
QIAsymphony DSP virus pathogen midi kit and patho-
gen complex 400 protocol of the QIAsymphony Sample
Processing system (Qiagen, Hilden, Germany), with an
input volume of 400 µL and output volume of 110 µL. The
amplification reaction was done in a volume of 25 µL
with TaqMan Fast Virus 1-Step Master Mix (Thermofisher)
and 10 µL extracted nucleic acids. A duplex PCR for
E gene and PDV13,14 with optimised primer and probe
con cen trations were done. Amplifi cation with Rotorgene
(QIAgen) consisted of 5 min at 50°C and 15 min at 95°C
followed by 45 cycles of 15 s at 95°C, 30 s at 60°C, and 15 s
at 72°C. Validations of RT-PCR procedures were done
according to Interna tional Standards Organization
guidelines (15189).15
For WGS, samples were selected based on a cycle
threshold value less than 32. A SARS-CoV-2-specific
multiplex PCR for nanopore sequencing was done, as
previously described.16 The resulting raw sequence data
were demultiplexed using qcat. Primers were trimmed
using cutadapt,17 after which a reference-based align-
ment to the GISAID (Global Initiative on Sharing All
Influenza Data) sequence EPI_ISL_412973 was done using
minimap2.18 The consensus genome was extracted and
positions with a coverage less than 30 reads were replaced
with N using a custom script using biopython software
(version 1.74) and the python module pysam (version 0.15.3),
as previously described.19 Mutations in the genome were
confirmed by manually checking the alignment, and
homopolymeric regions were manually checked and
resolved, consulting the reference genome. Genomes were
included when having greater than 90% genome coverage.
All available full-length SARS-CoV-2 genomes were
retrieved from GISAID20 on March 20, 2020 (appendix 1
pp 8–65), and aligned with the newly obtained SARS-CoV-2
sequences in this study using the multiple sequence
alignment software MUSCLE (version 3.8.1551).21 Sequences
with more than 10% of N position replace ments were
excluded. The alignment was manually checked for discre-
pancies, after which the phylogenomic software IQ-TREE
(version 1.6.8)22 was used to do a maximum-likelihood
phylogenetic analysis, with the generalised time reversible
substitution model GTR+F+I+G4 as best pre dicted model.
The ultrafast bootstrap option was used with 1000 replicates.
Clusters were ascertained based on visual clustering and
lineage designations.23
The code to generate the minimum spanning phylo-
genetic tree was written in the R pro gramming language.
Ape24 and igraph software packages were used to write the
code to generate the minimum spanning tree, and
the visNetwork software package was used to generate
the visualisation. Pairwise sequence distance (used to
generate the network) was calculated by adding up the
absolute nucleotide distance and indel-block distance.
Unambiguous positions were dealt with in a pairwise
manner. Sequences that were mistakenly identified
as identical, because of transient connections with
sequences containing missing data, were resolved.
The multiple sequence alignment was curated and any
error-rich sequences or sequences without a date were
removed. The alignment was manually inspected and
trimmed of the 5 and 3 untranslated regions in the
bioinformatics software Geneious (version 11.1.3) to
include only coding regions. The final length of the
alignment was 29 408 nucleotides. Bayesian phylogenetic
trees were estimated using BEAST version 1.10.4,25 with a
Hasegawa-Kishino-Yano nucleotide substitution model26
and a strict molecular clock. Two independent chains
were run for 100 million states, with a Skygrid coalescent
prior (appendix 1 p 3).27,28 and parameters were sampled
every 10 000 states. The LogCombiner program was used
to combine the independent chains and to remove the
burn-in from the tree file, and Tracer29 was used to assess
convergence. The maximum clade credibility tree was
inferred using the TreeAnnotator program and visualised
using baltic code and custom python scripts.
Statistical analysis
Epidemiological data obtained at structured interviews
were entered in Castor Electronic Data Capture,
version 2019. Continuous variables were expressed as
medians and ranges and categorical variables were
summarised as numbers and percentages. All analyses
were done with SPSS version 25.0 (IBM, Armonk, NY,
USA). Because of the descriptive nature of our study,
sample size calculations and analyses of significance
were not done. Results were reported following STROBE
guidelines for observational studies.
Role of the funding source
The funder had no role in study design, data collection,
data analysis, data interpretation, or writing of the report.
The corresponding author had full access to all data in
the study and had final responsibility for the decision to
submit for publication.
For more on LogCombiner see
https://beast.community/
logcombiner
For more on R see
https://r-project.org
For more on igraph see
https://igraph.org/
For more on visNetwork see
https://github.com/datastorm-
open/visNetwork
For more on Geneious see
https://geneious.com
For more on TreeAnnotator see
https://beast.community/
treeannotator
For more on baltic see https://
github.com/evogytis/baltic
For more on qcat see https://
github.com/nanoporetech/qcat
For more on GISAID see
https://www.gisaid.org/
For Castor Electronic Data
Capture see https://castoredc.
com
For more on biopython see
https://biopython.org/
For more on pysam see https://
pypi.org/project/pysam/
Articles
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Results
Between March 2 and March 12, 2020, 1796 (15%) of
12 022 health-care workers were voluntarily screened at the
three participating hos pitals (appendix 1 p 5). At Amphia
Hospital, 42 (5%) of 783 health-care workers tested positive
for SARS-CoV-2 RNA; at Bravis Hospital, ten (2%) of
443 health-care workers tested positive; and at Elisabeth-
TweeSteden Hospital, 44 (8%) of 570 health-care workers
tested positive. Characteristics of these 96 health-care
workers who tested positive for SARS-CoV-2 RNA are
shown in the table. The health-care workers were employed
in 58 dierent departments, including on 42 medical
wards. The median age of aected health-care workers was
49 years (range 22–66), and 80 (83%) of 96 were female,
reflecting the proportion of female health-care workers
among the total population employed in the participating
hospitals (ie, 9784 of 12 022 [81%]). 20 sta members who
did not have direct contact with patients tested positive for
SARS-CoV-2 RNA, of whom six (30%) reported contact
with colleagues who had also tested positive. Ten health-
care workers reported a history of foreign travel in the
14 days before onset of symptoms, three (30%) of whom
had travelled to northern Italy. 60 (63%) health-care
workers had celebrated carnival in the 14 days before onset
of symptoms, mostly in Breda, Prinsenbeek, and Tilburg.
One health-care worker (who reported first symptoms on
Feb 21, 2020) attended several carnival events while
symptomatic but unaware of having COVID-19. 31 (32%)
health-care workers reported close contact with an
individual with confirmed COVID-19 in the 14 days before
onset of symptoms, either a patient (n=3), colleague
(n=18), household member (n=1), or another person
outside the hospital (n=9).
Between March 2 and March 7, 2020 (Amphia Hospital),
March 2 and March 10, 2020 (Bravis Hospital), and Feb 29
and March 9, 2020 (Elisabeth-TweeSteden Hospital),
856 patients were tested for SARS-CoV-2 RNA, of whom
345 were at Amphia Hospital, 228 were at Bravis
Hospital, and 283 were at Elisabeth-TweeSteden Hospital
(appendix 1 p 5). 23 (3%) patients tested positive for
SARS-CoV-2 RNA, nine at Amphia Hospital and 14 at
Elisabeth-TweeSteden Hospital.
We obtained complete and near-complete SARS-CoV-2
genomes from 50 of 96 health-care workers (appendix 1 pp
4–5). 30 health-care workers were from Amphia Hospital,
six were from Bravis Hospital, and 14 were from Elisabeth-
TweeSteden Hospital. We obtained near-complete SARS-
CoV-2 sequences from seven patients at Amphia Hospital
and three patients at Elisabeth-TweeSteden Hospital.
46 (92%) of 50 sequences from health-care workers in
this study grouped in three clusters (figure, A; appendix 1
p 4; appendix 2). Ten (100%) of ten sequences from
patients in the study grouped into the same three
clusters: seven were in cluster 1, two were in cluster 2,
and one was in cluster 3.
Cluster 1 contained 29 sequences (of which 12 were
identical) of SARS-CoV-2 in samples taken from health-
care workers and patients at all three hospitals
(appendix 1 p 5). 13 (45%) sequences were from Amphia
Hospital, three (10%) were from Bravis Hospital, and
13 (45%) were from Elisabeth-TweeSteden Hospital
(figure, C). 11 (79%) of 14 health-care workers and
two (67%) of three patients at Elisabeth-TweeSteden
Hospital were in cluster 1.
Cluster 2 contained 20 sequences (of which ten were
identical) of SARS-CoV-2 in samples taken from
health-care workers and patients at all three hospitals
(appendix 1 p 5). 17 (85%) sequences originated from
Amphia Hospital, two (10%) were from Bravis Hospital,
Health-care workers (n=96)
Sex
Male 16 (17%)
Female 80 (83%)
Age, years 49 (22–66)
Residence
Breda 11 (11%)
Prinsenbeek 11 (11%)
Tilburg 24 (25%)
Other city 50 (52%)
Department
Medical 76 (79%)
Staff without direct patient contact 20 (21%)
Foreign travel, 14 days before onset of
symptoms
10 (10%)
Northern Italy 3 (3%)
Austria 3 (3%)
UK 1 (1%)
Spain 1 (1%)
Portugal 1 (1%)
Switzerland 1 (1%)
Attendance at carnival with 50 people or
more, 14 days before onset of symptoms
60 (63%)
Breda 7 (7%)
Prinsenbeek 11 (11%)
Tilburg 20 (21%)
Other city 22 (23%)
Attendance at other event with 50 people
or more, 14 days before onset of
symptoms
31 (32%)
Close contact with individual with
confirmed COVID-19, 14 days before
onset of symptoms
31 (32%)
Patient 3 (3%)
Colleague 18 (19%)
Household member 1 (1%)
Other, outside hospital 9 (9%)
Data are n (%) or median (range).
Table: Descriptive characteristics of 96 health-care workers testing
positive for severe acute respiratory syndrome coronavirus 2 RNA at
three hospitals in the south of the Netherlands in March, 2020
See Online for appendix 2
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www.thelancet.com/infection Published online July 2, 2020 https://doi.org/10.1016/S1473-3099(20)30527-2
5
A
Patient
Health-care worker
Other
Amphia Hospital
Elisabeth-TweeSteden Hospital
Bravis Hospital
Italy link
Netherlands
Other
(Figure continues on next page)
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www.thelancet.com/infection Published online July 2, 2020 https://doi.org/10.1016/S1473-3099(20)30527-2
and one (5%) was from Elisabeth-TweeSteden Hospital
(figure, B). Health-care workers in cluster 2 were
associated with Prinsenbeek and Breda, either by
attendance at the carnival or by residence, more frequently
compared with the other clusters (appendix 1 p 4).
Cluster 3 contained seven sequences (of which four
were identical) of SARS-CoV-2 in samples taken from
health-care workers and patients at all three hospitals.
Four sequences were from health-care workers at Amphia
hospital and one each was from Bravis Hospital and
Elisabeth-TweeSteden Hospital. One sequence from a
patient at Elisabeth-TweeSteden Hospital was also
included in this cluster. A relatively large proportion of
sequences in cluster 3 were from people with a travel
history to northern Italy, as described elsewhere.16
However, only two of six health-care workers in this
cluster reported recent travel to either Italy or Austria
(appendix 1 pp 4, 6–7).
Within each cluster, identical or near-identical
sequences in health-care workers at the same hospital,
and between patients and health-care workers at the
same hospital, were found, but no consistent link was
noted among health-care workers on the same ward or
between health-care workers and patients on the same
ward. Most (81–100%) health-care workers testing
positive for SARS-CoV-2 at the three hospitals did not
work on a ward with patients with confirmed COVID-19
(appendix 1 p 2). In wards with patients and health-care
workers infected with SARS-CoV-2, direct transmission
could be excluded in most cases, based on available
WGS data (appendix 1 p 2). Notably, in Bravis Hospital,
no patients with confirmed SARS-CoV-2 infection were
hospitalised within 2 days before health-care workers at
that hospital reported onset of symptoms. Additionally,
no clusters were reported of more than three health-care
workers on the same ward with identical or near-
identical (two nucleotide dierence or less) sequences.
However, we cannot exclude health-care workers being
infected in common hospital areas such as sta
restaurants.
Figure: Minimum spanning tree of available full-length SARS-CoV-2 genomes obtained from GISAID on March 20, 2020
The full tree (A) shows three clusters of SARS-CoV-2 genomes, obtained from sequencing samples from health-care workers and patients in the south of the
Netherlands in March, 2020. An interactive version of the full tree can be found in appendix 2; it can be accessed by unzipping and opening the visNetwork.html file.
Clusters 2 (B) and 1 (C) are shown in more detail. Numbers next to nodes indicate the number of sequences included. Numbers on branches indicate the difference in
number of nucleotides between sequences. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. GISAID=Global Initiative on Sharing All Influenza Data.
B
C
2
1
3
4
1
1
2
1
1
1
2
1
3
13
1
1
1
1
1
1
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1
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1
1
41
1
1
1
1
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1
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1
1
11
5
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1
1 1
21
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6
9
Patient
Health-care worker
Other
Amphia Hospital
Elisabeth-TweeSteden Hospital
Bravis Hospital
Italy link
Netherlands
Other
2
4
2
1
3
3
2
1
2
1
2
1
11
1
1
1
2
2
1
1
1
1
1
1
3
2
4
20
2
3
3
3
Articles
www.thelancet.com/infection Published online July 2, 2020 https://doi.org/10.1016/S1473-3099(20)30527-2
7
Discussion
In the present study, we combined epidemiological data
with WGS to obtain a deeper understanding of the
sources and modes of transmission of SARS-CoV-2 at
three hospitals in the south of the Netherlands, which
were the first hospitals to identify patients with COVID-19
in the Netherlands. Although possible hospital trans-
mission of SARS-CoV-2 and health-care workers with
COVID-19 have been reported,3,30,31 to our knowledge, our
study is the first to use WGS to analyse possible
SARS-CoV-2 nosocomial transmission. Infection of
health-care workers could have occurred through foreign
travel, community contacts, or nosocomial transmission.
The epidemiological data we obtained, combined with
the presence of identical viruses in all three hospitals,
and with non-hospitalised cases in other locations,
indicates widespread community transmission in a very
early phase of the outbreak. Mass gatherings, such as
carnivals, in which just under two-thirds of health-care
workers testing positive for SARS-CoV-2 participated,
possibly acted as local super-spreading events.
Health-care workers are at increased risk of being
exposed to viruses within hospitals but can also be a
source of transmission by introducing a virus into their
hospital. SARS-CoV-2 infections in health-care workers
can have a substantial eect, because pathogens are
introduced into settings with high numbers of individuals
with comorbidities, potentially causing high morbidity
and mortality among patients. The current study did not
find evidence of large-scale nosocomial transmission in
the early phase of the Dutch outbreak, and prevailing use
of PPE and other infectious disease prevention measures
were considered sucient based on these early analyses
and results.32
Outbreaks in health-care settings are traditionally
investigated by molecular diagnostic methods combined
with epidemiological data. However, previous studies
using WGS for hospital outbreak investigations have
shown that hypotheses on virus transmission routes can
be incorrect based solely on these data. By adding WGS
data, particularly if results can be generated in a timely
manner, and as long as sucient reference sequences
are available to allow a high resolution of the findings,
the sequence analysis can provide essential information
and inform subsequent infection control measures.33
The mutation rate of SARS-CoV-2 is estimated to be
around 1·16 × 10³ substitutions per site per year, which
corresponds to around one mutation every 2 weeks.34
Therefore, finding identical or near-identical sequences
in several locations and hospitals makes it dicult to
draw definite conclusions on individual direct health-
care worker-to-health-care worker or health-care worker-
to-patient transmissions based on sequence data alone
in this early stage of the SARS-CoV-2 outbreak, when
genetic diversity of the circulating pathogen was
negligible. Moreover, we did not obtain WGS of all
health-care workers and patients testing positive for
SARS-CoV-2 and, because of the small sample size, our
analyses should be interpreted with caution. However,
the finding of diverse clusters does exclude infection
from one source. Moreover, the sequence-based analysis
could be biased when sampling and sequencing is not
done systematically and when sequence data in some
areas are scarce, as is the case for COVID-19 inter-
nationally. For the Netherlands, we sequenced a sub-
stantial proportion of SARS-CoV-2 genomes as part of
the national public health response,16 which was used as
a reference set.
In conclusion, the genomic diversity recorded in our
study is consistent with multiple introductions through
community-acquired infections, and some local ampli-
fication related to specific social events in the community,
rather than widespread within-hospital transmission.
Although direct transmission in hospitals cannot be
ruled out, our data do not support widespread nosocomial
transmission as the source of infection in patients or
health-care workers in our study. Because of the near-real-
time sequence generation and analysis, our information
was rapidly shared within the Dutch out break manage-
ment team. Partly based on these data, SARS-CoV-2 was
concluded to have already spread in the population in the
province of North Brabant, which led to a change of
policy, in which containment measures were comple-
mented by targeted physical distance measures, starting
in the south of the Netherlands initially and later
comprising the whole country.16
Contributors
RSS, SDP, MFQKvdB, and MPGK wrote the report. SDP, MFQKvdB,
and JAJWK set up sample and data collection. BBOM, AvdL, IC, MP, PL,
SvN, TB, CS, and RJO generated sequence data. WvdB, RGB, MMLvR,
AGMB, AJGvO, BMD, AMCB, AvdE, AT, JV, and RM were involved in
sample and data collection. RSS, DFN, AO’T, AR, BBOM, MPGK,
and MFQKvdB were involved in data analysis and interpretation.
RSS, SDP, JAJWK, MFQKvdB, and MPGK designed the study.
All authors provided critical feedback.
Declaration of interests
We declare no competing interests.
Acknowledgments
We thank David van der Vijver and Miranda de Graaf (Erasmus MC,
Rotterdam, Netherlands) for technical support. This study has been
partly funded by EU Horizon 2020 projects RECoVer (no 101003589),
VEO (no 874735), and the European Joint Programme One Health
METASTAVA (no 773830), and by the National Institute of Allergy and
Infectious Diseases, National Institutes of Health (contract
HHSN272201400008C).
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... Healthcare workers are at increased risk of contracting COVID-19, have had to work long hours, have had psychological stress, have had to deal with fatigue, have increased risk of occupational burnout and have experienced the risk and stigma of contracting COVID-19 and spreading it to others (WHO, 2020b;Bagcchi, 2020;The Lancet, 2020;Nagesh and Chakraborty, 2020). Since the emergence of COVID-19, reports of infections and deaths among healthcare workers have occurred worldwide (WHO, 2020d;WHO, 2020e;Sikkema et al, 2020;Bahrs et al, 2020). Healthcare workers, in particular those in contact with and/or who care for patients, are at greater risk of contracting COVID-19 than the general population (WHO, 2020d). ...
... It is important to understand the epidemiology and factors associated with COVID-19 among healthcare workers in order to reduce its incidence (WHO, 2020a). There are differences in the COVID-19 pandemic by region and country (TMA, 2020;Sikkema et al, 2020;Bahrs et al, 2020;Luo et al, 2020;Papagiannis et al, 2020). COVID-19 mortality and morbidity rates continue to rise among healthcare workers in Turkey (TMA, 2020;Akçakaya, 2021;Beyazadam and Alimoglu, 2020;Elbek, 2020). ...
... H e a l t h c a r e w o r k e r s a r e a t increased risk of contracting COVID-19 (Bandyopadhyay et al, 2020;Du et al, 2021;Sikkema et al, 2020;Nguyen et al, 2020;Zheng et al, 2020). It is important to understand how SARS-CoV-2 is spread in order to develop measures to prevent this (WHO, 2020f). ...
Research
Full-text available
Health care workers are at risk for acquiring Coronavirus disease-2019 (COVID-19). In this study we aimed to determine the knowledge, attitudes and practices (KAP) of healthcare workers in Turkey regarding COVID-19 in order to inform efforts to prevent COVID-19 infection in the study population. Study subjects were healthcare workers working at several different health care facilities in Ankara, Turkey. Each study subject was asked to complete a semi-structured sent to them by email or social media asking about their KAP regarding COVID-19. A total of 340 subjects were included in the study; 76.2% female. The mean (+standard deviation) age of study subjects was 28 (+8; range: 18-55) years. Thirty-six point five (36.5) percent of subjects worked with COVID-19 patients. Ninety-one point four (91.4) percent of subjects knew SARS-CoV-2 is spread through respiratory droplets. Ninety-one point two (91.2) percent of subjects obtained their information about COVID-19 from the Turkey Ministry of Health and 63.2% from the World Health Organization. All the participants (100%) stated they wore face masks, 98.2% stated they had regular good hand hygiene, 96.8% stated they had good respiratory hygiene (covering their mouth and nose with a piece of tissue paper when coughing or sneezing and disposing of the tissue appropriately) and 90.9% stated they had good surface and environment cleaning/disinfection practices. There were no significant differences in subject responses by gender except to the question, "Who is at greatest risk of contracting COVID-19?" in which the most common answer among female subjects was health care workers (52.1% of female subjects) and the most common answer among male subjects was the elderly (59.3% of male subjects) (p<0.05). The perceived risk of contracting COVID-19 (72.4%) was significantly greater (p<0.05) among physicians than other healthcare workers. In summary, our study subject overall COVID-19 knowledge level was good, the overall attitude level was only fair and the overall practices level was good. We conclude there is a need for an education program for study subjects to improve their KAPs regarding COVID-19. Further studies are needed after implementation of this program to determine its effect in the study population.
... Recent studies have reported that virus transmission involving HCWs in non-occupational settings might be exceeding than in occupational settings [4][5][6].This warrants the need of additional effort to prevent exposures to the virus in their daily life. In order to protect HCWs from the risk of non-occupational exposures to the virus, several infection prevention practices (IPPs) recommended by the WHO such as social distancing, avoiding 3Cs (crowded places, closed spaces and close-contact) may be key elements [2,7]. ...
Article
Full-text available
Background While healthcare workers (HCWs) are at risk of occupational exposure to SARS-CoV-2 infection, the virus transmission involving them might be exceeding in the non-occupational settings. This study examined the extent of adherence to infection prevention practices (IPPs) against COVID-19 in their daily life and its associated factors among staff members in a national medical center designated for COVID-19 treatment in Tokyo, Japan. Methods This cross-sectional study was conducted in July 2020 among 1,228 staff of National Center for Global Health and Medicine (NCGM). We asked participants about their adherence on six IPPs recommended by the WHO in their daily lives, which included wearing masks, maintaining hand and respiratory hygiene, avoiding 3Cs and social distancing. We defined 100% adherence (6 points) to IPPs as good adherence and run logistic regression model to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of IPPs. Results Nearly 100% of NCGM staff members adhered to four out of six IPPs assessed in this study: washing or sanitizing hands (99.6%), good cough etiquette (99.6%), wearing mask (98.9%), and avoiding 3Cs (98.3%). Doctors (AOR = 2.18, CI: 1.36–3.49) and female staff members (AOR = 1.95, CI: 1.36–3.49) were more likely to adhere to IPPs compared with non-clinical staffs and male counterparts. Good adherence to IPPs tended to increase with older age, with highest adherence among those who were 50 years or above (AOR = 2.53, CI: 1.49–4.29). Conclusion This study revealed that the IPPs among NCGM staff was remarkably good. Older and female staff members, and doctors showed a higher adhere to IPPs compared with their counterparts. Additional effort to improve adherence to IPPs among the younger and male staff members could contribute to reduce infection risk in their daily life, which can eventually prevent nosocomial infection.
... Neonates may also be infected during community outbreaks or family cluster outbreaks (17)(18)(19). Nosocomial SARS-CoV-2 infection has been reported in adults (20), but there are few reports of nosocomial infections in neonates from LMIC (21)(22)(23)(24)(25)(26)(27). In national population studies in the United Kingdom and Spain, nosocomial-acquired cases were identified in 8/66 (12%) and 14/40 (35%) of positive neonates. ...
Article
Full-text available
Introduction The provision of kangaroo mother care (KMC) involving continuous skin-to-skin care (SSC) is an important intervention in neonatal care, which is recommended even when women are infected with severe acute respiratory syndrome coronavirus (SARS-CoV-2). We report on a nosocomial outbreak of SARS-CoV-2 infections in a KMC ward. Methods Contact tracing was conducted following the diagnosis of SARS-CoV-2 in a mother lodging in the KMC ward. All mother-newborn dyads in the KMC and healthcare workers (HCW) were tested for SARS-CoV-2 within 24–72 h of diagnosing the index case. Nasopharyngeal swab samples were obtained and tested from contacts, with a nucleic acid amplification test (NAAT) assay. Next-generation sequencing was done on positive samples. The secondary attack rate (SAR) was calculated assuming that the mother who presented with symptoms was the source of infection. Results Twelve (70.6%) of 17 mothers and 8 (42.1%) of 19 neonates who were in the KMC ward with the index case were found to be positive with SARS-CoV-2. Seven (87.5%) of the 8 neonates who tested positive had mothers who also tested positive. Seventy-five percent (9/12) of the mothers and 62.5% (5/8) of the neonates who tested positive were asymptomatic. Eight (27.6%) of 29 HCW were found to be positive and were all asymptomatic. One neonate died from Acinetobacter baumannii sepsis, and his post-mortem lung histopathology showed features compatible with SARS-CoV-2 pneumonia. The sequencing of 13 specimens, which included 1 mother-newborn dyad, indicated clustering to the same phylogenetic lineage with identical mutations. In assessing for factors contributing to this outbreak, it was found that spaces between beds were less than 1 m and mothers had their meals around the same table at the same time. Conclusion We report on a nosocomial outbreak of SARS-CoV-2 in a KMC ward, affecting a high number of mothers and neonates, and to a lesser extent HCWs. Although it is difficult to point to the index case as the source of this outbreak, as asymptomatic individuals can spread infection, the inadequate adherence to non-pharmaceutical interventions was assessed to have contributed to the spread of infection. This highlights the need for awareness and adherence to mitigation strategies to avoid SARS-CoV-2 outbreaks.
... While such exposure could have occurred within or outside the workplace, we and others have previously reported that SARS-CoV-2 infections among health-care workers are more likely to be associated with community exposure rather than work-related exposure. 12,14,[16][17][18] In line with our findings, an Italian investigation found that workers with minimal exposure had significant low infection in the early months of 2020, from May to June. 2 Workers in the unrestricted group were >4 times more likely to report contact with a confirmed case, though for the current study we did not ascertain where such contact occurred. Workers in the unrestricted group, which were exclusively health-care workers, were nearly 3 times more likely to have SARS-CoV-2 infection than workers in the restricted group. ...
Article
Full-text available
Objective: To determine the prevalence of SARS-CoV-2 virus infection among female workers who were restricted to working from home compared with those who continued to attend in-person work. Methods: As part of national surveillance program, serum samples for SARS-CoV-2 antibody testing and nasopharyngeal swabs for SARS-CoV-2 PCR were obtained on 1636 female school staff and salon/spa workers who were restricted to work remotely (restricted group) and 1190 female health-care workers who continued in-person work (unrestricted group). Results: Seropositivity rate was 5.1% among the restricted and 22.7% among the unrestricted group (P < 0.0001). Presence of symptoms at baseline (adjusted odds ratio [aOR], 2.88; 95% CI 2.09-3.97), contact with a confirmed case (aOR 2.34; 95% CI 1.37-3.98), and unrestricted work type (aOR 4.71; 95% CI 3.24-6.86) were associated with a higher risk of infection, while increasing age was associated with a lower risk of infection. Conclusion: Prevalence of SARS-CoV-2 infection as determined by seropositivity was higher among women who were not subject to workplace restrictions.
... These affect between 4.7-80% of all cases, depending on the study and the definitions used 180 190,191 . Infections in HCWs may dispose to significant viral propagation 192 and staff sickness, with associated absences that may affect patient safety. It was therefore important to rapidly understand and learn from HAIs in order to introduce measures to prevent transmission. ...
Thesis
Infectious diseases continue to pose major threats to human health. This manifests in different ways, from the incessant rise of antimicrobial resistance, to seasonal epidemics of respiratory viruses and global pandemics, all of which cause high levels of morbidity, mortality and burden on healthcare systems. In this thesis I have investigated three pathogens that are archetypes of these threats: the Gram-negative bacterium Klebsiella pneumoniae, the seasonal respiratory virus influenza and the pandemic coronavirus SARS-CoV-2. Using isolates prospectively collected at Cambridge University Hospitals, I have utilised a combination of genomic, epidemiological and clinical datasets to characterise these pathogens. Phylogenetic analysis of K. pneumoniae bacteraemia isolates from a four year period show considerable genomic diversity and possible cryptic transmission events involving a lineage associated with hospital outbreaks. Using a novel method of high content imaging using confocal microscopy, I have developed high throughput pipelines that can quantify morphological changes induced in multiple bacterial species by a range of clinically relevant antimicrobials. I have used this approach to determine the phenotypic variation in a collection of 175 K. pneumoniae isolates that represent the diversity of the species. In paired imaging and RNAseq experiments using clinical isolates, I have identified large numbers of genes that are differentially expressed in the presence of antimicrobials. Among them are pathways associated with antimicrobial resistance, including mutagenesis, drug efflux and plasmid conjugation. Together, these data suggest that rather than passively selecting resistant isolates, antimicrobials may also actively drive resistance in K. pneumoniae. Using large genomic epidemiology studies I have identified extensive networks of nosocomial transmission of influenza and SARS-CoV-2 in CUH, involving patients and healthcare workers with an associated high inpatient mortality. For hospitalised influenza patients, I have shown the protective effect of the antiviral oseltamivir in multivariable analyses, and how rates of hospital acquired infection and mortality have fallen in response to multidisciplinary interventions over three winters. During the COVID-19 pandemic, real-time genomic-epidemiology analyses have been integrated with clinical services to understand and reduce viral spread. Finally, I have applied these approaches to a community setting, identifying SARS-CoV-2 transmission dynamics in the University of Cambridge and how they have been interrupted by local and national measures to control the COVID-19 pandemic. In particular, I have detailed the implementation and evaluation of a large regular screening programme for asymptomatic SARS-CoV-2 infection using pooled sampling, a programme that has provided insights into the efficacy of mass testing approaches.
... The lack of association of other symptoms that are predictive of the disease might have been due to the size of the study population. 22,23 In addition, the lack of data on the prevalence of IgG in Guatemala (this is the only study that has been previously carried out in the country) precludes estimating whether health services personnel are at higher risk than the general population. ...
Article
Full-text available
Introduction: The study of anti-SARS-CoV-2 IgG antibodies allows asymptomatic individuals with COVID-19 to be identified, and post-infection and post-vaccination immunity status to be evaluated. Objective: To know the behavior of anti-SARS-CoV-2 IgG antibodies before and after vaccination in workers of a cancer center. Methods: Prior to the application of the vaccine, the presence of anti-SARS-CoV-2 IgG antibodies (n = 171) was analyzed by evaluating anti-N IgG antibodies; post-vaccination, after receiving the second dose, anti-S IgG antibodies were evaluated (n = 60). Results: Prior to vaccination, IgG antibodies were present in 18.71% of participants; they were detected in 65.22% of those with prior history of COVID-19 diagnosis and in 11.49% of those without it. The positions with the highest prevalence were nurses (28.26%), paramedics (27.59%) and administrative workers (27.78%), p < 0.01. Anosmia, ageusia and chest tightness were associated with the presence of IgG (p < 0.05). Post-vaccination, all participants developed IgG antibodies; people with a previous COVID-19 diagnosis had higher titers: 10,277 vs. 6,819 AU/mL, p < 0.001. Conclusions: The study of anti-SARS-CoV-2 IgG antibodies allowed asymptomatic health workers to be identified. A high percentage of participants with prior COVID-19 diagnosis had antibodies. All participants developed IgG antibodies after vaccination, with higher titers being identified in those with previous infection.
Preprint
Full-text available
Background. Guidelines on COVID-19 management are developed as we learn from this pandemic. However, most research has been done on hospitalised patients and the impact of the disease on non-hospitalised and their role in transmission are not yet well understood. The COVID HOME study conducts research among COVID-19 patients and their family members who were not hospitalised during acute disease, to guide patient care and inform public health guidelines for infection prevention and control in the community and household. Methods. An ongoing prospective longitudinal observational study of COVID-19 outpatients was established in March 2020 in the Netherlands. Laboratory confirmed SARS-CoV-2 infected individuals of all ages that did not merit hospitalisation, and their household (HH) members, were enrolled after written informed consent. Enrolled participants were visited at home within 48 hours after initial diagnosis, and then weekly on days 7, 14 and 21 to obtain clinical data, a blood sample for biochemical parameters/cytokines and serological determination; and a nasopharyngeal/throat swab plus urine, stool and sperm or vaginal secretion (if consenting) to test for SARS-CoV-2 by RT-PCR (viral shedding) and for viral culturing. Weekly nasopharyngeal/throat swabs and stool samples, plus a blood sample on days 0 and 21 were also taken from HH members to determine whether and when they became infected. All participants were invited to continue follow-up at 3-, 6-, 12- and 18-months post-infection to assess long-term sequelae and immunological status. Preliminary Results. A total of 256 participants belonging to 103 HH were included of which, 190 (74.2%) were positive for SARS-CoV-2 infection. Most individuals (183/190, 96.3%) developed mild to moderate disease. At the time of writing, all participants had reached the 3 and 6 month time-points of the long-term follow-up, while approximately 78% reached 12 month and 23% the 18 month time-point. Preliminary analysis showed that 43% (52/121) positive individuals reported having complaints at 3 months post-infection, while 42.7% (61/143) had complaints at 6 months.
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Objective Because of their increased interaction with patients, healthcare workers (HCWs) face greater vulnerability to COVID-19 exposure than the general population. We examined prevalence and correlates of ever COVID-19 diagnosis and vaccine uncertainty among HCWs. Design Cross-sectional data from the Household Pulse Survey (HPS) conducted during July to October 2021. Setting HPS is designed to yield representative estimates of the US population aged ≥18 years nationally, by state and across selected metropolitan areas. Participants Our primary analytical sample was adult HCWs in the New York Metropolitan area (n=555), with HCWs defined as individuals who reported working in a ‘Hospital’; ‘Nursing and residential healthcare facility’; ‘Pharmacy’ or ‘Ambulatory healthcare setting’. In the entire national sample, n=25 909 HCWs completed the survey. Descriptive analyses were performed with HCW data from the New York Metropolitan area, the original epicentre of the pandemic. Multivariable logistic regression analyses were performed on pooled national HCW data to explore how HCW COVID-19-related experiences, perceptions and behaviours varied as a function of broader geographic, clinical and sociodemographic characteristics. Results Of HCWs surveyed in the New York Metropolitan area, 92.3% reported being fully vaccinated, and 20.9% had ever been diagnosed of COVID-19. Of the subset of HCWs in the New York Metropolitan area not yet fully vaccinated, 41.8% were vaccine unsure, 4.5% planned to get vaccinated for the first time soon, 1.6% had got their first dose but were not planning to receive the remaining dose, while 52.1% had got their first dose and planned to receive the remaining dose. Within pooled multivariable analysis of the national HCW sample, personnel in nursing/residential facilities were less likely to be fully vaccinated (adjusted OR, AOR 0.79, 95% CI 0.63 to 0.98) and more likely to report ever COVID-19 diagnosis (AOR 1.35, 95% CI 1.13 to 1.62), than those working in hospitals. Of HCWs not yet vaccinated nationally, vaccine-unsure individuals were more likely to be White and work in pharmacies, whereas vaccine-accepting individuals were more likely to be employed by non-profit organisations and work in ambulatory care facilities. Virtually no HCW was outrightly vaccine-averse, only unsure. Conclusions Differences in vaccination coverage existed by individual HCW characteristics and healthcare operational settings. Targeted efforts are needed to increase vaccination coverage.
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Objective To identify characteristics associated with positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) tests in healthcare personnel. Design Retrospective cohort study. Setting A multihospital healthcare system. Participants Employees who reported SARS-CoV-2 exposures and/or symptoms of coronavirus disease 2019 (COVID-19) between March 30, 2020, and September 20, 2020, and were subsequently referred for SARS-CoV-2 PCR testing. Methods Data from exposure and/or symptom reports were linked to the corresponding SARS-CoV-2 PCR test result. Employee demographic characteristics, occupational characteristics, SARS-CoV-2 exposure history, and symptoms were evaluated as potential risk factors for having a positive SARS-CoV-2 PCR test. Results Among 6,289 employees who received SARS-CoV-2 PCR testing, 873 (14%) had a positive test. Independent risk factors for a positive PCR included: working in a patient care area (relative risk [RR], 1.82; 95% confidence interval [CI], 1.37–2.40), having a known SARS-CoV-2 exposure (RR, 1.20; 95% CI, 1.04–1.37), reporting a community versus an occupational exposure (RR, 1.87; 95% CI, 1.49–2.34), and having an infected household contact (RR, 2.47; 95% CI, 2.11–2.89). Nearly all HCP (99%) reported symptoms. Symptoms associated with a positive PCR in a multivariable analysis included loss of sense of smell (RR, 2.60; 95% CI, 2.09–3.24) or taste (RR, 1.75; 95% CI, 1.40–2.20), cough (RR, 1.95; 95% CI, 1.40–2.20), fever, and muscle aches. Conclusions In this cohort of >6,000 healthcare system and academic medical center employees early in the pandemic, community exposures, and particularly household exposures, were associated with greater risk of SARS-CoV-2 infection than occupational exposures. This work highlights the importance of COVID-19 prevention in the community and in healthcare settings to prevent COVID-19.
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Background The ongoing COVID-19 pandemic significantly burdens hospitals and other healthcare facilities. Therefore, understanding the entry and transmission of SARS-CoV-2 is critical for effective prevention and preparedness measures. We performed surveillance and analysis of testing and transmission of SARS-CoV-2 infections in a tertiary-care hospital in Germany during the second and third pandemic waves in fall/winter 2020. Methods Between calendar weeks 41/2020 and 1/2021 40% of all positive patient and staff samples (284 total) were subjected to full-length viral genome sequencing. Clusters were defined based on similar genotypes indicating common sources of infection. We integrated phylogenetic, spatial, and temporal metadata to detect nosocomial infections and outbreaks, uncover transmission chains, and evaluate containment measures’ effectiveness. Results Epidemiologic data and contact tracing readily recognize most healthcare-associated patient infections. However, sequencing data reveal that temporally preceding index cases and transmission routes can be missed using epidemiologic methods, resulting in delayed interventions and serially linked outbreaks being counted as independent events. While hospital-associated transmissions were significantly elevated at a moderate rate of community transmission during the second wave, systematic testing and high vaccination rates among staff have led to a substantial decrease in healthcare-associated infections at the end of the second/beginning of the third wave despite high community transmissions. Conclusions While epidemiologic analysis is critical for immediate containment of healthcare-associated SARS-CoV-2 outbreaks, integration of genomic surveillance revealed weaknesses in identifying staff contacts. Our study underscores the importance of high testing frequency and genomic surveillance to detect, contain and prevent SARS-CoV-2-associated infections in healthcare settings.
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In late December 2019, a cluster of cases of pneumonia of unknown etiology were reported linked to a market in Wuhan, China1. The causative agent was identified as the species Severe acute respiratory syndrome-related coronavirus and was named SARS-CoV-2 (ref. 2). By 16 April the virus had spread to 185 different countries, infected over 2,000,000 people and resulted in over 130,000 deaths3. In the Netherlands, the first case of SARS-CoV-2 was notified on 27 February. The outbreak started with several different introductory events from Italy, Austria, Germany and France followed by local amplification in, and later also outside, the south of the Netherlands. The combination of near to real-time whole-genome sequence analysis and epidemiology resulted in reliable assessments of the extent of SARS-CoV-2 transmission in the community, facilitating early decision-making to control local transmission of SARS-CoV-2 in the Netherlands. We demonstrate how these data were generated and analyzed, and how SARS-CoV-2 whole-genome sequencing, in combination with epidemiological data, was used to inform public health decision-making in the Netherlands. The combination of near to real-time whole-genome sequence analysis and epidemiology resulted in reliable assessments of the extent of SARS-CoV-2 transmission in the community, facilitating early decision-making to control local transmission of SARS-CoV-2 in the Netherlands.
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The ongoing pandemic spread of a new human coronavirus, SARS-CoV-2, which is associated with severe pneumonia/disease (COVID-19), has resulted in the generation of tens of thousands of virus genome sequences. The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding phylogenetic diversity of SARS-CoV-2. Here, we present a rational and dynamic virus nomenclature that uses a phylogenetic framework to identify those lineages that contribute most to active spread. Our system is made tractable by constraining the number and depth of hierarchical lineage labels and by flagging and delabelling virus lineages that become unobserved and hence are probably inactive. By focusing on active virus lineages and those spreading to new locations, this nomenclature will assist in tracking and understanding the patterns and determinants of the global spread of SARS-CoV-2.
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Importance On February 27, 2020, the first patient with coronavirus disease 2019 (COVID-19) was reported in the Netherlands. During the following weeks, at 2 Dutch teaching hospitals, 9 health care workers (HCWs) received a diagnosis of COVID-19, 8 of whom had no history of travel to China or northern Italy, raising the question of whether undetected community circulation was occurring. Objective To determine the prevalence and clinical presentation of COVID-19 among HCWs with self-reported fever or respiratory symptoms. Design, Setting, and Participants This cross-sectional study was performed in 2 teaching hospitals in the southern part of the Netherlands in March 2020, during the early phase of the COVID-19 pandemic. Health care workers employed in the participating hospitals who experienced fever or respiratory symptoms were asked to voluntarily participate in a screening for infection with the severe acute respiratory syndrome coronavirus 2. Data analysis was performed in March 2020. Main Outcomes and Measures The prevalence of severe acute respiratory syndrome coronavirus 2 infection was determined by semiquantitative real-time reverse transcriptase–polymerase chain reaction on oropharyngeal samples. Structured interviews were conducted to document symptoms for all HCWs with confirmed COVID-19. Results Of 9705 HCWs employed (1722 male [18%]), 1353 (14%) reported fever or respiratory symptoms and were tested. Of those, 86 HCWs (6%) were infected with severe acute respiratory syndrome coronavirus 2 (median age, 49 years [range, 22-66 years]; 15 [17%] male), representing 1% of all HCWs employed. Most HCWs experienced mild disease, and only 46 (53%) reported fever. Eighty HCWs (93%) met a case definition of fever and/or coughing and/or shortness of breath. Only 3 (3%) of the HCWs identified through the screening had a history of travel to China or northern Italy, and 3 (3%) reported having been exposed to an inpatient with a known diagnosis of COVID-19 before the onset of symptoms. Conclusions and Relevance Within 2 weeks after the first Dutch case was detected, a substantial proportion of HCWs with self-reported fever or respiratory symptoms were infected with severe acute respiratory syndrome coronavirus 2, likely as a result of acquisition of the virus in the community during the early phase of local spread. The high prevalence of mild clinical presentations, frequently not including fever, suggests that the currently recommended case definition for suspected COVID-19 should be used less stringently.
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SARS-CoV-2 is a novel coronavirus that has rapidly spread across the globe. In the Netherlands, the first case of SARS-CoV-2 has been notified on the 27th of February. Here, we describe the first three weeks of the SARS-CoV-2 outbreak in the Netherlands, which started with several different introductory events from Italy, Austria, Germany and France followed by local amplification in, and later also, outside the South of the Netherlands. The timely generation of whole genome sequences combined with epidemiological investigations facilitated early decision making in an attempt to control local transmission of SARS-CoV-2 in the Netherlands.
Preprint
Full-text available
The ongoing pandemic spread of a novel human coronavirus, SARS-COV-2, associated with severe pneumonia disease (COVID-19), has resulted in the generation of thousands of virus genome sequences. The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding phylogenetic diversity of SARS-CoV-2. We present a rational and dynamic virus nomenclature that uses a phylogenetic framework to identify those lineages that contribute most to active spread. Our system is made tractable by constraining the number and depth of hierarchical lineage labels and by flagging and declassifying virus lineages that become unobserved and hence are likely inactive. By focusing on active virus lineages and those spreading to new locations this nomenclature will assist in tracking and understanding the patterns and determinants of the global spread of SARS-CoV-2.
Preprint
Full-text available
COVID-19 is spreading rapidly over the world. On February 27, 2020, the first patient with COVID-19 was reported in the Netherlands, linked to a trip to Northern Italy. In the following weeks, we identified nine Health Care Workers (HCW) of whom eight had no epidemiological link to countries with a high incidence of COVID-19 at that time. This suggested local spread of SARS-CoV-2 in the community and prompted a low-threshold screening in HCWs. Screening was performed in two large teaching hospitals in the southern part of the Netherlands. HCWs who suffered from fever or mild respiratory symptoms were tested for SARS-CoV-2 by RT-PCR on oropharyngeal samples. Structured interviews were conducted to document symptoms. Eighty-six (6.4%) out of 1,353 HCWs were infected with SARS-Cov-2. The median age was 49 years and 15 (17.4%) were male. Most suffered from relatively mild disease. Only 46 (53.5%) HCWs had fever during the course of illness. Seventy-nine (91.9%) HCWs met a case definition of fever and/or coughing and/or shortness of breath. The majority (n=54, 62.8%) reported to have worked while being symptomatic. Within one week after the first case was reported, a substantial proportion of HCWs with fever or respiratory symptoms were proven to be infected with SARS-Cov-2. This observation suggests that there is a relatively high prevalence of mild clinical presentations that may go undetected. The spectrum of symptoms present in HCWs with COVID-19, frequently not including fever, asks for less stringent use of the currently recommended case-definition for suspected COVID-19.
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Background Long-term care facilities are high-risk settings for severe outcomes from outbreaks of Covid-19, owing to both the advanced age and frequent chronic underlying health conditions of the residents and the movement of health care personnel among facilities in a region. Methods After identification on February 28, 2020, of a confirmed case of Covid-19 in a skilled nursing facility in King County, Washington, Public Health–Seattle and King County, aided by the Centers for Disease Control and Prevention, launched a case investigation, contact tracing, quarantine of exposed persons, isolation of confirmed and suspected cases, and on-site enhancement of infection prevention and control. Results As of March 18, a total of 167 confirmed cases of Covid-19 affecting 101 residents, 50 health care personnel, and 16 visitors were found to be epidemiologically linked to the facility. Most cases among residents included respiratory illness consistent with Covid-19; however, in 7 residents no symptoms were documented. Hospitalization rates for facility residents, visitors, and staff were 54.5%, 50.0%, and 6.0%, respectively. The case fatality rate for residents was 33.7% (34 of 101). As of March 18, a total of 30 long-term care facilities with at least one confirmed case of Covid-19 had been identified in King County. Conclusions In the context of rapidly escalating Covid-19 outbreaks, proactive steps by long-term care facilities to identify and exclude potentially infected staff and visitors, actively monitor for potentially infected patients, and implement appropriate infection prevention and control measures are needed to prevent the introduction of Covid-19.
Article
Background: Since December 2019, the world is captivated by SARS-CoV-2, a new coronavirus that shows a lot of similaritieswith previous coronaviruses such as SARS and MERS. Although it was initially seen mainly in China and the surrounding countries, now it also reached Europe, where a large region in northern Italy, in particular, encountered many infections. Case description: Here we describe the first Dutch patient with COVID-19, a 56-year-old man whose infection appeared to be related to a trip to Northern Italy one week before presentation. In the days that followed, the brother of the patient with whom he had traveled, his wife and daughter also tested positive. Conclusion: At the moment much is still unclear and it is particularly important to quickly identify patients with an increased risk of complications and to prevent unrestrained spread in the Netherlands.