Time-varying overdispersion of SARS-CoV-2 transmission during the periods when different variants of concern were circulating in Japan.

Japan has implemented a cluster-based approach for coronavirus disease 2019 (COVID-19) from the pandemic's beginning based on the transmission heterogeneity (overdispersion) of severe acute respiratory coronavirus 2 (SARS-CoV-2). However, studies analyzing overdispersion of transmission among new variants of concerns (VOCs), especially for Omicron, were limited. Thus, we aimed to clarify how the transmission heterogeneity has changed with the emergence of VOCs (Alpha, Delta, and Omicron) using detailed contact tracing data in Yamagata Prefecture, Japan. We estimated the time-varying dispersion parameter ([Formula: see text]) by fitting a negative binomial distribution for each transmission generation. Our results showed that even after the emergence of VOCs, there was transmission heterogeneity of SARS-CoV-2, with changes in [Formula: see text] during each wave. Continuous monitoring of transmission dynamics is vital for implementing appropriate measures. However, a feasible and sustainable epidemiological analysis system should be established to make this possible.

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.

Number of averted COVID-19 cases and deaths attributable to reduced risk in vaccinated individuals in Japan.

Background: In Japan, vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initiated on 17 February 2021, mainly using messenger RNA vaccines and prioritizing health care professionals. Whereas nationwide vaccination alleviated the coronavirus disease 2019 (COVID-19)-related burden, the population impact has yet to be quantified in Japan. We aimed to estimate the numbers of COVID-19 cases and deaths prevented that were attributable to the reduced risk among vaccinated individuals via a statistical modeling framework. Methods: We analyzed confirmed cases registered in the Health Center Real-time Information-sharing System on COVID-19 (3 March-30 November 2021) and publicly reported COVID-19-related deaths (24 March-30 November 2021). The vaccination coverage over this time course, classified by age and sex, was extracted from vaccine registration systems. The total numbers of prevented cases and deaths were calculated by multiplying the daily risk differences between unvaccinated and vaccinated individuals by the population size of vaccinated individuals. Findings: For both cases and deaths, the averted numbers were estimated to be the highest among individuals aged 65 years and older. In total, we estimated that 564,596 (95% confidence interval: 477,020-657,525) COVID-19 cases and 18,622 (95% confidence interval: 6522-33,762) deaths associated with SARS-CoV-2 infection were prevented owing to vaccination during the analysis period (i.e., fifth epidemic wave, caused mainly by the Delta variant). Female individuals were more likely to be protected from infection following vaccination than male individuals whereas more deaths were prevented in male than in female individuals. Interpretation: The vaccination program in Japan led to substantial reductions in the numbers of COVID-19 cases and deaths (33% and 67%, respectively). The preventive effect will be further amplified during future pandemic waves caused by variants with shared antigenicity. Funding: This project was supported by the Japan Science and Technology Agency; the Japan Agency for Medical Research and Development; the Japan Society for the Promotion of Science; and the Ministry of Health, Labour and Welfare.

Age-Dependent Effects of COVID-19 Vaccine and of Healthcare Burden on COVID-19 Deaths, Tokyo, Japan.

COVID-19 vaccine effectiveness against death in Japan remains unknown. Furthermore, although evidence indicates that healthcare capacity influences case-fatality risk (CFR), it remains unknown whether this relationship is mediated by age. With a modeling study, we analyzed daily COVID-19 cases and deaths during January-August 2021 by using Tokyo surveillance data to jointly estimate COVID-19 vaccine effectiveness against death and age-specific CFR. We also examined daily healthcare operations to determine the association between healthcare burden and age-specific CFR. Among fully vaccinated patients, vaccine effectiveness against death was 88.6% among patients 60-69 years of age, 83.9% among patients 70-79 years of age, 83.5% among patients 80-89 years of age, and 77.7% among patients >90 years of age. A positive association of several indicators of healthcare burden with CFR among patients >70 years of age suggested an age-dependent effect of healthcare burden on CFR in Japan.

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.

Integration of publicly available case-based data for real-time coronavirus disease 2019 risk assessment, Japan.

In response to the outbreak of coronavirus disease 2019 (COVID-19) in Japan, a national COVID-19 cluster taskforce (comprising governmental and nongovernmental experts) was established to support the country's Ministry of Health, Labour and Welfare in conducting daily risk assessment. The assessment was carried out using established infectious disease surveillance systems; however, in the initial stages of the pandemic these were not sufficient for real-time risk assessment owing to limited accessibility, delay in data entry and inadequate case information. Also, local governments were publishing anonymized data on confirmed COVID-19 cases on their official web sites as daily press releases. We developed a unique database for nationwide real-time risk assessment that included these case lists from local government web sites and integrated all case data into a standardized format. The database was updated daily and checked systematically to ensure comprehensiveness and quality. Between 15 January 2020 and 15 June 2021, 776 459 cases were logged in the database, allowing for analysis of real-time risk from the pandemic. This semi-automated database was used in daily risk assessments, and to evaluate and update control measures to prevent community transmission of COVID-19 in Japan. The data were reported almost every week to the Japanese Government Advisory Panel on COVID-19 for public health responses.

Secondary transmission of SARS-CoV-2 during the first two waves in Japan: Demographic characteristics and overdispersion.

OBJECTIVES: Super-spreading events caused by overdispersed secondary transmission are crucial in the transmission of COVID-19. However, the exact level of overdispersion, demographics, and other factors associated with secondary transmission remain elusive. In this study, we aimed to elucidate the frequency and patterns of secondary transmission of SARS-CoV-2 in Japan. METHODS: We analyzed 16,471 cases between January 2020 and August 2020. We generated the number of secondary cases distribution and estimated the dispersion parameter (k) by fitting the negative binomial distribution in each phase. The frequencies of the secondary transmission were compared by demographic and clinical characteristics, calculating the odds ratio using logistic regression models. RESULTS: We observed that 76.7% of the primary cases did not generate secondary cases with an estimated dispersion parameter k of 0.23. The demographic patterns of primary-secondary cases differed between phases, with 20-69 years being the predominant age group. There were higher proportions of secondary transmissions among older individuals, symptomatic patients, and patients with 2 days or more between onset and confirmation. CONCLUSIONS: The study showed the estimation of the frequency of secondary transmission of SARS-CoV-2 and the characteristics of people who generated the secondary transmission.

Epidemiological Factors Associated with COVID-19 Clusters in Medical and Social Welfare Facilities.

The characteristics of coronavirus disease 2019 (COVID-19) clusters in medical and social welfare facilities and the factors associated with cluster size are still not yet fully understood. We reviewed COVID-19 cases in Japan identified from January 15 to April 30, 2020 and analyzed the factors associated with cluster size in medical and social welfare facilities. In this study, COVID-19 clusters were identified in 56 medical and 34 social welfare facilities. The number of cases in those facilities peaked after the peak of the general population. The duration of occurrence of new cases in clusters was positively correlated with the number of cases in both types of facilities (rho = 0.44, P < 0.001; and rho = 0.69, P < 0.001, respectively). However, the number of days between the first case in a prefecture and the onset of clusters was negatively correlated with the number of cases only in clusters in social welfare facilities (rho = - 0.4, P = 0.004). Our results suggest that COVID-19 cases in those facilities were prevalent in the latter phase of the disease's community transmission, although the underlying mechanisms for such a trend could differ between medical and social welfare facilities.

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.

Roles of Children and Adolescents in COVID-19 Transmission in the Community: A Retrospective Analysis of Nationwide Data in Japan.

Background: Roles of children and adolescents in spreading coronavirus disease 2019 (COVID-19) in the community is not fully understood. Methods: We analyzed the data of 7,758 children and adolescents with COVID-19 and characteristics of secondary transmission generated by these cases using case information published by local governments. Ratio of pediatric and adolescent cases generating secondary transmission was calculated for various social settings. Results: The incidence of COVID-19 was 24.8 cases per 105 population aged between 0 and 9 years, and 59.2 among those aged between 10 and 19 years, which was lower than that among individuals of all age groups (79.6 per 105 population) between January 15 and October 31, 2020. The proportion of cases generating secondary cases was 8.3% among infants and young children in nursery schools and kindergartens, 16% among children and adolescents attending primary schools, 34% among those attending junior high schools, 43% among those attending high schools, 31% among those attending professional training colleges, and 24% in those attending universities. Households were the most common setting for secondary transmission. Conclusion: The risk of generating secondary cases might be limited among pediatric and adolescent cases with COVID-19, especially in settings outside households. Effectiveness of traditional mitigation measures (e.g., school closures) to suppress COVID-19 transmissions should be carefully evaluated.

Relationship of Test Positivity Rates with COVID-19 Epidemic Dynamics.

Detection and isolation of infected people are believed to play an important role in the control of the COVID-19 pandemic. Some countries conduct large-scale screenings for testing, whereas others test mainly people with high prior probability of infection such as showing severe symptoms and/or having an epidemiological link with a known or suspected case or cluster of cases. However, what a good testing strategy is and whether the difference in testing strategy shows a meaningful, measurable impact on the COVID-19 epidemic remain unknown. Here, we showed that patterns of association between effective reproduction number (Rt) and test positivity rate can illuminate differences in testing situation among different areas, using global and local data from Japan. This association can also evaluate the adequacy of current testing systems and what information is captured in COVID-19 surveillance. The differences in testing systems alone cannot predict the results of epidemic containment efforts. Furthermore, monitoring test positivity rates and severe case proportions among the nonelderly can predict imminent case count increases. Monitoring test positivity rates in conjunction with the concurrent Rt could be useful to assess and strengthen public health management and testing systems and deepen understanding of COVID-19 epidemic dynamics.

Familial Clusters of Coronavirus Disease in 10 Prefectures, Japan, February-May 2020.

The overall coronavirus disease secondary attack rate (SAR) in family members was 19.0% in 10 prefectures of Japan during February 22-May 31, 2020. The SAR was lower for primary cases diagnosed early, within 2 days after symptom onset. The SAR of asymptomatic primary cases was 11.8%.

Clusters of Coronavirus Disease in Communities, Japan, January-April 2020.

We analyzed 3,184 cases of coronavirus disease in Japan and identified 61 case-clusters in healthcare and other care facilities, restaurants and bars, workplaces, and music events. We also identified 22 probable primary case-patients for the clusters; most were 20-39 years of age and presymptomatic or asymptomatic at virus transmission.