Two factors that are often ignored but could play a crucial role in the progression of an infectious disease are the distributions of inherent susceptibility ($σ_{inh}$) and external infectivity ($ι_{ext}$), in a given population. While the former is determined by the immunity of an individual towards a disease, the latter depends on the duration of exposure to the infection. We model the spatio-temporal propagation of a pandemic using a generalized SIR (Susceptible-Infected-Removed) model by introducing the susceptibility and infectivity distributions to understand their combined effects, which appear to remain inadequately addressed till date. We consider the coupling between $σ_{inh}$ and $ι_{ext}$ through a new Critical Infection Parameter (CIP) ($γ_c$). We find that the neglect of these distributions, as in the naive SIR model, results in an overestimation of the amount of infection in a population, which leads to incorrect (higher) estimates of the infections required to achieve the herd immunity threshold. Additionally, we include the effects of seeding of infection in a population by long-range migration. We solve the resulting master equations by performing Kinetic Monte Carlo Cellular Automata (KMC-CA) simulations. Importantly, our simulations can reproduce the multiple infection peak scenario of a pandemic. The latent interactions between disease migration and the distributions of susceptibility and infectivity can render the progression a character vastly different from the naive SIR model. In particular, inclusion of these additional features renders the problem a character of a living percolating system where the disease cluster survives by migrating from region to region.
An epidemic multi-strain model with temporary cross-immunity shows chaos, even in a previously unexpected parameter region. Especially dengue fever models with strong enhanced infectivity on secondary infection have previously shown deterministic chaos motivated by experimental findings of antibody-dependent-enhancement (ADE). Including temporary cross-immunity in such models, which is common knowledge among field researchers in dengue, we find a deterministically chaotic attractor in the more realistic parameter region of reduced infectivity on secondary infection (''inverse ADE'' parameter r…
Fractional-order SIR models have become increasingly popular in the literature in recent years, however unlike the standard SIR model, they often lack a derivation from an underlying stochastic process. Here we derive a fractional-order infectivity SIR model from a stochastic process that incorporates a time-since-infection dependence on the infectivity of individuals. The fractional derivative appears in the generalised master equations of a continuous time random walk through SIR compartments, with a power-law function in the infectivity. We show that this model can also be formulated as an …
We analytically address disease outbreaks in large, random networks with heterogeneous infectivity and susceptibility. The transmissibility $T_{uv}$ (the probability that infection of $u$ causes infection of $v$) depends on the infectivity of $u$ and the susceptibility of $v$. Initially a single node is infected, following which a large-scale epidemic may or may not occur. We use a generating function approach to study how heterogeneity affects the probability that an epidemic occurs and, if one occurs, its attack rate (the fraction infected). For fixed average transmissibility, we find upper …
We take up a recently proposed compartmental SEIQR model with delays, ignore loss of immunity in the context of a fast pandemic, extend the model to a network structured on infectivity, and consider the continuum limit of the same with a simple separable interaction model for the infectivities $β$. Numerical simulations show that the evolving dynamics of the network is effectively captured by a single scalar function of time, regardless of the distribution of $β$ in the population. The continuum limit of the network model allows a simple derivation of the simpler model, which is a single scala…
During epidemics, estimation of the effective reproduction number (ERN) associated with infectious disease is a challenging topic for policy development and medical resource management. There is still an open question about the dominant factors to characterize in corona virus disease 2019 (COVID-19), although recent studies based on nonlinear regression with machine learning suggested mobility. The emergence of new viral variants is common in widespread pandemics. However, understanding the potential ERN of new variants is required for policy revision, including lockdown constraints. In this s…
High-throughput molecular screening is required to investigate the origin and diffusion of antimicrobial resistance in pathogen outbreaks. The most frequent cause of human infection is Escherichia coli, which is dominated by sequence type 131 (ST131), a set of rapidly radiating pandemic clones. The highly infectious clades of ST131 originated firstly by a mutation enhancing virulence and adhesion. Secondly, single-nucleotide polymorphisms occurred enabling fluoroquinolone-resistance, which is near-fixed in all ST131. Thirdly, broader resistance through beta-lactamases has been gained and lost …
One clear aspect of behaviour in the COVID-19 pandemic has been people's focus on, and response to, reported or observed infection numbers in their community. We describe a simple model of infectious disease spread in a pandemic situation where people's behaviour is influenced by the current risk of infection and where this behavioural response acts homeostatically to return infection risk to a certain preferred level. This model predicts that the reproduction rate $R$ will be centered around a median value of 1, and that a related measure of relative change in the number of new infections wil…
During a pandemic, there are conflicting demands arising from public health and economic cost. Lockdowns are a common way of containing infections, but they adversely affect the economy. We study the question of how to minimise the economic damage of a lockdown while still containing infections. Our analysis is based on the SIR model, which we analyse using a clock set by the virus. This use of the "virus time" permits a clean mathematical formulation of our problem. We optimise the economic cost for a fixed health cost and arrive at a strategy for navigating the pandemic. This involves adjust…
Mathematical models have come to play a key role in global pandemic preparedness and outbreak response: helping to plan for disease burden, hospital capacity, and inform non-pharmaceutical interventions. Such models have played a pivotal role in the COVID-19 pandemic, with transmission models and, by consequence, modelers guiding global, national, and local responses to SARS-CoV-2. However, these models have systematically failed to account for the social and structural factors which lead to socioeconomic, racial, and geographic health disparities. Why do epidemiologic models of emerging infec…
The infection fatality rate (IFR) of the Coronavirus Disease 2019 (COVID-19) is one of the most discussed figures in the context of this pandemic. Using German COVID-19 surveillance data and age-group specific IFR estimates from multiple international studies, this work investigates time-dependent variations in effective IFR over the course of the pandemic. Three different methods for estimating (effective) IFRs are presented: (a) population-averaged IFRs based on the assumption that the infection risk is independent of age and time, (b) effective IFRs based on the assumption that the age dist…
The effective reproduction number is a key figure to monitor the course of the COVID-19 pandemic. In this study we consider a retrospective modelling approach for estimating the effective reproduction number based on death counts during the first year of the pandemic in Germany. The proposed Bayesian hierarchical model incorporates splines to estimate reproduction numbers flexibly over time while adjusting for varying effective infection fatality rates. The approach also provides estimates of dark figures regarding undetected infections over time. Results for Germany illustrate that estimated …
An urgent problem in controlling COVID-19 spreading is to understand the role of undocumented infection. We develop a five-state model for COVID-19, taking into account the unique features of the novel coronavirus, with key parameters determined by the government reports and mathematical optimization. Tests using data from China, South Korea, Italy, and Iran indicate that the model is capable of generating accurate prediction of the daily accumulated number of confirmed cases and is entirely suitable for real-time prediction. The drastically disparate testing and diagnostic standards/policies …
Accurate and reliable forecasting of emerging dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants enables policymakers and vaccine makers to get prepared for future waves of infections. The last three waves of SARS-CoV-2 infections caused by dominant variants Omicron (BA.1), BA.2, and BA.4/BA.5 were accurately foretold by our artificial intelligence (AI) models built with biophysics, genotyping of viral genomes, experimental data, algebraic topology, and deep learning. Based on newly available experimental data, we analyzed the impacts of all possible viral spike (S)…
An AI-Enabled Agent-Based Simulation Platform for Studying COVID-19 Pandemic
Johns Hopkins University（约翰斯·霍普金斯大学）；University of Pennsylvania（宾夕法尼亚大学）；ICMR-National Institute for Research in Bacterial Infections（印度医学研究理事会-细菌性疾病研究所）；University of Nebraska-Lincoln（内布拉斯加大学林肯分校）
A mathematical model to calculate the transmissibility of SARS-Cov-2 in Wuhan City was developed and published recently by Tian-Mu Chen et al., Infectious Diseases of Poverty, 2020, https://doi.org/10.1186/s40249-020-00640-3. This paper improves this model in order to study the effect of different scenarios that include actions to contain the pandemic, such as isolation and quarantine of infected and at-risk people. Comparisons made between the different scenarios show that the progress of the infection is found to strongly depend on measures taken in each case. The particular case of Brazil w…
This work constructs, analyzes, and simulates a new compartmental SEIR-type model for the dynamics and potential control of the current COVID-19 pandemic. The novelty in this work is two-fold. First, the population is divided according to its compliance with disease control directives (lockdown, shelter-in-place, masks/face coverings, physical distancing, etc.) into those who fully comply and those who follow the directives partially, or are necessarily mobile (such as medical staff). This split, indirectly, reflects on the quality and consistency of these measures. This allows the assessment …
A new epidemic model for Covid-19 has been constructed and simulated for eight US states. The coefficients for this model, based on seven coupled differential equations, are carefully evaluated against recorded data on cases and deaths. These projections reveal that Covid-19 will become endemic, spreading for more than two years. If stay-at-home orders are relaxed, most states may experience a secondary peak in 2021. The number of Covid-19 deaths could have been significantly lower in most states that opened up, if lockdowns had been maintained. Additionally, our model predicts that decreasing…
Compartmental models are an important quantitative tool in epidemiology, enabling us to forecast the course of a communicable disease. However, the model parameters, such as the infectivity rate of the disease, are riddled with uncertainties, which has motivated the development and use of stochastic compartmental models. Here, we first show that a common stochastic model, which treats the uncertainties as white noise, is fundamentally flawed since it erroneously implies that greater parameter uncertainties will lead to the eradication of the disease. Then, we present a principled modeling of t…
During its first two years, the SARS-CoV-2 pandemic manifested as multiple waves shaped by complex interactions between variants of concern, non-pharmaceutical interventions, and the immunological landscape of the population. Understanding how the age-specific epidemiology of SARS-CoV-2 has evolved throughout the pandemic is crucial for informing policy decisions. We developed an inference-based modelling approach to reconstruct the burden of true infections and hospital admissions in children, adolescents and adults over the seven waves of four variants (wild-type, Alpha, Delta, Omicron BA.1)…
Much traditional statistical modelling assumes that the outcome variables of interest are independent of each other when conditioned on the explanatory variables. This assumption is strongly violated in the case of infectious diseases, particularly in close-contact settings such as households, where each individual's probability of infection is strongly influenced by whether other household members experience infection. On the other hand, general multi-type transmission models of household epidemics quickly become unidentifiable from data as the number of types increases. This has led to a sit…
Phenomenological and deterministic models are often used for the estimation of transmission parameters in an epidemic and for the prediction of its growth trajectory. Such analyses are usually based on single peak outbreak dynamics. In light of the present COVID-19 pandemic, there is a pressing need to better understand observed epidemic growth with multiple peak structures, preferably using first-principles methods. Along the lines of our previous work [Physica A 574, 126014 (2021)], here we apply 2D random-walk Monte Carlo calculations to better understand COVID-19 spread through contact int…
The SARS-CoV-2 pandemic has so far unfolded diversely across the fifty United States of America, reflected both in different time progressions of infection "waves" and in magnitudes of local infection rates. Despite a marked diversity of presentations, most U.S. states experienced their single greatest surge in daily new cases during the transition from Fall 2020 to Winter 2021. Popular media also cite additional similarities between states -- often despite disparities in governmental policies, reported mask-wearing compliance rates, and vaccination percentages. Here, we identify a set of robu…
COVID-19 is now the largest pandemic crisis of this century, with over 16 million registered cases worldwide. African countries have now begun registering an increasing number of cases, yet, not many models developed focus in specific African countries. In our study we use a simple SEIR model to evaluate and predict future scenarios regarding the pandemic crisis in Mozambique. We compare the effect of different policies on the infection curve and estimate epidemiological parameters such as the current infection reproduction number Rt and the growth rate g. We have found a low value for Rt, ran…
Epidemiological models with constant parameters may not capture satisfactory infection patterns in the presence of pharmaceutical and non-pharmaceutical mitigation measures during a pandemic, since infectiousness is a function of time. In this paper, an Epidemiology-Informed Neural Network algorithm is introduced to learn the time-varying transmission rate for the COVID-19 pandemic in the presence of various mitigation scenarios. There are asymptomatic infectives, mostly unreported, and the proposed algorithm learns the proportion of the total infective individuals that are asymptomatic infect…
Here we propose and implement a generalized mathematical model to find the time evolution of population in infectious diseases and apply the model to study the recent COVID-19 pandemic. Our model at the core is a non-local generalization of the widely used Kermack-McKendrick(KM) model where the susceptible(S) population evolves into two other categories, namely infectives(I) and removed(R). This is the well-known SIR model in which we further divide both S and I into high and low risk categories. We first formulate a set of non-local dynamical equations for the time evolution of distinct popul…
More and more countries show a significant slowdown in the number of new COVID-19 infections due to effective governmentally instituted lockdown and social distancing measures. We have analyzed the growth behavior of the top 25 most affected countries by means of a local slope analysis and found three distinct patterns that individual countries follow depending on the strictness of the lockdown protocols: exponential rise and fall, power law, or logistic. For countries showing power law growth we have determined the scaling exponents. For countries that showed a strong slowdown in the rate of …
Epidemic models play a key role in understanding and responding to the emerging COVID-19 pandemic. Widely used compartmental models are static and are of limited use to evaluate intervention strategies with the emerging pandemic. Applying the technology of data assimilation, we propose a Bayesian updating approach for estimating epidemiological parameters using observable information for the purpose of assessing the impacts of different intervention strategies. We adopt a concise renewal model and propose new parameters by disentangling the reduction of instantaneous reproduction number Rt int…
After the first lockdown in response to the COVID-19 outbreak, many countries faced difficulties in balancing infection control with economics. Due to limited prior knowledge, economists began researching this issue using cost-benefit analysis and found that infection control processes significantly affect economic efficiency. A UK study used economic parameters to numerically demonstrate an optimal balance in the process, including keeping the infected population stationary. However, universally applicable knowledge, which is indispensable for the guiding principles of infection control, has …
A simple analytical model for modeling the evolution of the 2020 COVID-19 pandemic is presented. The model is based on the numerical solution of the widely used Susceptible-Infectious-Removed (SIR) populations model for describing epidemics. We consider an expanded version of the original Kermack-McKendrick model, which includes a decaying value of the parameter $β$ (the effective contact rate) due to externally imposed conditions, to which we refer as the forced-SIR (FSIR) model. We introduce an approximate analytical solution to the differential equations that represent the FSIR model which …
The Influenza Pandemic of 1918-1919, also called Spanish Flu Pandemic, was one of the severest pandemics in history. It is thought that the First World War much influenced the spread of the pandemic. In this paper, we model the pandemic considering both civil and military traffic. We propose a hybrid model to determine how the pandemic spread through the world. Our approach considers both the SEIR-based model for local areas and the network model for global connection between countries. First, we reproduce the situation in 12 countries. Then, we simulate another scenario: there was no military…
We model and forecast the early evolution of the COVID-19 pandemic in Brazil using Brazilian recent data from February 25, 2020 to March 30, 2020. This early period accounts for unawareness of the epidemiological characteristics of the disease in a new territory, sub-notification of the real numbers of infected people and the timely introduction of social distancing policies to flatten the spread of the disease. We use two variations of the SIR model and we include a parameter that comprises the effects of social distancing measures. Short and long term forecasts show that the social distancin…
A model of reactive social distancing in epidemics is proposed, in which the infection rate changes with the number infected. The final-size equation for the total number that the epidemic will infect can be derived analytically, as can the peak infection proportion. This model could assist planners during for example the COVID-19 pandemic.
The spread of COVID-19 during the initial phase of the first half of 2020 was curtailed to a larger or lesser extent through measures of social distancing imposed by most countries. In this work, we link directly, through machine learning techniques, infection data at a country level to a single number that signifies social distancing effectiveness. We assume that the standard SIR model gives a reasonable description of the dynamics of spreading, and thus the social distancing aspect can be modeled through time-dependent infection rates that are imposed externally. We use an exponential ansatz…
The COVID-19 pandemic has posed a policy making crisis where efforts to slow down or end the pandemic conflict with economic priorities. This paper provides mathematical analysis of optimal disease control policies with idealized compartmental models for disease propagation and simplistic models of social and economic costs. Two locally optimal control strategies are found and categorized as `suppression' and `mitigation' strategies. We analyze how these strategies change when we incorporate vaccination into the model and find a new optimal `delay-mitigation' strategy.
Cities become mission-critical zones during pandemics and it is vital to develop a better understanding of the factors that are associated with infection levels. The COVID-19 pandemic has impacted many cities severely; however, there is significant variance in its impact across cities. Pandemic infection levels are associated with inherent features of cities (e.g., population size, density, mobility patterns, socioeconomic condition, and health environment), which need to be better understood. Intuitively, the infection levels are expected to be higher in big urban agglomerations, but the meas…
Among the many aspects that characterize the COVID-19 pandemic, two seem particularly challenging to understand: (i) the great geographical differences in the degree of virus contagiousness and lethality which were found in the different phases of the epidemic progression, and (ii) the potential role of the infected people's blood type in both the virus infectivity and the progression of the disease. A recent hypothesis could shed some light on both aspects. Specifically, it has been proposed that in the subject-to-subject transfer SARS-CoV-2 conserves on its capsid the erythrocytes' antigens …
COVID-19 pandemic is one of the major disasters that humanity has ever faced. In this paper, we try to model the effect of vaccination in controlling the pandemic, particularly in context to the third wave which is predicted to hit globally. Here we have modified the SEIRD model by introducing a vaccination term. One of our main assumptions is that the infection rate (\b{eta}(t)) is oscillatory. This oscillatory nature has been discussed earlier in literature with reference to the seasonality of epidemics. However, in our case we invoke this nature of the infection rate (\b{eta}(t)) to model t…
Given a mathematical model quantifying the viral infection of pandemic influenza H1N1pdm09-H275 wild type (WT) and H1N1pdm09-H275Y mutant (MUT) strains, we describe a simple method of estimating the model's constant parameters using Monte Carlo methods. Monte Carlo parameter estimation methods present certain advantages over the bootstrapping methods previously used in such studies: the result comprises actual parameter distributions (posteriors) that can be used to compare different viral strains; the recovered parameter distributions offer an exact method to compute credible intervals (simil…
The slogan "nobody is safe until everybody is safe" is a dictum to raise awareness that in an interconnected world, pandemics such as COVID-19, require a global approach. Motivated by the ongoing COVID-19 pandemic, we model here the spread of a virus in interconnected communities and explore different vaccination scenarios, assuming that the efficacy of the vaccination wanes over time. We start with susceptible populations and consider a susceptible-vaccinated-infected-recovered model with unvaccinated ("Bronze"), moderately vaccinated ("Silver") and very well vaccinated ("Gold") communities, …
The new coronavirus known as COVID-19 is spread world-wide since December 2019. Without any vaccination or medicine, the means of controlling it are limited to quarantine and social distancing. Here we study the spatio-temporal propagation of the first wave of the COVID-19 virus in China and compare it to other global locations. We provide a comprehensive picture of the spatial propagation from Hubei to other provinces in China in terms of distance, population size, and human mobility and their scaling relations. Since strict quarantine has been usually applied between cities, more insight abo…
Countries highly exposed to incoming traffic from China were expected to be at the highest risk of COVID-19 spread. However, COVID-19 case numbers (infection levels) are negatively correlated with incoming traffic-level. Moreover, infection levels are positively correlated with population-size, while the latter should only affect infection-level once herd immunity is reached. These could be explained if a low-virulence strain (LVS) began spreading a few months earlier from China, providing immunity from the later emerging known SARS-CoV-2 high-virulence strain (HVS). We find that the dynamics …
University of Cambridge（剑桥大学）；UNC-Chapel Hill（北卡罗来纳大学教堂山分校）；UNC Gilling School of Global Public Health（北卡罗来纳大学吉林斯全球公共卫生学院）；Canadian Institute for Theoretical Astrophysics（加拿大理论天体物理研究所）；University of Toronto（多伦多大学）；Canadian Institute for Advanced Research（加拿大高等研究院）；California State University Fullerton（加州州立大学富勒顿分校）；Oberlin College（欧柏林学院）
We present a new mathematical model to explicitly capture the effects that the three restriction measures: the lockdown date and duration, social distancing and masks, and, schools and border closing, have in controlling the spread of COVID-19 infections $i(r, t)$. Before restrictions were introduced, the random spread of infections as described by the SEIR model grew exponentially. The addition of control measures introduces a mixing of order and disorder in the system's evolution which fall under a different mathematical class of models that can eventually lead to critical phenomena. A gener…
The COVID-19 pandemic has affected all countries of the world producing a substantial number of fatalities accompanied by a major disruption in their social, financial, and educational organization. The strict disciplinary measures implemented by China were very effective and thus were subsequently adopted by most world countries to various degrees. The infection duration and number of infected persons are of critical importance for the battle against the pandemic. We use the quantitative landscape of the disease spreading in China as a benchmark and utilize infection data from eight countries…
We show that the COVID-19 pandemic under social distancing exhibits universal dynamics. The cumulative numbers of both infections and deaths quickly cross over from exponential growth at early times to a longer period of power law growth, before eventually slowing. In agreement with a recent statistical forecasting model by the IHME, we show that this dynamics is well described by the erf function. Using this functional form, we perform a data collapse across countries and US states with very different population characteristics and social distancing policies, confirming the universal behavior…
Analyzing the SARS-CoV-2 pandemic outbreak based on actual data while reflecting the characteristics of the real city provides beneficial information for taking reasonable infection control measures in the future. We demonstrate agent-based modeling for Tokyo based on GPS information and official national statistics and perform a spatiotemporal analysis of the infection situation in Tokyo. As a result of the simulation during the first wave of SARS-CoV-2 in Tokyo using real GPS data, the infection occurred in the service industry, such as restaurants, in the city center, and then the infected …
Covid-19 is raging a devastating trail with the highest mortality-to-infected ratio ever for a pandemic. Lack of vaccine and therapeutic has rendered social exclusion through lockdown as the singular mode of containment. Harnessing the predictive powers of Machine Learning within a 6 dimensional infection kinetic model, depicting interactive evolution of 6 infection stages - healthy susceptible ($H$), predisposed comorbid susceptible ($P$), infected ($I$), recovered ($R$), herd immunized ($V$) and mortality ($D$) - the model, PHIRVD, provides the first accurate mortality prediction of 18 count…
Stanford University（斯坦福大学）；National University of Singapore（新加坡国立大学）；Imperial College London（帝国理工学院）
Since COVID-19 vaccines became available, no studies have quantified how different disaster evacuation strategies can mitigate pandemic risks in shelters. Therefore, we applied an age-structured epidemiological model, known as the Susceptible-Exposed-Infectious-Recovered (SEIR) model, to investigate to what extent different vaccine uptake levels and the Diversion protocol implemented in Taiwan decrease infections and delay pandemic peak occurrences. Taiwan's Diversion protocol involves diverting those in self-quarantine due to exposure, thus preventing them from mingling with the general publi…
