key: cord-0754793-s5x8uwx9
authors: Contejean, Adrien; Leporrier, Jérémie; Canouï, Etienne; Alby-Laurent, Fanny; Lafont, Emmanuel; Beaudeau, Lauren; Parize, Perrine; Lecieux, Fabienne; Greffet, Agnès; Chéron, Gérard; Gauzit, Rémy; Fourgeaud, Jacques; L’Honneur, Anne-Sophie; Tréluyer, Jean-Marc; Charlier, Caroline; Casetta, Anne; Frange, Pierre; Leruez-Ville, Marianne; Rozenberg, Flore; Lortholary, Olivier; Kernéis, Solen
title: Comparing dynamics and determinants of SARS-CoV-2 transmissions among health care workers of adult and pediatric settings in central Paris
date: 2020-07-15
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa977
sha: bd89f6b0049653dacaf5f5378aee93180e703e13
doc_id: 754793
cord_uid: s5x8uwx9

BACKGROUND: Health-care workers (HCW) have paid a heavy toll to the coronavirus disease-19 (COVID-19) outbreak. Routes of transmission remain to be fully understood. METHODS: This prospective study compared a 1,500-bed adult and a 600-bed pediatric setting of a tertiary-care university hospital located in central Paris. From February 24(th) until April 10(th), 2020, all symptomatic HCW were screened for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on a nasopharyngeal swab. HCW screened positive were questioned on their profession, symptoms, occupational and non-occupational exposures to SARS-CoV-2. RESULTS: Among 1344 HCW tested, 373 were positive (28%) and 336 (90%) corresponding questionnaires were completed. Three hospitalizations and no death were reported. Most HCW (70%) had patient-facing occupational activities (22% in COVID-19 dedicated units). The total number of HCW cases peaked on March 23(rd), then decreased slowly, concomitantly with a continuous increase of compliance to preventive measures (including universal medical masking and personal protective equipment (PPE) for direct care to COVID-19 patients). Attack rates were of 3.2% and 2.3% in the adult and pediatric setting, respectively (p=0.0022). In the adult setting, HCW more frequently reported exposure to COVID-19 patients without PPE (25% versus 15%, p=0.046). Report of contacts with children attending out-of-home care facilities dramatically decreased over the study period. CONCLUSION: Universal masking, reinforcement of hand hygiene, and PPE with medical masks for patients’ care allowed protection of HCW and containment of the outbreak. Residual transmissions were related to persistent exposures with undiagnosed patients or colleagues and not to contacts with children attending out-of-home care facilities.

From the start of the pandemic, health-care workers (HCW) have been particularly exposed to nosocomial transmissions of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As of February 11 th , 2020, China reported more than 1,700 infected HCW in Hubei alone [1] , contributing to 3.8% of total coronavirus disease-19 cases, and at least 23 had died [2] . Occupational transmission of SARS-CoV-2 to HCW was lately reported in other countries as in the United-Kingdom [3, 4] and the United States (US) [5] .

Front-line HCW paid a heavy price to previous Coronavirus outbreaks. During the 2003-SARS epidemic in Singapore, the index patient started off a chain of nosocomial cases resulting in transmission to 60 HCW, with attack rates of up to 32% for ward-based staff [6] . Nosocomial transmissions have been recognized as an important amplifier in Coronavirus epidemics. Crosstransmissions both drive a shortage of HCW and raise anxiety and fear among hospital staff. This cascading effect further contributes to saturation of the health-care system. Protection of HCW is therefore a key concern. As the pandemic declared then accelerated, knowledge on ways of transmission of SARS-CoV-2 also advanced. Epidemiological data and temporal patterns of viral shedding now suggest that infectiousness starts from two days before symptom onset and declines within seven days in most cases [7] . Patients with severe or critical COVID-19 or with immunosuppressive conditions may shed infectious virus for longer periods of time compared to what has been reported in patients with mild illness [8, 9] . The virus mainly spreads by droplets transmission and may survive on surfaces up to 72 hours [9] . Most guidelines recommend that HCW in contact with COVID-19 patients should wear personal protective equipment (PPE) including gowns, gloves, eye protections, medical masks for standard care and FFP2 during aerosol-generating procedures [10] [11] [12] [13] [14] .

In France, the first imported case of COVID-19 was detected on January 24 th , 2020 in a 31-year-old Chinese male tourist from Wuhan [15] . By February 29 th , a total of 100 COVID-19 cases had been confirmed (https://www.santepubliquefrance.fr). Two administrative regions (Ile-de-France, including Paris, and Grand-Est) were most rapidly and severely affected. Social distancing strategies were successively implemented by the French Government by mid-March 2020. In health-care settings, in addition to PPE for direct care of COVID-19 patients, symptomatic staff were recommended A c c e p t e d M a n u s c r i p t 5 systematic screening for SARS-CoV-2 and prompted to stay isolated when positive. Nevertheless, as of April 20 th , 4,180 professionals were infected in the Assistance Publique-Hôpitaux de Paris (AP-HP, the largest French hospital institution, accounting for about 100,000 employees [http://www.aphp.fr]), raising questions on persistent routes of transmission and on the respective role of in-hospital and outhospital exposures. Here, we describe the spread of the COVID-19 outbreak among HCW of two settings of the AP-HP (one mainly caring for children and the other adults) and compared their occupational and non-occupational exposures to SARS-CoV-2.

The study was conducted in two settings of a 2,100-bed tertiary-care university hospital (AP-HP.Centre, Université de Paris) located in central Paris, France. Cochin-Broca ("Adult setting") is a 1,500-bed healthcare setting mainly caring for adult patients, except for a neonatology unit (63 beds). In health-care settings, from the start of the epidemic in February 2020, PPE was recommended for HCW caring for suspected or confirmed COVID-19 patients. In brief, PPE consisted in gowns, gloves, eye protections and either medical masks for standard care or FFP2 masks during airway aerosol-generating procedures. In addition to specific precautions for patients' care, social distancing and universal masking with medical masks was advised for all hospital employees from March 16 th in the AP-HP. All employees were encouraged to wear a face mask as often as possible in hospital (particularly in the presence of other persons), to wash/disinfect their hands regularly (and after every contact with other persons), to stay at least 2 meters away from others, to cover their mouth and nose with a tissue or sleeve when coughing or sneezing, to put used tissues in the bin immediately and wash hands afterwards, to avoid touching eyes, mouth. Educational messages were released on the internal website and on posters placed in all hospital premises. Testing for SARS-CoV-2 of symptomatic staff started on February 24 th in the Adult setting, and on March 5 th in the children setting. Hospital employees presenting either with fever (reported or measured >37.8°C), cough, rhinorrhea, muscle pain, shivers, loss of smell or taste, unusual persistent headaches or severe asthenia, were referred to the two on-site screening pods. Trained medical doctors or nurses collected a nasopharyngeal swab for each symptomatic staff member. Test results were communicated within 24 hours via a secured email or by phone. If they felt well enough to do so, HCW with pending tests were allowed to continue working, on condition to strictly comply with the hygiene protocol (careful hand hygiene and mask wearing at any time) while waiting for the results. HCW with positive results were sent home and able to return to work after seven days (including two days after resolution of any symptoms).

A c c e p t e d M a n u s c r i p t 7

Shortly thereafter, HCW with positive results were prospectively contacted by phone and invited to participate. After three unsuccessful attempts, they were considered unreachable. Data were collected on a standardized questionnaire on age, gender, profession, date of symptoms onset, and exposure to SARS-CoV-2 in the 10 preceding days. For confidentiality reasons, we did not collect data on past medical history and comorbidities. Exposures were classified as: in-hospital related to patients' care (average number of close contacts per day with COVID-19 index patients with and without PPE, compliance to infection prevention and control [IPC] protocols), in-hospital related to other activities (contacts with colleagues during meal breaks, meetings, etc.) and out-hospital (frequentation of public transports, contacts with household members, especially children kept outside the household). Index cases were patients with COVID-19 infection, either probable (compatible clinical signs and radiographic evidence of pneumonia on thoracic computed tomography scan) or confirmed (detection of SARS-CoV-2 RNA in a clinical specimen using rt-PCR). A contact at a distance <2 meters for >10 minutes was defined as close contact [15] .

Virology methods SARS-CoV-2 was detected by amplification of E, RdRp and N genes using the Allplex Eurobio® reagent or the RealStar® rtPCR kit, a triplex PCR amplifying the viral genome in the E and S genes and an internal control. The result was considered positive if three out of the three targets were amplified. A control sample was requested if only one or two target genes were amplified.

The number of cases was computed on a daily basis. Continuous variables are presented as medians 

This study was approved by the Ethical Review Committee for publications of the Cochin university Hospital (CLEP) (N°: AAA-2020-08012). According to French policy, a non-opposition statement was obtained for all participants, meaning that all had received written detailed information on the objectives of the study and were free to request withdrawal of their data at any time. reported contacts with COVID-19 patients, including four in the same geriatric ward. Mask wearing outside home increased but capped around 60% as of April 10 th ( Figure 2E) . Conversely, the proportion reporting childcare outside home fell dramatically over the study period ( Figure 2F ). Preventive measures including universal masking, reinforcement of hands hygiene and social distancing were applied from mid-March in our two settings. One week later, the epidemic curve flattened, although HCW were increasingly exposed to COVID-19 patients and the outbreak was concomitantly peaking in the region Ile-de-France. This shift is consistent with the SARS-CoV-2 incubation interval [7] and data reported elsewhere [3] . Our results support that current adopted practices (medical masks in most patients and N95/FFP2 in aerosol generating procedures) [11, 14] can largely protect HCW against contaminations. This observation, in real-life conditions, further suggests that SARS-CoV-2 is primarily transmitted via droplets, despite discussion on the possibility of airborne transmission, raised by experimental studies [9] . Lack of compliance to mask wearing reported during breaks, and recent data evidencing viral shedding occurring before symptoms A c c e p t e d M a n u s c r i p t 11 onset [7] , also underscore the importance of maintaining physical distancing rules between hospital employees during out-of-duty activities.

The attack rate was significantly lower in the Children setting, possibly related to a lower number of COVID-19 patients admitted in this setting, and to higher awareness and compliance to IPC measures.

Indeed, in pediatric settings, gowns and droplet precautions are routinely recommended even out of a pandemic context [16] , and compliance to hands hygiene is reported to be higher [17] .

Children have been initially suspected to play a central role in transmission of SARS-CoV-2.

However, recent data have been more balanced [18] [19] [20] . Attack rates in children may be lower than in adults [21, 22] . Moreover, in a French cluster of 12 COVID-19 cases, the only child involved did not cause any documented secondary case despite multiple contacts while symptomatic [23] . In France, The main limitation of our study is the lack of a control group (i.e. HCW that were not infected by SARS-CoV-2). This limitation in study design prevents from adequately adjusting for potential confounding variables and accounting for effect modification, and deserves cautious interpretation of A c c e p t e d M a n u s c r i p t 12 the results. Identification of negative controls is nevertheless difficult. Indeed, sensitivity of the rt-PCR on nasopharyngeal swabs is imperfect [24] . Serologic assessment may contribute to definitively rule out the diagnosis of COVID-19. However, serological assays for SARS-CoV-2 are still under investigation before large implementation among French HCW. We chose to rapidly communicate timely data in order to guide decisions in view of the soon upcoming lift of containment measures.

Further investigations are planned to identify negative controls and formally compare their exposures to HCW of our cohort. Our study also only captured symptomatic infections; we were then unable to assess exposures in the whole cohort of HCW who developed COVID-19 (particularly in those who remained asymptomatic), and potentially missed additional routes of acquisition. Another limitation is the recall bias which is inherent to the use of questionnaires in epidemiological studies, however infected HCW were interrogated prospectively and shortly after PCR assessment. Last, exposures were self-reported. We did not perform a formal phylogenetic viral analysis that could have allowed definitive confirmation of the true source of infections.

Several conclusions can be drawn from our results: (i) HCW are exposed to emerging viral diseases, particularly at the early phase of the epidemic; (ii) compliance to control measures increased over the study period, concomitantly with containment of the outbreak among hospital staff ; (iii) incidence was lower in HCW of the Children setting, likely related to a better adherence to IPC measures by the pediatric staff and (iv) residual transmissions observed at the late phase of the epidemic among HCW were related to persistent exposures with undiagnosed patients or colleagues and not to contacts with children attending out-of-home care facilities.

A c c e p t e d M a n u s c r i p t

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Medical Masks vs N95 Respirators for Preventing COVID-19 in Health Care Workers A Systematic Review and Meta-Analysis of Randomized Trials

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First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures

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Coronavirus Infections in Children Including COVID-19: An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children

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Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study

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Detection of SARS-CoV-2 in Different Types of Clinical Specimens

The authors warmly thank medical students involved in data collection: Laurence Clastres, Mathilde Lehmann, Aline Pellegrini, Marine Sisouvan, Ilana Slotine, Diem Soubou and Abigaëlle Vergnet, the following physicians and nurses who actively contributed to the screening: Claire Aguilar, Chantal

AC, JL, OL and SK designed the study and drafted the paper. AC, JL, ML, FR, OL and SK contributed to data analysis and interpretation. All authors critically revised the manuscript for important intellectual content and gave final approval for the version to be published. OL and SK had full access to all the data in the study and had final responsibility for the decision to submit for publication.A c c e p t e d M a n u s c r i p t 15 A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t 18