Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval). METHODS AND FINDINGS: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths. CONCLUSIONS: COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year.

flepiMoP: The evolution of a flexible infectious disease modeling pipeline during the COVID-19 pandemic.

The COVID-19 pandemic led to an unprecedented demand for projections of disease burden and healthcare utilization under scenarios ranging from unmitigated spread to strict social distancing policies. In response, members of the Johns Hopkins Infectious Disease Dynamics Group developed flepiMoP (formerly called the COVID Scenario Modeling Pipeline), a comprehensive open-source software pipeline designed for creating and simulating compartmental models of infectious disease transmission and inferring parameters through these models. The framework has been used extensively to produce short-term forecasts and longer-term scenario projections of COVID-19 at the state and county level in the US, for COVID-19 in other countries at various geographic scales, and more recently for seasonal influenza. In this paper, we highlight how the flepiMoP has evolved throughout the COVID-19 pandemic to address changing epidemiological dynamics, new interventions, and shifts in policy-relevant model outputs. As the framework has reached a mature state, we provide a detailed overview of flepiMoP's key features and remaining limitations, thereby distributing flepiMoP and its documentation as a flexible and powerful tool for researchers and public health professionals to rapidly build and deploy large-scale complex infectious disease models for any pathogen and demographic setup.

The US COVID-19 and Influenza Scenario Modeling Hubs: Delivering long-term projections to guide policy.

Between December 2020 and April 2023, the COVID-19 Scenario Modeling Hub (SMH) generated operational multi-month projections of COVID-19 burden in the US to guide pandemic planning and decision-making in the context of high uncertainty. This effort was born out of an attempt to coordinate, synthesize and effectively use the unprecedented amount of predictive modeling that emerged throughout the COVID-19 pandemic. Here we describe the history of this massive collective research effort, the process of convening and maintaining an open modeling hub active over multiple years, and attempt to provide a blueprint for future efforts. We detail the process of generating 17 rounds of scenarios and projections at different stages of the COVID-19 pandemic, and disseminating results to the public health community and lay public. We also highlight how SMH was expanded to generate influenza projections during the 2022-23 season. We identify key impacts of SMH results on public health and draw lessons to improve future collaborative modeling efforts, research on scenario projections, and the interface between models and policy.

Reconstruction and analysis of the transmission network of African swine fever in People's Republic of China, August 2018-September 2019.

Introduction of African swine fever (ASF) to China in mid-2018 and the subsequent transboundary spread across Asia devastated regional swine production, affecting live pig and pork product-related markets worldwide. To explore the spatiotemporal spread of ASF in China, we reconstructed possible ASF transmission networks using nearest neighbour, exponential function, equal probability, and spatiotemporal case-distribution algorithms. From these networks, we estimated the reproduction numbers, serial intervals, and transmission distances of the outbreak. The mean serial interval between paired units was around 29 days for all algorithms, while the mean transmission distance ranged 332 -456 km. The reproduction numbers for each algorithm peaked during the first two weeks and steadily declined through the end of 2018 before hovering around the epidemic threshold value of 1 with sporadic increases during 2019. These results suggest that 1) swine husbandry practices and production systems that lend themselves to long-range transmission drove ASF spread; 2) outbreaks went undetected by the surveillance system. Efforts by China and other affected countries to control ASF within their jurisdictions may be aided by the reconstructed spatiotemporal model. Continued support for strict implementation of biosecurity standards and improvements to ASF surveillance is essential for halting transmission in China and spread across Asia.

Accumulation of Immunity in Heavy-Tailed Sexual Contact Networks Shapes Mpox Outbreak Sizes.

Many countries affected by the global outbreak of mpox in 2022 have observed a decline in cases. Our mathematical model accounting for heavy-tailed sexual partnership distributions suggests that mpox epidemics can hit the infection-derived herd immunity threshold and begin to decline, with <1% of sexually active men who have sex with men infected regardless of interventions or behavioral changes. We consistently found that many countries and US states experienced an epidemic peak, with cumulative cases of around 0.1% to 0.5% among men who have sex with men. The observed decline in cases may not necessarily be attributable to interventions or behavioral changes primarily.

Potential impact of annual vaccination with reformulated COVID-19 vaccines: lessons from the U.S. COVID-19 Scenario Modeling Hub.

Importance: COVID-19 continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Objective: To project COVID-19 hospitalizations and deaths from April 2023-April 2025 under two plausible assumptions about immune escape (20% per year and 50% per year) and three possible CDC recommendations for the use of annually reformulated vaccines (no vaccine recommendation, vaccination for those aged 65+, vaccination for all eligible groups). Design: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023-April 15, 2025 under six scenarios representing the intersection of considered levels of immune escape and vaccination. State and national projections from eight modeling teams were ensembled to produce projections for each scenario. Setting: The entire United States. Participants: None. Exposure: Annually reformulated vaccines assumed to be 65% effective against strains circulating on June 15 of each year and to become available on September 1. Age and state specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. Main outcomes and measures: Ensemble estimates of weekly and cumulative COVID-19 hospitalizations and deaths. Expected relative and absolute reductions in hospitalizations and deaths due to vaccination over the projection period. Results: From April 15, 2023-April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November-January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% PI: 1,438,000-4,270,000) hospitalizations and 209,000 (90% PI: 139,000-461,000) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% CI: 104,000-355,000) fewer hospitalizations and 33,000 (95% CI: 12,000-54,000) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI: 29,000-69,000) fewer deaths. Conclusion and Relevance: COVID-19 is projected to be a significant public health threat over the coming two years. Broad vaccination has the potential to substantially reduce the burden of this disease.

Evaluation of the US COVID-19 Scenario Modeling Hub for informing pandemic response under uncertainty.

Our ability to forecast epidemics far into the future is constrained by the many complexities of disease systems. Realistic longer-term projections may, however, be possible under well-defined scenarios that specify the future state of critical epidemic drivers. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make months ahead projections of SARS-CoV-2 burden, totaling nearly 1.8 million national and state-level projections. Here, we find SMH performance varied widely as a function of both scenario validity and model calibration. We show scenarios remained close to reality for 22 weeks on average before the arrival of unanticipated SARS-CoV-2 variants invalidated key assumptions. An ensemble of participating models that preserved variation between models (using the linear opinion pool method) was consistently more reliable than any single model in periods of valid scenario assumptions, while projection interval coverage was near target levels. SMH projections were used to guide pandemic response, illustrating the value of collaborative hubs for longer-term scenario projections.

Informing pandemic response in the face of uncertainty. An evaluation of the U.S. COVID-19 Scenario Modeling Hub.

Our ability to forecast epidemics more than a few weeks into the future is constrained by the complexity of disease systems, our limited ability to measure the current state of an epidemic, and uncertainties in how human action will affect transmission. Realistic longer-term projections (spanning more than a few weeks) may, however, be possible under defined scenarios that specify the future state of critical epidemic drivers, with the additional benefit that such scenarios can be used to anticipate the comparative effect of control measures. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make 6-month ahead projections of the number of SARS-CoV-2 cases, hospitalizations and deaths. The SMH released nearly 1.8 million national and state-level projections between February 2021 and November 2022. SMH performance varied widely as a function of both scenario validity and model calibration. Scenario assumptions were periodically invalidated by the arrival of unanticipated SARS-CoV-2 variants, but SMH still provided projections on average 22 weeks before changes in assumptions (such as virus transmissibility) invalidated scenarios and their corresponding projections. During these periods, before emergence of a novel variant, a linear opinion pool ensemble of contributed models was consistently more reliable than any single model, and projection interval coverage was near target levels for the most plausible scenarios (e.g., 79% coverage for 95% projection interval). SMH projections were used operationally to guide planning and policy at different stages of the pandemic, illustrating the value of the hub approach for long-term scenario projections.

Evaluation of FluSight influenza forecasting in the 2021-22 and 2022-23 seasons with a new target laboratory-confirmed influenza hospitalizations.

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. Forecasting teams were asked to provide national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one through four weeks ahead for the 2021-22 and 2022-23 influenza seasons. Across both seasons, 26 teams submitted forecasts, with the submitting teams varying between seasons. Forecast skill was evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperformed the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble was the 2nd most accurate model measured by WIS in 2021-22 and the 5th most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degraded over longer forecast horizons and during periods of rapid change. Current influenza forecasting efforts help inform situational awareness, but research is needed to address limitations, including decreased performance during periods of changing epidemic dynamics.

Decrease in overdispersed secondary transmission of COVID-19 over time in Japan.

Coronavirus disease 2019 (COVID-19) has been described as having an overdispersed offspring distribution, i.e. high variation in the number of secondary transmissions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) per single primary COVID-19 case. Accordingly, countermeasures focused on high-risk settings and contact tracing could efficiently reduce secondary transmissions. However, as variants of concern with elevated transmissibility continue to emerge, controlling COVID-19 with such focused approaches has become difficult. It is vital to quantify temporal variations in the offspring distribution dispersibility. Here, we investigated offspring distributions for periods when the ancestral variant was still dominant (summer, 2020; wave 2) and when Alpha variant (B.1.1.7) was prevailing (spring, 2021; wave 4). The dispersion parameter (k) was estimated by analysing contact tracing data and fitting a negative binomial distribution to empirically observed offspring distributions from Nagano, Japan. The offspring distribution was less dispersed in wave 4 (k = 0.32; 95% confidence interval (CI) 0.24-0.43) than in wave 2 (k = 0.21 (95% CI 0.13-0.36)). A high proportion of household transmission was observed in wave 4, although the proportion of secondary transmissions generating more than five secondary cases did not vary over time. With this decreased variation, the effectiveness of risk group-focused interventions may be diminished.

Model-informed COVID-19 exit strategy with projections of SARS-CoV-2 infections generated by variants in the Republic of Korea.

BACKGROUND: With the prompt administration of coronavirus disease 2019 (COVID-19) vaccines, highly vaccinated countries have begun to lift their stringent control measures. However, considering the spread of highly transmissible new variants, resuming socio-economic activities may lead to the resurgence of incidence, particularly in nations with a low proportion of individuals who have natural immunity. Here, we aimed to quantitatively assess an optimal COVID-19 exit strategy in the Republic of Korea, where only a small number of cumulative incidences have been recorded as of September 2021, comparing epidemiological outcomes via scenario analysis. METHODS: A discrete-time deterministic compartmental model structured by age group was used, accounting for the variant-specific transmission dynamics and the currently planned nationwide vaccination. All parameters were calibrated using comprehensive empirical data obtained from the Korea Disease Control and Prevention Agency. RESULTS: Our projection suggests that tapering the level of social distancing countermeasures to the minimum level from November 2021 can efficiently suppress a resurgence of incidence given the currently planned nationwide vaccine roll-out. In addition, considering the spread of the Delta variant, our model suggested that gradual easing of countermeasures for more than 4 months can efficiently withstand the prevalence of severe COVID-19 cases until the end of 2022. CONCLUSIONS: Our model-based projections provide evidence-based guidance for an exit strategy that allows society to resume normal life while sustaining the suppression of the COVID-19 epidemic in countries where the spread of COVID-19 has been well controlled.

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.

The Possible Impact of Nationwide Vaccination on Outcomes of the COVID-19 Epidemic in North Korea: A Modelling Study.

BACKGROUND: The Democratic People's Republic of Korea (North Korea) had successfully suppressed the coronavirus disease 2019 (COVID-19) epidemic via border closures. However, a rapid surge in incidence was reported due to the spread of the omicron variant (B.1.1.529), leading to a national emergency declaration in May 2022. Moreover, with the lack of vaccine accessibility and medical facilities, it is unclear how the disease burden may be exacerbated. Despite the limited epidemiological data, we aimed to project the COVID-19 transmissions in North Korea and quantify the potential impact of nationwide vaccination, comparing epidemiological outcomes via scenario analysis. METHODS: A discrete-time deterministic compartmental model was used. The parameters were calibrated using empirical data. Numerical simulations incorporated nationwide COVID-19 vaccination into the proposed model with various asymptomatic proportions. RESULTS: Our model suggested that the stringent public health and social measures (PHSMs) reduced the severe acute respiratory syndrome coronavirus 2 transmissibility by more than 80% in North Korea. Projections that explicitly incorporated vaccination indicated that nationwide vaccination would be necessary to suppress a huge resurgence in both COVID-19 cases and hospitalizations after the stringent PHSMs are eased. Moreover, vaccinating more than 80% of the population with two doses may keep the peak prevalence of hospitalizations below 1,500, averting more than 40,000 hospitalizations across all scenarios. CONCLUSION: Nationwide vaccination would be essential to suppress the prevalence of COVID-19 hospitalizations in North Korea after the stringent PHSMs are lifted, especially in the case of a small asymptomatic proportion.

Effects of Mono- and Bifunctional Surface Ligands of Cu-In-Se Quantum Dots on Photoelectrochemical Hydrogen Production.

Semiconductor nanocrystal quantum dots (QDs) are promising materials for solar energy conversion because of their bandgap tunability, high absorption coefficient, and improved hot-carrier generation. CuInSe2 (CISe)-based QDs have attracted attention because of their low toxicity and wide light-absorption range, spanning visible to near-infrared light. In this work, we study the effects of the surface ligands of colloidal CISe QDs on the photoelectrochemical characteristics of QD-photoanodes. Colloidal CISe QDs with mono- and bifunctional surface ligands are prepared and used in the fabrication of type-II heterojunction photoanodes by adsorbing QDs on mesoporous TiO2. QDs with monofunctional ligands are directly attached on TiO2 through partial ligand detachment, which is beneficial for electron transfer between QDs and TiO2. In contrast, bifunctional ligands bridge QDs and TiO2, increasing the amount of QD adsorption. Finally, photoanodes fabricated with oleylamine-passivated QDs show a current density of ~8.2 mA/cm2, while those fabricated with mercaptopropionic-acid-passivated QDs demonstrate a current density of ~6.7 mA/cm2 (at 0.6 VRHE under one sun illumination). Our study provides important information for the preparation of QD photoelectrodes for efficient photoelectrochemical hydrogen generation.

Response to COVID-19 during the Tokyo Olympic Games: Did we properly assess the risk?

BACKGROUND: The number of coronavirus disease 2019 (COVID-19) cases was expected to increase during the Tokyo Olympic Games because of the increased physical contact within and between the domestic population and international participants of the Games. The rapid rise of the Delta variant (B.1.617) in Japan meant that hosting the Olympic Games without any restrictions was likely to lead to an increase in cases. We aimed to quantitatively assess possible COVID-19 response strategies for the Olympic Games, comparing the prevalence of severe cases and the cumulative number of COVID-19 deaths via scenario analysis. METHODS: We used a discrete-time deterministic compartmental model structured by age group. Parameters were calibrated using the age-stratified COVID-19 incidence data in Osaka. Numerical simulations incorporated the planned Olympics Games and nationwide COVID-19 vaccination into the proposed model, alongside various subjects and types of countermeasures. RESULTS: Our model-informed approach suggested that having spectators at the Tokyo Olympic Games could lead to a surge in both cases and hospitalization. Projections for the scenario that explicitly incorporated the spread of the Delta variant (i.e., time-dependent increase in the relative transmissibility) showed that imposing stringent social distancing measures (Rt=0.7) for more than 8 weeks from the end of the Olympic Games might be required to suppress the prevalence of severe cases of COVID-19 to avoid overwhelming the intensive care unit capacity in Tokyo. CONCLUSIONS: Our modeling analyses guided an optimal choice of COVID-19 response during and after the Tokyo Olympic Games, allowing the epidemic to be brought under control despite such a large mass gathering.

High population burden of Omicron variant (B.1.1.529) is associated with the emergence of severe hepatitis of unknown etiology in children.

OBJECTIVES: To explore a potential country-based ecological link between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) infection and an apparent current global outbreak of severe hepatitis of unknown etiology among children. METHODS: We examined country-level statistical associations between reported detection of one or more unexplained severe hepatitis cases in children and the cumulative number of Omicron (B.1.1.529) cases in 38 Organisation for Economic Co-operation and Development (OECD) member countries plus Romania. RESULTS: At least one focal hepatitis case was detected in 12 of the 39 countries included in our analysis. Numbers of confirmed Omicron cases reported in these 12 countries ranged from 4.4 to 11.9 million. Among the remaining 27 countries, this measure ranged from 0.5 to 5.5 million cases. Countries which reported focal hepatitis cases experienced higher precedent population burdens of Omicron cases relative to those which did not report any such hepatitis cases (p=0.013). CONCLUSION: Prior exposure to Omicron variant (B.1.1.529) may be associated with an increased risk for severe hepatitis among children, indicating a critical need to conduct cofactor studies.

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.

Not all fun and games: Potential incidence of SARS-CoV-2 infections during the Tokyo 2020 Olympic Games.

The Tokyo 2020 Olympic and Paralympic Games represent the most diverse international mass gathering event held since the start of the coronavirus disease 2019 (COVID-19) pandemic. Postponed to summer 2021, the rescheduled Games were set to be held amidst what would become the highest-ever levels of COVID-19 transmission in the host city of Tokyo. At the same time, the Delta variant of concern was gaining traction as the dominant viral strain and Japan had yet to exceed fifteen percent of its population fully vaccinated against COVID-19. To quantify the potential number of secondary cases that might arise during the Olympic Games, we performed a scenario analysis using a multitype branching process model. We considered the different contributions to transmission of Games accredited individuals, the general Tokyo population, and domestic spectators. In doing so, we demonstrate how transmission might evolve in these different groups over time, cautioning against any loosening of infection prevention protocols and supporting the decision to ban all spectators. If prevention measures were well observed, we estimated that the number of new cases among Games accredited individuals would approach zero by the end of the Games. However, if transmission was not controlled our model indicated hundreds of Games accredited individuals would become infected and daily incidence in Tokyo would reach upwards of 4,000 cases. Had domestic spectators been allowed (at 50% venue capacity), we estimated that over 250 spectators might have arrived infected to Tokyo venues, potentially generating more than 300 additional secondary infections while in Tokyo/at the Games. We also found the number of cases with infection directly attributable to hypothetical exposure during the Games was highly sensitive to the local epidemic dynamics. Therefore, reducing and maintaining transmission levels below epidemic levels using public health measures would be necessary to prevent cross-group transmission.