Epidemiological and health economic implications of symptom propagation in respiratory pathogens: A mathematical modelling investigation.

BACKGROUND: Respiratory pathogens inflict a substantial burden on public health and the economy. Although the severity of symptoms caused by these pathogens can vary from asymptomatic to fatal, the factors that determine symptom severity are not fully understood. Correlations in symptoms between infector-infectee pairs, for which evidence is accumulating, can generate large-scale clusters of severe infections that could be devastating to those most at risk, whilst also conceivably leading to chains of mild or asymptomatic infections that generate widespread immunity with minimal cost to public health. Although this effect could be harnessed to amplify the impact of interventions that reduce symptom severity, the mechanistic representation of symptom propagation within mathematical and health economic modelling of respiratory diseases is understudied. METHODS AND FINDINGS: We propose a novel framework for incorporating different levels of symptom propagation into models of infectious disease transmission via a single parameter, α. Varying α tunes the model from having no symptom propagation (α = 0, as typically assumed) to one where symptoms always propagate (α = 1). For parameters corresponding to three respiratory pathogens-seasonal influenza, pandemic influenza and SARS-CoV-2-we explored how symptom propagation impacted the relative epidemiological and health-economic performance of three interventions, conceptualised as vaccines with different actions: symptom-attenuating (labelled SA), infection-blocking (IB) and infection-blocking admitting only mild breakthrough infections (IB_MB). In the absence of interventions, with fixed underlying epidemiological parameters, stronger symptom propagation increased the proportion of cases that were severe. For SA and IB_MB, interventions were more effective at reducing prevalence (all infections and severe cases) for higher strengths of symptom propagation. For IB, symptom propagation had no impact on effectiveness, and for seasonal influenza this intervention type was more effective than SA at reducing severe infections for all strengths of symptom propagation. For pandemic influenza and SARS-CoV-2, at low intervention uptake, SA was more effective than IB for all levels of symptom propagation; for high uptake, SA only became more effective under strong symptom propagation. Health economic assessments found that, for SA-type interventions, the amount one could spend on control whilst maintaining a cost-effective intervention (termed threshold unit intervention cost) was very sensitive to the strength of symptom propagation. CONCLUSIONS: Overall, the preferred intervention type depended on the combination of the strength of symptom propagation and uptake. Given the importance of determining robust public health responses, we highlight the need to gather further data on symptom propagation, with our modelling framework acting as a template for future analysis.

Correction: Seasonal influenza: Modelling approaches to capture immunity propagation.

[This corrects the article DOI: 10.1371/journal.pcbi.1007096.].

Prioritising older individuals for COVID-19 booster vaccination leads to optimal public health outcomes in a range of socio-economic settings.

The rapid development of vaccines against SARS-CoV-2 altered the course of the COVID-19 pandemic. In most countries, vaccinations were initially targeted at high-risk populations, including older individuals and healthcare workers. Now, despite substantial infection- and vaccine-induced immunity in host populations worldwide, waning immunity and the emergence of novel variants continue to cause significant waves of infection and disease. Policy makers must determine how to deploy booster vaccinations, particularly when constraints in vaccine supply, delivery and cost mean that booster vaccines cannot be administered to everyone. A key question is therefore whether older individuals should again be prioritised for vaccination, or whether alternative strategies (e.g. offering booster vaccines to the individuals who have most contacts with others and therefore drive infection) can instead offer indirect protection to older individuals. Here, we use mathematical modelling to address this question, considering SARS-CoV-2 transmission in a range of countries with different socio-economic backgrounds. We show that the population structures of different countries can have a pronounced effect on the impact of booster vaccination, even when identical booster vaccination targeting strategies are adopted. However, under the assumed transmission model, prioritising older individuals for booster vaccination consistently leads to the most favourable public health outcomes in every setting considered. This remains true for a range of assumptions about booster vaccine supply and timing, and for different assumed policy objectives of booster vaccination.

Emergence of SARS-CoV-2 Delta Variant and Effect of Nonpharmaceutical Interventions, British Columbia, Canada.

In British Columbia, Canada, initial growth of the SARS-CoV-2 Delta variant was slower than that reported in other jurisdictions. Delta became the dominant variant (>50% prevalence) within ≈7-13 weeks of first detection in regions within the United Kingdom and United States. In British Columbia, it remained at <10% of weekly incident COVID-19 cases for 13 weeks after first detection on March 21, 2021, eventually reaching dominance after 17 weeks. We describe the growth of Delta variant cases in British Columbia during March 1-June 30, 2021, and apply retrospective counterfactual modeling to examine factors for the initially low COVID-19 case rate after Delta introduction, such as vaccination coverage and nonpharmaceutical interventions. Growth of COVID-19 cases in the first 3 months after Delta emergence was likely limited in British Columbia because additional nonpharmaceutical interventions were implemented to reduce levels of contact at the end of March 2021, soon after variant emergence.

Modelling the epidemiological implications for SARS-CoV-2 of Christmas household bubbles in England.

The emergence of SARS-CoV-2 saw severe detriments to public health being inflicted by COVID-19 disease throughout 2020. In the lead up to Christmas 2020, the UK Government sought an easement of social restrictions that would permit spending time with others over the Christmas period, whilst limiting the risk of spreading SARS-CoV-2. In November 2020, plans were published to allow individuals to socialise within 'Christmas bubbles' with friends and family. This policy involved a planned easing of restrictions in England between 23-27 December 2020, with Christmas bubbles allowing people from up to three households to meet throughout the holiday period. We estimated the epidemiological impact of both this and alternative bubble strategies that allowed extending contacts beyond the immediate household. We used a stochastic individual-based model for a synthetic population of 100,000 households, with demographic and SARS-CoV-2 epidemiological characteristics comparable to England as of November 2020. We evaluated five Christmas bubble scenarios for the period 23-27 December 2020, assuming our populations of households did not have symptomatic infection present and were not in isolation as the eased social restrictions began. Assessment comprised incidence and cumulative infection metrics. We tested the sensitivity of the results to a situation where it was possible for households to be in isolation at the beginning of the Christmas bubble period and also when there was lower adherence to testing, contact tracing and isolation interventions. We found that visiting family and friends over the holiday period for a shorter duration and in smaller groups was less risky than spending the entire five days together. The increases in infection from greater amounts of social mixing disproportionately impacted the eldest. We provide this account as an illustration of a real-time contribution of modelling insights to a scientific advisory group, the Scientific Pandemic Influenza Group on Modelling, Operational sub-group (SPI-M-O) for the Scientific Advisory Group for Emergencies (SAGE) in the UK, during the COVID-19 pandemic. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

Assessing the impact of lateral flow testing strategies on within-school SARS-CoV-2 transmission and absences: A modelling study.

Rapid testing strategies that replace the isolation of close contacts through the use of lateral flow device tests (LFTs) have been suggested as a way of controlling SARS-CoV-2 transmission within schools that maintain low levels of pupil absences. We developed an individual-based model of a secondary school formed of exclusive year group bubbles (five year groups, with 200 pupils per year) to assess the likely impact of strategies using LFTs in secondary schools over the course of a seven-week half-term on transmission, absences, and testing volume, compared to a policy of isolating year group bubbles upon a pupil returning a positive polymerase chain reaction (PCR) test. We also considered the sensitivity of results to levels of participation in rapid testing and underlying model assumptions. While repeated testing of year group bubbles following case detection is less effective at reducing infections than a policy of isolating year group bubbles, strategies involving twice weekly mass testing can reduce infections to lower levels than would occur under year group isolation. By combining regular testing with serial contact testing or isolation, infection levels can be reduced further still. At high levels of pupil participation in lateral flow testing, strategies replacing the isolation of year group bubbles with testing substantially reduce absences, but require a high volume of testing. Our results highlight the conflict between the goals of minimising within-school transmission, minimising absences and minimising testing burden. While rapid testing strategies can reduce school transmission and absences, they may lead to a large number of daily tests.

Modelling livestock infectious disease control policy under differing social perspectives on vaccination behaviour.

The spread of infection amongst livestock depends not only on the traits of the pathogen and the livestock themselves, but also on the veterinary health behaviours of farmers and how this impacts their implementation of disease control measures. Controls that are costly may make it beneficial for individuals to rely on the protection offered by others, though that may be sub-optimal for the population. Failing to account for socio-behavioural properties may produce a substantial layer of bias in infectious disease models. We investigated the role of heterogeneity in vaccine response across a population of farmers on epidemic outbreaks amongst livestock, caused by pathogens with differential speed of spread over spatial landscapes of farms for two counties in England (Cumbria and Devon). Under different compositions of three vaccine behaviour groups (precautionary, reactionary, non-vaccination), we evaluated from population- and individual-level perspectives the optimum threshold distance to premises with notified infection that would trigger responsive vaccination by the reactionary vaccination group. We demonstrate a divergence between population and individual perspectives in the optimal scale of reactive voluntary vaccination response. In general, minimising the population-level perspective cost requires a broader reactive uptake of the intervention, whilst optimising the outcome for the average individual increased the likelihood of larger scale disease outbreaks. When the relative cost of vaccination was low and the majority of premises had undergone precautionary vaccination, then adopting a perspective that optimised the outcome for an individual gave a broader spatial extent of reactive response compared to a perspective wanting to optimise outcomes for everyone in the population. Under our assumed epidemiological context, the findings identify livestock disease intervention receptiveness and cost combinations where one would expect strong disagreement between the intervention stringency that is best from the perspective of a stakeholder responsible for supporting the livestock industry compared to a sole livestock owner. Were such discord anticipated and achieving a consensus view across perspectives desired, the findings may also inform those managing veterinary health policy the requisite reduction in intervention cost and/or the required extent of nurturing beneficial community attitudes towards interventions.

Modelling optimal vaccination strategy for SARS-CoV-2 in the UK.

The COVID-19 outbreak has highlighted our vulnerability to novel infections. Faced with this threat and no effective treatment, in line with many other countries, the UK adopted enforced social distancing (lockdown) to reduce transmission-successfully reducing the reproductive number R below one. However, given the large pool of susceptible individuals that remain, complete relaxation of controls is likely to generate a substantial further outbreak. Vaccination remains the only foreseeable means of both containing the infection and returning to normal interactions and behaviour. Here, we consider the optimal targeting of vaccination within the UK, with the aim of minimising future deaths or quality adjusted life year (QALY) losses. We show that, for a range of assumptions on the action and efficacy of the vaccine, targeting older age groups first is optimal and may be sufficient to stem the epidemic if the vaccine prevents transmission as well as disease.

A network modelling approach to assess non-pharmaceutical disease controls in a worker population: An application to SARS-CoV-2.

As part of a concerted pandemic response to protect public health, businesses can enact non-pharmaceutical controls to minimise exposure to pathogens in workplaces and premises open to the public. Amendments to working practices can lead to the amount, duration and/or proximity of interactions being changed, ultimately altering the dynamics of disease spread. These modifications could be specific to the type of business being operated. We use a data-driven approach to parameterise an individual-based network model for transmission of SARS-CoV-2 amongst the working population, stratified into work sectors. The network is comprised of layered contacts to consider the risk of spread in multiple encounter settings (workplaces, households, social and other). We analyse several interventions targeted towards working practices: mandating a fraction of the population to work from home; using temporally asynchronous work patterns; and introducing measures to create 'COVID-secure' workplaces. We also assess the general role of adherence to (or effectiveness of) isolation and test and trace measures and demonstrate the impact of all these interventions across a variety of relevant metrics. The progress of the epidemic can be significantly hindered by instructing a significant proportion of the workforce to work from home. Furthermore, if required to be present at the workplace, asynchronous work patterns can help to reduce infections when compared with scenarios where all workers work on the same days, particularly for longer working weeks. When assessing COVID-secure workplace measures, we found that smaller work teams and a greater reduction in transmission risk reduced the probability of large, prolonged outbreaks. Finally, following isolation guidance and engaging with contact tracing without other measures is an effective tool to curb transmission, but is highly sensitive to adherence levels. In the absence of sufficient adherence to non-pharmaceutical interventions, our results indicate a high likelihood of SARS-CoV-2 spreading widely throughout a worker population. Given the heterogeneity of demographic attributes across worker roles, in addition to the individual nature of controls such as contact tracing, we demonstrate the utility of a network model approach to investigate workplace-targeted intervention strategies and the role of test, trace and isolation in tackling disease spread.

Predictions of COVID-19 dynamics in the UK: Short-term forecasting and analysis of potential exit strategies.

Efforts to suppress transmission of SARS-CoV-2 in the UK have seen non-pharmaceutical interventions being invoked. The most severe measures to date include all restaurants, pubs and cafes being ordered to close on 20th March, followed by a "stay at home" order on the 23rd March and the closure of all non-essential retail outlets for an indefinite period. Government agencies are presently analysing how best to develop an exit strategy from these measures and to determine how the epidemic may progress once measures are lifted. Mathematical models are currently providing short and long term forecasts regarding the future course of the COVID-19 outbreak in the UK to support evidence-based policymaking. We present a deterministic, age-structured transmission model that uses real-time data on confirmed cases requiring hospital care and mortality to provide up-to-date predictions on epidemic spread in ten regions of the UK. The model captures a range of age-dependent heterogeneities, reduced transmission from asymptomatic infections and produces a good fit to the key epidemic features over time. We simulated a suite of scenarios to assess the impact of differing approaches to relaxing social distancing measures from 7th May 2020 on the estimated number of patients requiring inpatient and critical care treatment, and deaths. With regard to future epidemic outcomes, we investigated the impact of reducing compliance, ongoing shielding of elder age groups, reapplying stringent social distancing measures using region based triggers and the role of asymptomatic transmission. We find that significant relaxation of social distancing measures from 7th May onwards can lead to a rapid resurgence of COVID-19 disease and the health system being quickly overwhelmed by a sizeable, second epidemic wave. In all considered age-shielding based strategies, we projected serious demand on critical care resources during the course of the pandemic. The reintroduction and release of strict measures on a regional basis, based on ICU bed occupancy, results in a long epidemic tail, until the second half of 2021, but ensures that the health service is protected by reintroducing social distancing measures for all individuals in a region when required. Our work confirms the effectiveness of stringent non-pharmaceutical measures in March 2020 to suppress the epidemic. It also provides strong evidence to support the need for a cautious, measured approach to relaxation of lockdown measures, to protect the most vulnerable members of society and support the health service through subduing demand on hospital beds, in particular bed occupancy in intensive care units.

An analysis of school absences in England during the COVID-19 pandemic.

BACKGROUND: The introduction of SARS-CoV-2, the virus that causes COVID-19 infection, in the UK in early 2020, resulted in the introduction of several control policies to reduce disease spread. As part of these restrictions, schools were closed to all pupils in March (except for vulnerable and key worker children), before re-opening to certain year groups in June. Finally, all school children returned to the classroom in September. METHODS: Here, we analyse data on school absences in late 2020 as a result of COVID-19 infection and how that varied through time as other measures in the community were introduced. We utilise data from the Department for Education Educational Settings database and examine how pupil and teacher absences change in both primary and secondary schools. RESULTS: Our results show that absences as a result of COVID-19 infection rose steadily following the re-opening of schools in September. Cases in teachers declined during the November lockdown, particularly in regions previously in tier 3, the highest level of control at the time. Cases in secondary school pupils increased for the first 2 weeks of the November lockdown, before decreasing. Since the introduction of the tier system, the number of absences with confirmed infection in primary schools was observed to be (markedly) lower than that in secondary schools. In December, we observed a large rise in the number of absences per school in secondary school settings in the South East and London, but such rises were not observed in other regions or in primary school settings. We conjecture that the increased transmissibility of the new variant in these regions may have contributed to this rise in secondary school cases. Finally, we observe a positive correlation between cases in the community and cases in schools in most regions, with weak evidence suggesting that cases in schools lag behind cases in the surrounding community. CONCLUSIONS: We conclude that there is no significant evidence to suggest that schools are playing a substantial role in driving spread in the community and that careful monitoring may be required as schools re-open to determine the effect associated with open schools upon community incidence.

Optimising age coverage of seasonal influenza vaccination in England: A mathematical and health economic evaluation.

For infectious disease prevention, policy-makers are typically required to base policy decisions in light of operational and monetary restrictions, prohibiting implementation of all candidate interventions. To inform the evidence-base underpinning policy decision making, mathematical and health economic modelling can be a valuable constituent. Applied to England, this study aims to identify the optimal target age groups when extending a seasonal influenza vaccination programme of at-risk individuals to those individuals at low risk of developing complications following infection. To perform this analysis, we utilise an age- and strain-structured transmission model that includes immunity propagation mechanisms which link prior season epidemiological outcomes to immunity at the beginning of the following season. Making use of surveillance data from the past decade in conjunction with our dynamic model, we simulate transmission dynamics of seasonal influenza in England from 2012 to 2018. We infer that modified susceptibility due to natural infection in the previous influenza season is the only immunity propagation mechanism to deliver a non-negligible impact on the transmission dynamics. Further, we discerned case ascertainment to be higher for young infants compared to adults under 65 years old, and uncovered a decrease in case ascertainment as age increased from 65 to 85 years of age. Our health economic appraisal sweeps vaccination age space to determine threshold vaccine dose prices achieving cost-effectiveness under differing paired strategies. In particular, we model offering vaccination to all those low-risk individuals younger than a given age (but no younger than two years old) and all low-risk individuals older than a given age, while maintaining vaccination of at-risk individuals of any age. All posited strategies were deemed cost-effective. In general, the addition of low-risk vaccination programmes whose coverage encompassed children and young adults (aged 20 and below) were highly cost-effective. The inclusion of elder age-groups to the low-risk programme typically lessened the cost-effectiveness. Notably, elderly-centric programmes vaccinating from 65-75 years and above had the least permitted expense per vaccine.

Seasonal influenza: Modelling approaches to capture immunity propagation.

Seasonal influenza poses serious problems for global public health, being a significant contributor to morbidity and mortality. In England, there has been a long-standing national vaccination programme, with vaccination of at-risk groups and children offering partial protection against infection. Transmission models have been a fundamental component of analysis, informing the efficient use of limited resources. However, these models generally treat each season and each strain circulating within that season in isolation. Here, we amalgamate multiple data sources to calibrate a susceptible-latent-infected-recovered type transmission model for seasonal influenza, incorporating the four main strains and mechanisms linking prior season epidemiological outcomes to immunity at the beginning of the following season. Data pertaining to nine influenza seasons, starting with the 2009/10 season, informed our estimates for epidemiological processes, virological sample positivity, vaccine uptake and efficacy attributes, and general practitioner influenza-like-illness consultations as reported by the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We performed parameter inference via approximate Bayesian computation to assess strain transmissibility, dependence of present season influenza immunity on prior protection, and variability in the influenza case ascertainment across seasons. This produced reasonable agreement between model and data on the annual strain composition. Parameter fits indicated that the propagation of immunity from one season to the next is weaker if vaccine derived, compared to natural immunity from infection. Projecting the dynamics forward in time suggests that while historic immunity plays an important role in determining annual strain composition, the variability in vaccine efficacy hampers our ability to make long-term predictions.

The impact of surveillance and control on highly pathogenic avian influenza outbreaks in poultry in Dhaka division, Bangladesh.

In Bangladesh, the poultry industry is an economically and socially important sector, but it is persistently threatened by the effects of H5N1 highly pathogenic avian influenza. Thus, identifying the optimal control policy in response to an emerging disease outbreak is a key challenge for policy-makers. To inform this aim, a common approach is to carry out simulation studies comparing plausible strategies, while accounting for known capacity restrictions. In this study we perform simulations of a previously developed H5N1 influenza transmission model framework, fitted to two separate historical outbreaks, to assess specific control objectives related to the burden or duration of H5N1 outbreaks among poultry farms in the Dhaka division of Bangladesh. In particular, we explore the optimal implementation of ring culling, ring vaccination and active surveillance measures when presuming disease transmission predominately occurs from premises-to-premises, versus a setting requiring the inclusion of external factors. Additionally, we determine the sensitivity of the management actions under consideration to differing levels of capacity constraints and outbreaks with disparate transmission dynamics. While we find that reactive culling and vaccination policies should pay close attention to these factors to ensure intervention targeting is optimised, across multiple settings the top performing control action amongst those under consideration were targeted proactive surveillance schemes. Our findings may advise the type of control measure, plus its intensity, that could potentially be applied in the event of a developing outbreak of H5N1 amongst originally H5N1 virus-free commercially-reared poultry in the Dhaka division of Bangladesh.

Symptom propagation in respiratory pathogens of public health concern: a review of the evidence.

Symptom propagation occurs when the symptom set an individual experiences is correlated with the symptom set of the individual who infected them. Symptom propagation may dramatically affect epidemiological outcomes, potentially causing clusters of severe disease. Conversely, it could result in chains of mild infection, generating widespread immunity with minimal cost to public health. Despite accumulating evidence that symptom propagation occurs for many respiratory pathogens, the underlying mechanisms are not well understood. Here, we conducted a scoping literature review for 14 respiratory pathogens to ascertain the extent of evidence for symptom propagation by two mechanisms: dose-severity relationships and route-severity relationships. We identify considerable heterogeneity between pathogens in the relative importance of the two mechanisms, highlighting the importance of pathogen-specific investigations. For almost all pathogens, including influenza and SARS-CoV-2, we found support for at least one of the two mechanisms. For some pathogens, including influenza, we found convincing evidence that both mechanisms contribute to symptom propagation. Furthermore, infectious disease models traditionally do not include symptom propagation. We summarize the present state of modelling advancements to address the methodological gap. We then investigate a simplified disease outbreak scenario, finding that under strong symptom propagation, isolating mildly infected individuals can have negative epidemiological implications.

Improving modelling for epidemic responses: reflections from members of the UK infectious disease modelling community on their experiences during the COVID-19 pandemic.

Background: The COVID-19 pandemic both relied and placed significant burdens on the experts involved from research and public health sectors. The sustained high pressure of a pandemic on responders, such as healthcare workers, can lead to lasting psychological impacts including acute stress disorder, post-traumatic stress disorder, burnout, and moral injury, which can impact individual wellbeing and productivity. Methods: As members of the infectious disease modelling community, we convened a reflective workshop to understand the professional and personal impacts of response work on our community and to propose recommendations for future epidemic responses. The attendees represented a range of career stages, institutions, and disciplines. This piece was collectively produced by those present at the session based on our collective experiences. Results: Key issues we identified at the workshop were lack of institutional support, insecure contracts, unequal credit and recognition, and mental health impacts. Our recommendations include rewarding impactful work, fostering academia-public health collaboration, decreasing dependence on key individuals by developing teams, increasing transparency in decision-making, and implementing sustainable work practices. Conclusions: Despite limitations in representation, this workshop provided valuable insights into the UK COVID-19 modelling experience and guidance for future public health crises. Recognising and addressing the issues highlighted is crucial, in our view, for ensuring the effectiveness of epidemic response work in the future.

The impacts of SARS-CoV-2 vaccine dose separation and targeting on the COVID-19 epidemic in England.

In late 2020, the JCVI (the Joint Committee on Vaccination and Immunisation, which provides advice to the Department of Health and Social Care, England) made two important recommendations for the initial roll-out of the COVID-19 vaccine. The first was that vaccines should be targeted to older and vulnerable people, with the aim of maximally preventing disease rather than infection. The second was to increase the interval between first and second doses from 3 to 12 weeks. Here, we re-examine these recommendations through a mathematical model of SARS-CoV-2 infection in England. We show that targeting the most vulnerable had the biggest immediate impact (compared to targeting younger individuals who may be more responsible for transmission). The 12-week delay was also highly beneficial, estimated to have averted between 32-72 thousand hospital admissions and 4-9 thousand deaths over the first ten months of the campaign (December 2020-September 2021) depending on the assumed interaction between dose interval and efficacy.

Incorporating heterogeneity in farmer disease control behaviour into a livestock disease transmission model.

Human behaviour is critical to effective responses to livestock disease outbreaks, especially with respect to vaccination uptake. Traditionally, mathematical models used to inform this behaviour have not taken heterogeneity in farmer behaviour into account. We address this by exploring how heterogeneity in farmers vaccination behaviour can be incorporated to inform mathematical models. We developed and used a graphical user interface to elicit farmers (n = 60) vaccination decisions to an unfolding fast-spreading epidemic and linked this to their psychosocial and behavioural profiles. We identified, via cluster analysis, robust patterns of heterogeneity in vaccination behaviour. By incorporating these vaccination behavioural groupings into a mathematical model for a fast-spreading livestock infection, using computational simulation we explored how the inclusion of heterogeneity in farmer disease control behaviour may impact epidemiological and economic focused outcomes. When assuming homogeneity in farmer behaviour versus configurations informed by the psychosocial profile cluster estimates, the modelled scenarios revealed a disconnect in projected distributions and threshold statistics across outbreak size, outbreak duration and economic metrics.

Coughs, colds and "freshers' flu" survey in the University of Cambridge, 2007-2008.

Universities provide many opportunities for the spread of infectious respiratory illnesses. Students are brought together into close proximity from all across the world and interact with one another in their accommodation, through lectures and small group teaching and in social settings. The COVID-19 global pandemic has highlighted the need for sufficient data to help determine which of these factors are important for infectious disease transmission in universities and hence control university morbidity as well as community spillover. We describe the data from a previously unpublished self-reported university survey of coughs, colds and influenza-like symptoms collected in Cambridge, UK, during winter 2007-2008. The online survey collected information on symptoms and socio-demographic, academic and lifestyle factors. There were 1076 responses, 97% from University of Cambridge students (5.7% of the total university student population), 3% from staff and <1% from other participants, reporting onset of symptoms between September 2007 and March 2008. Undergraduates are seen to report symptoms earlier in the term than postgraduates; differences in reported date of symptoms are also seen between subjects and accommodation types, although these descriptive results could be confounded by survey biases. Despite the historical and exploratory nature of the study, this is one of few recent detailed datasets of influenza-like infection in a university context and is especially valuable to share now to improve understanding of potential transmission dynamics in universities during the current COVID-19 pandemic.

The effect of notification window length on the epidemiological impact of COVID-19 contact tracing mobile applications.

Background: The reduction in SARS-CoV-2 transmission facilitated by mobile contact tracing applications (apps) depends both on the proportion of relevant contacts notified and on the probability that those contacts quarantine after notification. The proportion of relevant contacts notified depends upon the number of days preceding an infector's positive test that their contacts are notified, which we refer to as an app's notification window. Methods: We use an epidemiological model of SARS-CoV-2 transmission that captures the profile of infection to consider the trade-off between notification window length and active app use. We focus on 5-day and 2-day windows, the notification windows of the NHS COVID-19 app in England and Wales before and after 2nd August 2021, respectively. Results: Our analyses show that at the same level of active app use, 5-day windows result in larger reductions in transmission than 2-day windows. However, short notification windows can be more effective at reducing transmission if they are associated with higher levels of active app use and adherence to isolation upon notification. Conclusions: Our results demonstrate the importance of understanding adherence to interventions when setting notification windows for COVID-19 contact tracing apps.

After submitting a positive SARS-CoV-2 test result, mobile contact-tracing apps identify 'recent' high-risk encounters with other app users, who are then notified of potential exposure. An app's success at limiting further transmission depends on the proportion of infected contacts notified. This depends on what counts as 'recent', e.g. notifying contacts from 5 days prior to the positive test can capture more infections than notifying contacts from 2 days prior. We call this number of days an app's notification window. However, an app's effectiveness also depends on whether or not exposed contacts use the app and adhere to isolation if notified. If shorter windows are associated with higher levels of active app use, they can be more effective at reducing transmission than longer windows, demonstrating the importance of considering the potential impact on active app use when setting an app's notification window length.