Assessing Public Health and Social Measures Against COVID-19 in Japan From March to June 2021.

Background: Public health and social measures (PHSM) against COVID-19 in Japan involve requesting the public to voluntarily reduce social contact; these measures are not legally binding. The effectiveness of such PHSM has been questioned with emergence of the SARS-CoV-2 Alpha variant (B.1.1.7), which exhibited elevated transmissibility. Materials and Methods: We investigated the epidemic dynamics during the fourth epidemic wave in Japan from March to June 2021 involving pre-emergency measures and declaration of a state of emergency (SoE). We estimated the effective reproduction number (R t ) before and after these interventions, and then analyzed the relationship between lower R t values and each PHSM. Results: With implementation of pre-emergency measures (PEM) in 16 prefectures, the R t was estimated to be < 1 in six prefectures; its average relative reduction ranged from 2 to 19%. During the SoE, 8 of 10 prefectures had an estimated R t < 1, and the average relative reduction was 26%-39%. No single intervention was identified that uniquely resulted in an R t value < 1. Conclusion: An SoE can substantially reduce the R t and may be required to curb a surge in cases caused by future SARS-CoV-2 variants of concern with elevated transmissibility. More customized interventions did not reduce the R t value to < 1 in this study, but that may be partly attributable to the greater transmissibility of the Alpha variant.

Basic reproduction number of the COVID-19 Delta variant: Estimation from multiple transmission datasets.

The basic reproduction number, $ R_0 $, plays a central role in measuring the transmissibility of an infectious disease, and it thus acts as the fundamental index for planning control strategies. In the present study, we apply a branching process model to meticulously observed contact tracing data from Wakayama Prefecture, Japan, obtained in early 2020 and mid-2021. This allows us to efficiently estimate $ R_0 $ and the dispersion parameter $ k $ of the wild-type COVID-19, as well as the relative transmissibility of the Delta variant and relative transmissibility among fully vaccinated individuals, from a very limited data. $ R_0 $ for the wild type of COVID-19 is estimated to be 3.78 (95% confidence interval [CI]: 3.72-3.83), with $ k = 0.236 $ (95% CI: 0.233-0.240). For the Delta variant, the relative transmissibility to the wild type is estimated to be 1.42 (95% CI: 0.94-1.90), which gives $ R_0 = 5.37 $ (95% CI: 3.55-7.21). Vaccine effectiveness, determined by the reduction in the number of secondary transmissions among fully vaccinated individuals, is estimated to be 91% (95% CI: 85%-97%). The present study highlights that basic reproduction numbers can be accurately estimated from the distribution of minor outbreak data, and these data can provide further insightful epidemiological estimates including the dispersion parameter and vaccine effectiveness regarding the prevention of transmission.

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.

Assessing Public Health and Social Measures Against COVID-19 in Japan From March to June 2021

Background Public health and social measures (PHSM) against COVID-19 in Japan involve requesting the public to voluntarily reduce social contact;these measures are not legally binding. The effectiveness of such PHSM has been questioned with emergence of the SARS-CoV-2 Alpha variant (B.1.1.7), which exhibited elevated transmissibility. Materials and Methods We investigated the epidemic dynamics during the fourth epidemic wave in Japan from March to June 2021 involving pre-emergency measures and declaration of a state of emergency (SoE). We estimated the effective reproduction number (Rt) before and after these interventions, and then analyzed the relationship between lower Rt values and each PHSM. Results With implementation of pre-emergency measures (PEM) in 16 prefectures, the Rt was estimated to be < 1 in six prefectures;its average relative reduction ranged from 2 to 19%. During the SoE, 8 of 10 prefectures had an estimated Rt < 1, and the average relative reduction was 26%–39%. No single intervention was identified that uniquely resulted in an Rt value < 1. Conclusion An SoE can substantially reduce the Rt and may be required to curb a surge in cases caused by future SARS-CoV-2 variants of concern with elevated transmissibility. More customized interventions did not reduce the Rt value to < 1 in this study, but that may be partly attributable to the greater transmissibility of the Alpha variant.

Age-Dependent Risks of COVID-19 Putatively Caused by Variant Alpha in Japan.

Background: Osaka, the third largest prefecture in Japan, experienced a rapid replacement of preexisting strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by variant alpha during March-April 2021. Assessing the burden of variant alpha on health centers and medical institutions is vital to anticipating the surge of patients. The present study aimed to estimate the age-dependent risks of coronavirus disease (COVID-19) putatively caused by variant alpha in Japan, focusing on epidemiological dynamics in Osaka. Methods: Descriptive analyses were conducted using data on confirmed, severe and fatal cases of COVID-19 from 16 November 2020 to 22 May 2021. All cases were divided into 6-9 age groups to compare the risks of confirmed diagnosis, severe illness and death from COVID-19 with variant alpha to those caused by preexisting strains. Results: Individuals with COVID-19 aged under 30 years were more likely to be infected with variant alpha than those in their 40s. The incidence of severe illness and death among all age groups with COVID-19 due to variant alpha was higher than that due to preexisting strains. Patients older than 40 years experienced an increased risk of severe illness and death if infected with variant alpha. However, the proportion of severe cases was lower in the group aged 80 years and older infected with variant alpha than in those infected with preexisting strains. Conclusion: Our analysis suggests that the incidence of infection among young people aged below 30 years old increased relative to ordinary strains. Risks of severe illness and death in patients with variant alpha COVID-19 was higher than in those with preexisting strains in Osaka, Japan. However, a decrease in the risk of severe illness was observed in people aged ≥80 years, which is probably because medical facilities in Osaka were overwhelmed in April and May 2021. Continuous monitoring of COVID-19 cases with new variants is vital to secure sufficient medical resources for all patients who require medical care.

Prioritizing COVID-19 vaccination. Part 2: Real-time comparison between single-dose and double-dose in Japan.

Japan successfully implemented a mass vaccination program for coronavirus disease 2019 (COVID-19), immunizing more than 1 million persons a day by July 2021. Given the COVID-19 vaccination capacity limitations, an urgent question was raised regarding whether it would be better to (ⅰ) complete double-dose COVID-19 vaccination among healthcare personnel and older adults before beginning double-dose vaccination of younger adults (double-dose strategy) or (ⅱ) allocate a single dose of COVID-19 vaccine to all adults regardless of age before administering the second dose (single-dose-first strategy). We used an age-structured susceptible-infectious-recovered (SIR) compartment model to compare the effectiveness of possible COVID-19 vaccination strategies and the length of public health and social measures (PHSM) to minimize the cumulative COVID-19 disease risk and death toll. Our results indicate that if the single-dose-first strategy was taken, an estimated total of 1,387,078 persons, i.e., 263,315 children, 928,518 young adults, and 195,245 older adults, would develop COVID-19, resulting in 15,442 deaths. In contrast, if the double-dose strategy was taken instead, an estimated total of 1,900,172 persons, i.e., 377,107 children, 1,315,927 young adults, and 207,138 older adults, would develop COVID-19, yielding 17,423 deaths. Real-time investigation favored the disease transmission blocking option, i.e., single-dose vaccination strategy. Applying the single-dose-first strategy should yield a smaller epidemic size than applying the double-dose strategy; however, for both strategies, PHSM will be essential by the time second-dose COVID-19 vaccination is complete among all adults.

Prioritizing COVID-19 vaccination. Part 1: Final size comparison between a single dose and double dose.

In response to the coronavirus disease 2019 (COVID-19) pandemic, Japan conducted mass vaccination. Seventy-two million doses of vaccine (i.e., for 36 million people if a double dose is planned per person) were obtained, with initial vaccination of the older population (≡ 65 years). Because of the limited number of vaccines, the government discussed shifting the plan to administering only a single dose so that younger individuals (<65 years) could also be vaccinated with one shot. This study aimed to determine the optimal vaccine distribution strategy using a simple mathematical method. After accounting for age-dependent relative susceptibility after single- and double-dose vaccination (vs and vd, respectively, compared with unvaccinated), we used the age-dependent transmission model to compute the final size for various patterns of vaccine distributions. Depending on the values of vs, the cumulative risk of death would be lower if all 72 million doses were used as a double dose for older people than if a single-dose program was conducted in which half is administered to older people and the other half is administered to adults (i.e., 1,856,000 deaths in the former program and 1,833,000-2,355,000 deaths [depending on the values of vs] in the latter). Even if 90% of older people were vaccinated twice and 100% of adults were vaccinated once, the effective reproduction number would be reduced from 2.50 to1.14. Additionally, the cumulative risk of infection would range from 12.0% to 54.6% and there would be 421,000-1,588,000deaths (depending on the values of vs). If an epidemic appears only after completing vaccination, vaccination coverage using a single-dose program with widespread vaccination among adults will not outperform a double-dose strategy.

Epidemiology of coronavirus disease 2019 (COVID-19) in Japan during the first and second waves.

Following the emergence and worldwide spread of coronavirus disease 2019 (COVID-19), each country has attempted to control the disease in different ways. The first patient with COVID-19 in Japan was diagnosed on 15 January 2020, and until 31 October 2020, the epidemic was characterized by two large waves. To prevent the first wave, the Japanese government imposed several control measures such as advising the public to avoid the 3Cs (closed spaces with poor ventilation, crowded places with many people nearby, and close-contact settings such as close-range conversations) and implementation of "cluster buster" strategies. After a major epidemic occurred in April 2020 (the first wave), Japan asked its citizens to limit their numbers of physical contacts and announced a non-legally binding state of emergency. Following a drop in the number of diagnosed cases, the state of emergency was gradually relaxed and then lifted in all prefectures of Japan by 25 May 2020. However, the development of another major epidemic (the second wave) could not be prevented because of continued chains of transmission, especially in urban locations. The present study aimed to descriptively examine propagation of the COVID-19 epidemic in Japan with respect to time, age, space, and interventions implemented during the first and second waves. Using publicly available data, we calculated the effective reproduction number and its associations with the timing of measures imposed to suppress transmission. Finally, we crudely calculated the proportions of severe and fatal COVID-19 cases during the first and second waves. Our analysis identified key characteristics of COVID-19, including density dependence and also the age dependence in the risk of severe outcomes. We also identified that the effective reproduction number during the state of emergency was maintained below the value of 1 during the first wave.

Phenomenological and mechanistic models for predicting early transmission data of COVID-19.

Forecasting future epidemics helps inform policy decisions regarding interventions. During the early coronavirus disease 2019 epidemic period in January-February 2020, limited information was available, and it was too challenging to build detailed mechanistic models reflecting population behavior. This study compared the performance of phenomenological and mechanistic models for forecasting epidemics. For the former, we employed the Richards model and the approximate solution of the susceptible-infected-recovered (SIR) model. For the latter, we examined the exponential growth (with lockdown) model and SIR model with lockdown. The phenomenological models yielded higher root mean square error (RMSE) values than the mechanistic models. When using the numbers from reported data for February 1 and 5, the Richards model had the highest RMSE, whereas when using the February 9 data, the SIR approximation model was the highest. The exponential model with a lockdown effect had the lowest RMSE, except when using the February 9 data. Once interventions or other factors that influence transmission patterns are identified, they should be additionally taken into account to improve forecasting.

Relative Reproduction Number of SARS-CoV-2 Omicron (B.1.1.529) Compared with Delta Variant in South Africa.

The world identified the rapidly increasing incidence of the causative variant of SARS-CoV-2 Pangolin B [...].

Age dependence of the natural history of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): an analysis of Diamond Princess data.

BACKGROUND: Following an outbreak of coronavirus disease 2019 (COVID-19) on the cruise ship Diamond Princess, passengers and crew were followed-up to determine prognosis. This study examined the epidemiological determinants of COVID-19 natural history using these follow-up data. METHODS: Infection status, diagnosis, clinical symptoms and prognosis were analysed for all passengers and crew members on the Diamond Princess. In addition, the risk of infection associated with exposure within cabin rooms, as well as the risks of various clinical manifestations of disease, along with their epidemiological determinants, were analysed. RESULTS: The adjusted odds ratio (aOR) of infection for individuals tested by polymerase chain reaction on or after 12 February 2020 compared with individuals tested before this date was 0.53 [95% confidence interval (CI) 0.39-0.72], reflecting decreased transmission during onboard quarantine. Among infected individuals, older age was associated with elevated odds of symptomatic illness (aOR 1.01, 95% CI 1.00-1.02), severe disease (aOR 1.08, 95% CI 1.05-1.12) and death (aOR 1.12, 95% CI 1.05-1.21). CONCLUSIONS: Severe COVID-19 disease, death and symptomatic illness were more frequent among older individuals on the Diamond Princess. Older elderly cases (age ≥80 years) had the highest risks of severe disease and death. Inter-room transmission was prevented successfully by the onboard quarantine.

Containment, Contact Tracing and Asymptomatic Transmission of Novel Coronavirus Disease (COVID-19): A Modelling Study.

When a novel infectious disease emerges, enhanced contact tracing and isolation are implemented to prevent a major epidemic, and indeed, they have been successful for the control of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which have been greatly reduced without causing a global pandemic. Considering that asymptomatic and pre-symptomatic infections are substantial for the novel coronavirus disease (COVID-19), the feasibility of preventing the major epidemic has been questioned. Using a two-type branching process model, the present study assesses the feasibility of containing COVID-19 by computing the probability of a major epidemic. We show that if there is a substantial number of asymptomatic transmissions, cutting chains of transmission by means of contact tracing and case isolation would be very challenging without additional interventions, and in particular, untraced cases contribute to lowering the feasibility of containment. Even if isolation of symptomatic cases is conducted swiftly after symptom onset, only secondary transmissions after the symptom onset can be prevented.

Communicating the Risk of Death from Novel Coronavirus Disease (COVID-19).

To understand the severity of infection for a given disease, it is common epidemiological practice to estimate the case fatality risk, defined as the risk of death among cases. However, there are three technical obstacles that should be addressed to appropriately measure this risk. First, division of the cumulative number of deaths by that of cases tends to underestimate the actual risk because deaths that will occur have not yet observed, and so the delay in time from illness onset to death must be addressed. Second, the observed dataset of reported cases represents only a proportion of all infected individuals and there can be a substantial number of asymptomatic and mildly infected individuals who are never diagnosed. Third, ascertainment bias and risk of death among all those infected would be smaller when estimated using shorter virus detection windows and less sensitive diagnostic laboratory tests. In the ongoing COVID-19 epidemic, health authorities must cope with the uncertainty in the risk of death from COVID-19, and high-risk individuals should be identified using approaches that can address the abovementioned three problems. Although COVID-19 involves mostly mild infections among the majority of the general population, the risk of death among young adults is higher than that of seasonal influenza, and elderly with underlying comorbidities require additional care.

Assessing the Impact of Reduced Travel on Exportation Dynamics of Novel Coronavirus Infection (COVID-19).

The impact of the drastic reduction in travel volume within mainland China in January and February 2020 was quantified with respect to reports of novel coronavirus (COVID-19) infections outside China. Data on confirmed cases diagnosed outside China were analyzed using statistical models to estimate the impact of travel reduction on three epidemiological outcome measures: (i) the number of exported cases, (ii) the probability of a major epidemic, and (iii) the time delay to a major epidemic. From 28 January to 7 February 2020, we estimated that 226 exported cases (95% confidence interval: 86,449) were prevented, corresponding to a 70.4% reduction in incidence compared to the counterfactual scenario. The reduced probability of a major epidemic ranged from 7% to 20% in Japan, which resulted in a median time delay to a major epidemic of two days. Depending on the scenario, the estimated delay may be less than one day. As the delay is small, the decision to control travel volume through restrictions on freedom of movement should be balanced between the resulting estimated epidemiological impact and predicted economic fallout.

The Rate of Underascertainment of Novel Coronavirus (2019-nCoV) Infection: Estimation Using Japanese Passengers Data on Evacuation Flights.

From 29 to 31 January 2020, a total of 565 Japanese citizens were evacuated from Wuhan, China on three chartered flights. All passengers were screened upon arrival in Japan for symptoms consistent with novel coronavirus (2019-nCoV) infection and tested for presence of the virus. Assuming that the mean detection window of the virus can be informed by the mean serial interval (estimated at 7.5 days), the ascertainment rate of infection was estimated at 9.2% (95% confidence interval: 5.0, 20.0). This indicates that the incidence of infection in Wuhan can be estimated at 20,767 infected individuals, including those with asymptomatic and mildly symptomatic infections. The infection fatality risk (IFR)-the actual risk of death among all infected individuals-is therefore 0.3% to 0.6%, which may be comparable to Asian influenza pandemic of 1957-1958.

The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020.

A cluster of pneumonia cases linked to a novel coronavirus (2019-nCoV) was reported by China in late December 2019. Reported case incidence has now reached the hundreds, but this is likely an underestimate. As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057). The most plausible number of infections is in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than the one in the epidemiologically linked seafood market in Wuhan have occurred.

Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data.

The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2-14 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3-4 days without truncation and at 5-9 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk.