Redefining pandemic preparedness: Multidisciplinary insights from the CERP modelling workshop in infectious diseases, workshop report.

In July 2023, the Center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the Covid-19 pandemic. This report summarizes the rich discussions that occurred during the workshop. The workshop participants discussed multisource data integration and highlighted the benefits of combining traditional surveillance with more novel data sources like mobility data, social media, and wastewater monitoring. Significant advancements were noted in the development of predictive models, with examples from various countries showcasing the use of machine learning and artificial intelligence in detecting and monitoring disease trends. The role of open collaboration between various stakeholders in modelling was stressed, advocating for the continuation of such partnerships beyond the pandemic. A major gap identified was the absence of a common international framework for data sharing, which is crucial for global pandemic preparedness. Overall, the workshop underscored the need for robust, adaptable modelling frameworks and the integration of different data sources and collaboration across sectors, as key elements in enhancing future pandemic response and preparedness.

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.

Modelling the transmission of dengue, zika and chikungunya: a scoping review protocol.

INTRODUCTION: Aedes mosquitoes are the primary vectors for the spread of viruses like dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), all of which affect humans. Those diseases contribute to global public health issues because of their great dispersion in rural and urban areas. Mathematical and statistical models have become helpful in understanding these diseases' epidemiological dynamics. However, modelling the complexity of a real phenomenon, such as a viral disease, should consider several factors. This scoping review aims to document, identify and classify the most important factors as well as the modelling strategies for the spread of DENV, ZIKV and CHIKV. METHODS AND ANALYSIS: We will conduct searches in electronic bibliographic databases such as PubMed, MathSciNet and the Web of Science for full-text peer-reviewed articles written in English, French and Spanish. These articles should use mathematical and statistical modelling frameworks to study dengue, zika and chikungunya, and their cocirculation/coinfection with other diseases, with a publication date between 1 January 2011 and 31 July 2023. Eligible studies should employ deterministic, stochastic or statistical modelling approaches, consider control measures and incorporate parameters' estimation or considering calibration/validation approaches. We will exclude articles focusing on clinical/laboratory experiments or theoretical articles that do not include any case study. Two reviewers specialised in zoonotic diseases and mathematical/statistical modelling will independently screen and retain relevant studies. Data extraction will be performed using a structured form, and the findings of the study will be summarised through classification and descriptive analysis. Three scoping reviews will be published, each focusing on one disease and its cocirculation/co-infection with other diseases. ETHICS AND DISSEMINATION: This protocol is exempt from ethics approval because it is carried out on published manuscripts and without the participation of humans and/or animals. The results will be disseminated through peer-reviewed publications and presentations in conferences.

SARS-CoV-2 in Nursing Homes: Analysis of Routine Surveillance Data in Four European Countries.

Transmission of SARS-CoV-2 in nursing homes is poorly documented. Using surveillance data of 228 European private nursing homes, we estimated weekly SARS-CoV-2 incidences among 21,467 residents and 14,371 staff members, compared to that in the general population, between August 3, 2020, and February 20, 2021. We studied the outcomes of "episodes of introduction" where one case was first detected and computed attack rates, reproduction ratio (R), and dispersion parameter (k). Out of 502 episodes of SARS-CoV-2 introduction, 77.1% (95%CI, 73.2%-80.6%) led to additional cases. Attack rates were highly variable, ranging from 0.4% to 86.5%. The R was 1.16 (95%CI, 1.11-1.22) with k at 2.5 (95%CI, 0.5-4.5). The timing of viral circulation in nursing homes did not mirror that in the general population (p-values<0.001). We estimated the impact of vaccination in preventing SARS-CoV-2 transmission. Before vaccination's roll-out, a cumulated 5,579 SARS-CoV-2 infections were documented among residents and 2,321 among staff. Higher staffing ratio and previous natural immunization reduced the probability of an outbreak following introduction. Despite strong preventive measures, transmission likely occurred, regardless of building characteristics. Vaccination started on January 15, 2021, and coverage reached 65.0% among residents, and 42.0% among staff by February 20, 2021. Vaccination yielded a 92% reduction (95%CI, 71%-98%) of outbreak probability, and lowered R to 0.87 (95%CI, 0.69-1.10). In the post-pandemic era, much attention will have to be paid to multi-lateral collaboration, policy making, and prevention plans.

Pandemic modelling for regions implementing an elimination strategy.

During the COVID-19 pandemic, some countries, such as Australia, China, Iceland, New Zealand, Thailand, and Vietnam successfully implemented an elimination strategy, enacting strict border control and periods of lockdowns to end community transmission. Atlantic Canada and Canada's territories implemented similar policies, and reported long periods with no community cases. In Newfoundland and Labrador (NL), Nova Scotia, and Prince Edward Island a median of 80% or more of daily reported cases were travel-related from July 1, 2020 to May 31, 2021. With increasing vaccination coverage, it may be appropriate to exit an elimination strategy, but most existing epidemiological frameworks are applicable only to situations where most cases occur in the community, and are not appropriate for regions that have implemented an elimination strategy. To inform the pandemic response in regions that are implementing an elimination strategy, we extend importation modelling to consider post-arrival travel restrictions, and pharmaceutical and non-pharmaceutical interventions in the local community. We find that shortly after the Omicron variant had begun spreading in Canada, the expected daily number of spillovers, infections spread to NL community members from travellers and their close contacts, was higher than any time previously in the pandemic. By December 24, 2021, the expected number of spillovers was 44% higher than the previous high, which occurred in late July 2021 shortly after travel restrictions were first relaxed. We develop a method to assess the characteristics of potential future community outbreaks in regions that are implementing an elimination strategy. We apply this method to predict the effect of variant and vaccination coverage on the size of hypothetical community outbreaks in Mount Pearl, a suburb of the St. John's metropolitan area in NL. Our methodology can be used to evaluate alternative plans to relax public health restrictions when vaccine coverage is high in regions that have implemented an elimination strategy. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

Assessing transmission risks and control strategy for monkeypox as an emerging zoonosis in a metropolitan area.

To model the spread of monkeypox (MPX) in a metropolitan area for assessing the risk of possible outbreaks, and identifying essential public health measures to contain the virus spread. The animal reservoir is the key element in the modeling of zoonotic disease. Using a One Health approach, we model the spread of the MPX virus in humans considering potential animal hosts such as rodents (e.g., rats, mice, squirrels, chipmunks, etc.) and emphasize their role and transmission of the virus in a high-risk group, including gay and bisexual men-who-have-sex-with-men (gbMSM). From model and sensitivity analysis, we identify key public health factors and present scenarios under different transmission assumptions. We find that the MPX virus may spill over from gbMSM high-risk groups to broader populations if the efficiency of transmission increases in the higher-risk group. However, the risk of outbreak can be greatly reduced if at least 65% of symptomatic cases can be isolated and their contacts traced and quarantined. In addition, infections in an animal reservoir will exacerbate MPX transmission risk in the human population. Regions or communities with a higher proportion of gbMSM individuals need greater public health attention. Tracing and quarantine (or "effective quarantine" by postexposure vaccination) of contacts with MPX cases in high-risk groups would have a significant effect on controlling the spreading. Also, monitoring for animal infections would be prudent.

Modeling vaccination and control strategies for outbreaks of monkeypox at gatherings.

Background: The monkeypox outbreak in non-endemic countries in recent months has led the World Health Organization (WHO) to declare a public health emergency of international concern (PHEIC). It is thought that festivals, parties, and other gatherings may have contributed to the outbreak. Methods: We considered a hypothetical metropolitan city and modeled the transmission of the monkeypox virus in humans in a high-risk group (HRG) and a low-risk group (LRG) using a Susceptible-Exposed-Infectious-Recovered (SEIR) model and incorporated gathering events. Model simulations assessed how the vaccination strategies combined with other public health measures can contribute to mitigating or halting outbreaks from mass gathering events. Results: The risk of a monkeypox outbreak was high when mass gathering events occurred in the absence of public health control measures. However, the outbreaks were controlled by isolating cases and vaccinating their close contacts. Furthermore, contact tracing, vaccinating, and isolating close contacts, if they can be implemented, were more effective for the containment of monkeypox transmission during summer gatherings than a broad vaccination campaign among HRG, when accounting for the low vaccination coverage in the overall population, and the time needed for the development of the immune responses. Reducing the number of attendees and effective contacts during the gathering could also prevent a burgeoning outbreak, as could restricting attendance through vaccination requirements. Conclusion: Monkeypox outbreaks following mass gatherings can be made less likely with some restrictions on either the number and density of attendees in the gathering or vaccination requirements. The ring vaccination strategy inoculating close contacts of confirmed cases may not be enough to prevent potential outbreaks; however, mass gatherings can be rendered less risky if that strategy is combined with public health measures, including identifying and isolating cases and contact tracing. Compliance with the community and promotion of awareness are also indispensable to containing the outbreak.

Effect of Movement on the Early Phase of an Epidemic.

The early phase of an epidemic is characterized by a small number of infected individuals, implying that stochastic effects drive the dynamics of the disease. Mathematically, we define the stochastic phase as the time during which the number of infected individuals remains small and positive. A continuous-time Markov chain model of a simple two-patch epidemic is presented. An algorithm for formalizing what is meant by small is presented, and the effect of movement on the duration of the early stochastic phase of an epidemic is studied.

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.

Mathematical modelling of vaccination rollout and NPIs lifting on COVID-19 transmission with VOC: a case study in Toronto, Canada.

BACKGROUND: Since December 2020, public health agencies have implemented a variety of vaccination strategies to curb the spread of SARS-CoV-2, along with pre-existing Nonpharmaceutical Interventions (NPIs). Initial strategies focused on vaccinating the elderly to prevent hospitalizations and deaths, but with vaccines becoming available to the broader population, it became important to determine the optimal strategy to enable the safe lifting of NPIs while avoiding virus resurgence. METHODS: We extended the classic deterministic SIR compartmental disease-transmission model to simulate the lifting of NPIs under different vaccine rollout scenarios. Using case and vaccination data from Toronto, Canada between December 28, 2020, and May 19, 2021, we estimated transmission throughout past stages of NPI escalation/relaxation to compare the impact of lifting NPIs on different dates on cases, hospitalizations, and deaths, given varying degrees of vaccine coverages by 20-year age groups, accounting for waning immunity. RESULTS: We found that, once coverage among the elderly is high enough (80% with at least one dose), the main age groups to target are 20-39 and 40-59 years, wherein first-dose coverage of at least 70% by mid-June 2021 is needed to minimize the possibility of resurgence if NPIs are to be lifted in the summer. While a resurgence was observed for every scenario of NPI lifting, we also found that under an optimistic vaccination coverage (70% coverage by mid-June, along with postponing reopening from August 2021 to September 2021) can reduce case counts and severe outcomes by roughly 57% by December 31, 2021. CONCLUSIONS: Our results suggest that focusing the vaccination strategy on the working-age population can curb the spread of SARS-CoV-2. However, even with high vaccination coverage in adults, increasing contacts and easing protective personal behaviours is not advisable since a resurgence is expected to occur, especially with an earlier reopening.

Bistability in deterministic and stochastic SLIAR-type models with imperfect and waning vaccine protection.

Various vaccines have been approved for use to combat COVID-19 that offer imperfect immunity and could furthermore wane over time. We analyze the effect of vaccination in an SLIARS model with demography by adding a compartment for vaccinated individuals and considering disease-induced death, imperfect and waning vaccination protection as well as waning infections-acquired immunity. When analyzed as systems of ordinary differential equations, the model is proven to admit a backward bifurcation. A continuous time Markov chain (CTMC) version of the model is simulated numerically and compared to the results of branching process approximations. While the CTMC model detects the presence of the backward bifurcation, the branching process approximation does not. The special case of an SVIRS model is shown to have the same properties.

Efficacy of a "stay-at-home" policy on SARS-CoV-2 transmission in Toronto, Canada: a mathematical modelling study.

BACKGROUND: Globally, nonpharmaceutical interventions for COVID-19, including stay-at-home policies, limitations on gatherings and closure of public spaces, are being lifted. We explored the effect of lifting a stay-at-home policy on virus resurgence under different conditions. METHODS: Using confirmed case data from Toronto, Canada, between Feb. 24 and June 24, 2020, we ran a compartmental model with household structure to simulate the impact of the stay-at-home policy considering different levels of compliance. We estimated threshold values for the maximum number of contacts, probability of transmission and testing rates required for the safe reopening of the community. RESULTS: After the implementation of the stay-at-home policy, the contact rate outside the household fell by 39% (from 11.58 daily contacts to 7.11). The effective reproductive number decreased from 3.56 (95% confidence interval [CI] 3.02-4.14) on Mar. 12 to 0.84 (95% CI 0.79-0.89) on May 6. Strong adherence to stay-at-home policies appeared to prevent SARS-CoV-2 resurgence, but extending the duration of stay-at-home policies beyond 2 months had little added effect on cumulative cases (25 958 for 65 days of a stay-at-home policy and 23 461 for 95 days, by July 2, 2020) and deaths (1404 for 65 days and 1353 for 95 days). To avoid a resurgence, the average number of contacts per person per day should be kept below 9, with strict nonpharmaceutical interventions in place. INTERPRETATION: Our study demonstrates that the stay-at-home policy implemented in Toronto in March 2020 had a substantial impact on mitigating the spread of SARS-CoV-2. In the context of the early pandemic, before the emergence of variants of concern, reopening schools and workplaces was possible only with other nonpharmaceutical interventions in place.

Disease transmission and mass gatherings: a case study on meningococcal infection during Hajj.

BACKGROUND: Mass gatherings can not only trigger major outbreaks on-site but also facilitate global spread of infectious pathogens. Hajj is one of the largest mass gathering events worldwide where over two million pilgrims from all over the world gather annually creating intense congestion. METHODS: We developed a meta-population model to represent the transmission dynamics of Neisseria meningitidis and the impact of Hajj pilgrimage on the risk of invasive meningococcal disease (IMD) for pilgrims population, local population at the Hajj site and country of origin of Hajj pilgrims. This model was calibrated using data on IMD over 17 years (1995-2011) and further used to simulate potential changes in vaccine policy and endemic conditions. RESULTS: The effect of increased density of contacts during Hajj was estimated to generate a 78-fold increase in disease transmission that impacts not only pilgrims but also the local population. Quadrivalent ACWY vaccination was found to be very effective in reducing the risk of outbreak during Hajj. Hajj has more limited impact on IMD transmission and exportation in the pilgrim countries of origin, although not negligible given the size of the population considered. CONCLUSION: The analysis performed highlighted the amplifying effect of mass gathering on N. meningitidis transmission and confirm vaccination as a very effective preventive measure to mitigate outbreak risks.

Risk of COVID-19 variant importation - How useful are travel control measures?

We consider models for the importation of a new variant COVID-19 strain in a location already seeing propagation of a resident variant. By distinguishing contaminations generated by imported cases from those originating in the community, we are able to evaluate the contribution of importations to the dynamics of the disease in a community. We find that after an initial seeding, the role of importations becomes marginal compared to that of community-based propagation. We also evaluate the role of two travel control measures, quarantine and travel interruptions. We conclude that quarantine is an efficacious way of lowering importation rates, while travel interruptions have the potential to delay the consequences of importations but need to be applied within a very tight time window following the initial emergence of the variant.

The origins and potential future of SARS-CoV-2 variants of concern in the evolving COVID-19 pandemic.

One year into the global COVID-19 pandemic, the focus of attention has shifted to the emergence and spread of SARS-CoV-2 variants of concern (VOCs). After nearly a year of the pandemic with little evolutionary change affecting human health, several variants have now been shown to have substantial detrimental effects on transmission and severity of the virus. Public health officials, medical practitioners, scientists, and the broader community have since been scrambling to understand what these variants mean for diagnosis, treatment, and the control of the pandemic through nonpharmaceutical interventions and vaccines. Here we explore the evolutionary processes that are involved in the emergence of new variants, what we can expect in terms of the future emergence of VOCs, and what we can do to minimise their impact.

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.

Modelling scenarios of the epidemic of COVID-19 in Canada.

BACKGROUND: Severe acute respiratory syndrome virus 2 (SARS-CoV-2), likely a bat-origin coronavirus, spilled over from wildlife to humans in China in late 2019, manifesting as a respiratory disease. Coronavirus disease 2019 (COVID-19) spread initially within China and then globally, resulting in a pandemic. OBJECTIVE: This article describes predictive modelling of COVID-19 in general, and efforts within the Public Health Agency of Canada to model the effects of non-pharmaceutical interventions (NPIs) on transmission of SARS-CoV-2 in the Canadian population to support public health decisions. METHODS: The broad objectives of two modelling approaches, 1) an agent-based model and 2) a deterministic compartmental model, are described and a synopsis of studies is illustrated using a model developed in Analytica 5.3 software. RESULTS: Without intervention, more than 70% of the Canadian population may become infected. Non-pharmaceutical interventions, applied with an intensity insufficient to cause the epidemic to die out, reduce the attack rate to 50% or less, and the epidemic is longer with a lower peak. If NPIs are lifted early, the epidemic may rebound, resulting in high percentages (more than 70%) of the population affected. If NPIs are applied with intensity high enough to cause the epidemic to die out, the attack rate can be reduced to between 1% and 25% of the population. CONCLUSION: Applying NPIs with intensity high enough to cause the epidemic to die out would seem to be the preferred choice. Lifting disruptive NPIs such as shut-downs must be accompanied by enhancements to other NPIs to prevent new introductions and to identify and control any new transmission chains.

A simple model for COVID-19.

An S L 1 L 2 I 1 I 2 A 1 A 2 R epidemic model is formulated that describes the spread of an epidemic in a population. The model incorporates an Erlang distribution of times of sojourn in incubating, symptomatically and asymptomatically infectious compartments. Basic properties of the model are explored, with focus on properties important in the context of current COVID-19 pandemic.

Mathematical epidemiology in a data-rich world.

I discuss the acquisition and use of "background" data in mathematical epidemiology models, advocating a proactive approach to the incorporation of said data. I illustrate various mechanisms for acquiring data, mainly from open data sources. I also discuss incorporating this data into models.