key: cord-0892286-ls5v1hli
authors: Paltansing, S.; Sikkema, R.S.; Man, S.J.de; Koopmans, M.P.G.; Munnink, B.B. Oude; Man, P.de
title: Transmission of SARS-CoV-2 among healthcare workers and patients in a teaching hospital in the Netherlands confirmed by whole genome sequencing
date: 2021-02-08
journal: J Hosp Infect
DOI: 10.1016/j.jhin.2021.02.005
sha: 2497f1c79465d10438bd9d4146f4b9a34eab0124
doc_id: 892286
cord_uid: ls5v1hli

We investigated the sources of infection among healthcare workers (HCWs) and patients in a teaching hospital during the early stages of the COVID-19 pandemic with epidemiological and whole genome sequencing data. This retrospective study is performed in a Dutch teaching hospital with nursing facilities located in Rotterdam and Schiedam with around 45,000 admissions per year. From 3(rd) April to 11(th) May 2020 88 HCWs and 215 patients were diagnosed with SARS-CoV-2 infection. Whole genome sequences were obtained for 30 HCWs and 20 patients. We found 7 sequence types in HCW and 11 in patients. Sequence Cluster A was the most predominant sequence type detected in 23 (77%) HCW, of whom 14 (74%) had direct patient contact and 9 (90%) with indirect patient contact. In addition, seven patients outside of the COVID-19 cohort isolation ward who became positive during their admission were infected with SARS-CoV-2 cluster A. Following universal masking of all HCWs and emphasis on physical distancing during meals and breaks, no further evidence was found for patient to HCW or HCW-to-HCW transmission or vice versa. The identification of genomic cluster A in patients and HCWs infected with SARS-CoV-2 by whole genome sequencing suggests transmission between HCWs, but also from HCWs to patients.

We investigated the sources of infection among healthcare workers (HCWs) and patients in a 29

teaching hospital during the early stages of the COVID-19 pandemic with epidemiological 30 and whole genome sequencing data. This retrospective study is performed in a Dutch 31

teaching hospital with nursing facilities located in Rotterdam and Schiedam with around 32 45,000 admissions per year. 33

From 3 rd April to 11 th May 2020 88 HCWs and 215 patients were diagnosed with SARS-CoV-2 34

infection. Whole genome sequences were obtained for 30 HCWs and 20 patients. We found 35 7 sequence types in HCW and 11 in patients. Sequence Cluster A was the most predominant 36 sequence type detected in 23 (77%) HCW, of whom 14 (74%) had direct patient contact and 37 9 (90%) with indirect patient contact. In addition, seven patients outside of the COVID-19 38 cohort isolation ward who became positive during their admission were infected with SARS-39

CoV-2 cluster A. Following universal masking of all HCWs and emphasis on physical 40

distancing during meals and breaks, no further evidence was found for patient to HCW or 41 HCW-to-HCW transmission or vice versa. 42

The identification of genomic cluster A in patients and HCWs infected with SARS-CoV-2 by 43 whole genome sequencing suggests transmission between HCWs, but also from HCWs to 44

patients. sequencing, yielding 50 whole-genome sequences from 30 HCWs and 20 patients (Table 1) . 124

Four sequence clusters were observed while 12 samples did not cluster with other 125 sequences from the facility (Figure 2 ). Cluster A was the most predominant cluster, with 31 126 (62%) sequences belonging to this cluster while 7 (14%) sequences were part of the smaller 127 clusters B (n=3), C (n=2) and D (n=2). Cluster A was also the most predominant sequence 128

cluster detected during the outbreak in HCWs on the non-COVID ward in 23 (77%) HCWs. 129

This incidence was higher among HCWs with indirect patient contact such as cleaning the 130 rooms and distributing food. Of those 9 out of 10 (90%) sequenced isolates belonged to 131 cluster type A. Among the infected HCWs with direct patient contact 14 of the 19 (74%) 132

sequenced isolates belonged to the type A cluster.

The epidemic curve combined with WGS sequencing of SARS-CoV-2 infected HCWs and 135 patients is shown in Figure 1 . 13 of 20 (65%) SARS-CoV-2 positive patients presented with 136 symptoms of COVID-19 disease in the emergency ward. These patients were transferred to 137 the COVID-19 cohort isolation ward (Figure 1 ). Patient ID 1 was infected by a SARS-CoV-2 138

cluster A virus. Patient ID 5 and 6 were admitted on the same day with SARS-CoV-2 cluster B.

We did not find a direct link, but both patients resided only 2 km apart. The remaining 140

sequences of patients sampled on admission were unique (U). Patient ID 14 was already 141 J o u r n a l P r e -p r o o f sampled 4 days prior to admission. None of these sequences were identified in infected 142 HCW, showing that infection prevention policy was effective in this patient group. 143

In the subsequent period, seven patients at different non-COVID wards, who became 144 positive during their admission were infected with SARS-CoV-2 cluster A (Figure 1) . Patient ID 145 20 tested positive on 30 th April 2020, one day after transfer to a nursing home. The time 146

relation between patient admissions and the moment of positive sampling (4 to 19 days 147 after admission) and the onset of symptoms as recorded in their medical records (data not 148

shown) suggests that the COVID-19 infections were acquired during hospital admission.

A total of eight HCWs working at the same non-COVID nursing ward tested positive on April 150 21 st . In response to this, all HCWs who worked at this ward were instructed to wear surgical 151 masks at all times. In the following days multiple HCWs were tested positive. 152

Our whole genome analysis included all SARS-CoV-2 sequences detected in the Netherlands 153 thus far (n = 1477). Cluster A was phylogenetically related in HCWs and patients from the 154 teaching hospital (Figure 2 ). Only one other person from the Rotterdam area was detected 155

with SARS-CoV-2 cluster A in the same time period. Epidemiological data of this case were 156 not available.

After the analysis it became clear that on the ward with the cluster of HCWs that triggered 159 us to investigate the transmission there was only one cluster A patient day. Thus it is less 160

likely that patient-to-HCW transmission played a significant role in this ward.

The voluntary questionnaire was completed by 16 of the 30 positive HCWs. HCWs 163 mentioned that they worked on both locations, and the data from the questionnaires 164

showed that food and cleaning staff worked at different departments in the hospitals, and 165 multiple patient transfers between wards occurred. Seven HCWs reported to have had close 166 contact with colleagues during breaks who later became symptomatic and tested positive. 167

Three HCWs reported unprotected care for a patient that later turned out to be positive with 168

cluster A during admission. During three weeks of follow up no additional positive HCWs 169

were detected. The combination of epidemiological and WGS analysis was highly suggestive 170

for HCW-to-HCW and HCW-to-patient transmission. 171 172 173

Discussion 174

In this study, we combined epidemiological data with WGS to analyse the extent of intra-175 hospital spread of SARS-CoV-2 in a teaching hospital. We showed that, in spite of all efforts 176

to implement strict infection control measures, HCWs and patients acquired SARS-CoV-2 in 177

hospital. The identification of genomic cluster A in patients hospitalized for other conditions, 178

and HCWs infected with SARS-CoV-2 by WGS suggests transmission between HCWs but also 179 from HCWs to patients on the non-COVID ward. Identical or near identical sequences were 180 not found among all SARS-CoV-2 sequences detected in the Netherlands thus far, indicating 181 that this specific cluster is linked to this hospital outbreak.

A previous study using WGS observed widespread community transmission of SARS-CoV-2 183

among HCWs in a very early phase of the epidemic in the Netherlands. No evidence of 184

widespread nosocomial transmission was found [9,10]. However, during ongoing 185 community transmission there remains a potential risk of unnoticed hospital introduction of 186 SARS-CoV-2 through HCWs and subsequent onward transmission among HCWs, but also 187 from HCWs to patients nursed outside of dedicated wards. 188 J o u r n a l P r e -p r o o f HCWs are at increased risk of being exposed to unsuspected cases of COVID-19 within 189

hospitals [11] . However, they can also become sources of onward transmission. Maltezou et 190 al. reported that in almost 50% of HCWs infected with Sars-CoV-2 a colleague was the source 191

of COVID-19 exposure [12] . During the outbreak, we followed our national policy at that 192 time that HCWs with mild respiratory symptoms should be tested for SARS-CoV-2. Positive 193

HCWs were not allowed to work and were placed on a mandatory 7-day medical leave or 194 longer until all symptoms resolved completely. However, recent work from the Netherlands 195

showed that 63% of HCW had worked despite mild symptoms in the early stage of the 196 epidemic [13] . 197 In addition, screening of HCWs in a large UK hospital highlighted the role of asymptomatic 198 carriage in SARS-CoV-2 transmission [14] . In our experience, the analysis of this particular 199 outbreak and the knowledge that asymptomatic and presymptomatic carriers can be 200 contagious motivated us to change our SARS-CoV-2 testing policy. In case of an unexpected 201

finding of a SARS-CoV-2 positive case in a HCW or patient after admission, we recommend to 202 test all close contacts immediately and subsequently on day 3 and 7 regardless of symptoms. 203

Patients are isolated pending test results. HCWs are allowed to work with surgical masks 204

awaiting their test results.

The main route for transmission of SARS-CoV-2 is considered to be from person-to-person 206 via droplet transmission but other routes such as aerosol transmission via hospital 207

ventilation systems are suggested [15] . Some ventilation systems recirculate indoor air or 208 mix air in common ventilation ducts to reduce energy costs. We established that the hospital 209

ventilation system worked properly, did not have recirculation routes and had well 210 separated air intakes and outlets. 211

There are several limitations to our study. Firstly, we were unable to sequence all HCWs and 212 patients involved in this outbreak. In our analysis, the timing of positivity of patient ID 1 and 213 the subsequent findings of (near-to) identical genomes in patients and HCWs suggests 214 spread from patient ID 1 to HCWs and patients after admission. However, our analysis was 215 incomplete and did not cover the whole development of the transmission, so another 216 scenario cannot be excluded. Furthermore, we were unable to track the ward location of all 217

HCWs during their shifts, because some worked at more departments or locations 218

simultaneously. Nevertheless, we could identify unprotected contact moments between 219

infected HCWs and infected patients, and we did observe that cleaners and food assistants 220 did not adhere to social distancing rules during coffee breaks and meals. Although these are 221 potential transmission routes, our study cannot confirm these routes with certainty. In 222 addition, a sequence related to cluster A was also observed in the general population, 223 detected due to random regional sampling efforts. 

COVID-19 in health-care workers in three hospitals in the south of the Netherlands: a 287 cross-sectional study

Infections Among Healthcare Workers

Infection in Healthcare Personnel With High-risk Occupational Exposure: 295 Evaluation of 7-Day Exclusion From Work Policy

Rapid 298 assessment of regional SARS-CoV-2 community transmission through a convenience sample 299 of healthcare workers, the Netherlands

Screening of 303 healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in 304 COVID-19 transmission

Impact of building ventilation 306 systems and habitual indoor incense burning on SARS-CoV-2 virus transmissions in 307 Middle Eastern countries

Contributors: SP and PdM conceived the project. PdM set up data collection. SdM