Protection against SARS-CoV-2 BA.4 and BA.5 subvariants via vaccination and natural infection: A modeling study.

With continuing emergence of new SARS-CoV-2 variants, understanding the proportion of the population protected against infection is crucial for public health risk assessment and decision-making and so that the general public can take preventive measures. We aimed to estimate the protection against symptomatic illness caused by SARS-CoV-2 Omicron variants BA.4 and BA.5 elicited by vaccination against and natural infection with other SARS-CoV-2 Omicron subvariants. We used a logistic model to define the protection rate against symptomatic infection caused by BA.1 and BA.2 as a function of neutralizing antibody titer values. Applying the quantified relationships to BA.4 and BA.5 using two different methods, the estimated protection rate against BA.4 and BA.5 was 11.3% (95% confidence interval [CI]: 0.01-25.4) (method 1) and 12.9% (95% CI: 8.8-18.0) (method 2) at 6 months after a second dose of BNT162b2 vaccine, 44.3% (95% CI: 20.0-59.3) (method 1) and 47.3% (95% CI: 34.1-60.6) (method 2) at 2 weeks after a third BNT162b2 dose, and 52.3% (95% CI: 25.1-69.2) (method 1) and 54.9% (95% CI: 37.6-71.4) (method 2) during the convalescent phase after infection with BA.1 and BA.2, respectively. Our study indicates that the protection rate against BA.4 and BA.5 are significantly lower compared with those against previous variants and may lead to substantial morbidity, and overall estimates were consistent with empirical reports. Our simple yet practical models enable prompt assessment of public health impacts posed by new SARS-CoV-2 variants using small sample-size neutralization titer data to support public health decisions in urgent situations.

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.

Go To Travel campaign and the geographic spread of COVID-19 in Japan.

BACKGROUND: In 2020, the Japanese government implemented first of two Go To Travel campaigns to promote the tourism sector as well as eating and drinking establishments, especially in remote areas. The present study aimed to explore the relationship between enhanced travel and geographic propagation of COVID-19 across Japan, focusing on the second campaign with nationwide large-scale economic boost in 2020. METHODS: We carried out an interrupted time-series analysis to identify the possible cause-outcome relationship between the Go To Travel campaign and the spread of infection to nonurban areas in Japan. Specifically, we counted the number of prefectures that experienced a weekly incidence of three, five, and seven COVID-19 cases or more per 100,000 population, and we compared the rate of change before and after the campaign. RESULTS: Three threshold values and three different models identified an increasing number of prefectures above the threshold, indicating that the inter-prefectural spread intensified following the launch of the second Go To Travel campaign from October 1st, 2020. The simplest model that accounted for an increase in the rate of change only provided the best fit. We estimated that 0.24 (95% confidence interval 0.15 to 0.34) additional prefectures newly exceeded five COVID-19 cases per 100,000 population per week during the second campaign. CONCLUSIONS: The enhanced movement resulting from the Go To Travel campaign facilitated spatial spread of COVID-19 from urban to nonurban locations, where health-care capacity may have been limited.

Doubling time of infectious diseases.

The concept of doubling time has been increasingly used since the onset of the coronavirus disease 2019 (COVID-19) pandemic, but its characteristics are not well understood, especially as applied to infectious disease epidemiology. The present study aims to be a practical guide to monitoring the doubling time of infectious diseases. Via simulation exercise, we clarify the epidemiological characteristics of doubling time, allowing possible interpretations. We show that the commonly believed relationship between the doubling time and intrinsic growth rate in population ecology does not strictly apply to infectious diseases, and derive the correct relationship between the two. We examined the impact of varying (i) the growth rate, (ii) the starting point of counting cumulative number of cases, and (iii) the length of observation on statistical estimation of doubling time. It was difficult to recover values of growth rate from doubling time, especially when the growth rate was small. Starting time period is critical when the statistical estimation of doubling time occurs during the course of an epidemic. The length of observation was critical in determining the overall magnitude of doubling time, and when only the latest 1-2 weeks' data were used, the resulting doubling time was very short, regardless of the intrinsic growth rate r. We suggest that doubling time estimates of infectious disease epidemics should at a minimum be accompanied by descriptions of (i) the starting time at which the cumulative count is initiated and (ii) the length of observation.

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.

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 [...].

"Go To Travel" Campaign and Travel-Associated Coronavirus Disease 2019 Cases: A Descriptive Analysis, July-August 2020.

The Japanese government initiated the Go To Travel campaign on 22 July 2020, offering deep discounts on hotel charges and issuing coupons to be used for any consumption at travel destinations in Japan. In the present study, we aimed to describe the possible epidemiological impact of the tourism campaign on increasing travel-associated cases of coronavirus disease 2019 (COVID-19) in the country. We compared the incidence rates of travel-associated and tourism-related cases prior to and during the campaign. The incidence of travel-associated COVID-19 cases during the tourism campaign was approximately three times greater than the control period 22 June to 21 July 2020 and approximately 1.5 times greater than the control period of 15 to 19 July. The incidence owing to tourism was approximately 8 times and 2-3 times greater than the control periods of 22 June to 21 July and 15 to 19 July, respectively. Although the second epidemic wave in Japan had begun to decline by mid-August, enhanced domestic tourism may have contributed to increasing travel-associated COVID-19 cases during 22 to 26 July, the early stage of the Go To Travel campaign.

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.