The reconstruction of phylogenetic trees based on viral genetic sequence data sequentially sampled from an epidemic provides estimates of the past transmission dynamics, by fitting epidemiological models to these trees. To our knowledge, none of the epidemiological models currently used in phylogenetics can account for recovery rates and sampling rates dependent on the time elapsed since transmission.
Here we introduce an epidemiological model where infectives leave the epidemic, either by recovery or sampling, after some random time which may follow an arbitrary distribution.
We derive an expression for the likelihood of the phylogenetic tree of sampled infectives under our general epidemiological model. The analytic concept developed in this paper will facilitate inference of past epidemiological dynamics and provide an analytical framework for performing very efficient simulations of phylogenetic trees under our model. The main idea of our analytic study is that the non-Markovian epidemiological model giving rise to phylogenetic trees growing vertically as time goes by, can be represented by a Markovian "coalescent point process" growing horizontally by the sequential addition of pairs of coalescence and sampling times.
As examples, we discuss two special cases of our general model, namely an application to influenza and an application to HIV. Though phrased in epidemiological terms, our framework can also be used for instance to fit macroevolutionary models to phylogenies of extant and extinct species, accounting for general species lifetime distributions.
One of the cornerstones in combating the HIV pandemic is being able to assess the current state and evolution of local HIV epidemics. This remains a complex problem, as many HIV infected individuals remain unaware of their infection status, leading to parts of HIV epidemics being undiagnosed and under-reported. To that end, we firstly present a method to learn epidemiological parameters from phylogenetic trees, using approximate Bayesian computation (ABC). The epidemiological parameters learned as a result of applying ABC are subsequently used in epidemiological models that aim to simulate a s…
We are interested in describing the infected size of the SIS Epidemic model using Birth-Death Markov process. The Susceptible-Infected-Susceptible (SIS) model is defined within a population of constant size $M$; the size is kept constant by replacing each death with a newborn healthy individual. The life span of each individual in the population is modelled by an exponential distribution with parameter $α$; and the disease spreads within the population is modelled by a Poisson process with a rate $λ_{I}$. $λ_{I}=βI(1-\frac{I}{M}) $ is similar to the instantaneous rate in the logistic populatio…
The statistical estimation of phylogenies is always associated with uncertainty, and accommodating this uncertainty is an important component of modern phylogenetic comparative analysis. The birth-death polytomy resolver is a method of accounting for phylogenetic uncertainty that places missing (unsampled) taxa onto phylogenetic trees, using taxonomic information alone. Recent studies of birds and mammals have used this approach to generate pseudo-posterior distributions of phylogenetic trees that are complete at the species level, even in the absence of genetic data for many species. Many res…
Multiple epidemiological models have been proposed to predict the spread of Ebola in West Africa. These models include consideration of counter-measures meant to slow and, eventually, stop the spread of the disease. Here, we examine one component of Ebola dynamics that is of growing concern -- the transmission of Ebola from the dead to the living. We do so by applying the toolkit of mathematical epidemiology to analyze the consequences of post-death transmission. We show that underlying disease parameters cannot be inferred with confidence from early-stage incidence data (that is, they are not…
Reconstructing pathogen dynamics from genetic data as they become available during an outbreak or epidemic represents an important statistical scenario in which observations arrive sequentially in time and one is interested in performing inference in an 'online' fashion. Widely-used Bayesian phylogenetic inference packages are not set up for this purpose, generally requiring one to recompute trees and evolutionary model parameters de novo when new data arrive. To accommodate increasing data flow in a Bayesian phylogenetic framework, we introduce a methodology to efficiently update the posterio…
A birth-death-sampling model gives rise to phylogenetic trees with samples from the past and the present. Interpreting "birth" as branching speciation, "death" as extinction, and "sampling" as fossil preservation and recovery, this model -- also referred to as the fossilized birth-death (FBD) model -- gives rise to phylogenetic trees on extant and fossil samples. The model has been mathematically analyzed and successfully applied to a range of datasets on different taxonomic levels, such as penguins, plants, and insects. However, the current mathematical treatment of this model does not allow …
The severe acute respiratory syndrome COVID-19 has been in the center of the ongoing global health crisis in 2020. The high prevalence of mild cases facilitates sub-notification outside hospital environments and the number of those who are or have been infected remains largely unknown, leading to poor estimates of the crude mortality rate of the disease. Here we use a simple model to describe the number of accumulated deaths caused by COVID-19. The close connection between the proposed model and an approximate solution of the SIR model provides a system of equations whose solutions are robust …
Background: Following the outbreak of the coronavirus epidemic in early 2020, municipalities, regional governments and policymakers worldwide had to plan their Non-Pharmaceutical Interventions (NPIs) amidst a scenario of great uncertainty. At this early stage of an epidemic, where no vaccine or medical treatment is in sight, algorithmic prediction can become a powerful tool to inform local policymaking. However, when we replicated one prominent epidemiological model to inform health authorities in a region in the south of Brazil, we found that this model relied too heavily on manually predeter…
In a given country, the cumulative death toll of the first wave of the COVID-19 epidemic follows a sigmoid curve as a function of time. In most cases, the curve is well described by the Gompertz function, which is characterized by two essential parameters, the initial growth rate and the decay rate as the first epidemic wave subsides. These parameters are determined by socioeconomic factors and the countermeasures to halt the epidemic. The Gompertz model implies that the total death toll depends exponentially, and hence very sensitively, on the ratio between these rates. The remarkably differe…
The death toll for Covid-19 may be reduced by dividing the population into two classes, the vulnerable and the fit, with different lockdown regimes. Instead of one reproduction number there now are four parameters. These make it possible to quantify the effect of the social distancing measures. There is a simple stochastic model for epidemics in a two type population. Apart from the size of the population of the vulnerable and the fit, and the initial number of infected in the two classes, only the four reproduction parameters are needed to run the two type Reed-Frost model. The program is sim…
We assess the impact of COVID-19 response measures implemented in Germany and Switzerland on cumulative COVID-19-related hospitalization and death rates. Our analysis exploits the fact that the epidemic was more advanced in some regions than in others when certain lockdown measures came into force, based on measuring health outcomes relative to the region-specific start of the epidemic and comparing outcomes across regions with earlier and later start dates. When estimating the effect of the relative timing of measures, we control for regional characteristics and initial epidemic trends by lin…
We shall apply a generalized SEIR model to study the outbreak of COVID-19 in Brazil. In particular, we would like to explain the projections of the increase in the level of infection over a long period of time, overlapping large local outbreaks in the most populous states in the country. A time-dependent dynamic SEIR model inspired in a model previously used during the outbreak in China was used to analyses the time trajectories of infected, recovered, and deaths. The model has parameters that vary with time and are fitted considering a nonlinear least-squares method. The simulations starting …
Simultaneous reconstruction of evolutionary history and epidemiological dynamics from viral sequences with the birth-death SIR model
RNA病毒如HIV、丙型肝炎病毒和流感病毒的进化如此之快，以至于病毒的基因组包含了过去生态动态的信息。因此，我们开发了一种动态的方法，使联合估计的流行病学参数和系统发育史。该方法基于房室易感染-感染-清除（SIR）模型，提供了关于感染发生率和患病率的单独信息。关于宿主种群动力学和进化历史相互作用的详细信息可以为如何控制或完全避免疾病爆发的决策提供信息。我们应用我们的死亡SIR方法（BDSIR）的两个病毒数据集。首先，分析了1999年至2003年期间在英国采样的5个人类免疫缺陷病毒1型簇。估计的基本繁殖比在集群之间的范围从1.9到3.2。所有集群都显示，在90年代中期或末期，当地流行病的增长率有所下降。对丙型肝炎病毒（HCV）基因型2c数据集的分析表明，科尔多瓦市Cruz del Eje的当地流行病起源于1906年左右（中位数），与1880- 1920年从欧洲到阿根廷中部的移民潮相吻合。估计流行高峰期在1970年左右。
Objective: To conduct an early estimation of the Basic Reproduction Number (BRN) induced by government interference, and to project resulting day to day number of in-patients, ICU-patients and cumulative number of deaths in a Danish setting. Method: We used the Kermack and McKendrick model with varying basic reproduction number to estimate number infected and age stratified percentages to estimate number of in-patients, ICU-patients and cumulative number of deaths. Changes in basic reproduction number was estimated based on current in-patient numbers. Results: The basic reproductive number in …
Many countries are managing COVID-19 epidemic by switching between lighter and heavier restrictions. While an open-close and a close-open cycle have comparable socio-economic costs, the former leads to a much heavier burden in terms of deaths and pressure on the healthcare system. An empirical demonstration of the toll ensuing from procrastination was recently observed in Israel, where both cycles were enforced from late August to mid-December 2020, yielding some 1,600 deaths with open-close compared to 440 with close-open.
The SARS-CoV-2 pandemic has necessitated mitigation efforts around the world. We use only reported deaths in the two weeks after the first death to determine infection parameters, in order to make predictions of hidden variables such as the time dependence of the number of infections. Early deaths are sporadic and discrete so the use of network models of epidemic spread is imperative, with the network itself a crucial random variable. Location-specific population age distributions and population densities must be taken into account when attempting to fit these events with parametrized models. …
We are currently living in a state of uncertainty due to the pandemic caused by the Sars-CoV-2 virus. There are several factors involved in the epidemic spreading such as the individual characteristics of each city/country. The true shape of the epidemic dynamics is a large, complex system such as most of the social systems. In this context, Complex networks are a great candidate to analyze these systems due to their ability to tackle structural and dynamical properties. Therefore this study presents a new approach to model the COVID-19 epidemic using a multi-layer complex network, where nodes…
We develop an agent-based model to assess the cumulative number of deaths during hypothetical Covid-19-like epidemics for various non-pharmaceutical intervention strategies. We consider local and non-local modes of disease transmission. The first simulates transmission through social contacts in the vicinity of the place of residence while the second through social contacts in public places: schools, hospitals, airports, etc., where many people meet, who live in remote geographic locations. Epidemic spreading is modeled as a discrete-time stochastic process on random geometric networks. We use…
Coronavirus disease (COVID-2019) is a severe ongoing novel pandemic that is spreading quickly across the world. Italy, that is widely considered one of the main epicenters of the pandemic, has registered the highest COVID-2019 death rates and death toll in the world, to the present day. In this article I estimate an autoregressive integrated moving average (ARIMA) model to forecast the epidemic trend over the period after April 4, 2020, by using the Italian epidemiological data at national and regional level. The data refer to the number of daily confirmed cases officially registered by the It…
Within the context of SEIR models, we consider a lockdown that is both imposed and lifted at an early stage of an epidemic. We show that, in these models, although such a lockdown may delay deaths, it eventually does not avert a significant number of fatalities. Therefore, in these models, the efficacy of a lockdown cannot be gauged by simply comparing figures for the deaths at the end of the lockdown with the projected figure for deaths by the same date without the lockdown. We provide a simple but robust heuristic argument to explain why this conclusion should generalize to more elaborate co…
With growing exchanges of people and merchandise between countries, epidemics have become an issue of increasing importance and huge amounts of data are being collected every day. Hence, analyses that were usually run in personal computers and desktops are no longer feasible. It is now common to run such tasks in High-performance computing (HPC) environments and/or dedicated systems. On the other hand we are often dealing in these analyses with graphs and trees, and running algorithms to find patterns in such structures. Hence, although graph oriented databases and processing systems can be of…
In a previous article [1] we have described the temporal evolution of the Sars- Cov-2 in Italy in the time window February 24-April 1. As we can see in [1] a generalized logistic equation captures both the peaks of the total infected and the deaths. In this article our goal is to study the missing peak, i.e. the currently infected one (or total currently positive). After the April 7 the large increase in the number of swabs meant that the logistical behavior of the infected curve no longer worked. So we decided to generalize the model, introducing new parameters. Moreover, we adopt a similar a…
The temporal growth in the number of deaths in the COVID-19 epidemic is subexponential. Here we show that a piecewise quadratic law provides an excellent fit during the thirty days after the first three fatalities on January 20 and later since the end of March 2020. There is also a brief intermediate period of exponential growth. During the second quadratic growth phase, the characteristic time of the growth is about eight times shorter than in the beginning, which can be understood as the occurrence of separate hotspots. Quadratic behavior can be motivated by peripheral growth when further sp…
In this paper, we propose a two-group SIR epidemic model to simulate the outcome of stay-at-home policy and wearing face masks during the first COVID-19 epidemic wave in the United States. Based on our proposed model, we further use the optimal control approach (with the objective of minimizing total deaths) to find the optimal dynamical distribution of face masks between the healthcare workers and the general public. It is not surprising that all the face masks should be solely reserved for the healthcare workers if the supply is short. However, when the supply is indeed sufficient, our numer…
The Covid-19 pandemic has made clear the need to improve modern multivariate time-series forecasting models. Current state of the art predictions of future daily deaths and, especially, hospital resource usage have confidence intervals that are unacceptably wide. Policy makers and hospitals require accurate forecasts to make informed decisions on passing legislation and allocating resources. We used US county-level data on daily deaths and population statistics to forecast future deaths. We extended the SIR epidemiological model to a novel model we call the PECAIQR model. It adds several new v…
The data analysis on deaths in the Lombardy Region and of both the provinces of Bergamo and Brescia shows a twofold aspect on the trend of the epidemic: - all the data show a bias linked to the event of March 10th (day for which the Lombardy region data is partial) and the subsequent change in the way in which positive cases and deaths are calculated; - following the containment measures of the Prime Minister's Decree of March 11th, the spread of the epidemic, although still exponential in nature, has a reduced multiplication coefficient. Our analysis concludes that the situation is not yet co…
Recent advances have allowed for both morphological fossil evidence and molecular sequences to be integrated into a single combined inference of divergence dates under the rule of Bayesian probability. In particular the fossilized birth-death tree prior and the Lewis-Mk model of discrete morphological evolution allow for the estimation of both divergence times and phylogenetic relationships between fossil and extant taxa. We exploit this statistical framework to investigate the internal consistency of these models by producing phylogenetic estimates of the age of each fossil in turn, within tw…
In this paper we develop a predictive model for the spread of COVID-19 infection at a provincial (i.e. EU NUTS-3) level in Italy by using official data from the Italian Ministry of Health integrated with data extracted from daily official press conferences of regional authorities and from local newspaper websites. This integration is mainly concerned with COVID-19 cause specific death data which are not available at NUTS-3 level from open official data data channels. An adjusted time-dependent SIRD model is used to predict the behavior of the epidemic, specifically the number of susceptible, i…
We propose an SEIR-type meta-population model to simulate and monitor the Covid-19 epidemic evolution. The basic model consists of seven compartments, namely susceptible (S), exposed (E), three infective classes, recovered (R), and deceased (D). We define these compartments for n age and gender groups in m different spatial locations. So, the resulting model has, for each age group, gender, and place, all epidemiological classes. The mixing between them is accomplished by means of time-dependent infection rate matrices. The model is calibrated with the curve of daily new infections in New York…
The 2014 epidemic of the Ebola virus is governed by a genetically diverse viral population. In the early Sierra Leone outbreak, a recent study has identified new mutations that generate genetically distinct sequence clades. Here we find evidence that major Sierra Leone clades have systematic differences in growth rate and reproduction number. If this growth heterogeneity remains stable, it will generate major shifts in clade frequencies and influence the overall epidemic dynamics on time scales within the current outbreak. Our method is based on simple summary statistics of clade growth, which…
Using the continuous-time susceptible-infected-susceptible (SIS) model on networks, we investigate the problem of inferring the class of the underlying network when epidemic data is only available at population-level (i.e. the number of infected individuals at a finite set of discrete times of a single realisation of the epidemic), the only information likely to be available in real world settings. To tackle this, epidemics on networks are approximated by a Birth-and-Death process which keeps track of the number of infected nodes at population level. The rates of this surrogate model encode bo…
Estimation of epidemiological and population parameters from molecular sequence data has become central to the understanding of infectious disease dynamics. Various models have been proposed to infer details of the dynamics that describe epidemic progression. These include inference approaches derived from Kingman's coalescent theory. Here, we use recently described coalescent theory for epidemic dynamics to develop stochastic and deterministic coalescent SIR tree priors. We implement these in a Bayesian phylogenetic inference framework to permit joint estimation of SIR epidemic parameters and…
Several epidemiological models have been proposed to study the evolution of COVID-19 pandemic. In this paper, we propose an extension of the SUIHTER model, first introduced in [Parolini et al, Proc R. Soc. A., 2021] to analyse the COVID-19 spreading in Italy, which accounts for the vaccination campaign and the presence of new variants when they become dominant. In particular, the specific features of the variants (e.g. their increased transmission rate) and vaccines (e.g. their efficacy to prevent transmission, hospitalization and death) are modeled, based on clinical evidence. The new model i…
Bayesian inference of sampled ancestor trees for epidemiology and fossil calibration
系统发育分析包括化石或分子序列，这些序列是通过时间采样的，需要模型允许一个样本是另一个样本的直接祖先。由于以前可用的系统发育推断工具假设所有样品都是尖端，因此它们不允许这种可能性。我们已经开发并实现了一个贝叶斯马尔可夫链蒙特卡罗（MCMC）算法来推断我们所谓的采样祖先树，也就是说，树中的采样个人可以直接祖先的其他采样个人。我们使用了一系列的出生-死亡模型，其中个体在采样后可能会保留在树过程中，特别是我们将出生-死亡天际线模型[Stadler et al，2013]扩展到采样的祖先树。该方法允许检测采样的祖先以及估计个体在被采样时将从过程中移除的概率。我们发现，所有样本来自不同的时间点的采样祖先出生死亡模型是不可识别的，因此需要一个参数是已知的，以推断其他参数。我们将这种方法应用于流行病学数据，其中采样祖先的可能性使我们能够识别在采样后感染其他个体的个体，并推断基本的流行病学参数。我们还应用该方法来推断分歧的时间和多样化率时，化石包括在物种样本中，使antilisation事件建模为树分支过程的一部分。这种建模有许多优点，在文献中争论。采样器可以作为开源BEAST 2包（https：//github.com/gavryushkina/sampled-ancestors）获得。
Nowcasting and forecasting of epidemic spreading rely on incidence series of reported cases to derive the fundamental epidemiological parameters for a given pathogen. Two relevant drawbacks for predictions are the unknown fractions of undocumented cases and levels of nonpharmacological interventions, which span highly heterogeneously across different places and times. We describe a simple data-driven approach using a compartmental model including asymptomatic and presymptomatic contagions that allows to estimate both the level of undocumented infections and the value of effective reproductive …
In this note we analyze the temporal dynamics of the coronavirus disease 2019 outbreak in China, Italy and France in the time window $22/01-09/03/2020$. A first analysis of simple day-lag maps points to some universality in the epidemic spreading, suggesting that simple mean-field models can be meaningfully used to gather a quantitative picture of the epidemic spreading, and notably the height and time of the peak of confirmed infected individuals. The analysis of the same data within a simple susceptible-(confirmed) infected-recovered-deaths model indicates that the kinetic parameter that des…
Gene gain-loss-duplication models are commonly based on continuous-time birth-death processes. Employed in a phylogenetic context, such models have been increasingly popular in studies of gene content evolution across multiple genomes. While the applications are becoming more varied and demanding, bioinformatics methods for probabilistic inference on copy numbers (or integer-valued evolutionary characters, in general) are scarce. We describe a flexible probabilistic framework for phylogenetic gene-loss-duplication models. The framework is based on a novel elementary representation by dependent…
