key: cord-0766769-w7knt9fa authors: Yamamoto, Shohei; Tanaka, Akihito; Oshiro, Yusuke; Ishii, Masamichi; Ishiwari, Hironori; Konishi, Maki; Matsuda, Kouki; Ozeki, Mitsuru; Miyo, Kengo; Maeda, Kenji; Mizoue, Tetsuya; Sugiura, Wataru; Mitsuya, Hiroaki; Sugiyama, Haruhito; Ohmagari, Norio title: Seroprevalence of SARS-CoV-2 antibodies in a national hospital and affiliated facility after the second epidemic wave of Japan date: 2021-05-25 journal: J Infect DOI: 10.1016/j.jinf.2021.05.017 sha: ce98b1edf97e7f5e9c187d75306fde75cfc97b08 doc_id: 766769 cord_uid: w7knt9fa nan Healthcare workers (HCWs) are at high risk for coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1, 2). However, relative to the general population, there was no increase in the infection risk among HCWs in hospitals with adequate control measures against the infection (3) . Studies on the source of infection among HCWs showed a stronger association with community factors than occupational factors (4) (5) (6) , suggesting the importance of infection prevention outside the hospital. Although Japan recorded a relatively high number of COVID-19 cases in Asia, data on SARS-CoV-2 infection and its source among HCWs are limited. The National Center for Global Health and Medicine (NCGM) has played a leading role in patient care and COVID-19 research since the early phase of the epidemic in Japan. Additionally, the staff were involved in screening for returnees from Wuhan, infection control on the Diamond Princess cruise ship, and running a fever clinic and local polymerase chain reaction (PCR) testing center (7) . To estimate the cumulative SARS-CoV-2 infection rate over time, we designed a repeat seroprevalence study among the NCGM staff. Previously, we reported a very low seroprevalence of SARS-CoV-2 IgG antibody (0.16%) as of July 2020, after the first COVID-19 wave in Japan (8). Here, we report the seroprevalence and its related factors in a follow-up survey after the second, larger wave ( Figure) . We invited all NCGM staff (Toyama and Kohnodai areas) and asked participants to complete a questionnaire and donate venous blood in October (Toyama) and December (Kohnodai) 2020. We collected data on demographics, occupational factors, close contact with patients with COVID-19, symptoms indicative of COVID-19, PCR testing results, use of public transportation, and adherence to infection prevention practices (IPPs). We qualitatively measured IgG (Abbott ARCHITECT ® ) and total antibodies (Roche Elecsys ® ) against the SARS-CoV-2 nucleocapsid protein, according to the manufacturers' instructions at an in-house (Toyama) or external laboratory (Kohnodai). We performed a confirmatory analysis of seropositive samples on either test with the EUROIMMUN anti-S IgG immunoassay. If it was positive, neutralizing antibody titers were measured using the live virus (Supplemental Text). Written informed consent was obtained from each participant. This study was approved by the ethics committee of NCGM. Seropositivity was defined as positivity of either test (sensitivity priority). Seroprevalence with 95% confidence intervals (CI) were calculated using the exact binomial technique. We performed Poisson regression with a robust variance estimator to assess the association between exposure variables and seropositivity. Participants who had both tests positive were classified as being seropositive (specificity priority). Of 2,893 staff invited, 2,563 (88.6%) participated. The major occupations included nurses (36%), doctors (16%), allied healthcare professionals (14%), and administrative staff (11%). Nearly half of the participants (47.6%) had been engaged in COVID-19-related work (Table) . The adherence to the recommended A history of loss of taste and smell and PCR testing were associated with an increased seropositivity rate. Close contact with patients with COVID-19 at home and in the community (family members, cohabitants, acquaintances, or friends), but not in the hospital (coworker or patients), was associated with seropositivity. The seropositivity rate was not high among those working in the COVID-19 ward or engaged in COVID-19-related work (Table) . After the second COVID-19 wave in Japan, the seroprevalence rate among the NCGM staff remained low (0.70%), which was even lower than those of the general population in Tokyo during the same period (1.94%, recalculated according to the definition used in this study) (9). We found no evidence of clustering of seropositive staff in the center and no significant association between occupational factors and seropositivity. These data refute an increased risk of inpatient-to-HCW and HCW-to-HCW transmission in hospitals well prepared for COVID-19. NCGM has introduced and strengthened multiple infection control measures since the early phase of the epidemic, including the provision of personal protective equipment, universal masking, hand washing, and routine checking of staff's body temperature, and PCR testing in case of suspected infection (8). These results support the effectiveness of these measures against infection associated with occupational exposure. Regarding non-occupational factors, close contact with patients with COVID-19 at home and in the community was associated with increased seropositivity. Given few seropositive staff who had close contact in these settings (n=2, 11% of seropositive staff), it is reasonable to assume that the primary route of infection might be unrecognized contact with asymptomatic cases in the community. The NCGM is located in an epicenter of the second wave; therefore, the infection control division sends e-mails to all staff weekly to enhance their awareness of preventive behaviors (8), leading to high adherence to the recommended IPPs by the staff (Figure S1 ). With the correlation between the infection rate of HCWs and the cumulative community incidence (4, 10), there is need for more emphasis on the prevention of community-acquired infection in preventing nosocomial infection. This study provides more evidence on the contribution of comprehensive control measures targeting both occupational and community risk of SARS-CoV-2 infection in the protection of HCWs from infection during the epidemic. Antibody test reagents were provided by Abbott and Roche Diagnostic. COVID-19 in Health-Care Workers: A Living Systematic Review and Meta-Analysis of Prevalence, Risk Factors, Clinical Characteristics, and Outcomes Seroprevalence of SARS-CoV-2 antibodies and associated factors in healthcare workers: a systematic review and meta-analysis Prevalence of SARS-CoV-2 Infection Among Health Care Workers in a Tertiary Community Hospital Risk Factors Associated With SARS-CoV-2 Seropositivity Among US Health Care Personnel COVID-19 in health-care workers in three hospitals in the south of the Netherlands: a cross-sectional study. The Lancet Infectious Diseases Quantification of Occupational and Community Risk Factors for SARS-CoV-2 Seropositivity Among Health Care Workers in a Large U.S. Health Care System Lessons from COVID-19 -record and experience in NCGM-. Feel the NCGM We thank the members of the working group of the Clinical Epidemiology Study on SARS-CoV-2 Antibody among the NCGM staff (Shinji Kobayashi, Ryuma Hirabayashi, Tomoko Nakayama, Ayako Mikami, Moto Kimura) for their support in this survey. This work was supported by the NCGM COVID-19 Gift Fund and the Japan Health Research Promotion Bureau Research Fund (2020-B-09). The funder did not play any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.