Monitoring real-time transmission heterogeneity from incidence data.

The transmission heterogeneity of an epidemic is associated with a complex mixture of host, pathogen and environmental factors. And it may indicate superspreading events to reduce the efficiency of population-level control measures and to sustain the epidemic over a larger scale and a longer duration. Methods have been proposed to identify significant transmission heterogeneity in historic epidemics based on several data sources, such as contact history, viral genomes and spatial information, which may not be available, and more importantly ignore the temporal trend of transmission heterogeneity. Here we attempted to establish a convenient method to estimate real-time heterogeneity over an epidemic. Within the branching process framework, we introduced an instant-individualheterogenous infectiousness model to jointly characterize the variation in infectiousness both between individuals and among different times. With this model, we could simultaneously estimate the transmission heterogeneity and the reproduction number from incidence time series. We validated the model with data of both simulated and real outbreaks. Our estimates of the overall and real-time heterogeneities of the six epidemics were consistent with those presented in the literature. Additionally, our model is robust to the ubiquitous bias of under-reporting and misspecification of serial interval. By analyzing recent data from South Africa, we found evidence that the Omicron might be of more significant transmission heterogeneity than Delta. Our model based on incidence data was proved to be reliable in estimating the real-time transmission heterogeneity.

Bayesian nowcasting with leading indicators applied to COVID-19 fatalities in Sweden.

The real-time analysis of infectious disease surveillance data is essential in obtaining situational awareness about the current dynamics of a major public health event such as the COVID-19 pandemic. This analysis of e.g., time-series of reported cases or fatalities is complicated by reporting delays that lead to under-reporting of the complete number of events for the most recent time points. This can lead to misconceptions by the interpreter, for instance the media or the public, as was the case with the time-series of reported fatalities during the COVID-19 pandemic in Sweden. Nowcasting methods provide real-time estimates of the complete number of events using the incomplete time-series of currently reported events and information about the reporting delays from the past. In this paper we propose a novel Bayesian nowcasting approach applied to COVID-19-related fatalities in Sweden. We incorporate additional information in the form of time-series of number of reported cases and ICU admissions as leading signals. We demonstrate with a retrospective evaluation that the inclusion of ICU admissions as a leading signal improved the nowcasting performance of case fatalities for COVID-19 in Sweden compared to existing methods.

Modelling preventive measures and their effect on generation times in emerging epidemics.

We present a stochastic epidemic model to study the effect of various preventive measures, such as uniform reduction of contacts and transmission, vaccination, isolation, screening and contact tracing, on a disease outbreak in a homogeneously mixing community. The model is based on an infectivity process, which we define through stochastic contact and infectiousness processes, so that each individual has an independent infectivity profile. In particular, we monitor variations of the reproduction number and of the distribution of generation times. We show that some interventions, i.e. uniform reduction and vaccination, affect the former while leaving the latter unchanged, whereas other interventions, i.e. isolation, screening and contact tracing, affect both quantities. We provide a theoretical analysis of the variation of these quantities, and we show that, in practice, the variation of the generation time distribution can be significant and that it can cause biases in the estimation of reproduction numbers. The framework, because of its general nature, captures the properties of many infectious diseases, but particular emphasis is on COVID-19, for which numerical results are provided.

Quantifying the preventive effect of wearing face masks.

An important task in combating the current Covid-19 pandemic lies in estimating the effect of different preventive measures. Here, we focus on the preventive effect of enforcing the use of face masks. Several publications study this effect, however, often using different measures such as: the relative attack rate in case-control studies, the effect on incidence growth/decline in a specific time frame and the effect on the number of infected in a given time frame. These measures all depend on community-specific features and are hence not easily transferred to other community settings. We argue that a more universal measure is the relative reduction in the reproduction number, which we call the face mask effect, E FM. It is shown how to convert the other measures to E FM. We also apply the methodology to four empirical studies using different effect-measures. When converted to estimates of E FM, all estimates lie between 15 and 40%, suggesting that mandatory face masks reduce the reproduction number by an amount in this range, when compared with no individuals wearing face masks.

The risk for a new COVID-19 wave and how it depends on R 0, the current immunity level and current restrictions.

The COVID-19 pandemic has hit different regions differently. The current disease-induced immunity level î in a region approximately equals the cumulative fraction infected, which primarily depends on two factors: (i) the initial potential for COVID-19 in the region (R 0), and (ii) the preventive measures put in place. Using a mathematical model including heterogeneities owing to age, social activity and susceptibility, and allowing for time-varying preventive measures, the risk for a new epidemic wave and its doubling time are investigated. Focus lies on quantifying the minimal overall effect of preventive measures p Min needed to prevent a future outbreak. It is shown that î plays a more influential roll than when immunity is obtained from vaccination. Secondly, by comparing regions with different R 0 and î it is shown that regions with lower R 0 and low î may need higher preventive measures (p Min) compared with regions having higher R 0 but also higher î, even when such immunity levels are far from herd immunity. Our results are illustrated on different regions but these comparisons contain lots of uncertainty due to simplistic model assumptions and insufficient data fitting, and should accordingly be interpreted with caution.

Key questions for modelling COVID-19 exit strategies.

Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.

A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2.

Despite various levels of preventive measures, in 2020, many countries have suffered severely from the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Using a model, we show that population heterogeneity can affect disease-induced immunity considerably because the proportion of infected individuals in groups with the highest contact rates is greater than that in groups with low contact rates. We estimate that if R 0 = 2.5 in an age-structured community with mixing rates fitted to social activity, then the disease-induced herd immunity level can be ~43%, which is substantially less than the classical herd immunity level of 60% obtained through homogeneous immunization of the population. Our estimates should be interpreted as an illustration of how population heterogeneity affects herd immunity rather than as an exact value or even a best estimate.