Fatal SARS-CoV-2 Infection among Children, Japan, January-September 20221.

To determine the characteristics of pediatric patients 0-19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1-September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were <1 year of age, 59% had no underlying disease, and 88% eligible for vaccination were unvaccinated. Nonrespiratory symptoms were more common than respiratory symptoms. Out-of-hospital cardiac arrest affected 46% of patients, and time from symptom onset to death was <7 days for 77%. Main suspected causes of death were central nervous system abnormalities (35%) and cardiac abnormalities (20%). We recommend careful follow-up of pediatric patients after SARS-CoV-2 infection during the first week after symptom onset, regardless of underlying diseases.

SARS-CoV-2 Variants and Age-Dependent Infection Rates among Household and Nonhousehold Contacts.

To determine the effects of age and variants of concern on transmission of SARS-CoV-2, we analyzed infection rates among close contacts over 4 periods in Toyama Prefecture, Japan. Among household contacts, odds of infection were 6.2 times higher during the period of the Omicron variant than during previous periods, particularly among children and adolescents.

Incidence of lower respiratory tract infection and associated viruses in a birth cohort in the Philippines.

BACKGROUND: Lower respiratory tract infection (LRTI) is an important cause of morbidity and mortality in infants and young children. However, the etiological role of viruses and the timing of developing LRTI are not well defined. METHODS: We analyzed the data of a prospective cohort study in the Philippines as a birth cohort. We detected LRTI among children who visited healthcare facilities with respiratory symptom, and collected nasopharyngeal swabs for virus detection. We analyzed the incidence rates (IRs) and cumulative proportion of LRTI and severe LRTI by age group and each virus detected. RESULTS: A total of 350 LRTI episodes were observed from 473 child-years yielded from 419 children. The IRs of LRTI were 70.8, 70.7, and 80.8 per 100 child-years for 0-5, 6-11, and 12-23 months of age, respectively. By 12 months of age, 45% of children developed LRTI at least once. Rhinovirus and respiratory syncytial virus were the most frequently detected viruses in all age groups. However, the IRs of influenza virus were low especially at 0-5 months of age. CONCLUSIONS: We identified various patterns of age-specific IRs of LRTI and severe LRTI for different viruses, which should be considered to establish more effective interventions including vaccinations.

Risk of Transmission and Viral Shedding From the Time of Infection for Respiratory Syncytial Virus in Households.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection worldwide, but reports of temporal changes in the risk of transmission among close contacts has been scarce. This study aimed to examine an association between the viral load trajectory and transmission risk to develop a better control strategy for the disease spread. We conducted a household-based prospective cohort study in Biliran Province, the Philippines, and enrolled 451 participants to observe the development of acute respiratory infection. Including the cases found at the health-care facility, we analyzed the data of viral loads with symptom records obtained from 172 followed participants who had household member positive for RSV with a rapid test during an RSV outbreak in 2018-2019. We developed a model estimating a temporal change in the viral shedding from the infection and evaluated transmission dynamics. We found that most transmission events occurred within approximately 7 days of the household exposure, including potential presymptomatic transmissions. The inferred risk of infection among those younger than 5 years was 3.5 times higher than that of those older than 5 years. This finding suggested that the initial week after the household exposure is particularly important for preventing RSV spread.

[Response to Ebola Virus Disease Outbreak: Experience in Field Epidemiology in Sierra Leone].

The Ebola virus disease (EVD) outbreak that occurred in West Africa in 2014 was the largest ever in the world. In Sierra Leone, the number of cases reported peaked in December 2014 and gradually declined. However, the outbreak was not immediately terminated. To support the response of the World Health Organization (WHO) to EVD, the WHO Western Pacific Regional Office established the Western Pacific Ebola Support Team (WEST) with the aim of eliminating EVD in Port Loko District, where a certain number of new cases were still being reported in March 2015. We were dispatched to join WEST as WHO short term consultants in epidemiology for about six weeks from March to June 2015. Here, we describe our activities in the field as epidemiologists to show how Japan can contribute in the area of epidemiology during infectious disease outbreaks of international concern. The analysis suggested that the surveillance data for all the deaths and suspected EVD cases were underreporting the actual number of EVD cases in Port Loko District. Although contact tracing was conducted, new EVD cases were often found among untraced contacts because of inadequate information from residents or insufficient investigation by the contact tracing team. In addition, incomplete monitoring of the health status of close contacts resulted in secondary transmission of the disease. Data managers established a database by centralizing data from the surveillance and contact tracing teams, laboratories, and healthcare facilities. The number of deaths per week recorded by these data sources was lower than the number of deaths per week that would be expected from the national mortality statistics. The team strengthened surveillance and social mobilization in the regions with wide disparities between the actual and reported numbers of deaths. For the on-the-ground activities, the field coordinator, epidemiologists, and social mobilizers, as well as the logistic and administrative support personnel, were all indispensable in supporting the field investigation of these infectious disease outbreaks of public health concern. A field coordinator, in particular, requires outstanding knowledge, experience and skills to lead team operations in liaison with international and local partners and to build confidence among local residents. The development of these human resources and the maintenance of a response team are required for potential future outbreaks, and this is an important area that Japan could prepare for and then contribute to future outbreaks. This report does not represent an official view of the WHO or our affiliates.

Analysis of influenza transmission in the households of primary and junior high school students during the 2012-13 influenza season in Odate, Japan.

BACKGROUND: Households are one of the major settings of influenza transmission in the community and transmission is frequently initiated by school-aged children. We surveyed households with primary school (PS) and/ or junior high school (JH) children for the 2012-13 influenza season in Odate, Japan then characterized the epidemiology of influenza household transmission as well as estimated the serial intervals. METHODS: We delivered a self-reported questionnaire survey to households with PS and/or JH school children in Odate City, Japan. Influenza A (H3N2) virus predominantly circulated during the 2012-13 influenza season. We investigated the epidemiological characteristics of within-household transmission and calculated the serial intervals (SI). SIs were drew by a non-parametric model and compared with parametric models by the Akaike Information Criterion. The covariable contributions were investigated by the accelerated failure model. RESULTS: Household influenza transmission was identified in 255 out of 363 household respondents. Primary school (PS) children accounted for 45.1 % of primary cases, and disease transmission was most commonly observed between PS children and parents, followed by transmission from PS children to siblings. In primary cases of PS or JH children, younger age and longer absence from school were significantly associated with household transmission events. The mean SI was estimated as 2.8 days (95 % confidence interval 2.6-3.0 days) in the lognormal model. The estimated acceleration factors revealed that while secondary school age and the absence duration > 7 days were associated with shorter and longer SIs, respectively, antiviral prescriptions for primary cases made no contribution. CONCLUSIONS: High frequencies of household transmission from primary school with shorter SI were found. These findings contribute to the development of future mitigation strategies against influenza transmission in Japan.

SOCIO-DEMOGRAPHIC CHARACTERISTICS AND GEOGRAPHIC DISTRIBUTION OF REPORTED MALARIA CASES IN BANGKA DISTRICT, BABEL ISLAND PROVINCE, INDONESIA DURING 2008-2012.

Malaria is a major health problem in many developing countries including Indonesia. The purpose of this study was to investigate the socio-demographic characteristics and geographic distribution of malaria cases in Bangka District, Bangka-Belitung Island Province, Indonesia. Bangka District is a malaria endemic area of Indonesia. We analyzed the epidemiological data of all reported malaria cases during 2008-2012 in Bangka District. Of the 4,756 malaria-confirmed cases reported during the study period, 3,234 (68. 0%) were among persons aged ≥ 15 years, 1,024 (21.5%) were among persons aged 5-14 years and 498 (10.5%) were among persons aged < 5 years. Malaria cases were primarily located along the sea coast and less frequently in inland. Malaria cases were found not only among the local population but also among migrant workers. The monthly incidence of reported malaria cases in the study population ranged from 0.06 to 1.06 per 1,000 person-months. The cases were mostly due to Plasmodium vivax (57.1%) followed by Plasmodiumfalciparum (40.2%). Plasmodiumfalciparum was more common among migrant workers while Plasmodium vivax was more common among the local population (Odds ratio 1.2; p = 0.03). The main transmission vector found in the coastal area was Anopheles sundaicus. An. letifer and An. barbirostris were found inland. We identified "malaria hot-spots" in the study area using a Geographic Information System. The results of this study will contribute to the malaria control program.

Analysis of medical consultation interval between the symptom onset and consultation observed in multiple medical facilities in Odate city, Japan, 2011/2012 and 2012/2013 seasons.

BACKGROUND: Influenza remains one of the most important causes of respiratory infection despite the widespread availability of vaccines. Anti-influenza viral agents such as neuraminidase inhibitors are generally efficacious in alleviating the symptoms if they are administered within 2 days of the illness onset. However, few studies have examined the situation of interval between illness onset and medical consultation in influenza outpatients on community level. And the predictors or determinants for longer medical consultation interval have not been well-defined. MATERIAL AND METHOD: An enhanced surveillance study was conducted in Odate city of Japan in 2 consecutive seasons from 2011 to 2013. The late consultation rate (>2 days) and its risk factors were investigated in confirmed influenza outpatients. RESULTS: A proportion of 5.5% of patients visited doctors beyond 2 days of illness onset. Illness onset during non-high-incidence period, infection with influenza B and being adult or elderly were identified as independent risk factors for late consultation and the risk increased with the number of risk factors. CONCLUSION: The consultation behavior for influenza was generally well in our study population. Identified risk factors should be addressed in health education and promotion for the late consultation.

Investigation of an Influenza A (H3N2) outbreak in evacuation centres following the Great East Japan earthquake, 2011.

BACKGROUND: The Great East Japan Earthquake of magnitude 9.0 that struck on 11 March 2011 resulted in more than 18000 deaths or cases of missing persons. The large-scale tsunami that followed the earthquake devastated many coastal areas of the Tohoku region, including Miyagi Prefecture, and many residents of the tsunami-affected areas were compelled to reside in evacuation centres (ECs). In Japan, seasonal influenza epidemics usually occur between December and March. At the time of the Great East Japan Earthquake on 11 March 2011, influenza A (H3N2) was still circulating and there was a heightened concern regarding severe outbreaks due to influenza A (H3N2). METHODS: After local hospital staff and public health nurses detected influenza cases among the evacuees, an outbreak investigation was conducted in five ECs that had reported at least one influenza case from 23 March to 11 April 2011. Cases were confirmed by point-of-care tests and those residues were obtained and subjected to reverse transcription PCR and/or real time RT-PCR for sub-typing of influenza. RESULTS: There were 105 confirmed cases detected during the study period with a mean attack rate of 5.3% (range, 0.8%-11.1%). An epidemiological tree for two ECs demonstrated same-room and familial links that accounted for 88.5% of cases. The majority of cases occurred in those aged 15-64 years, who were likely to have engaged in search and rescue activities. No deaths were reported in this outbreak. Familial link accounted for on average 40.5% of influenza cases in two ECs and rooms where two or more cases were reported accounted for on average 85% in those ECs. A combination of preventative measures, including case cohorting, personal hygiene, wearing masks, and early detection and treatment, were implemented during the outbreak period. CONCLUSIONS: Influenza can cause outbreaks in a disaster setting when the disaster occurs during an epidemic influenza season. The transmission route is more likely to be associated with sharing room and space and with familial links. The importance of influenza surveillance and early treatments should be emphasized in EC settings for implementing preventive control measures.

Effects of coronavirus disease 2019 on the spread of respiratory-transmitted human-to-human bacteria.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has necessitated significant changes in medical systems, social behaviours, and non-pharmaceutical interventions (NPIs). We aimed to determine the effect of the COVID-19 pandemic on changes in the epidemiology of respiratory-transmitted bacteria that have been unexplored. METHODS: We utilised a comprehensive national surveillance database from 2018 to 2021 to compare monthly number of patients with four respiratory-transmitted human-to-human bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes) before and after the COVID-19 pandemic, stratified by specimen sources and age groups. RESULTS: The incidence of detected patients with S. pneumoniae, H. influenzae, and S. pyogenes from both respiratory and blood cultures significantly decreased from 2019 to 2020. In 2021, the incidence of detected patients with the respiratory-transmitted bacterial species, except for S. pyogenes, from respiratory cultures, increased again from April to July, primarily affecting the 0-4-year age group. CONCLUSIONS: Our comprehensive national surveillance data analysis demonstrates the dynamic changes and effects of NPIs on respiratory-transmitted bacteria during the COVID-19 pandemic, with variations observed among species, specimen sources, and age groups.

Impact of the Tohoku earthquake and tsunami on pneumonia hospitalisations and mortality among adults in northern Miyagi, Japan: a multicentre observational study.

BACKGROUND: On 11 March 2011, the Tohoku earthquake and tsunami struck off the coast of northeastern Japan. Within 3 weeks, an increased number of pneumonia admissions and deaths occurred in local hospitals. METHODS: A multicentre survey was conducted at three hospitals in Kesennuma City (population 74 000), northern Miyagi Prefecture. All adults aged ≥18 years hospitalised between March 2010 and June 2011 with community-acquired pneumonia were identified using hospital databases and medical records. Segmented regression analyses were used to quantify changes in the incidence of pneumonia. RESULTS: A total of 550 pneumonia hospitalisations were identified, including 325 during the pre-disaster period and 225 cases during the post-disaster period. The majority (90%) of the post-disaster pneumonia patients were aged ≥65 years, and only eight cases (3.6%) were associated with near-drowning in the tsunami waters. The clinical pattern and causative pathogens were almost identical among the pre-disaster and post-disaster pneumonia patients. A marked increase in the incidence of pneumonia was observed during the 3-month period following the disaster; the weekly incidence rates of pneumonia hospitalisations and pneumonia-associated deaths increased by 5.7 times (95% CI 3.9 to 8.4) and 8.9 times (95% CI 4.4 to 17.8), respectively. The increases were largest among residents in nursing homes followed by those in evacuation shelters. CONCLUSIONS: A substantial increase in the pneumonia burden was observed among adults after the Tohoku earthquake and tsunami. Although the exact cause remains unresolved, multiple factors including population aging and stressful living conditions likely contributed to this pneumonia outbreak.

Molecular evolution of the hemagglutinin and neuraminidase genes of pandemic (H1N1) 2009 influenza viruses in Sendai, Japan, during 2009-2011.

Analyzing the evolutionary pattern of the influenza A(H1N1)pdm09 strain in different regions is important for understanding its diversification. We therefore conducted this study to elucidate the genetic variability and molecular evolution of the influenza A(H1N1)pdm09 strains that circulated during the 2009-2010 and 2010-2011 influenza seasons in Sendai, Japan. Nasopharyngeal swab specimens were collected from patients with influenza-like illnesses who visited outpatient clinics in Sendai City, Japan, from September 2009 to April 2011. A total of 75 isolates were selected from September 2009 to April 2011 to analyze the genetic changes in the entire hemagglutinin 1 (HA1) segment of the HA gene and the neuraminidase (NA) gene based on sequence analysis. Bayesian coalescent Markov chain Monte Carlo analyses of HA1 and NA gene sequences were performed for further analysis. High sequence identities were observed for HA1 and NA in influenza A(H1N1)pdm09, displaying 99.06 and 99.33 % nucleotide identities, respectively, with the A(H1N1)pdm09 vaccine strain A/California/07/2009. The substitution rates of nucleotides for HA1 in the 2009-2010 and 2010-2011 were 1.5 × 10-3 and 1.6 × 10-3 substitutions per site per year, respectively. Phylogenetic tree analysis demonstrated that Sendai isolates were clustered into global clade 7, which is characterized by an S203T mutation in the HA1 gene. Moreover, two distinct circulation clusters were present in the 2010-2011 season. Mutations were present in antigenic or receptor-binding domains of the HA1 segment, including A141V, S143G, S183P, S185T, and S203T. The Bayesian skyline plot model illustrated a steady rate for the maintenance of genetic diversity, followed by a slight increase in the later part of the 2010-2011 season. Selection analysis revealed that the HA1 (position 197) and NA (position 46) sites were under positive selection; however, no known mutation conferring resistance to NA inhibitors such as H275Y was observed. The effect on control of the influenza A(H1N1)pdm09 virus, including vaccine strain selection, requires continuous monitoring of the strain by genetic surveillance.

[Infectious disease surveillance in Miyagi after the Great East Japan Earthquake].

OBJECTIVES: The Great East Japan Earthquake, which occurred on March 11, 2011, damaged many health facilities and compelled many inhabitants to live in evacuation centers. For the purpose of monitoring infectious disease outbreaks, infectious disease surveillance targeted at evacuation centers was established in Miyagi Prefecture. In this study, we summarized the monitoring activities of infectious diseases through this surveillance after the earthquake. METHODS: Infectious disease surveillance was implemented from March 18 to November 6, 2011. The surveillance consisted of two phases (hereafter, surveillance 1 and 2) reflecting the difference in frequencies of reporting as well as the number of targeted diseases. Surveillance 1 operated between March 18 and May 13, 2011, and Surveillance 2 operated between May 10 and November 6, 2011. We reviewed the number of cases reported, the number of evacuation centers, and demographic information of evacuees with the surveillance. RESULTS: In Surveillance 1, there were 8,737 reported cases; 84% of them were acute respiratory symptoms, and 16% were acute digestive symptoms. Only 4.4% of evacuation centers were covered by the surveillance one week after the earthquake. In Surveillance 2, 1,339 cases were reported; 82% of them were acute respiratory symptoms, and 13% were acute digestive symptoms. Surveillance 2 revealed that the proportion of children aged 5 years and younger was lower than that of other age groups in all targeted diseases. No particular outbreaks were detected through those surveillances. CONCLUSION: Infectious disease surveillance operated from one week after the earthquake to the closure of all evacuation centers in Miyagi Prefecture. No outbreaks were detected in that period. However, low coverage of evacuation centers just after the earthquake as well as skewed frequencies of reported syndromes draw attention to the improvement of the early warning system. It is important to coordinate with the medical aid team that visits the evacuation centers on a regular basis and to obtain information about the characteristics of evacuees. It is necessary to establish a surveillance system that can monitor infectious disease efficiently from an early phase.

[Researches on virology at the Tohoku University Research Center in the Philippines].

Tohoku University Graduate School of Medicine has established the Tohoku-RITM Collaborative Research Center on Emerging and Re-emerging Diseases at Research Institute for Tropical Medicine (RITM) in the Philippines in 2008. Our aim of the center is to conduct operational researches, which can contribute to control of infectious diseases in the Philippines. Therefore most of our researches in the Philippines are being conducted in the fields. Main research themes include severe acute respiratory infections in children, influenza disease burden study, molecular epidemiology of rabies, and viral etiology of acute diarrhea. The study on severe acute respiratory infections in children in Leyte Island has recruited hospitalized cases with severe pneumonia. We showed that enterovirus 68 was one of important causative agents in severe pneumonia cases. We also conducted other analyses including molecular epidemiology of respiratory syncytial virus (RSV) and pathogenesis of human rhinoviruses (HRV). Based on these studies, we initiated more comprehensive researches in the Philippines since 2010.

Protective effect of previous infection and vaccination against reinfection with BA.5 Omicron subvariant: a nationwide population-based study in Japan.

Background: The Omicron variant of SARS-CoV-2 was reported to evade immunity derived from vaccination and previous infection. A better understanding of hybrid immunity informs effective infection control strategies. Since the reinfection risk was not well-assessed in East Asia, this study aims to evaluate the risk of infection with Omicron subvariant BA.5 among previously infected individuals in Japan. Methods: All notified cases were extracted from the Japanese national COVID-19 surveillance database including 20,297,335 records up to 25 September 2022. Reinfection with BA.5 was defined as the infection notified during the BA.5 dominated period with any prior SARS-CoV-2 infection. The protective effect of prior infections against reinfections with BA.5 was estimated by applying a case-population design and the protective effect of vaccination was estimated by a multivariable Cox regression adjusting for age, sex, variants of prior infection, and the time since the last vaccination. Findings: Among 19,830,548 SARS-CoV-2 first infections, 233,424 (1.2%) were reinfected with BA.5. The protective effect against BA.5 reinfection of prior infection with Wuhan strain was 46%, Alpha variant was 35%, Delta variant was 41%, and BA.1/BA.2 subvariant was 74%. The reduced risk of BA.5 reinfection by 7%, 33%, and 66% was associated with two, three, and four doses of vaccination, respectively, compared with one-dose vaccination. Interpretation: The prior infections with Omicron subvariant BA.1/BA.2 protected BA.5 reinfection more than pre-Omicron variants. Increased frequency of vaccination led to more protection from reinfection with BA.5. Up-to-date vaccination may be encouraged to prevent future reinfection among the previously infected population. Funding: None.

National seroepidemiological study of COVID-19 after the initial rollout of vaccines: Before and at the peak of the Omicron-dominant period in Japan.

Background: Based on routine surveillance data, Japan has been affected much less by COVID-19 compared with other countries. To validate this, we aimed to estimate SARS-CoV-2 seroprevalence and examine sociodemographic factors associated with cumulative infection in Japan. Methods: A population-based serial cross-sectional seroepidemiological investigation was conducted in five prefectures in December 2021 (pre-Omicron) and February-March 2022 (Omicron [BA.1/BA.2]-peak). Anti-nucleocapsid and anti-spike antibodies were measured to detect infection-induced and vaccine/infection-induced antibodies, respectively. Logistic regression was used to identify associations between various factors and past infection. Results: Among 16 296 participants (median age: 53 [43-64] years), overall prevalence of infection-induced antibodies was 2.2% (95% CI: 1.9-2.5%) in December 2021 and 3.5% (95% CI: 3.1-3.9%) in February-March 2022. Factors associated with past infection included those residing in urban prefectures (Tokyo: aOR 3.37 [95% CI: 2.31-4.91], Osaka: aOR 3.23 [95% CI: 2.17-4.80]), older age groups (60s: aOR 0.47 [95% CI 0.29-0.74], 70s: aOR 0.41 [95% CI 0.24-0.70]), being vaccinated (twice: aOR 0.41 [95% CI: 0.28-0.61], three times: aOR 0.21 [95% CI: 0.12-0.36]), individuals engaged in occupations such as long-term care workers (aOR: 3.13 [95% CI: 1.47-6.66]), childcare workers (aOR: 3.63 [95% CI: 1.60-8.24]), food service workers (aOR: 3.09 [95% CI: 1.50-6.35]), and history of household contact (aOR: 26.4 [95% CI: 20.0-34.8]) or non-household contact (aOR: 5.21 [95% CI:3.80-7.14]) in February-March 2022. Almost all vaccinated individuals (15 670/15 681) acquired binding antibodies with higher titers among booster dose recipients. Conclusions: Before Omicron, the cumulative burden was >10 times lower in Japan (2.2%) compared with the US (33%), the UK (25%), or global estimates (45%), but most developed antibodies owing to vaccination.

Protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant: a systematic review and meta-analysis.

OBJECTIVES: The rapid spread of the SARS-CoV-2 Omicron variant has raised concerns regarding waning vaccine-induced immunity and durability. We evaluated protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant and its sublineages. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic databases and other resources (PubMed, Embase, CENTRAL, MEDLINE, CINAHL PLUS, APA PsycINFO, Web of Science, Scopus, ScienceDirect, MedRxiv and bioRxiv) were searched until December 2022. STUDY ELIGIBILITY CRITERIA: We included studies that assessed the effectiveness of mRNA vaccine booster doses against SARS-CoV-2 infection and severe COVID-19 outcomes caused by the subvariant. DATA EXTRACTION AND SYNTHESIS: Estimates of vaccine effectiveness (VE) at different time points after the third-dose and fourth-dose vaccination were extracted. Random-effects meta-analysis was used to compare VE of the third dose versus the primary series, no vaccination and the fourth dose at different time points. The certainty of the evidence was assessed by Grading of Recommendations, Assessments, Development and Evaluation approach. RESULTS: This review included 50 studies. The third-dose VE, compared with the primary series, against SARS-CoV-2 infection was 48.86% (95% CI 44.90% to 52.82%, low certainty) at ≥14 days, and gradually decreased to 38.01% (95% CI 13.90% to 62.13%, very low certainty) at ≥90 days after the third-dose vaccination. The fourth-dose VE peaked at 14-30 days (56.70% (95% CI 50.36% to 63.04%), moderate certainty), then quickly declined at 61-90 days (22% (95% CI 6.40% to 37.60%), low certainty). Compared with no vaccination, the third-dose VE was 75.84% (95% CI 40.56% to 111.12%, low certainty) against BA.1 infection, and 70.41% (95% CI 49.94% to 90.88%, low certainty) against BA.2 infection at ≥7 days after the third-dose vaccination. The third-dose VE against hospitalisation remained stable over time and maintained 79.30% (95% CI 58.65% to 99.94%, moderate certainty) at 91-120 days. The fourth-dose VE up to 60 days was 67.54% (95% CI 59.76% to 75.33%, moderate certainty) for hospitalisation and 77.88% (95% CI 72.55% to 83.21%, moderate certainty) for death. CONCLUSION: The boosters provided substantial protection against severe COVID-19 outcomes for at least 6 months, although the duration of protection remains uncertain, suggesting the need for a booster dose within 6 months of the third-dose or fourth-dose vaccination. However, the certainty of evidence in our VE estimates varied from very low to moderate, indicating significant heterogeneity among studies that should be considered when interpreting the findings for public health policies. PROSPERO REGISTRATION NUMBER: CRD42023376698.

Replacement of SARS-CoV-2 strains with variants carrying N501Y and L452R mutations in Japan: an epidemiological surveillance assessment.

Objective: Monitoring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important due to concerns regarding infectivity, transmissibility, immune evasion and disease severity. We evaluated the temporal and regional replacement of previous SARS-CoV-2 variants by the emergent strains, Alpha and Delta. Methods: We obtained the results of polymerase chain reaction screening tests for variants conducted in multiple commercial laboratories. Assuming that all previous strains would be replaced by one variant, the new variant detection rate was estimated by fitting a logistic growth model. We estimated the transmission advantage of each new variant over the pre-existing virus strains. Results: The variant with the N501Y mutation was first identified in the Kinki region in early February 2021, and by early May, it had replaced more than 90% of the previous strains. The variant with the L452R mutation was first detected in the Kanto-Koshin region in mid-May, and by early August, it comprised more than 90% of the circulating strains. Compared with pre-existing strains, the variant with the N501Y mutation showed transmission advantages of 48.2% and 40.3% in the Kanto-Koshin and Kinki regions, respectively, while the variant with the L452R mutation showed transmission advantages of 60.1% and 71.9%, respectively. Discussion: In Japan, Alpha and Delta variants displayed regional differences in the replacement timing and their relative transmission advantages. Our method is efficient in monitoring and estimating changes in the proportion of variant strains in a timely manner in each region.

Impact of the Coming-of-Age Day and ceremony on the risk of SARS-CoV-2 transmission in Japan: A natural-experimental study based on national surveillance data.

BACKGROUND: Quantifying the impact on COVID-19 transmission from a single event has been difficult due to the virus transmission dynamics, such as lag from exposure to reported infection, non-linearity arising from the person-to-person transmission, and the modifying effects of non-pharmaceutical interventions over time. To address these issues, we aimed to estimate the COVID-19 transmission risk of social events focusing on the Japanese Coming-of-Age Day and Coming-of-Age ceremony in which "new adults" practice risky behavior on that particular day. METHODS: Using national surveillance data in Japan in 2021 and 2022, we conducted difference-in-differences regression against COVID-19 incidences by setting "new adults" cases as the treatment group and the cases 1 year younger or older than these "new adults" as the control group. In addition, we employed a triple differences approach to estimate the risk of holding the Coming-Age ceremony by using a binary variable regarding the presence or absence of the ceremony in each municipality. RESULTS: We estimated the relative risks (RRs) of the Coming-of-Age Day as 1.27 (95% confidence interval [CI] 1.02-1.57) in 2021 and 3.22 (95% CI 2.68-3.86) in 2022. The RR of the Coming-of-Age ceremony was also large, estimated as 2.83 (1.81-4.43) in 2022. CONCLUSIONS: When planning large social events, it is important to be aware of the unique risks associated with these gatherings, along with effective public health messages to best communicate these risks.