key: cord-0890091-c91xcwh0
authors: Velay, A; Gallais, F; Wendling, MJ; Bayer, S; Reix, N; Schneider, A; Glady, L; Collongues, N; Lessinger, JM; Hansmann, Y; Kling-Pillitteri, L; De Sèze, J; Gonzalez, M; Schmidt-Mutter, C; Meyer, N; Fafi-Kremer, S
title: COVID-19 exposure in SARS-CoV-2-seropositive hospital staff members during the first pandemic wave at Strasbourg University Hospital, France
date: 2021-11-11
journal: Infect Dis Now
DOI: 10.1016/j.idnow.2021.11.002
sha: 9a0963caf5741576eba0adb4dec343c8b0276ee3
doc_id: 890091
cord_uid: c91xcwh0

Objectives. Strasbourg University Hospital faced an important COVID-19 first wave, from early March 2020. We performed a longitudinal prospective cohort study to describe clinical and virological data, exposure history to COVID-19, and adherence to strict hygiene standards during the first pandemic wave in 1,497 workers undergoing a SARS-CoV-2 serological test at our hospital, with a follow up of serology result three months later. Patients and Methods. 1,497 patients were enrolled from April 6 to May 7, 2020. Antibody response to SARS-CoV-2 was measured, and COVID-19 exposure routes were analyzed according to SARS-CoV-2 serological status. Results. 515 patients (34.4%) were seropositive, mainly medical students (13.2%) and assistant nurses (12.0%). A history of COVID-19 exposure in a professional and/or private setting was mentioned by 83.1% of seropositive subjects (p<0.05; odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.8-3.4). COVID-19 exposure factors associated with seropositive status were non-professional exposure (OR: 1.9, 95%CI: 1.3-2.7), especially outside the immediate family circle (OR: 2.2, 95%CI: 1.2-3.9) and contact with a COVID-19 patient (OR: 1.6; 95%CI: 1.1-2.2). Among professionally exposed workers, systematic adherence to strict hygiene standards was well observed except for the use of a surgical mask (p<0.05, OR: 1.9, 95%CI: 1.3-2.8). Of those who reported occasionally or never wearing a surgical mask, nurses (25.7%), assistant nurses (16.2%), and medical students (11.7%) were predominant. Conclusion. Infection of staff members during the first pandemic wave in our hospital occurred after both professional and private COVID-19 exposure, underlining the importance of continuous training in strict hygiene standards.

In early December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the city of Wuhan in China's Hubei Province. This highly contagious virus, mainly transmitted via droplets, is the causative agent of the Coronavirus Disease 2019 (COVID-19) [1] . Given the current COVID-19 pandemic, infection of medical and nursing staff is a common occurrence. Shortly after the first wave of the pandemic, the occupational risk of J o u r n a l P r e -p r o o f contamination among healthcare workers (HCWs) was well identified [2] [3] [4] , with contamination rates ranging from 3.5% to 29% amongst hospitals in Wuhan [5] .

Whilst RT-PCR tests were mostly performed in symptomatic patients, especially during the first wave, the mass testing which followed revealed the predominance of asymptomatic forms of this infection. Since viral replication, and therefore contamination, can take place before symptoms appear, or even in the absence of symptoms, those in contact with COVID-19-positive cases, such as hospital staff, also constitute a population of potentially infected people. Antibodies to SARS-CoV-2 are detectable from around 15 days after symptom onset and seem to persist for at least 6 months [6] . Serological tools could provide precious information by detecting antibodies induced by previous SARS-CoV-2 infection, especially among populations which are highly exposed to the virus such as HCWs.

At the end of February 2020, a cluster of SARS-CoV-2 infections was detected following an annual religious gathering attended by more than 2,000 people in Mulhouse, eastern France.

Infected individuals were admitted to regional hospitals. Strasbourg University Hospital (SUH) (2,566 beds including 97 in the intensive care unit [ICU] ) faced this early first wave of COVID-19, which was of high intensity compared to other areas in France. All hospital staff were at high risk of SARS-CoV-2 exposure, both occupationally and outside the hospital. The occurrence of the early epidemic wave in our hospital represented an opportunity to study the SARS-CoV-2 antibody response in staff members and to identify risk factors for SARS-CoV-2 infection, at a time when knowledge about COVID-19 remained sparse.

We performed a longitudinal prospective cohort study to describe clinical and virological data, exposure history to COVID-19, and adherence to strict hygiene standards during the first pandemic wave in 1,497 workers undergoing a SARS-CoV-2 serological test at our J o u r n a l P r e -p r o o f hospital, with a follow up of serology result 3 months later. The effectiveness of prevention measures for first-line and non-first-line workers in the hospital setting is also discussed.

Participants were randomly selected among the entire SUH staff members by the occupational health department and invited by phone call to participate in this study.

Individuals were enrolled in the study from April 6 to May 7, 2020 (Visit 0, V0) and followed up 3 months later (V1 

Categorical data were described as frequencies and proportions. Quantitative data were described by the median and interquartile range (IQR). Seronegative and seropositive subjects were included using a complex survey design, stratified by the 35 hospital sectors.

Data were analyzed using the sampling weight with either a chi-square test for contingency tables or a logistic regression. Data are described with raw values in tables, but p-values were calculated including the sampling design. A value of p<0.05 was considered significant.

Categorical variables are presented as proportions, and reported as odds ratio (OR) and 95%

confidence intervals (95%CI). Subjects for whom data was not completed were excluded from the statistical analysis. Computations were carried out using the survey package in R 3.5.2.

This study was registered in ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT04441684).

The protocol was approved by the institutional review board of CPP Sud Méditerranée III. All participants provided written informed consent.

The study population demographics, corresponding to 1,497 subjects, is shown in 

Serological results are displayed in Table 1 and COVID-19 symptoms were reported by 95.7% of seropositive individuals and by 74.8% of seronegative workers, respectively (Table 1) . Each symptom was more frequently observed in seropositive subjects (Table 1) , especially in those who were previously detected positive by RT-PCR ( Figure 2 ). However, the difference was far more significantly marked for anosmia and dysgeusia (OR: 21.2, 95%CI: 15.2-29.5) ( Figure 3 ).

Serological results at V1 were available for 1,230 subjects. Among the 444 seropositive subjects at V0 who were followed at V1, 87.8% (390/444) were still seropositive at V1. Those who were previously tested positive for the presence of SARS-CoV-2 by RT-PCR mainly still had antibodies at V1 (320/331; 96.7%), while those previously tested negative by RT-PCR or who were not previously tested by RT-PCR were more likely to present with antibody decrease with 57.9% (33/57) and 66.1% (37/56) of them still seropositive at V1, respectively (Table 2) . A total of 754 workers were still seronegative at V1, and 484 of them reported mild COVID-19 symptoms, including five individuals who reported a positive SARS-CoV-2 RT-J o u r n a l P r e -p r o o f

A history of COVID-19 exposure in a professional and/or private setting (overall exposure) was mentioned by 83.1% of seropositive subjects and 66.4% of seronegative subjects at V0 (p<0.05; OR: 2.5; 95%CI: 1.8-3.4) ( Figure 4 , Figure 5 , and Table 3 ).

We first considered the occurrence of non-professional exposure to COVID-19 among participants, outside of the hospital setting. Non-professional COVID-19 exposure (family and other personal contacts) was significantly more often reported by seropositive subjects at V0 (21.1%) than seronegative subjects (12.5%) (p<0.05; OR: 1.9, 95%CI: 1.3-2.7), especially outside the immediate family circle (OR: 2.2, 95%CI: 1.2-3.9) ( Figure 5 and Table 3 ). Among extra-professionally exposed workers, 79.2% of seropositive subjects and 42.1% of seronegative subjects at V0 could date their exposure precisely. The median time between presumed contact and onset of first symptoms was 5 days in both groups of participants.

Occupational COVID-19 exposure analysis showed that professional exposure to COVID-19 (patients and/or colleagues) was reported in 54.2% of seropositive workers and in 42.6% of seronegative workers at V0 (OR: 1.6; 95%CI: 1.2-2.1). The distribution of seropositive and seronegative subjects between different professional categories was equivalent at V0, except for medical students (13.2% versus 9.5%, respectively) and assistant nurses (12.0% versus 9.9%, respectively). Regardless of serological status, professional exposure and more specifically COVID-19 patient exposure, were predominantly reported in nurses (35.0% and 33.0%, respectively), clinicians (16.0% and 14.2%), and assistant nurses (16.0% and 12.8%).

Seropositive subjects at V0 were significantly more exposed to COVID-19 patients than those who were seronegative at V0 (p<0.05; OR: 1.6; 95%CI: 1.1-2.2), whereas exposure to COVID-J o u r n a l P r e -p r o o f exposed staff members, only 42.2% of seropositive workers and 24.1% of seronegative workers at V0 were able to provide a precise date of exposure. For those reporting a precise date of exposure, the median time between supposed contact and onset of initial symptoms was 5.5 days (range: 0-30) for seropositive workers at V0 and 7 days (0-30) for workers seronegative at V0. Neither the initial ward of occupation (p=0.05) nor a change of ward (p=0.17) due to hospital reorganization during the pandemic were found to impact SARS-CoV-2 serological status of staff members. A total of 138 (12.5%) participants reported COVID-19 exposure in both professional and private settings; this proportion did not differ between seropositive and seronegative subjects.

Adherence to strict hygiene standards among COVID-19 professionally exposed subjects

We analyzed the extent of systematic adherence to strict hygiene standards among occupationally exposed participants, according to their serological status (Table 4) .

Participants were asked about their systematic use of hand hygiene by alcohol-based hand sanitizer, surgical masks, FFP2 masks, gloves, protective glasses, isolation gowns, and head caps. Among all PPE reported, only the use of a surgical mask was significantly less frequently reported by seropositive subjects than seronegative subjects at V0 (p=0.0007, OR: not detected by the serological assays that we used [8] or may have developed symptoms in response to another respiratory disease, such as the flu, which was circulating at the same time.

Defining the immunity status among HCWs is of particular interest to health authorities, to estimate the exposure risk and to distinguish potential chains of infection in clinical settings from those due to COVID-19 contacts in the household or private sphere. It has long been established that exposure in settings with personal contacts greatly increases the potential for SARS-CoV-2 transmission, and dramatically hinders any slowdown of the pandemic [9] . In [11] .

Irrespective of the serological status, clinicians, nurses, and assistant nurses were those who predominantly reported professional exposure, in particular COVID-19 patient exposure.

These observations are consistent with those reported by others [12; 13] . However, we found that medical students and assistant nurses were more represented among seropositive subjects. Neither the initial department of occupation, nor a change of department due to hospital reorganization appeared to impact SARS-CoV-2 serological status of the workers. We therefore carried out a further analysis regarding the appropriate use of PPE and respect of strict hygiene standards among professionally exposed workers.

Except for the systematic use of a surgical mask (p<0.05, OR: 1.9, 95%CI: 1.3-2.8), systematic adherence to strict hygiene standards was similar between seropositive and seronegative subjects. Among those who reported occasionally or never wearing a surgical mask, nurses, assistant nurses, and medical students were predominant, despite the fact that these professional categories were precisely those most frequently exposed to COVID-19 patients.

In many countries, a major issue during the first wave of the pandemic was sufficient access The main limitation of this study is its single-center setting, potentially leading to a selection bias. SUH was particularly impacted by the first wave of the COVID-19 pandemic and our results may probably differ from other less severely affected French hospitals during the same period. In addition, the retrospective use of declarative information collected from enrolled workers could affect the accuracy of certain data, such as the identification of a precise date of exposure. Although serological interpretation may be impacted by the varying sensitivities of SARS-CoV-2 serological tools, we chose to associate two different assays in order to limit this source of potential bias [7] .

Our results not only support an occupational risk of SARS-CoV-2 transmission to SUH staff members from COVID-19 patient contact, but also and to a similar extent, in their private sphere, not only household contacts but also and especially outside the immediate family circle. Concerning COVID-19 professional exposure, it seems imperative to regularly ensure awareness of good practice and respect of strict hygiene standards.

We are grateful to all study participants who donated blood, the team of Cellule d'Appel, 

This study was registered in ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT04441684).

The protocol was approved by the institutional review board of CPP Sud Méditerranée III. All participants provided a written informed consent.

Inclusion visit V0 April 6, 2020 -May 7, 2020

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