Assessing the transmissibility of epidemics involving epidemic zoning.

BACKGROUND: Epidemic zoning is an important option in a series of measures for the prevention and control of infectious diseases. We aim to accurately assess the disease transmission process by considering the epidemic zoning, and we take two epidemics with distinct outbreak sizes as an example, i.e., the Xi'an epidemic in late 2021 and the Shanghai epidemic in early 2022. METHODS: For the two epidemics, the total cases were clearly distinguished by their reporting zone and the Bernoulli counting process was used to describe whether one infected case in society would be reported in control zones or not. Assuming the imperfect or perfect isolation policy in control zones, the transmission processes are respectively simulated by the adjusted renewal equation with case importation, which can be derived on the basis of the Bellman-Harris branching theory. The likelihood function containing unknown parameters is then constructed by assuming the daily number of new cases reported in control zones follows a Poisson distribution. All the unknown parameters were obtained by the maximum likelihood estimation. RESULTS: For both epidemics, the internal infections characterized by subcritical transmission within the control zones were verified, and the median control reproduction numbers were estimated as 0.403 (95% confidence interval (CI): 0.352, 0.459) in Xi'an epidemic and 0.727 (95% CI: 0.724, 0.730) in Shanghai epidemic, respectively. In addition, although the detection rate of social cases quickly increased to 100% during the decline period of daily new cases until the end of the epidemic, the detection rate in Xi'an was significantly higher than that in Shanghai in the previous period. CONCLUSIONS: The comparative analysis of the two epidemics with different consequences highlights the role of the higher detection rate of social cases since the beginning of the epidemic and the reduced transmission risk in control zones throughout the outbreak. Strengthening the detection of social infection and strictly implementing the isolation policy are of great significance to avoid a larger-scale epidemic.

A Discrete Model for the Evolution of Infection Prior to Symptom Onset

We consider a between-host model for a single epidemic outbreak of an infectious disease. According to the progression of the disease, hosts are classified in regard to the pathogen load. Specifically, we are assuming four phases: non-infectious asymptomatic phase, infectious asymptomatic phase (key-feature of the model where individuals show up mild or no symptoms), infectious symptomatic phase and finally an immune phase. The system takes the form of a non-linear Markov chain in discrete time where linear transitions are based on geometric (main model) or negative-binomial (enhanced model) probability distributions. The whole system is reduced to a single non-linear renewal equation. Moreover, after linearization, at least two meaningful definitions of the basic reproduction number arise: firstly as the expected secondary asymptomatic cases produced by an asymptomatic primary case, and secondly as the expected number of symptomatic individuals that a symptomatic individual will produce. We study the evolution of infection transmission before and after symptom onset. Provided that individuals can develop symptoms and die from the disease, we take disease-induced mortality as a measure of virulence and it is assumed to be positively correlated with a weighted average transmission rate. According to our findings, transmission rate of the infection is always higher in the symptomatic phase yet under a suitable condition, most of the infections take place prior to symptom onset.

Filtering and improved Uncertainty Quantification in the dynamic estimation of effective reproduction numbers.

The effective reproduction number Rt measures an infectious disease's transmissibility as the number of secondary infections in one reproduction time in a population having both susceptible and non-susceptible hosts. Current approaches do not quantify the uncertainty correctly in estimating Rt, as expected by the observed variability in contagion patterns. We elaborate on the Bayesian estimation of Rt by improving on the Poisson sampling model of Cori et al. (2013). By adding an autoregressive latent process, we build a Dynamic Linear Model on the log of observed Rts, resulting in a filtering type Bayesian inference. We use a conjugate analysis, and all calculations are explicit. Results show an improved uncertainty quantification on the estimation of Rt's, with a reliable method that could safely be used by non-experts and within other forecasting systems. We illustrate our approach with recent data from the current COVID19 epidemic in Mexico.

Modeling COVID-19 Incidence by the Renewal Equation after Removal of Administrative Bias and Noise.

The sanitary crisis of the past two years has focused the public's attention on quantitative indicators of the spread of the COVID-19 pandemic. The daily reproduction number Rt, defined by the average number of new infections caused by a single infected individual at time t, is one of the best metrics for estimating the epidemic trend. In this paper, we provide a complete observation model for sampled epidemiological incidence signals obtained through periodic administrative measurements. The model is governed by the classic renewal equation using an empirical reproduction kernel, and subject to two perturbations: a time-varying gain with a weekly period and a white observation noise. We estimate this noise model and its parameters by extending a variational inversion of the model recovering its main driving variable Rt. Using Rt, a restored incidence curve, corrected of the weekly and festive day bias, can be deduced through the renewal equation. We verify experimentally on many countries that, once the weekly and festive days bias have been corrected, the difference between the incidence curve and its expected value is well approximated by an exponential distributed white noise multiplied by a power of the magnitude of the restored incidence curve.

Inferring the reproduction number using the renewal equation in heterogeneous epidemics.

Real-time estimation of the reproduction number has become the focus of modelling groups around the world as the SARS-CoV-2 pandemic unfolds. One of the most widely adopted means of inference of the reproduction number is via the renewal equation, which uses the incidence of infection and the generation time distribution. In this paper, we derive a multi-type equivalent to the renewal equation to estimate a reproduction number which accounts for heterogeneity in transmissibility including through asymptomatic transmission, symptomatic isolation and vaccination. We demonstrate how use of the renewal equation that misses these heterogeneities can result in biased estimates of the reproduction number. While the bias is small with symptomatic isolation, it can be much larger with asymptomatic transmission or transmission from vaccinated individuals if these groups exhibit substantially different generation time distributions to unvaccinated symptomatic transmitters, whose generation time distribution is often well defined. The bias in estimate becomes larger with greater population size or transmissibility of the poorly characterized group. We apply our methodology to Ebola in West Africa in 2014 and the SARS-CoV-2 in the UK in 2020-2021.

Computing the daily reproduction number of COVID-19 by inverting the renewal equation using a variational technique.

The COVID-19 pandemic has undergone frequent and rapid changes in its local and global infection rates, driven by governmental measures or the emergence of new viral variants. The reproduction number Rt indicates the average number of cases generated by an infected person at time t and is a key indicator of the spread of an epidemic. A timely estimation of Rt is a crucial tool to enable governmental organizations to adapt quickly to these changes and assess the consequences of their policies. The EpiEstim method is the most widely accepted method for estimating Rt But it estimates Rt with a significant temporal delay. Here, we propose a method, EpiInvert, that shows good agreement with EpiEstim, but that provides estimates of Rt several days in advance. We show that Rt can be estimated by inverting the renewal equation linking Rt with the observed incidence curve of new cases, it Our signal-processing approach to this problem yields both Rt and a restored it corrected for the "weekend effect" by applying a deconvolution and denoising procedure. The implementations of the EpiInvert and EpiEstim methods are fully open source and can be run in real time on every country in the world and every US state.

The stochastic dynamics of early epidemics: probability of establishment, initial growth rate, and infection cluster size at first detection.

Emerging epidemics and local infection clusters are initially prone to stochastic effects that can substantially impact the early epidemic trajectory. While numerous studies are devoted to the deterministic regime of an established epidemic, mathematical descriptions of the initial phase of epidemic growth are comparatively rarer. Here, we review existing mathematical results on the size of the epidemic over time, and derive new results to elucidate the early dynamics of an infection cluster started by a single infected individual. We show that the initial growth of epidemics that eventually take off is accelerated by stochasticity. As an application, we compute the distribution of the first detection time of an infected individual in an infection cluster depending on testing effort, and estimate that the SARS-CoV-2 variant of concern Alpha detected in September 2020 first appeared in the UK early August 2020. We also compute a minimal testing frequency to detect clusters before they exceed a given threshold size. These results improve our theoretical understanding of early epidemics and will be useful for the study and control of local infectious disease clusters.

A renewal equation model to assess roles and limitations of contact tracing for disease outbreak control.

We propose a deterministic model capturing essential features of contact tracing as part of public health non-pharmaceutical interventions to mitigate an outbreak of an infectious disease. By incorporating a mechanistic formulation of the processes at the individual level, we obtain an integral equation (delayed in calendar time and advanced in time since infection) for the probability that an infected individual is detected and isolated at any point in time. This is then coupled with a renewal equation for the total incidence to form a closed system describing the transmission dynamics involving contact tracing. We define and calculate basic and effective reproduction numbers in terms of pathogen characteristics and contact tracing implementation constraints. When applied to the case of SARS-CoV-2, our results show that only combinations of diagnosis of symptomatic infections and contact tracing that are almost perfect in terms of speed and coverage can attain control, unless additional measures to reduce overall community transmission are in place. Under constraints on the testing or tracing capacity, a temporary interruption of contact tracing may, depending on the overall growth rate and prevalence of the infection, lead to an irreversible loss of control even when the epidemic was previously contained.

A phenomenological estimate of the true scale of CoViD-19 from primary data.

Estimation of the prevalence of undocumented SARS-CoV-2 infections is critical for understanding the overall impact of CoViD-19, and for implementing effective public policy intervention strategies. We discuss a simple yet effective approach to estimate the true number of people infected by SARS-CoV-2, using raw epidemiological data reported by official health institutions in the largest EU countries and the USA.

Range of reproduction number estimates for COVID-19 spread.

To monitor local and global COVID-19 outbreaks, and to plan containment measures, accessible and comprehensible decision-making tools need to be based on the growth rates of new confirmed infections, hospitalization or case fatality rates. Growth rates of new cases form the empirical basis for estimates of a variety of reproduction numbers, dimensionless numbers whose value, when larger than unity, describes surging infections and generally worsening epidemiological conditions. Typically, these determinations rely on noisy or incomplete data gained over limited periods of time, and on many parameters to estimate. This paper examines how estimates from data and models of time-evolving reproduction numbers of national COVID-19 infection spread change by using different techniques and assumptions. Given the importance acquired by reproduction numbers as diagnostic tools, assessing their range of possible variations obtainable from the same epidemiological data is relevant. We compute control reproduction numbers from Swiss and Italian COVID-19 time series adopting both data convolution (renewal equation) and a SEIR-type model. Within these two paradigms we run a comparative analysis of the possible inferences obtained through approximations of the distributions typically used to describe serial intervals, generation, latency and incubation times, and the delays between onset of symptoms and notification. Our results suggest that estimates of reproduction numbers under these different assumptions may show significant temporal differences, while the actual variability range of computed values is rather small.