Modelling disease mitigation at mass gatherings: A case study of COVID-19 at the 2022 FIFA World Cup.

The 2022 FIFA World Cup was the first major multi-continental sporting Mass Gathering Event (MGE) of the post COVID-19 era to allow foreign spectators. Such large-scale MGEs can potentially lead to outbreaks of infectious disease and contribute to the global dissemination of such pathogens. Here we adapt previous work and create a generalisable model framework for assessing the use of disease control strategies at such events, in terms of reducing infections and hospitalisations. This framework utilises a combination of meta-populations based on clusters of people and their vaccination status, Ordinary Differential Equation integration between fixed time events, and Latin Hypercube sampling. We use the FIFA 2022 World Cup as a case study for this framework (modelling each match as independent 7 day MGEs). Pre-travel screenings of visitors were found to have little effect in reducing COVID-19 infections and hospitalisations. With pre-match screenings of spectators and match staff being more effective. Rapid Antigen (RA) screenings 0.5 days before match day performed similarly to RT-PCR screenings 1.5 days before match day. Combinations of pre-travel and pre-match testing led to improvements. However, a policy of ensuring that all visitors had a COVID-19 vaccination (second or booster dose) within a few months before departure proved to be much more efficacious. The State of Qatar abandoned all COVID-19 related travel testing and vaccination requirements over the period of the World Cup. Our work suggests that the State of Qatar may have been correct in abandoning the pre-travel testing of visitors. However, there was a spike in COVID-19 cases and hospitalisations within Qatar over the World Cup. Given our findings and the spike in cases, we suggest a policy requiring visitors to have had a recent COVID-19 vaccination should have been in place to reduce cases and hospitalisations.

Estimating social contacts in mass gatherings for disease outbreak prevention and management: case of Hajj pilgrimage.

BACKGROUND: Most mass gathering events have been suspended due to the SARS-CoV-2 pandemic. However, with vaccination rollout, whether and how to organize some of these mass gathering events arises as part of the pandemic recovery discussions, and this calls for decision support tools. The Hajj, one of the world's largest religious gatherings, was substantively scaled down in 2020 and 2021 and it is still unclear how it will take place in 2022 and subsequent years. Simulating disease transmission dynamics during the Hajj season under different conditions can provide some insights for better decision-making. Most disease risk assessment models require data on the number and nature of possible close contacts between individuals. METHODS: We sought to use integrated agent-based modeling and discrete events simulation techniques to capture risky contacts among the pilgrims and assess different scenarios in one of the Hajj major sites, namely Masjid-Al-Haram. RESULTS: The simulation results showed that a plethora of risky contacts may occur during the rituals. Also, as the total number of pilgrims increases at each site, the number of risky contacts increases, and physical distancing measures may be challenging to maintain beyond a certain number of pilgrims in the site. CONCLUSIONS: This study presented a simulation tool that can be relevant for the risk assessment of a variety of (respiratory) infectious diseases, in addition to COVID-19 in the Hajj season. This tool can be expanded to include other contributing elements of disease transmission to quantify the risk of the mass gathering events.

Modeling COVID-19 Outbreaks in Long-Term Care Facilities Using an Agent-Based Modeling and Simulation Approach.

The elderly, especially those individuals with pre-existing health problems, have been disproportionally at a higher risk during the COVID-19 pandemic. Residents of long-term care facilities have been gravely affected by the pandemic and resident death numbers have been far above those of the general population. To better understand how infectious diseases such as COVID-19 can spread through long-term care facilities, we developed an agent-based simulation tool that uses a contact matrix adapted from previous infection control research in these types of facilities. This matrix accounts for the average distinct daily contacts between seven different agent types that represent the roles of individuals in long-term care facilities. The simulation results were compared to actual COVID-19 outbreaks in some of the long-term care facilities in Ontario, Canada. Our analysis shows that this simulation tool is capable of predicting the number of resident deaths after 50 days with a less than 0.1 variation in death rate. We modeled and predicted the effectiveness of infection control measures by utilizing this simulation tool. We found that to reduce the number of resident deaths, the effectiveness of personal protective equipment must be above 50%. We also found that daily random COVID-19 tests for as low as less than 10% of a long-term care facility's population will reduce the number of resident deaths by over 75%. The results further show that combining several infection control measures will lead to more effective outcomes.

Non-pharmaceutical intervention levels to reduce the COVID-19 attack ratio among children.

The attack ratio in a subpopulation is defined as the total number of infections over the total number of individuals in this subpopulation. Using a methodology based on an age-stratified transmission dynamics model, we estimated the attack ratio of COVID-19 among children (individuals 0-11 years) when a large proportion of individuals eligible for vaccination (age 12 and above) are vaccinated to contain the epidemic among this subpopulation, or the effective herd immunity (with additional physical distancing measures). We describe the relationship between the attack ratio among children, the time to remove infected individuals from the transmission chain and the children-to-children daily contact rate while considering the increased transmissibility of virus variants (using the Delta variant as an example). We illustrate the generality and applicability of the methodology established by performing an analysis of the attack ratio of COVID-19 among children in the population of Canada and in its province of Ontario. The clinical attack ratio, defined as the number of symptomatic infections over the total population, can be informed from the attack ratio and both can be reduced substantially via a combination of reduced social mixing and rapid testing and isolation of the children.

Lessons drawn from China and South Korea for managing COVID-19 epidemic: Insights from a comparative modeling study.

We conducted a comparative study of the COVID-19 epidemic in three different settings: mainland China, the Guangdong province of China and South Korea, by formulating two disease transmission dynamics models which incorporate epidemic characteristics and setting-specific interventions, and fitting the models to multi-source data to identify initial and effective reproduction numbers and evaluate effectiveness of interventions. We estimated the initial basic reproduction number for South Korea, the Guangdong province and mainland China as 2.6 (95% confidence interval (CI): (2.5, 2.7)), 3.0 (95%CI: (2.6, 3.3)) and 3.8 (95%CI: (3.5,4.2)), respectively, given a serial interval with mean of 5 days with standard deviation of 3 days. We found that the effective reproduction number for the Guangdong province and mainland China has fallen below the threshold 1 since February 8th and 18th respectively, while the effective reproduction number for South Korea remains high until March 2nd Moreover our model-based analysis shows that the COVID-19 epidemics in South Korean is almost under control with the cumulative confirmed cases tending to be stable as of April 14th. Through sensitivity analysis, we show that a coherent and integrated approach with stringent public health interventions is the key to the success of containing the epidemic in China and especially its provinces outside its epicenter. In comparison, we find that the extremely high detection rate is the key factor determining the success in controlling the COVID-19 epidemics in South Korea. The experience of outbreak control in mainland China and South Korea should be a guiding reference for the rest of the world.

A window of opportunity for intensifying testing and tracing efforts to prevent new COVID-19 outbreaks due to more transmissible variants.

BACKGROUND: When public health interventions are being loosened after several days of decline in the number of coronavirus disease 2019 (COVID-19) cases, it is of critical importance to identify potential strategies to ease restrictions while mitigating a new wave of more transmissible variants of concern (VOCs). We estimated the necessary enhancements to public health interventions for a partial reopening of the economy while avoiding the worst consequences of a new outbreak, associated with more transmissible VOCs. METHODS: We used a transmission dynamics model to quantify conditions that combined public health interventions must meet to reopen the economy without a large outbreak. These conditions are those that maintain the control reproduction number below unity, while accounting for an increase in transmissibility due to VOC. RESULTS: We identified combinations of the proportion of individuals exposed to the virus who are traced and quarantined before becoming infectious, the proportion of symptomatic individuals confirmed and isolated, and individual daily contact rates needed to ensure the control reproduction number remains below unity. CONCLUSION: Our analysis indicates that the success of restrictive measures including lockdown and stay-at-home orders, as reflected by a reduction in number of cases, provides a narrow window of opportunity to intensify case detection and contact tracing efforts to prevent a new wave associated with circulation of more transmissible VOCs.

Optimal Reopening Pathways With COVID-19 Vaccine Rollout and Emerging Variants of Concern.

We developed a stochastic optimization technology based on a COVID-19 transmission dynamics model to determine optimal pathways from lockdown toward reopening with different scales and speeds of mass vaccine rollout in order to maximize social economical activities while not overwhelming the health system capacity in general, hospitalization beds, and intensive care units in particular. We used the Province of Ontario, Canada as a case study to demonstrate the methodology and the optimal decision trees; but our method and algorithm are generic and can be adapted to other settings. Our model framework and optimization strategies take into account the likely range of social contacts during different phases of a gradual reopening process and consider the uncertainties of these contact rates due to variations of individual behaviors and compliance. The results show that, without a mass vaccination rollout, there would be multiple optimal pathways should this strategy be adopted right after the Province's lockdown and stay-at-home order; however, once reopening has started earlier than the timing determined in the optimal pathway, an optimal pathway with similar constraints no longer exists, and sub-optimal pathways with increased demand for intensive care units can be found, but the choice is limited and the pathway is narrow. We also simulated the situation when the reopening starts after the mass vaccination has been rolled out, and we concluded that optimal pathways toward near pre-pandemic activity level is feasible given an accelerated vaccination rollout plan, with the final activity level being determined by the vaccine coverage and the transmissibility of the dominating strain.

Quantifying the shift in social contact patterns in response to non-pharmaceutical interventions.

Social contact mixing plays a critical role in influencing the transmission routes of infectious diseases. Moreover, quantifying social contact mixing patterns and their variations in a rapidly evolving pandemic intervened by changing public health measures is key for retroactive evaluation and proactive assessment of the effectiveness of different age- and setting-specific interventions. Contact mixing patterns have been used to inform COVID-19 pandemic public health decision-making; but a rigorously justified methodology to identify setting-specific contact mixing patterns and their variations in a rapidly developing pandemic, which can be informed by readily available data, is in great demand and has not yet been established. Here we fill in this critical gap by developing and utilizing a novel methodology, integrating social contact patterns derived from empirical data with a disease transmission model, that enables the usage of age-stratified incidence data to infer age-specific susceptibility, daily contact mixing patterns in workplace, household, school and community settings; and transmission acquired in these settings under different physical distancing measures. We demonstrated the utility of this methodology by performing an analysis of the COVID-19 epidemic in Ontario, Canada. We quantified the age- and setting (household, workplace, community, and school)-specific mixing patterns and their evolution during the escalation of public health interventions in Ontario, Canada. We estimated a reduction in the average individual contact rate from 12.27 to 6.58 contacts per day, with an increase in household contacts, following the implementation of control measures. We also estimated increasing trends by age in both the susceptibility to infection by SARS-CoV-2 and the proportion of symptomatic individuals diagnosed. Inferring the age- and setting-specific social contact mixing and key age-stratified epidemiological parameters, in the presence of evolving control measures, is critical to inform decision- and policy-making for the current COVID-19 pandemic.

Modelling the linkage between influenza infection and cardiovascular events via thrombosis.

There is a heavy burden associated with influenza including all-cause hospitalization as well as severe cardiovascular and cardiorespiratory events. Influenza associated cardiac events have been linked to multiple biological pathways in a human host. To study the contribution of influenza virus infection to cardiovascular thrombotic events, we develop a dynamic model which incorporates some key elements of the host immune response, inflammatory response, and blood coagulation. We formulate these biological systems and integrate them into a cohesive modelling framework to show how blood clotting may be connected to influenza virus infection. With blood clot formation inside an artery resulting from influenza virus infection as the primary outcome of this integrated model, we demonstrate how blood clot severity may depend on circulating prothrombin levels. We also utilize our model to leverage clinical data to inform the threshold level of the inflammatory cytokine TNFα which initiates tissue factor induction and subsequent blood clotting. Our model provides a tool to explore how individual biological components contribute to blood clotting events in the presence of influenza infection, to identify individuals at risk of clotting based on their circulating prothrombin levels, and to guide the development of future vaccines to optimally interact with the immune system.

Quantifying the annual incidence and underestimation of seasonal influenza: A modelling approach.

BACKGROUND: Seasonal influenza poses a significant public health and economic burden, associated with the outcome of infection and resulting complications. The true burden of the disease is difficult to capture due to the wide range of presentation, from asymptomatic cases to non-respiratory complications such as cardiovascular events, and its seasonal variability. An understanding of the magnitude of the true annual incidence of influenza is important to support prevention and control policy development and to evaluate the impact of preventative measures such as vaccination. METHODS: We use a dynamic disease transmission model, laboratory-confirmed influenza surveillance data, and randomized-controlled trial (RCT) data to quantify the underestimation factor, expansion factor, and symptomatic influenza illnesses in the US and Canada during the 2011-2012 and 2012-2013 influenza seasons. RESULTS: Based on 2 case definitions, we estimate between 0.42-3.2% and 0.33-1.2% of symptomatic influenza illnesses were laboratory-confirmed in Canada during the 2011-2012 and 2012-2013 seasons, respectively. In the US, we estimate between 0.08-0.61% and 0.07-0.33% of symptomatic influenza illnesses were laboratory-confirmed in the 2011-2012 and 2012-2013 seasons, respectively. We estimated the symptomatic influenza illnesses in Canada to be 0.32-2.4 million in 2011-2012 and 1.8-8.2 million in 2012-2013. In the US, we estimate the number of symptomatic influenza illnesses to be 4.4-34 million in 2011-2012 and 23-102 million in 2012-2013. CONCLUSIONS: We illustrate that monitoring a representative group within a population may aid in effectively modelling the transmission of infectious diseases such as influenza. In particular, the utilization of RCTs in models may enhance the accuracy of epidemiological parameter estimation.

Quantifying the role of social distancing, personal protection and case detection in mitigating COVID-19 outbreak in Ontario, Canada.

Public health interventions have been implemented to mitigate the spread of coronavirus disease 2019 (COVID-19) in Ontario, Canada; however, the quantification of their effectiveness remains to be done and is important to determine if some of the social distancing measures can be relaxed without resulting in a second wave. We aim to equip local public health decision- and policy-makers with mathematical model-based quantification of implemented public health measures and estimation of the trend of COVID-19 in Ontario to inform future actions in terms of outbreak control and de-escalation of social distancing. Our estimates confirm that (1) social distancing measures have helped mitigate transmission by reducing daily infection contact rate, but the disease transmission probability per contact remains as high as 0.145 and case detection rate was so low that the effective reproduction number remained higher than the threshold for disease control until the closure of non-essential business in the Province; (2) improvement in case detection rate and closure of non-essential business had resulted in further reduction of the effective control number to under the threshold. We predict the number of confirmed cases according to different control efficacies including a combination of reducing further contact rates and transmission probability per contact. We show that improved case detection rate plays a decisive role to reduce the effective reproduction number, and there is still much room in terms of improving personal protection measures to compensate for the strict social distancing measures.

De-Escalation by Reversing the Escalation with a Stronger Synergistic Package of Contact Tracing, Quarantine, Isolation and Personal Protection: Feasibility of Preventing a COVID-19 Rebound in Ontario, Canada, as a Case Study.

Since the beginning of the COVID-19 pandemic, most Canadian provinces have gone through four distinct phases of social distancing and enhanced testing. A transmission dynamics model fitted to the cumulative case time series data permits us to estimate the effectiveness of interventions implemented in terms of the contact rate, probability of transmission per contact, proportion of isolated contacts, and detection rate. This allows us to calculate the control reproduction number during different phases (which gradually decreased to less than one). From this, we derive the necessary conditions in terms of enhanced social distancing, personal protection, contact tracing, quarantine/isolation strength at each escalation phase for the disease control to avoid a rebound. From this, we quantify the conditions needed to prevent epidemic rebound during de-escalation by simply reversing the escalation process.

Individual based modeling and analysis of pathogen levels in poultry chilling process.

Pathogen control during poultry processing critically depends on more enhanced insight into contamination dynamics. In this study we build an individual based model (IBM) of the chilling process. Quantifying the relationships between typical Canadian processing specifications, water chemistry dynamics and pathogen levels both in the chiller water and on individual carcasses, the IBM is shown to provide a useful tool for risk management as it can inform risk assessment models. We apply the IBM to Campylobacter spp. contamination on broiler carcasses, illustrating how free chlorine (FC) sanitization, organic load in the water, and pre-chill carcass pathogen levels affect pathogen levels of post-chill broilers. In particular, given a uniform distribution of Campylobacter levels on incoming poultry we quantify the efficacy of FC control in not only reducing pathogen levels on average, but also the variation of pathogen levels on poultry exiting the chill tank. Furthermore, we demonstrate that the absence/presence of FC input dramatically influences when, during a continuous chilling operation, cross-contamination will be more likely.