key: cord-0948385-9on733t9 authors: Erber, J.; Kappler, V.; Haller, B.; Mijocevic, H.; Galhoz, A.; Prazeres da Costa, C.; Gebhardt, F.; Graf, N.; Hoffmann, D.; Thaler, M.; Lorenz, E.; Roggendorf, H.; Kohlmayer, F.; Henkel, A.; Menden, M. M.; Ruland, J.; Spinner, C. D.; Protzer, U.; Knolle, P.; Lingor, P. title: Strategies for infection control and prevalence of anti-SARS-CoV-2 IgG in 4,554 employees of a university hospital in Munich, Germany date: 2020-10-06 journal: nan DOI: 10.1101/2020.10.04.20206136 sha: d254966e1c060983972a63d6211c9c1cae49a170 doc_id: 948385 cord_uid: 9on733t9 Background Hospital staff are at high risk of infection during the coronavirus disease (COVID-19) pandemic. We analysed the exposure characteristics, efficacy of protective measures, and transmission dynamics in this hospital-wide prospective seroprevalence study. Methods and Findings Overall, 4554 individuals were tested for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies using a chemiluminescent immunoassay. Individual risk factors, use of personal protective equipment (PPE), occupational exposure, previous SARS-CoV-2 infection, and symptoms were assessed using a questionnaire and correlated to anti-SARS-CoV-2 IgG antibody titres and PCR testing results. Odds ratios with corresponding exact 95% confidence intervals were used to evaluate associations between individual factors and seropositivity. Spatio-temporal trajectories of SARS-CoV-2-infected patients and staff mobility within the hospital were visualised to identify local hotspots of virus transmission. The overall seroprevalence of anti-SARS-CoV-2-IgG antibody was 2.4% [95% CI 1.9-2.9]. Patient-facing staff, including those working in COVID-19 areas, had a similar probability of being seropositive as non-patient-facing staff. Prior interaction with SARS-CoV-2-infected co-workers or private contacts and unprotected exposure to COVID-19 patients increased the probability of seropositivity. Loss of smell and taste had the highest positive predictive value for seropositivity. The rate of asymptomatic SARS-CoV-2 infections was 25.9%, and higher anti-SARS-CoV-2 IgG antibody titres were observed in symptomatic individuals. Spatio-temporal hotspots of SARS-CoV-2-positive staff and patients only showed partial overlap. Conclusions Patient-facing work in a healthcare facility during the SARS-CoV-2 pandemic may be safe if adequate PPE and hygiene measures are applied. The high numbers of asymptomatic SARS-CoV-2 infections that escaped detection by symptomatic testing underline the value of cross-sectional seroprevalence studies. Unprotected contact is a major risk factor for infection and argues for the rigorous implementation of hygiene measures. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 90 was declared a pandemic and global health emergency by the World Health 91 Organization in March 2020 and continues to pose significant challenges to 92 healthcare systems [1] . Alarming infection rates, morbidity, and mortality have been 93 reported among medical staff fighting the pandemic, threatening the functionality of 94 healthcare facilities and emphasising the need to implement effective infection 95 control measures [2] [3] [4] . The reported prevalence of anti-SARS-CoV-2 IgG antibodies 96 in health care workers (HCW) varies from 13.7% in the New York City area, 10.2% in 97 a nationwide study in Spain, 7.5% in 580 HCW in a Spanish hospital, 6.4% in >3000 98 HCW in a tertiary hospital in Belgium, 4.0% in >28790 HCW in Denmark, and 0.4% to To better understand the epidemiology and immune response to SARS-CoV-2 and to 114 identify best-practice approaches protecting staff and patients, a prospective, 115 observational cohort study was initiated to assess the risk factors and evidence for 116 infection, including clinical symptoms, and to determine the seroprevalence of SARS- 117 CoV-2 antibodies. 118 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) 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 October 6, 2020. co-workers, or private contacts; symptom history; previous PCR testing for SARS-permitted to return to work when they had been asymptomatic for at least 48 hours. 145 In case of a positive test result, staff were quarantined for 14 days, then retested and 146 only allowed to continue working if the PCR tests were negative on two consecutive 147 days. The PCR-results of staff testing were included in the present analysis if the 148 study participants consented. Wiesbaden, Germany) and subjected to SARS-CoV-2 PCR using oligo-dT for 168 reverse transcription and N1 and N3 primer and probe sets for detection according to 169 the protocol of the Centre for Disease Control and Prevention, Atlanta, USA. 170 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) 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 October 6, 2020. (which was not certified by peer review) 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 October 6, 2020. (which was not certified by peer review) 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 October 6, 2020. Positive anti-SARS-CoV-2 IgG antibodies were found in 108/4554 study participants. 217 In 102 individuals, additional assays confirmed the anti-SARS-CoV-2 IgG screening 218 result (S1 Table) . Two additional individuals reporting a positive PCR test 219 seroconverted during follow-up. Four individuals with IgG titres of 5-10 AU/mL in the 220 screening assay, which is below the cut-off, were found to be positive in at least two 221 other assays (S1 and S2 Tables). In five individuals, the screening result could not be 222 confirmed by the other assays used; in one, there was insufficient material available 223 to complete testing (S3 Table) The first patient with PCR-confirmed COVID-19 was admitted to our university 229 hospital on March 6, 2020, and 163 COVID-19 patients were hospitalised between 230 March 6, 2020 and May 29, 2020 ( Fig 1A) . Infection prevention measures were 231 dynamically adjusted according to the prevalent pandemic situation (Fig 1A) . 232 Individual risk factors for infection were identified through correlation of self-reported 233 survey data with seropositivity for anti-SARS-CoV-2 IgG antibodies. We found an 234 association between seropositivity and male sex (OR 1.54 [95% CI, 1.03-2.27]) or 235 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) 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 October 6, 2020. (which was not certified by peer review) 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 October 6, 2020. . https://doi.org/10.1101/2020.10.04.20206136 doi: medRxiv preprint (Table 2, (which was not certified by peer review) 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 October 6, 2020. (which was not certified by peer review) 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 October 6, 2020. . https://doi.org/10.1101/2020.10.04.20206136 doi: medRxiv preprint type of protective equipment used was not associated with seroprevalence, but 98% 309 of staff reported routinely using medical masks, which was required by internal (which was not certified by peer review) 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 October 6, 2020. . https://doi.org/10.1101/2020.10.04.20206136 doi: medRxiv preprint results) (S8 Fig, No. 14, 29) . This may be explained by false-positive PCR results or (which was not certified by peer review) 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 October 6, 2020. The current study has several limitations. First, because this was a voluntary 378 assessment, participation was incomplete and may have biased the results. We 379 cannot exclude the possibility that staff members with a higher perceived risk of 380 infection were more likely to participate. Furthermore, as most students stayed at 381 home during lock-down, their participation rate was low. Second, symptoms and 382 exposures were retrospectively assessed and self-reported and thus subject to a 383 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) 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 October 6, 2020. (which was not certified by peer review) 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 October 6, 2020. (which was not certified by peer review) 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 October 6, 2020. (which was not certified by peer review) 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 October 6, 2020. . https://doi.org/10.1101/2020.10.04.20206136 doi: medRxiv preprint (which was not certified by peer review) 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 October 6, 2020. . https://doi.org/10.1101/2020.10.04.20206136 doi: medRxiv preprint (which was not certified by peer review) 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 October 6, 2020. . https://doi.org/10.1101/2020.10.04.20206136 doi: medRxiv preprint (which was not certified by peer review) 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 October 6, 2020. (which was not certified by peer review) 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 October 6, 2020. (which was not certified by peer review) 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 October 6, 2020. (which was not certified by peer review) 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 October 6, 2020. (which was not certified by peer review) 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 October 6, 2020. . https://doi.org/10.1101/2020.10.04.20206136 doi: medRxiv preprint A cluster of health care workers 458 with COVID-19 pneumonia caused by SARS-CoV-2 Clinical characteristics of 54 medical staff 461 with COVID-19: A retrospective study in a single center in Wuhan Pandemic peak SARS-CoV-2 464 infection and seroconversion rates in London frontline health-care workers Antibodies in Health Care Personnel in the New York City Area 469 Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based 470 seroepidemiological study Seroprevalence of immunoglobulin M and G 472 antibodies against SARS-CoV-2 in China Risk of 474 COVID-19 in health-care workers in Denmark: an observational cohort study. The Lancet Infectious 475 Diseases CoV-2 Antibody Screening in 3056 Staff in a Tertiary Center in Belgium Seroprevalence of antibodies against SARS-CoV-2 among health care workers in a large Spanish 480 reference hospital SARS-CoV-2 antibody screening in healthcare workers in a 482 tertiary centre in North West England Data Integration for Future Medicine 486 (DIFUTURE) Intensive Care Risk 488 Estimation in COVID-19 Pneumonia Based on Clinical and Imaging Parameters: Experiences from the 489 Munich Cohort Epidemiology of and Risk Factors for 491 Coronavirus Infection in Health Care Workers Seroprevalence of 493 anti-SARS-CoV-2 IgG antibodies in Perceived versus 496 proven SARS-CoV-2-specific immune responses in health-care professionals SARS-CoV-2 and 498 COVID-19: A review of reviews considering implications for public health policy and practice. Tob 499 Induc Dis Risk factors for hospital admission in 501 the 28 days following a community-acquired pneumonia diagnosis in older adults, and their 502 contribution to increasing hospitalisation rates over time: a cohort study Risk Factors for Community-Acquired Pneumonia in 505 Adults: A Systematic Review of Observational Studies Smoking and the risk of COVID-19 in a 507 large observational population study Editorial: 509 Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system SARS-CoV-2 disease severity and diabetes: why the connection and 512 what is to be done? Clinical and immunological assessment 514 of asymptomatic SARS-CoV-2 infections