Case fatality rate considering the lag time from the onset of COVID-19 infection to related death from 2020 to 2022 in Japan

Importance : On an ecological scale, the lag time between COVID-19 infection and related fatality has varied among different infection waves and prefectures in Japan. The variability in lag across areas of Japan during the seventh distinct infection phases can help derive a more appropriate estimation of the weekly confirmed case fatality rate (CFR) of COVID-19. Objective : Because of the ongoing COVID-19 pandemic, this study aims to estimate the seven days-moving average CFR across area block level in Japan from February 2020 t July 2022 using the lag time between the COVID-19 infection and related fatality. Main outcomes and measures : Seven days-moving average CFR of COVID-19 for area block in Japan considering the lag time between infection and death (total and subgroup analysis of elderly). Results : We found that the lag varied substantially among prefectures in Japan from the first to the seventh phase of the COVID-19 epidemic. The estimated seven days-moving average CFR based on the lag time reflects the Japanese COVID-19 pandemic and related policy intervention (e.g., vaccination for elderly people) well rather than other standard CFR estimations. Conclusions and relevance : The variation in the estimated lag time across prefectures in Japan for different infection waves indicates that it is inadequate to directly use the clinical results of the period from the start of infection to death for ecological-scale evaluation of the CFR. Moreover, we found that the lag time between infection and related fatality could be either shorter or longer than the clinically reported period. This revealed that preliminary reports of CFR may be overestimated or underestimated even if they consider the lag based on clinical reports.

SARS-CoV-2 evolution among patients with immunosuppression in a nosocomial cluster of a Japanese medical center during the Delta (AY.29 sublineage) surge.

Background: Previous studies have shown that patients with immunosuppression tend to have longer-lasting SARS-CoV-2 infections and a number of mutations were observed during the infection period. However, these studies were, in general, conducted longitudinally. Mutation evolution among groups of patients with immunosuppression have not been well studied, especially among Asian populations. Methods: Our study targeted a nosocomial cluster of SARS-CoV-2 infection in a Japanese medical center during Delta surge (AY.29 sublineage), involving ward nurses and inpatients. Whole-genome sequencing analyses were performed to examine mutation changes. Haplotype and minor variant analyses were furtherly performed to detect the mutations on the viral genomes in detail. In addition, sequences of the first wild-type strain hCoV-19/Wuhan/WIV04/2019 and AY.29 wild-type strain hCoV-19/Japan/TKYK15779/2021 were used as references to assess the phylogenetical development of this cluster. Results: A total of 6 nurses and 14 inpatients were identified as a nosocomial cluster from September 14 through 28, 2021. All were Delta variant (AY.29 sublineage) positive. 92.9% of infected patients (13 out of 14) were either cancer patients and/or receiving immunosuppressive or steroid treatments. Compared to AY.29 wild type, a total of 12 mutations were found in the 20 cases. Haplotype analysis found one index group of eight cases with F274F (N) mutation and 10 other haplotypes with one to three additional mutations. Furthermore, we found that cases with more than three minor variants were all cancer patients under immunosuppressive treatments. The phylogenetical tree analysis, including 20 nosocomial cluster-associated viral genomes, the first wild-type strain and the AY.29 wild-type strain as references, indicated the mutation development of the AY.29 virus in this cluster. Conclusion: Our study of a nosocomial SARS-CoV-2 cluster highlights mutation acquisition during transmission. More importantly, it provided new evidence emphasizing the need to further improve infection control measures to prevent nosocomial infection among immunosuppressed patients.

Increased SARS-CoV-2 seroprevalence and spread of infection without awareness among healthcare workers through 2020-2022 in a Japanese medical center.

Despite Japan's high vaccination coverage, daily numbers of new COVID-19 cases have been high. However, studies on the seroprevalence among Japanese people and the causative factors for rapid spread have remained limited. In this study, we aimed to examine the seroprevalence and associated factors in healthcare workers (HCWs) of a medical center in Tokyo using blood samples drawn at annual check-ups from 2020 to 2022. We found that of the 3,788 HCWs in 2022 (by mid-June), 669 were seropositive for N-specific antibodies (tested by Roche Elecsys Anti-SARS-CoV-2 assay); the seroprevalence surged from 0.3% in 2020 and 1.6% in 2021 to 17.7% in 2022. Notably, our study found 325 (48.6%; 325/669) cases were infected without awareness. Among those with a previously PCR-confirmed SARS-CoV-2 infection during the past three years, 79.0% (282/357) were found after January 2022, after the Omicron variant was first detected in Tokyo at the end of 2021. This study indicates the fast spread of the SARS-CoV-2 among HCWs during the Omicron surge in Japan. The high percentage of infection without awareness may be a key driving factor causing rapid person-to-person transmission, as shown in this medical center with high vaccination coverage and strict infection control measures.

Mortality Prediction of COVID-19 in Hospitalized Patients Using the 2020 Diagnosis Procedure Combination Administrative Database of Japan.

Objectives Numerous people have died from coronavirus disease 2019 (COVID-19) infection. Identifying crucial predictive biomarkers of disease mortality is critical to support decision-making and logistic planning in healthcare systems. This study investigated the association between mortality and medical factors and prescription records in 2020 in Japan, where COVID-19 prevalence and mortality remain relatively low. Methods This retrospective cohort study analyzed anonymous administrative data from the Diagnosis Procedure Combination (DPC) database in Japan. Results A total of 22,795 patients were treated in DPC hospitals in 2020 in Japan, and of these, 5,980 patients over 50 years old were hospitalized, with 299 (5.0%) dying. There were 2,399 severe patients among 11,440 total hospitalized patients (all ages). The results of a logistic model analysis revealed that an older age, male sex, Parkinson's disease, cerebrovascular diseases, and chronic kidney diseases were risk factors for mortality. A machine learning analysis identified an older age, male sex (mortality), pneumonia, drugs for acid-related disorders, analgesics, anesthesia, upper respiratory tract disease, drugs for functional gastrointestinal disorders, drugs for obstructive airway diseases, topical products for joint and muscular pain, diabetes, lipid-modifying agents, calcium channel blockers, drugs for diabetes, and agents acting on the renin-angiotensin system as risk factors for a severe status. Conclusions This COVID-19 mortality risk tool is a well-calibrated and accurate model for predicting mortality risk among hospitalized patients with COVID-19 in Japan, which is characterized by a relatively low COVID-19 prevalence, aging society, and high population density. This COVID-19 mortality prediction model can assist in resource utilization and patient and caregiver education and be useful as a risk stratification instrument for future research trials.

Performance evaluation of the Ortho VITROS SARS-CoV-2 Spike-Specific Quantitative IgG test by comparison with the surrogate virus neutralizing antibody test and clinical assessment.

BACKGROUND: Despite the worldwide campaigns of COVID-19 vaccinations, the pandemic is still a major medical and social problem. The Ortho VITROS SARS-CoV-2 spike-specific quantitative IgG (VITROS S-IgG) assay has been developed to assess neutralizing antibody (NT antibody) against SARS-CoV-2 spike (S) antibodies. However, it has not been evaluated in Japan, where the total cases and death toll are lower than the rest of the world. METHODS: The clinical performance of VITROS S-IgG was evaluated by comparing with the NT antibody levels measured by the surrogate virus neutralizing antibody test (sVNT). A total of 332 serum samples from 188 individuals were used. Of these, 219 samples were from 75 COVID-19 patients: 96 samples from 20 severe/critical cases (Group S), and 123 samples from 55 mild/moderate cases (Group M). The remaining 113 samples were from 113 healthcare workers who had received 2 doses of the BNT162b2 vaccine. RESULTS: VITROS S-IgG showed good correlation with the cPass sVNT assay (Spearman rho = 0.91). Both VITROS S-IgG and cPass sVNT showed significantly higher plateau levels of antibodies in Group S compared to Group M. Regarding the humoral immune responses after BNT162b2 vaccination, individuals who were negative for SARS-CoV-2 nucleocapsid (N)-specific antibodies had statistically lower titers of both S-IgG and sVNT compared to individuals with a history of COVID-19 and individuals who were positive for N-specific antibodies without history of COVID-19. In individuals who were positive for N-specific antibodies, S-IgG and sVNT titers were similar to individuals with a history of COVID-19. CONCLUSIONS: Although the automated quantitative immunoassay VITROS S-IgG showed a reasonable correlation with sVNT antibodies, there is some discrepancy between Vitros S-IgG and cPass sVNT in milder cases. Thus, VITROS S-IgG can be a useful diagnostic tool in assessing the immune responses to vaccination and herd immunity. However, careful analysis is necessary to interpret the results.

Novel indicator for the spread of new coronavirus disease 2019 and its association with human mobility in Japan.

The Japanese government adopted policies to control human mobility in 2020 to prevent the spread of severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). The present study examined the impact of human mobility on COVID-19 cases at the prefectural level in Japan by devising an indicator to have a relationship between the number of infected people and on human mobility. We calculated origin-destination travel mobility within prefectures in Japan from March 1st to December 31st, 2020, using mobile phone data. A cross-correlation function (CCF) was used to examine the relationship between human mobility and a COVID-19 infection acceleration indicator (IAI), which represents the rate of change in the speed of COVID-19 infection. The CCF of intraprefectural human mobility and the IAI in Tokyo showed a maximum value of 0.440 at lag day 12, and the IAI could be used as an indicator to predict COVID-19 cases. Therefore, the IAI and human mobility during the COVID-19 pandemic were useful for predicting infection status. The number of COVID-19 cases was associated with human mobility at the prefectural level in Japan in 2020. Controlling human mobility could help control infectious diseases in a pandemic, especially prior to starting vaccination.

IFN-λ3 and CCL17 as predictors of disease progression in patients with mild to moderate COVID-19: A cohort study in a real-world setting.

Coronavirus disease 2019 (COVID-19) has overwhelmed hospitals worldwide. In Japan, serum interferon lambda 3 (IFN-λ3) and C-C motif ligand (CCL) 17 levels have been used as predictive markers for disease progression to severe COVID-19. However, the relationship between these predictive markers and the disease progression of COVID-19 has not been well evaluated. We retrospectively evaluated the patient characteristics, serum IFN-λ3 and CCL17 levels, and comorbidities of 92 patients with mild (n = 20) and moderate (n = 72) COVID-19 who were hospitalized in our institution. The results of the multivariable analysis showed that the positive rates of IFN-λ3, CCL17, and the combination of these markers were significantly elevated in patients with progressed COVID-19. Furthermore, patients who were negative for both markers did not experience disease progression. This study illustrates the importance of measuring these markers to predict disease severity and progression in patients with COVID-19.

The impact of declaring the state of emergency on human mobility during COVID-19 pandemic in Japan.

Background/objectives: Japan has responded to the spread of COVID-19 through declaration of a state of emergency to regulate human mobility. Although the declaration was enforced by the government for prefectures, there is limited evidence as to whether the public complied with requests for voluntary stay at home. In this study, we evaluated the impact of declaring a state of emergency on human mobility during the COVID-19 pandemic in Japan. Methods: We utilized daily human mobility data for 47 prefectures in Japan. Data were collected via mobile phone from February 1, 2020 to April 30, 2021. Difference-in-difference analysis was utilized to estimate the effects of the declaration of a state of emergency on prefectures in the Tokyo Metropolitan Area (Tokyo, Kanagawa, Saitama, and Chiba) in comparison to other prefectures where the state of emergency was first lifted (Osaka, Hyogo, Fukuoka, and Aichi). Results: Human mobility was suppressed during the second state of emergency, from January 8 to March 21, 2021. However, the impact was weaker for the second state of emergency compared to the first. Conclusion: In Japan, government requests for stay at home, such as the declaration of a state of emergency, were temporarily able to control human mobility. However, the second state of emergency was not as effective as the first. If additional need to regulate human mobility arises, self-restraint with stronger enforcement should be considered.

Association between physiotherapist burnout and working environment during the coronavirus disease 2019 pandemic in Japan: A multicenter observational study.

Burnout among physiotherapists has been reported worldwide during the coronavirus disease 2019 (COVID-19) pandemic. However, no information was found on the prevalence of burnout among physiotherapists in Japan during the COVID-19 pandemic. Physiotherapists directly providing physiotherapy to patients with COVID-19 in the red zone of 487 medical facilities were evaluated for the prevalence of burnout using the Japanese version of the Maslach Burnout Inventory-General Survey (MBI-GS). The association between the presence or absence of burnout and the working environment was analyzed using logistic regression analysis. Among the 566 physiotherapists analyzed, 99 (17.5%) satisfied the MBI-GS criteria for burnout. Multivariate analysis showed that burnout was associated with the year of physiotherapy experiences [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-0.99], feeling slight burden with infection control (OR 0.53, 95% CI 0.32-0.87), not feeling too burdened with infection control (OR 0.27, 95% CI 0.06-0.83), establishment of staffing standards for physiotherapy according to the number of beds (OR 1.80, 95% CI 1.09-2.96), and relaxation time (OR 0.49, 95% CI 0.30-0.82). Moreover, the OR increased as the self-improvement time decreased (OR 38.3, 95% CI 6.64-731). In Japan, the prevalence of burnout among physiotherapists during the COVID-19 pandemic was an intermediate value between the prevalence of burnout among physicians and nurses reported in previous studies. This study found the need to establish appropriate staffing standards for physiotherapy and support systems including secure self-improvement time and appropriate training according to physiotherapy experiences and each medical facility.

Activation of SARS-CoV-2 neutralizing antibody is slower than elevation of spike-specific IgG, IgM, and nucleocapsid-specific IgG antibodies.

COVID-19 antibody testing has been developed to investigate humoral immune response in SARS-CoV-2 infection. To assess the serological dynamics and neutralizing potency following SARS-CoV-2 infection, we investigated the neutralizing (NT) antibody, anti-spike, and anti-nucleocapsid antibodies responses using a total of 168 samples obtained from 68 SARS-CoV-2 infected patients. Antibodies were measured using an authentic virus neutralization assay, the high-throughput laboratory measurements of the Abbott Alinity quantitative anti-spike receptor-binding domain IgG (S-IgG), semiquantitative anti-spike IgM (S-IgM), and anti-nucleocapsid IgG (N-IgG) assays. The quantitative measurement of S-IgG antibodies was well correlated with the neutralizing activity detected by the neutralization assay (r = 0.8943, p < 0.0001). However, the kinetics of the SARS-CoV-2 NT antibody in severe cases were slower than that of anti-S and anti-N specific antibodies. These findings indicate a limitation of using the S-IgG antibody titer, detected by the chemiluminescent immunoassay, as a direct quantitative marker of neutralizing activity capacity. Antibody testing should be carefully interpreted when utilized as a marker for serological responses to facilitate diagnostic, therapeutic, and prophylactic interventions.

COVID-19 pandemic and the international classification of functioning in multiple system atrophy: a cross-sectional, nationwide survey in Japan.

The present study aimed to determine the magnitude of and risk factors for the effects of the COVID-19 pandemic on the international classification of functioning, disability and health (ICF) in patients with multiple system atrophy (PwMSA). The study was part of a cross-sectional, nationwide, multipurpose mail survey for Japanese PwMSA from October to December, 2020. The primary outcome was the impact of the early COVID-19 pandemic on ICF functioning, consisting of body function, activity, and participation. Age, sex, disease type, disease duration, and dwelling place were asked as participants' characteristics, and the multiple system impairment questionnaire (MSIQ), patient health questionnaire-2, modified rankin scale, barthel index, life-space assessment (LSA), and EuroQoL were examined. Multivariate logistic regression analyses were performed to identify independent risk factors for a worse function score due to the COVID-19 pandemic for each ICF functioning domain. A total of 155 patients (mean age 65.6 [SD 8.1] years; 43.9% women; mean disease duration 8.0 [SD 6.2] years; 65% MSA with cerebellar ataxia, 13% MSA with parkinsonism, 9% MSA with predominant autonomic features) were analyzed. Of the ICF functioning domains, the respondents reported that the early COVID-19 pandemic affected body function in 17.4%, activity in 17.6%, and participation in 46.0%. The adjusted multivariate model identified MSIQ and LSA as the two variables that independently contributed to all domains. The COVID-19 pandemic affected ICF functioning of PwMSA in Japan, and the severity of disease-related impairments and a large daily living space were common risk factors. These results help support the focus on patient characteristics for medical and social welfare support.

Molecular characterization of SARS-CoV-2 detected in Tokyo, Japan during five waves: Identification of the amino acid substitutions associated with transmissibility and severity

Many variants of SARS-CoV-2 have emerged around the world. It is therefore important to understand its global viral evolution and the corresponding mutations associated with transmissibility and severity. In this study, we analyzed 112 whole genome sequences of SARS-CoV-2 collected from patients at Juntendo University Hospital in Tokyo and the genome data from entire Japan deposited in Global Initiative on Sharing Avian Influenza Data (GISAID) to examine the relationship of amino acid changes with the transmissibility and the severity of each strain/lineage. We identified 12 lineages, including B.1.1.284, B.1.1.214, R.1, AY.29, and AY.29.1, which were prevalent specifically in Japan. B.1.1.284 was most frequently detected in the second wave, but B.1.1.214 became the predominant lineage in the third wave, indicating that B.1.1.214 has a higher transmissibility than B.1.1.284. The most prevalent lineage during the fourth and fifth wave was B.1.1.7 and AY.29, respectively. In regard to the severity of identified lineages, B.1.1.214 was significantly lower than the reference lineage, B.1.1.284. Analysis of the genome sequence and other traits of each lineage/strain revealed the mutations in S, N, and NSPs that increase the transmissibility and/or severity. These mutations include S: M153T, N: P151L, NSP3: S543P, NSP5: P108S, and NSP12: A423V in B.1.1.284;S: W152L and E484K in R.1;S: H69del, V70del, and N501Y in the Alpha strain;S: L452R, T478K, and P681R in the Delta strain. Furthermore, it is suggested that the transmissibility of B.1.1.214 could be enhanced by the mutations N: M234I, NSP14: P43L, and NSP16: R287I. To address the issue of the virus evolution, it is necessary to continuously monitor the genomes of SARS-CoV-2 and analyze the effects of mutations for developing vaccines and antiviral drugs effective against SARS-CoV-2 variants.

Antibody response and seroprevalence in healthcare workers after the BNT162b2 vaccination in a University Hospital at Tokyo.

In 2020, we reported a low seroprevalence of N-specific antibodies in 4147 health care workers (HCWs) at a frontline hospital in Tokyo, Japan. In Japan, a vaccine campaign was launched in early 2021. We re-evaluated seroprevalences of N- and S-specific antibodies in 2202 HCWs who took two doses of the BNT162b2 vaccine. In 2021, N-specific seroprevalence remains as low as 1.59%. The seroprevalences were comparable among all HCWs regardless of exposure levels. Almost all of the HCWs elicited S-specific antibodies after vaccination. However, the HCWs who had COVID-19 elicited higher S-specific antibody titers than those who did not have COVID-19. In the HCWs without a history of COVID-19, 1.1% (23 out of 2185) were seropositive with N-specific antibodies, indicating the existence of asymptomatic infections. Also, S-specific antibody titers were higher in females and younger HCWs, and in those who had severe side effects. However, S-specific antibody titers were lower depending on the number of days after the second dose of vaccination specifically in elderly individuals. In conclusion, this study indicates N-specific seroprevalence remains low in HCWs at a frontline hospital in Tokyo. The mRNA vaccine elicited S-specific antibody in HCWs, however, the titers decreased as the days proceeded.

Changes in social environment due to the state of emergency and Go To campaign during the COVID-19 pandemic in Japan: An ecological study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic in Japan, the state of emergency, as a public health measure to control the spread of COVID-19, and the Go To campaign, which included the Go To Travel and Go To Eat campaigns and was purposed to stimulate economic activities, were implemented. This study investigated the impact of these government policies on COVID-19 spread. METHODS: This ecological study included all 47 prefectures in Japan as samples between February 3 and December 27, 2020. We used COVID-19 cases and mobility as variables. Additionally, places where social contacts could accrue, defined as restaurants, companies, transportation, and tourist spots; mean temperature and humidity; the number of inhabitants in their twenties to fifties; and the number of COVID-19 cases in the previous period, which were factors or covariates in the graphical modeling analysis, were divided into five periods according to the timing of the implementation of the state of emergency and Go To campaign. RESULTS: Graphical changes occurred throughout all five periods of COVID-19. During the state of emergency (period 2), a correlation between COVID-19 cases and those before the state of emergency (period 1) was observed, although this correlation was not significant in the period after the state of emergency was lifted (period 3). During the implementation of Go To Travel and the Go To Eat campaigns (period 5), the number of places where social contacts could accrue was correlated with COVID-19 cases, with complex associations and mobility. CONCLUSIONS: This study confirms that the state of emergency affected the control of COVID-19 spread and that the Go To campaign led to increased COVID-19 cases due to increased mobility by changing behavior in the social environment where social contacts potentially accrue.

Increased delta variant SARS-CoV-2 infections in a highly vaccinated medical center in Japan.

The Delta variant has dominated SARS-CoV-2 infections in Tokyo, Japan from June 2021 to date. We conducted a retrospective cohort study to assess BNT162b2 vaccine effectiveness during the surge in Delta among 3,911 healthcare workers (HCWs) at a medical center of Tokyo with a high vaccination rate of 84.1%. With strict infection control protocols including universal masking, only a small number of cases among vaccinated and unvaccinated HCWs were identified before June. As Delta spread in Tokyo, 16 cases among 3,289 fully vaccinated HCWs and 11 cases among 574 unvaccinated HCWs were reported in July and August (case rate in August: 4.0 vs. 19.2 per 1,000). All breakthrough cases were confirmed as Delta. While our study confirms a robust vaccine effectiveness of BNT162b2 vaccine against Delta, rising breakthrough cases suggest that continued infection control measures are warranted in higher risk environments, even when high rates of vaccination coverage are achieved.

Effects of COVID-19 on Japanese medical students' knowledge and attitudes toward e-learning in relation to performance on achievement tests.

The COVID-19 pandemic forced many educational institutions to turn to electronic learning to allow education to continue under the stay-at-home orders/requests that were commonly instituted in early 2020. In this cross-sectional study, we evaluated the effects of the COVID-19 pandemic on medical education in terms of students' attitudes toward online classes and their online accessibility; additionally, we examined the impacts of any disruption caused by the pandemic on achievement test performance based on the test results. The participants were 674 students (412 in pre-clinical, 262 in clinical) at Juntendo University Faculty of Medicine; descriptive analysis was used to examine the respondents' characteristics and responses. The majority of respondents (54.2%) preferred asynchronous classes. Mann-Whitney U tests revealed that while pre-clinical students preferred asynchronous classes significantly more than clinical students (39.6%, p < .001), students who preferred face-to-face classes had significantly higher total achievement test scores (U = 1082, p = .021, r = .22). To examine the impacts of pandemic-induced changes in learning, we conducted Kruskal-Wallis tests and found that the 2020 and 2021 scores were significantly higher than those over the last three years. These results suggest that while medical students may have experienced challenges adapting to electronic learning, the impact of this means of study on their performance on achievement tests was relatively low. Our study found that if possible, face-to-face classes are preferable in an electronic learning environment. However, the benefit of asynchronous classes, such as those that allow multiple viewings, should continue to be recognized even after the pandemic.

Elevated depressive symptoms among newer and younger healthcare workers in Japan during the COVID-19 pandemic.

AIM: Depression is a frequent outcome of long-term stress, but no studies have examined depression rates among Japanese healthcare workers fighting the COVID-19 pandemic. Therefore, we conducted a web-based interview of hospital employees to assess depression prevalence and factors. METHODS: This observational cohort study was conducted from July to August, 2020, as part of a mandatory health checkup of Juntendo University Hospital employees (Tokyo, Japan). A total of 4239 participants completed a web-based questionnaire on medical history and current health status. The Center for Epidemiologic Studies Depression Scale (CES-D) was used for self-assessment, with a score of ≥16 considered to indicate depression. RESULTS: Among all employees, the proportion of depression was 31.3% in 2020, the highest measured in the last 10 years and substantially greater than the pre-pandemic value in 2019 (27.5%). The proportion of depression for 2020 was significantly higher in new recruits than in employees with more than 2 years of experience (47.0% vs 29.9%, respectively, P < .0001) and in new recruits in 2019 (26.4%, P < .0001). When subdivided by occupation, nurses demonstrated the highest depression rate (43.2%), followed by paramedics (35.1%) and clerks (31.6%), whereas residents (22.9%), doctors (20.4%), teaching staff (18.0%), and part-time staff (15.3%) reported lower depression rates. The positive CES-D score significantly correlated with age (P < .0001). CONCLUSIONS: Younger and newer employees demonstrated the highest rates of depression independent of occupation. Therefore, mental healthcare programs focusing on these vulnerable groups need to be established.

SARS-CoV-2 seroprevalence in healthcare workers at a frontline hospital in Tokyo.

Healthcare workers (HCWs) are highly exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The actual coronavirus disease (COVID-19) situation, especially in regions that are less affected, has not yet been determined. This study aimed to assess the seroprevalence of SARS-CoV-2 in HCWs working in a frontline hospital in Tokyo, Japan. In this cross-sectional observational study, screening was performed on consented HCWs, including medical, nursing, and other workers, as part of a mandatory health checkup. The screening test results and clinical characteristics of the participants were recorded. The antibody seroprevalence rate among the 4147 participants screened between July 6 and August 21, 2020, was 0.34% (14/4147). There was no significant difference in the seroprevalence rate between frontline HCWs with a high exposure risk and HCWs working in other settings with a low exposure risk. Of those seropositive for SARS-CoV-2, 64% (9/14) were not aware of any symptoms and had not previously been diagnosed with COVID-19. In conclusion, this study provides insights into the extent of infection and immune status in HCWs in Japan, which has a relatively low prevalence of COVID-19. Our findings aid in formulating public health policies to control virus spread in regions with low-intensity COVID-19.