Disease burden of main bacterial infections in Japan, 2015-2020: A population-level study.

INTRODUCTION: Comprehensive evidence about the burden of infectious diseases in the Western Pacific Region is scarce. We thus examined the disease burden of infectious diseases in Japan in terms of disability-adjusted life years (DALYs). METHODS: We extracted national claims data from Japan's universal health insurance system to estimate the burden of disease for selected infections between 2015 and 2020 using DALYs. The mortality rate, disability duration and severity weight of each disease were estimated based on national data and literature reviews. RESULTS: Disease burden per 100,000 population was 1307.0 in 2015 and 972.1 in 2020 for bloodstream infections (BSI), 796.5 DALYs in 2015 and 498.9 DALYs in 2020 for pneumonia, 171.5 in 2015 and 149.4 in 2020 for meningitis and 11.6 in 2015 and 11.4 in 2020 for urinary tract infections (UTI). Only surgical site infections (SSI) showed a slightly increasing trend over the 5-year period, from 2.2 in 2015 to 2.8 in 2020. CONCLUSIONS: Our results showed that the disease burden of the five major infectious diseases was higher in Japan than in other countries. However, while the burden of SSI increased, the burden of pneumonia, meningitis, BSI and UTI gradually decreased year on year. The possible causes of the decreased morbidity should be examined in future work.

Bloodstream infections in the elderly Japanese population: Current reality and countermeasures.

We reviewed bloodstream infections in the elderly in Japan, referring to data recently reported from the National Center for Global Health and Medicine in Tokyo. We divided the locations of bloodstream infections into Hospital-onset (HO), healthcare-associated (HCA), and CA (community-acquired), as the elderly reside in different places. The study focused on the fact that the general condition and underlying diseases of the elderly differ by age group. And thus, we divided them into three groups: Pre-old (65-74 years), Old (75-89 years), and Super-old (≥ 90 years), and compared their characteristics of bloodstream infections. HO bacteremia was most common in the pre-old group. On the other hand, HCA bloodstream infections tended to increase as the population aged, and it was most prevalent in super-old group. According to the study results, early intervention through infectious diseases (ID) consultation may improve the prognosis of bloodstream infections even in the elderly. Since the rate of ID consultation is lower in the super-old group than in other groups, this group may be a significant target. In conclusion, a study of a cohort of elderly patients with bloodstream infections in Japan indicates that bloodstream infections in patients over 65 years is not uniform.

Pyelonephritis due to Escherichia coli in the older population in Japan: Impacts on activities of daily living and medical costs.

This study aimed to investigate differences in Activities of Daily Living (ADL), at admission and discharge, as well as the medical costs of pyelonephritis in older adults in Japan. Patients hospitalized for pyelonephritis between January 1, 2013 and March 31, 2019, were retrospectively enrolled. The inclusion criteria were urine culture within 48 h of admission with > 104 colony-forming units/mL of Escherichia coli and symptoms of pyelonephritis. Patients were divided into Young (20-64 years), Pre-old (65-74 years), Old (75-84 years), and Super-old (≥ 85 years). ADL and medical costs were compared. Finally, 393 patients were included: 112 (28.5%) were Young, 72 (18.3%) were Pre-old, 130 (33.1 %) were Old, and 79 (20.1%) were Super-old between January 1, 2013, and March 31, 2019. The median differences between Barthel Index (BI) scores, which indicates ADL, at admission and discharge were 0, 0, 25, and 23 in each age group, respectively (p < 0.001). No significant differences existed between the groups aged ≥ 65. Median medical costs were $3,368, $4,894, $5,372, and $6,078 for each age group, respectively (p < 0.001). Medical costs per day did not differ significantly between the groups (p = 0.163). Pyelonephritis due to E. coli in patients aged ≥ 75 is associated with a decline in ADL, longer hospital stays, and higher medical costs compared to that in young patients. Pre-old patients did not have lower ADL; however, they tended to have longer hospital stays and higher medical costs.

Epidemiology of post-COVID conditions beyond 3 years and factors associated with their persistence longer than 2 years: A cross-sectional study.

OBJECTIVE: This study aimed to investigate the epidemiology of post-coronavirus disease 2019 (COVID-19) conditions (PCCs) beyond 3 years and identify factors associated with their persistence longer than 2 years. STUDY DESIGN: Cross-sectional questionnaire-based survey. METHODS: We surveyed patients who had recovered from COVID-19 and visited our institution from February 2020 to November 2021. Demographic and clinical data and information on the presence and duration of PCCs were obtained. We identified factors associated with the persistence of PCCs longer than 2 years using multivariate linear regression analyses. RESULTS: Among 935 patients surveyed, 407 completed the survey. Among them, 360 patients had mild disease in the acute phase. The proportions of participants with at least one symptom at 1, 2, and 3 years after symptom onset or COVID-19 diagnosis were 33.2%, 29.8%, and 5.7%, respectively. The numbers of participants with and without any residual symptoms 2 years after the onset of COVID-19 were 87 and 193, respectively. After multivariate adjustment, persistence of PCCs longer than 2 years was associated with lower body mass index, presence of any underlying medical conditions, and number of symptoms lasting for more than 1 month ≥ 5. CONCLUSIONS: The prevalence of PCCs decreased 2 years after symptom onset or COVID-19 diagnosis. We also identified factors associated with PCC persistence longer than 2 years, which could help primary care physicians and patients with PCCs predict the duration of PCCs and better understand their natural history, thus reducing patients' anxiety about their duration.

Unfractionated Heparin Safety in COVID-19: Incidence and Risks of Bleeding Complications in Japan.

AIM: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH. METHODS: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality. RESULTS: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P ＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test). CONCLUSIONS: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

Analysis of Differences in Characteristics of High-Risk Endemic Areas for Contracting Japanese Spotted Fever, Tsutsugamushi Disease, and Severe Fever With Thrombocytopenia Syndrome.

Background: Tick-borne infections, including tsutsugamushi disease, Japanese spotted fever, and severe fever with thrombocytopenia syndrome (SFTS), are prevalent in East Asia with varying geographic distribution and seasonality. This study aimed to investigate the differences in the characteristics among endemic areas for contracting each infection. Methods: We conducted an ecologic study in Japan, using data from a nationwide inpatient database and publicly available geospatial data. We identified 4493 patients who were hospitalized for tick-borne infections between July 2010 and March 2021. Mixed-effects modified Poisson regression analysis was used to identify factors associated with a higher risk of contracting each tick-borne disease (Tsutsugamushi, Japanese spotted fever, and SFTS). Results: Mixed-effects modified Poisson regression analysis revealed that environmental factors, such as temperature, sunlight duration, elevation, precipitation, and vegetation, were associated with the risk of contracting these diseases. Tsutsugamushi disease was positively associated with higher temperatures, farms, and forests, whereas Japanese spotted fever and SFTS were positively associated with higher solar radiation and forests. Conclusions: Our findings from this ecologic study indicate that different environmental factors play a significant role in the risk of transmission of tick-borne infections. Understanding the differences can aid in identifying high-risk areas and developing public health strategies for infection prevention. Further research is needed to address causal relationships.

Cumulative antibiogram preparation among hospitals participating in the Japan Surveillance for Infection Prevention and Healthcare Epidemiology.

BACKGROUND: The cumulative antibiogram is essential to guide empirical therapy for infectious diseases and monitor the trend of antimicrobial resistance. However, the status of antibiogram generation at medical institutions in Japan is uncertain. METHODS: A web-based questionnaire survey was conducted in February 2023 on the status of antibiogram preparation among facilities participating in the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE), an infection control surveillance system in Japan. RESULTS: The questionnaire collection rate was 19.6% (379/1931). Of all facilities, 47% (178/379) performed microbiological tests mainly in-house, while 53% (201/379) performed microbiological tests mainly outsourced. Of all facilities, 78% (296/379) prepared antibiograms. Of those without antibiograms, 33% (27/83) were considering the development in the future. Some facilities cited staff shortage as a barrier to preparing antibiograms. Of the 214 facilities with antibiograms that could use the J-SIPHE system to prepare antibiograms, 19% (41/214) were using the J-SIPHE system to prepare their antibiograms. CONCLUSIONS: One-quarter of the facilities that responded to the survey had not prepared antibiograms. Technical support for surveillance and awareness activity for using cumulative antibiograms might promote antibiogram preparation in Japan, which may improve antimicrobial stewardship and antimicrobial resistance measures.

Efficacy and viral dynamics of tecovirimat in patients with MPOX: A multicenter open-label, double-arm trial in Japan.

INTRODUCTION: Tecovirimat's application in treating mpox remains under-researched, leaving gaps in clinical and virological understanding. METHODS: The Tecopox study in Japan evaluated the efficacy and safety of tecovirimat in patients with smallpox or mpox, who were divided into oral tecovirimat and control groups. Patients with mpox enrolled between June 28, 2022, and April 30, 2023, were included. Demographic and clinical details along with blood, urine, pharyngeal swab, and skin lesion samples were gathered for viral analysis. A multivariable Tobit regression model was employed to identify factors influencing prolonged viral detection. RESULTS: Nineteen patients were allocated to the tecovirimat group, and no patients were allocated to the control group. The median age was 38.5 years, and all patients were males. Ten patients (52.6%) were infected with human immunodeficiency virus (HIV). Sixteen patients (84.2%) had severe disease. Nine of the 15 patients (60.0%) (four patients withdrew before day 14) had negative PCR results for skin lesion specimens 14 days after inclusion. The mortality rates were 0% on days 14 and 30. No severe adverse events were reported. HIV status and the number of days from symptom onset to tecovirimat administration were associated with lower Ct values (p = 0.027 and p < 0.001, respectively). The median number of days when PCR testing did not detect the mpox virus in each patient was 19.5 days. CONCLUSION: Early tecovirimat administration might reduce viral shedding duration, thereby mitigating infection spread. Moreover, patients infected with HIV showed prolonged viral shedding, increasing the transmission risk compared to those without HIV.

Real-world effectiveness of full and booster mRNA vaccination for coronavirus disease 2019 against disease severity during the delta- and omicron-dominant phases: A propensity score-matched cohort study using the nationwide registry data in Japan.

BACKGROUND: To date, few studies from the Asian region have reported the effectiveness of messenger ribonucleic acid coronavirus disease 2019 (COVID-19) vaccines against disease progression and death after hospitalization. METHODS: We evaluated the data from the COVID-19 registry in Japan during the delta- and omicron-dominant phases. A propensity score-matched cohort study was conducted between the incompletely (0-1 dose) and fully (2 doses) vaccinated groups during the delta-dominant phase and among the incompletely, fully, and booster (3 doses) vaccinated groups during the omicron-dominant phase. RESULTS: In the delta-dominant phase, 411 pairs were matched. The fully vaccinated group showed a significantly lower oxygen supplementation rate (24.1 % vs. 41.1 %, p < 0.001) but little difference in the mortality rate (2.2 % vs. 2.9 %, p = 0.66). In the omicron-dominant phase, 1494 pairs from the incompletely and fully vaccinated groups, and 425 pairs from the fully and booster vaccinated groups were matched. Full vaccination reduced both the oxygen supplementation rate (18.6 % vs 25.7 %, p < 0.001) and mortality rate (0.7 % vs 2.3 %, p < 0.001). Booster vaccination showed little difference in either the rate of oxygen supplementation (21.2 % vs. 24.7 %, p = 0.25) or mortality (1.2 % vs. 2.6 %, p = 0.21) compared with full vaccination. CONCLUSIONS: Full vaccination reduced disease severity during the delta- and omicron-dominant phases; booster vaccination did not further enhance the protective effects against disease progression during the omicron-dominant phase compared to full vaccination. Future vaccine strategies and policy decisions should consider preventing infection or disease progression in the target population, as well as the characteristics of the dominant variant in that phase.

Large-scale resurgence of herpangina in Japan, following the easing of COVID-19 measures.

Objectives: This study examined the rise in herpangina cases and its demographic trends in Japan post-easing of COVID-19 restrictions in the summer of 2023, assessing its potential strain on pediatric healthcare. Methods: Weekly herpangina cases data from the National Institute of Infectious Diseases from 2017 to 2023 were analyzed using difference-in-differences methodology and Poisson regression models, incorporating variables such as time, the COVID-19 pandemic, and the easing of measures. Statistical significance was set at a two-sided P-value of 0.05. Results: A significant increase in herpangina cases was observed from the 19th to the 27th week of 2023, with a notable shift in age distribution compared to that of pre-pandemic years. Poisson regression analysis revealed a positive correlation between the number of herpangina cases and the easing of infection control measures. There was an increase in other respiratory illnesses, including respiratory syncytial virus, particularly in children aged 3 and above. Conclusion: We found a surge in herpangina cases in Japan after the easing of the COVID-19 restrictions during the summer of 2023, along with a noticeable increase in other respiratory illnesses, emphasizing the potential strain on pediatric healthcare and reinforcing the ongoing significance of implementing general infection prevention strategies.

Trends in teicoplanin loading dose implementation from 2010 to 2019 and evaluation of safety and efficacy factors: a retrospective cohort study based on a Japanese administrative claims database.

BACKGROUND: The loading dose of teicoplanin (TEIC) is recommended for implementation. However, there is significant discrepancy between the dose settings in the package insert and, in the guidelines, and the actual status of loading doses in Japan is unclear. Furthermore, TEIC causes liver injury as side effect. Although the risk of developing liver injury has not been reported to be increased following a loading dose based on the guidelines, there is a lack of reports in large populations. Therefore, we evaluated the trend in the loading dose and factors affecting the efficacy and safety of TEIC administration. METHODS: A Japanese administrative claims database was used in this study. Trends in loading doses were evaluated in target populations administered TEIC between 2010 and 2019. Patient characteristics were adjusted by propensity score matching based on the guideline group (total dose of 3 days > 1,600 mg) and non-guideline group (≤ 1,600 mg) of the loading dose. Finally, univariable and multivariable conditional logistic regression analysis was performed to evaluate factors affecting 30-day mortality and liver injury. RESULTS: A total of 10,030 patients were selected based on these criteria. The proportion of loading doses based on the recommended guidelines showed an increase over time, regardless of the implementation of therapeutic drug monitoring (TDM), but especially so in cases where TDM was implemented, the loading doses were administered in accordance with the recommendations of the guidelines. Conditional logistic regression analysis showed a relationship between drug management and guidance fees (odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.36‒0.55), a reimbursement indicating pharmacist intervention, and a reduction in 30-day mortality. In addition, loading doses based on the recommended guidelines had no influence on liver injury, and other factors were not significantly associated with increased incidence of liver injury. CONCLUSION: Thus, this study implies the benefits of pharmacological management as indicated by drug management and guidance fee and supports the implementation of loading doses based on the guideline on TEIC administration.

Factors Associated with Geographical Variability of Antimicrobial Use in Japan.

INTRODUCTION: Evidence regarding the factors affecting the geographical variation of antimicrobial use (AMU) is relatively scarce. This study aimed to evaluate factors potentially associated with geographical variability of AMU per day per 1000 habitants in the 47 prefectures of Japan. METHODS: This is an observational ecological study using the Japanese national database in 2019. The outcome was the defined daily doses per 1000 inhabitants per day by prefecture. Multivariable negative binomial regression analysis was conducted using patient- and physician-level variables. RESULTS: The study included 605,391,054 defined daily doses of AMU in 2019 from the 47 prefectures. In the multivariable negative binomial regression analyses for the outcome of total AMU, the proportion of female individuals (adjusted rate ratio [aRR] 1.04 [1.01-1.08] per 1% increase, p = 0.021), the proportion of upper secondary graduates going to further education (aRR 1.01 [1.00-1.01] per 1% increase, p = 0.005), and the annual number of diagnoses related to upper respiratory infections (URIs) per 1000 inhabitants per day (aRR 1.21 [1.10-1.34], p < 0.001) were significantly correlated with total AMU. CONCLUSIONS: In this ecological study, the variability of total AMU by Japanese prefecture was associated with the proportion of female individuals, education level, and the number of URI diagnoses per population. The results suggest the potential need for additional stewardship efforts to reduce unnecessary antimicrobial prescriptions for URI.

Association between seasonal influenza vaccination and antimicrobial use in Japan from the 2015-16 to 2020-21 seasons: from the VENUS study.

BACKGROUND: Seasonal influenza vaccination might be considered an antimicrobial resistance (AMR) countermeasure because it can reduce unnecessary antimicrobial use for acute respiratory infection by mitigating the burden of such diseases. OBJECTIVES: To examine the association between seasonal influenza vaccination and antimicrobial use (AMU) in Japan at the community level and to examine the impact of influenza vaccination on the frequency of unnecessary antimicrobial prescription for upper respiratory infection. METHODS: For patients who visited any healthcare facility in one of the 23 wards of Tokyo, Japan, due to upper respiratory infection and who were aged 65 years or older, we extracted data from the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) study database, which includes all claims data and vaccination records from the 2015-16 to 2020-21 seasons. We used the average treatment effect (ATE) with 1:1 propensity score matching to examine the association of vaccination status with frequency of antibiotic prescription, frequency of healthcare facility consultation, risk of admission and risk of death in the follow-up period of the same season (from 1 January to 31 March). RESULTS: In total, 244 642 people were enrolled. Matched data included 101 734 people in each of the unvaccinated and vaccinated groups. The ATE of vaccination was -0.004 (95% CI -0.006 to -0.002) for the frequency of antibiotic prescription, -0.005 (-0.007 to -0.004) for the frequency of healthcare facility consultation, -0.001 (-0.002 to -0.001) for the risk of admission and 0.00 (0.00 to 0.00) for the risk of death. CONCLUSIONS: Our results suggest that seasonal influenza vaccination is associated with lower frequencies of unnecessary antibiotic prescription and of healthcare facility consultation.

Effectiveness of cefmetazole versus meropenem for invasive urinary tract infections caused by extended-spectrum ß-lactamase-producing Escherichia coli.

Cefmetazole is active against extended-spectrum ß-lactamase-producing Escherichia coli (ESBLEC) and is a potential candidate for carbapenem-sparing therapy. This multicenter, observational study included patients hospitalized for invasive urinary tract infection due to ESBLEC between March 2020 and November 2021 at 10 facilities in Japan, for whom either cefmetazole or meropenem was initiated as a definitive therapy within 96 h of culture collection and continued for at least 3 d. Outcomes included clinical and microbiological effectiveness, recurrence within 28 d, and all-cause mortality (14 d, 30 d, in-hospital). Outcomes were adjusted for the inverse probability of propensity scores for receiving cefmetazole or meropenem. Eighty-one and forty-six patients were included in the cefmetazole and meropenem groups, respectively. Bacteremia accounted for 43% of the cefmetazole group, and 59% of the meropenem group. The crude clinical effectiveness, 14 d, 30 d, and in-hospital mortality for patients in the cefmetazole and meropenem groups were 96.1% vs 90.9%, 0% vs 2.3%, 0% vs 12.5%, and 2.6% vs 13.3%, respectively. After propensity score adjustment, clinical effectiveness, the risk of in-hospital mortality, and the risk of recurrence were similar between the two groups (P = 0.54, P = 0.10, and P = 0.79, respectively). In all cases with available data (cefmetazole : n = 61, meropenem : n = 22), both drugs were microbiologically effective. In all isolates, bla CTX-M was detected as the extended-spectrum ß-lactamase gene. The predominant CTX-M subtype was CTX-M-27 (47.6%). Cefmetazole showed clinical and bacteriological effectiveness comparable to meropenem against invasive urinary tract infection due to ESBLECs.

Comparing the effects of antimicrobial stewardship at primary emergency centers.

BACKGROUND: Antimicrobial prescription rates tend to be high in outpatient settings and Primary Emergency Medical Centers (PECs) in Japan encounter difficulties in implementing antimicrobial stewardship programs (ASPs). While a nudge-based ASP publishing monthly newsletters reduces inappropriate prescription of oral third-generation cephalosporins (3GCs), which requires considerable effort. Therefore, developing more preferable ASP models in PECs is essential. METHODS: We conducted a three-center, retrospective observational study. Himeji City Emergency Medical Center (Site A) introduced a facility-specific guideline for antimicrobial stewardship with reference to national guidelines. The Kobe Children's Primary Emergency Medical Center (Site B) provided the results of monitoring antibiotics prescription in a monthly newsletter. The Hanshin-Kita Children's First-Aid Center (Site C) did not perform a specific ASP. Prescription rates for 3GCs were categorized into pre- and post-intervention and compared using Poisson regression analysis. The difference-in-difference method was used to assess the effect of these interventions. RESULTS: The numbers of patients pre- and post- intervention were 177,126 and 91,251, respectively. The 3GCs prescription rate at Site A, Site B, and Site C decreased from 6.7%, 4.2%, and 6.1% in 2016 to 2.3%, 1.0%, and 2.0% in 2019, respectively. Site B had a greater reduction than Site A and Site C (relative risk [RR] 0.71 [95% confidence interval (CI): 0.62-0.82]; p < 0.001, RR 0.71, [95% CI: 0.62-0.81]; p < 0.001). There was no significant difference between Site A and Site C (RR 1.00 [95% CI 0.88-1.13]; p = 0.963). CONCLUSION: A facility-specific guideline was less effective than a nudge-based ASP for decreasing oral 3GC prescriptions in PECs.

Protocol of Tecopox study: a multicentre, open-label, double-arm trial to evaluate the efficacy and safety of oral tecovirimat therapy for patients with smallpox or monkeypox.

INTRODUCTION: Monkeypox was originally endemic locally in West Africa; however, outbreaks in non-endemic countries have been recognised since May 2022. The effectiveness of tecovirimat has been estimated against smallpox, which belongs to the same Orthopoxvirus genus as monkeypox. Thus, tecovirimat is expected to be effective against monkeypox. This study aims to evaluate the efficacy and safety of oral tecovirimat therapy for patients with smallpox and monkeypox and to prepare a scheme for oral tecovirimat use in Japan. METHODS AND ANALYSIS: This nationwide, multicentre, non-randomised, open-label, double-arm study will involve viral examination of the blood, throat swabs, urine and skin lesions, performed periodically. Participants will freely decide whether to participate in an administered group (supportive treatment plus oral tecovirimat) or a non-administered group (only supportive treatment). Tecovirimat will be administered for 14 days. To ensure that financial problems do not preclude participation in the study, the research fund will cover the cost of tecovirimat and basic hospitalisation fees. The primary endpoint is the percentage of patients with negative PCR results (cycle threshold value ≥40) for skin lesion specimens at 14 days after inclusion in the study. Secondary endpoints include mortality at 14 and 30 days, viral load in each sample, duration of fever and adverse events. The sample size is estimated to be 50 patients with monkeypox or smallpox. ETHICS AND DISSEMINATION: Written informed consent will be obtained from all participants. This study was approved by the Certified Review Board of National Center for Global Health and Medicine and published in the Japan Registry of Clinical Trials. The results of this study will be published in peer-reviewed journals and/or in presentations at academic conferences. TRIAL REGISTRATION NUMBER: jRCTs031220169.

Effectiveness of inactivated influenza and COVID-19 vaccines in hospitalized children in 2022/23 season in Japan - The first season of co-circulation of influenza and COVID-19.

We have analyzed the inactivated vaccine effectiveness (VE)for preventing influenza hospitalization by test-negative design in the 2022/23 season. This is the first season of co-circulation of influenza and COVID-19, and a unique period because all inpatients received COVID-19 screening. Among 536 children hospitalized with fever, none were positive for both influenza and SARS-CoV-2. The adjusted VE for preventing influenza A for all children, the 6-12-year-old group, and those with underlying diseases was 34 % (95 ％CI, -16 %-61 %, n = 474), 76 % (95 ％ CI, 21 %-92 %, n = 81), and 92 % (95 ％ CI, 30 %-99 %, n = 86), respectively. Only 1 out of 35 hospitalized cases with COVID-19, and 42 out of 429 controls, had been immunized with COVID-19 vaccine. This is the first report showing influenza VE by age group in children in this limited season. We still recommend the inactivated influenza vaccine for children based on the significant VE in subgroup analysis.

The estimated disease burden of COVID-19 in Japan from 2020 to 2021.

BACKGROUND: To date, it is not fully understood to what extent COVID-19 has burdened society in Japan. This study aimed to estimate the total disease burden due to COVID-19 in Japan during 2020-2021. METHODS: We stratify disease burden estimates by age group and present it as absolute Quality Adjusted Life Years (QALYs) lost and QALYs lost per 100,000 persons. The total estimated value of QALYs lost consists of (1) QALYs lost brought by deaths due to COVID-19, (2) QALYs lost brought by inpatient cases, (3) QALYs lost brought by outpatient cases, and (4) QALYs lost brought by long-COVID. RESULTS: The total QALYs lost due to COVID-19 was estimated as 286,782 for two years, 114.0 QALYs per 100,000 population per year. 71.3% of them were explained by the burden derived from deaths. Probabilistic sensitivity analysis showed that the burden of outpatient cases was the most sensitive factor. CONCLUSIONS: The large part of disease burden due to COVID-19 in Japan from the beginning of 2020 to the end of 2021 was derived from Wave 3, 4, and 5 and the proportion of QALYs lost due to morbidity in the total burden increased gradually. The estimated disease burden was smaller than that in other high-income countries. It will be our future challenge to take other indirect factors into consideration.