key: cord-0922721-87wbwgce authors: CONTEJEAN, A.; LEPORRIER, J.; CANOUI, E.; FOURGEAUD, J.; MARIAGGI, A.-A.; ALBY-LAURENT, F.; LAFONT, E.; BEAUDEAU, L.; ROUZAUD, C.; LECIEUX, F.; GREFFET, A.; L'HONNEUR, A.-S.; TRELUYER, J.-M.; LANTERNIER, F.; CASETTA, A.; FRANGE, P.; LERUEZ-VILLE, M.; ROZENBERG, F.; LORTHOLARY, O.; KERNEIS, S. title: Transmission routes of SARS-CoV-2 among healthcare workers of a French university hospital in Paris, France: a case-control study date: 2020-11-03 journal: nan DOI: 10.1101/2020.10.30.20223081 sha: f351448c2dc43b1e3eb8c32cfafd5788cf131639 doc_id: 922721 cord_uid: 87wbwgce In this case-control study on 564 healthcare workers of a university hospital in Paris (France), contacts without protection with COVID-19 patients or with colleagues were associated with infection with SARS-CoV-2, while working in a COVID-dedicated unit, using public transportation and having children kept in childcare facilities were not. Effective protection of healthcare workers (HCW) against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requires precise assessment of the respective role of in-hospital and outof-hospital exposures on transmission routes in this at high-risk population. We previously published an observational multicenter cohort study on HCW infected by SARS-CoV-2 during the first French coronavirus disease-19 (COVID-19) breakthrough in 2020 spring [1] . Only 20% of the HCW screened positive for SARS-CoV-2 reported close contact with a suspected or confirmed COVID19 patient without Personal Protective Equipment (PPE), and 78% were not regularly posted in a COVID-19-dedicated unit. On the other hand, 54% declared frequent close contacts during occupational activities with colleagues without protection. We were however unable to compare positive HCW to a robust control group gathering personnel not infected with SARS-CoV-2. Diagnosis sensitivity of reverse transcriptase polymerase chain reaction (rtPCR) on nasopharyngeal swab for COVID-19 is imperfect [2] and serological assessment was not available at this time. IgG serological test has since been proven to be reliably associated with a COVID-19 past-infection [3] . We present here a case-control study which aimed to compare COVID-19 positive and negative HCW regarding their occupational activity, symptoms and in-hospital and out-of-hospital exposures to SARS-CoV-2, to determine the respective roles of different SARS-CoV-2 transmission routes. This case-control study was led among HCW of a 2,100-bed tertiary-care university hospital (AP-HP. Centre, Université de Paris) located in central Paris, France, employing 13,278 personnel. From 24 th February, to 10 th April 2020, symptomatic staff were referred to dedicated on-site screening centers where trained medical staff collected a nasopharyngeal swab for SARS-CoV-2 rtPCR. HCW who tested positive on rtPCR were included as cases (HCW+). For each confirmed case, we included a control symptomatic HCW tested for SARS-CoV-2 on the same day, who had a negative rtPCR and a negative serological assessment performed at least 1 month after symptoms onset (HCW-). Both cases and controls were questioned in detail on their professional activity, symptoms, occupational and non-. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.30.20223081 doi: medRxiv preprint occupational exposures to SARS-CoV-2 immediately after screening [1] . During this period, social distancing measures were implemented in France. On March 12 th all school and childcare facilities closed, except for children of hospital staff, and a nationwide lockdown started on March 17 th . Lift of containment measures occurred on May 11 th . SARS-CoV-2 rtPCR technique has been described elsewhere [1] . SARS-CoV-2 serology was determined by the Abbott® SARS-CoV-2 IgG assay, a chemiluminescent microparticle immunoassay intended for the qualitative detection of IgG antibodies to SARS-CoV-2. Continuous variables are presented as median (interquartile range) and categorical variables as number Between February 24 th and April 10 th , 2020, 1344 symptomatic HCW were screened for SARS-CoV-2 by rtPCR on a nasopharyngeal swab. Among them, 373 had positive rtPCR results (28%), 336 (90%) completed the questionnaire, and were included as cases (HCW+). Among 338 matched HCW with negative rtPCR, 247 (73%) had a serological assessment, and 228 (92%) tested negative. This group of 228 HCW with both negative rtPCR and serology constituted the control group (HCW-). Exposures reported by cases and controls are displayed in the Table. Cases and controls where comparable in terms of age, sex and professional category. Cases presented more frequently with . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.30.20223081 doi: medRxiv preprint anosmia or ageusia and with asthenia, fever, muscle pain, dyspnea, headaches and diarrhea than controls. Frequency of cough or rhinorrhea did not differ between groups. In the univariate analysis (table), occupational activities with direct patient facing or assignment to a COVID-19-dedicated unit were similar in cases and controls. However, cases reported more close contacts with suspected or confirmed COVID-19 patients without PPE. Controls declared better compliance to mask wearing during occupational activities or in the presence of colleagues. Out-ofhospital exposures did not differ between cases and controls except for mask wearing outside home. In particular, using public transportation, having a child at home or a child kept out of the household were not associated with a significant increased risk of COVID-19. Multivariate analysis showed that in the pre-lockdown period, close contacts with colleagues without was independently associated with an increased risk of COVID-19 in HCW. This case-control study among HCW highly exposed to SARS-CoV-2 suggests that PPE and especially medical mask is efficient in preventing COVID-19 transmission in HCW, including its systematic use outside hospital and home. To our knowledge, it is the first study to report both occupational and non-occupational exposures associated with SARS-CoV-2 infection in HCW since previous reports mainly focused on professional exposures and did not use IgG serology to contribute ruling-out COVID-19 in controls [4, 5] . Unsurprisingly, symptoms were significantly different between cases and controls. Anosmia and ageusia appeared to be strongly associated to SARS-CoV-2 infection as reported elsewhere [6, 7] , whereas cough or rhinorrhea were not. Clinical scores including number of symptoms statistically associated with COVID-19 have been developed and might be a useful tool to quickly sort symptomatic HCW before results of SARS-CoV-2 testing [7] . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. thus strict compliance to universal masking and social distancing measures are critical to prevent SARS-CoV-2 transmissions from asymptomatic patients or colleagues. Moreover, adherence to PPE during patient care is crucial to prevent COVID-19 infection in HCW, as we previously suggested [1] . Conversely, in our cohort, direct patient care was not associated with an increased risk of COVID-19 (including in COVID-19-dedicated wards), as long as HCW wear PPE. Of note, PPE supplies were immediately and fully available in our center, which was not the case in all French healthcare settings. Compliance to protective measures may also have been better among highly trained HCW of COVID-19-dedicated units. Recently, a large cohort study on 99,795 HCW suggested that frontline HCW were at increased risk of COVID-19 compared to community individuals, especially in case of exposition to patients with inadequate PPE [4] . Analysis of non-occupational exposures suggest that wearing a mask outside home may provide protection against COVID-19. The specific effect of mask wearing in the community is controversial. Indeed, HCW who reported wearing a mask outside home in our cohort (17%) were also probably more cautious regarding social activities and other suspected sources of SARS-CoV-2, which were not assessed in the questionnaire. Community use of facemasks have failed to demonstrate efficiency in prevention of influenzae transmission in a meta-analysis [9] . In Hong-Kong, a study suggested that the number of COVID-19 clusters were reduced when universal masking was recommended [10] , and a study conducted in the USA concluded that mask wearing mandatory permitted to reduce daily COVID-19 growth rates [11] . However, to our knowledge, no study with high level of evidence has been published yet on that question. As suggested in our first report [1] and here confirmed by the case-control study, HCW who reported to have children kept outside the family home did not have a higher risk of COVID-19 infection. However, childcare facilities that remained open for HCW's children during the national lockdown gathered a limited number of children simultaneously (<10). This question of SARS-CoV-2 transmission from children is highly debated since the beginning of the pandemic, but accumulating . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.30.20223081 doi: medRxiv preprint data suggest that children are not significant drivers for COVID-19 pandemic [12] . Therefore, our results suggest that keeping schools and childcare facilities open for HCW is acceptable especially in case of second containment period, when HCW should be fully available at hospital. We acknowledge several limitations, in particular recall bias, but cases and controls were interrogated prospectively and shortly after PCR assay. Additionally, our questionnaire included declarative data maybe not fully compressive regarding SARS-CoV-2 exposures. In conclusion, profession category, direct patient care or assignment to a COVID-19-dedicated unit were not associated with COVID-19 infection in our cohort of HCW. Conversely, close contacts with suspected or confirmed COVID-19 patients without PPE or multiplication of contacts with colleagues without mask may be risk factors for COVID-19 infection in HCW. Systematic mask wearing outside home was associated with a reduction of this risk during the pre-lockdown period. 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. SK had full access to all the data in the study and had final responsibility for the decision to submit for publication. All authors declare no conflict of interest in relation with the submitted work This study had no funding source or sponsor implicated in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the article for publication. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020. 10.30.20223081 doi: medRxiv preprint This study was approved by the Ethical Review Committee for publications of the Cochin University Hospital (number 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. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. Comparing dynamics and determinants of SARS-CoV-2 transmissions among health care workers of adult and pediatric settings in central Paris Detection of SARS-CoV-2 in Different Types of Clinical Specimens Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence in Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study Specific risk factors for SARS-CoV-2 transmission among health care workers in a university hospital Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms COVID-19 symptoms predictive of healthcare workers' SARS-CoV-2 PCR results Temporal dynamics in viral shedding and transmissibility of COVID-19 Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings-Personal Protective and Environmental Measures The role of community-wide wearing of face mask for control of coronavirus disease 2019 (COVID-19) epidemic due to SARS-CoV-2 Community Use Of Face Masks And COVID-19: Evidence From A Natural Experiment Of State Mandates In The US COVID-19 Transmission and Children: The Child Is Not to Blame The authors warmly thank medical students involved in data collection: Laurence Clastres, Mathilde