We consider the transmission dynamics of COVID-19 which is characterized by two distinct features. One is the existence of asymptomatic carriers which is a hidden variable in the problem. The other is the issue of latency which means that among the symptomatic carriers there could be a fraction whose symptoms develop after a couple of days. Our modelling is restricted to what we call the Phase -1 of the disease. During this phase the disease sets in and the number of infected people starts growing fast ( the number of new cases per day keeps growing on an average ) and then it slows down ( the number of new cases per day starts decreasing ) with the number of new cases decreasing to about one tenth of its peak value or even smaller). We define Phase-1 to be over when the daily cases start rising once again. We write down a Henon-like map to take various effects into account for this first phase.
According to the current perception, symptomatic, presymptomatic, and asymptomatic infectious persons can infect the healthy population susceptible to the SARS-Cov-2. More importantly, various reports indicate that the number of asymptomatic cases can be several-fold higher than the reported symptomatic cases. In this article, we take the reported cases in India and various states within the country till September 1, as the specimen to understand the progression of the COVID-19. Employing a modified SEIRD model, we predict the spread of COVID-19 by the symptomatic as well as asymptomatic infec…
What role do asymptomatically infected individuals play in the transmission dynamics? There are many diseases, such as norovirus and influenza, where some infected hosts show symptoms of the disease while others are asymptomatically infected, i.e. do not show any symptoms. The current paper considers a class of epidemic models following an SEIR (Susceptible $\to$ Exposed $\to$ Infectious $\to$ Recovered) structure that allows for both symptomatic and asymptomatic cases. The following question is addressed: what fraction $ρ$ of those individuals getting infected are infected by symptomatic (asy…
A mathematical model was developed describing the dynamic of the COVID-19 virus over a population considering that the infected can either be symptomatic or not. The model was calibrated using data on the confirmed cases and death from several countries like France, Philippines, Italy, Spain, United Kingdom, China, and the USA. First, we derived the basic reproduction number, $\mathcal{R}_0$, and estimated the effective reproduction $\mathcal{R}_{\rm eff}$ for each country. Second, we were interested in the merits of interventions, either by distancing or by treatment. Results revealed that to…
The aim of this study is to propose a modified Susceptible-Exposed-Infectious-Removed (SEIR) model that describes the behaviour of symptomatic, asymptomatic and hospitalized patients of COVID-19 epidemic, including the effect of demographic variation of population. It is shown that considering a population growth proportional to the total population leads to solutions with a qualitative behaviour different from the behaviour obtained in many studies, where constant growth ratio is assumed. An exhaustive theoretical study is carried out and the basic reproduction number $R_0$ is computed from t…
A significant proportion of the infections driving the current {SARS-CoV-2} pandemic are transmitted asymptomatically. Here we introduce and study a simple epidemic model with separate compartments comprising asymptomatic and symptomatic infected individuals. The linear dynamics determining the outbreak condition of the model is equivalent to a renewal theory approach with exponential waiting time distributions. Exploiting a nontrivial conservation law of the full nonlinear dynamics, we derive analytic bounds on the peak number of infections in the absence and presence of mitigation through is…
Testing for infection with SARS-CoV-2 is an important intervention in reducing onwards transmission of COVID-19, particularly when combined with the isolation and contact-tracing of positive cases. Many countries with the capacity to do so have made use of lab-processed Polymerase Chain Reaction (PCR) testing targeted at individuals with symptoms and the contacts of confirmed cases. Alternatively, Lateral Flow Tests (LFTs) are able to deliver a result quickly, without lab-processing and at a relatively low cost. Their adoption can support regular mass asymptomatic testing, allowing earlier det…
We measure the effect of different public health regulations to the spread of COVID-19, based on a SEIRA model -- a SEIR model including asymptomatic transmissions. The cumulative confirmed cases and death show nonlinear positive relationship with the value of asymptomatic rate. Based on this model, we analyze the inhibit effects to COVID-19 of three types of public health policies, i.e. isolation of laboratory confirmed cases, general personal protection and quarantine (lock-down). The simulations conclude that the isolation display limited effects to the asymptomatic viral carriers. The gene…
We present a compartmental SEIAR model of epidemic spread as a generalization of the SEIR model. We believe that the asymptomatic infectious cohort is an omitted part of the understanding of the epidemic dynamics of disease COVID-19. We introduce and derive the basic reproduction number as the weighted arithmetic mean of the basic reproduction numbers of the symptomatic and asymptomatic cohorts. Since the asymptomatic subjects people are not detected, they can spread the disease much longer, and this increases the COVID-19 $R_0$ up to around 9. We show that European epidemic outbreaks in vario…
There is increasing evidence that one of the most difficult problems in trying to control the ongoing COVID-19 epidemic is the presence of a large cohort of asymptomatic infectives. We develop a SIR-type model taking into account the presence of asymptomatic, or however undetected, infective, and the substantially long time these spend being infective and not isolated. We discuss how a SIR-based prediction of the epidemic course based on early data but not taking into account the presence of a large set of asymptomatic infectives would give wrong estimate of very relevant quantities such as th…
COVID-19--a viral infectious disease--has quickly emerged as a global pandemic infecting millions of people with a significant number of deaths across the globe. The symptoms of this disease vary widely. Depending on the symptoms an infected person is broadly classified into two categories namely, asymptomatic and symptomatic. Asymptomatic individuals display mild or no symptoms but continue to transmit the infection to otherwise healthy individuals. This particular aspect of asymptomatic infection poses a major obstacle in managing and controlling the transmission of the infectious disease. I…
In this paper, we develop an extension of standard epidemiological models, suitable for COVID-19. This extension incorporates the transmission due to pre-symptomatic or asymptomatic carriers of the virus. Furthermore, this model also captures the spread of the disease due to the movement of people to/from different administrative boundaries within a country. The model describes the probabilistic rise in the number of confirmed cases due to the concomitant effects of (incipient) human transmission and multiple compartments. The associated parameters in the model can help architect the public he…
A quantitative COVID-19 model that incorporates hidden asymptomatic patients is developed, and an analytic solution in parametric form is given. The model incorporates the impact of lockdown and resulting spatial migration of population due to announcement of lockdown. A method is presented for estimating the model parameters from real-world data. It is shown that increase of infections slows down and herd immunity is achieved when symptomatic patients are 4-6\% of the population for the European countries we studied, when the total infected fraction is between 50-56 \%. Finally, a method for …
Macroscopic growth laws, solutions of mean field equations, describe in an effective way an underlying complex dynamics. They are applied to study the spreading of infections, as in the case of CoviD-19, where the counting of the cumulated number $N(t)$ of detected infected individuals is a generally accepted, coarse-grain, variable to understand the epidemic phase. However $N(t)$ does not take into account the unknown number of asymptomatic, not detected, cases $A(t)$. Therefore, the question arises if the observed time series of data of $N(t)$ is a reliable tool for monitoring the evolution …
Studies on how to model the interplay between diseases and behavioral responses (so-called coupled disease-behavior interaction) have attracted increasing attention. Owing to the lack of obvious clinical evidence of diseases, or the incomplete information related to the disease, the risks of infection cannot be perceived and may lead to inappropriate behavioral responses. Therefore, how to quantitatively analyze the impacts of asymptomatic infection on the interplay between diseases and behavioral responses is of particular importance. In this Letter, under the complex network framework, we st…
Clostridium difficile infections (CDIs) affect patients in hospitals and in the community, but the relative importance of transmission in each setting is unknown. We developed a mathematical model of C. difficile transmission in a hospital and surrounding community that included infants, adults, and transmission from animal reservoirs. We assessed the role of these transmission routes in maintaining disease and evaluated the recommended classification system for hospital and community-acquired CDIs. The reproduction number in the hospital was <1 (range: 0.16-0.46) for all scenarios. Outside th…
The movie Ben-Hur highlights the dynamics of contagion associated with leprosy, a pattern of forced aggregation driven by the emergence of symptoms and the fear of contagion. The 2014 Ebola outbreaks reaffirmed the dynamics of redistribution among symptomatic and asymptomatic or non-infected individuals as a way to avoid contagion. In this manuscript, we explore the establishment of clusters of infection via density-dependence avoidance (diffusive instability). We illustrate this possibility in two ways: using a phenomenological driven model where disease incidence is assumed to be a decreasin…
The infection fatality rate (IFR) of COVID-19 is one of the measures of disease impact that can be of importance for policy making. Here we show that many of the studies on which these estimates are based are scientifically flawed for reasons which include: nonsensical equations, unjustified assumptions, small sample sizes, non-representative sampling (systematic biases), incorrect definitions of symptomatic and asymptomatic cases (identified and unidentified cases), typically assuming that cases which are asymptomatic at the time of testing are the same as completely asymptomatic (never sympt…
The COVID-19 epidemic has been spreading around the world for nearly three years, and asymptomatic infections have exacerbated the spread of the epidemic. To evaluate the role of asymptomatic infections in the spread of the epidemic, we develop mathematical models to assess the proportion of asymptomatic infections caused by different strains of the main covid-19 variants. The analysis shows that when the control reproduction number is less than 1, the disease-free equilibrium point of the model is globally asymptotically stable; and when the control reproduction number is greater than 1, the …
Dengue control in India is a challenging task due to complex healthcare settings. In yesteryears, an amplification of dengue infections in India posed the need for introspection of existing dengue control policies. Prior understanding of the impacts of control interventions is necessary for their future implementation. In this paper, we propose and analyze a compartmental model of dengue to assess the impact of active case finding (ACF) on dengue disease transmission. Currently, primary prevention of dengue is possible only with vector control and personal protection from the bites of infected…
Asymptomatic individuals in the context of malarial disease refers to subjects who carry a parasite load but do not show clinical symptoms. A correct understanding of the influence of asymptomatic individuals on transmission dynamics will provide a comprehensive description of the complex interplay between the definitive host (female \textit{Anopheles} mosquito), intermediate host (human) and agent (\textit{Plasmodium} parasite). The goal of this article is to conduct a rigorous mathematical analysis of a new compartmentalized malaria model accounting for asymptomatic human hosts for the purpo…
The detection and management of diseases become quite complicated when pathogens contain asymptomatic phenotypes amongst their ranks, as evident during the recent COVID-19 pandemic. Spreading of diseases has been studied extensively under the paradigm of Susceptible - Infected - Recovered - Deceased (SIRD) dynamics. Various game-theoretic approaches have also addressed disease spread, many of which consider S, I, R, and D as strategies rather than as states. Remarkably, most studies from the above approaches do not account for the distinction between the symptomatic or asymptomatic aspect of t…
We introduce an extended SEIR infectious disease model with data assimilation for the study of the spread of COVID-19. In this framework, undetected asymptomatic and pre-symptomatic cases are taken into account, and the impact of their uncertain proportion is fully investigated. The standard SEIR model does not consider these populations, while their role in the propagation of the disease is acknowledged. An ensemble Kalman filter is implemented to assimilate reliable observations of three compartments in the model. The system tracks the evolution of the effective reproduction number and estim…
A multi-scale immuno-epidemiological behavioral model for influenza-like illness: connecting scales through symptom scores
Mississippi State University（密西西比州立大学）；The University of Alabama in Huntsville（阿拉巴马大学亨茨维尔分校）；Florida Atlantic University（佛罗里达大西洋大学）；Texas Christian University（德克萨斯基督教大学）
We examine the spatial modeling of the outbreak of COVID-19 in two regions: the autonomous community of Andalusia in Spain and the mainland of Greece. We start with a 0D compartmental epidemiological model consisting of Susceptible, Exposed, Asymptomatic, (symptomatically) Infected, Hospitalized, Recovered, and deceased populations. We emphasize the importance of the viral latent period and the key role of an asymptomatic population. We optimize model parameters for both regions by comparing predictions to the cumulative number of infected and total number of deaths via minimizing the $\ell^2$…
The presence of a large number of infected individuals with few or no symptoms is an important epidemiological difficulty and the main mathematical feature of COVID-19. The A-SIR model, i.e. a SIR (Susceptible-Infected-Removed) model with a compartment for infected individuals with no symptoms or few symptoms was proposed by Giuseppe Gaeta, arXiv:2003.08720 [q-bio.PE] (2020). In this paper we investigate a slightly generalized version of the same model and propose a scheme for fitting the parameters of the model to real data using the time series only of the deceased individuals. The scheme is…
In India the COVID-19 infected population has not yet been accurately established. As always in the early stages of any epidemic, the need to test serious cases first has meant that the population with asymptomatic or mild sub-clinical symptoms has not yet been analyzed. Using counts of fatalities, and previously estimated parameters for the progress of the disease, we give statistical estimates of the infected population. The doubling time is a crucial unknown input parameter which affects these estimates, and may differ strongly from one geographical location to another. We suggest a method …
We study Susceptible-Exposed-Asymptomatic-Infectious-Recovered (SEAIR) epidemic spreading model of COVID-19. It captures two important characteristics of the infectiousness of COVID-19: delayed start and its appearance before onset of symptoms, or even with total absence of them. The model is theoretically analyzed in continuous-time compartmental version and discrete-time version on random regular graphs and complex networks. We show analytically that there are relationships between the epidemic thresholds and the equations for the susceptible populations at the endemic equilibrium in all thr…
Within a short period of time, COVID-19 grew into a world-wide pandemic. Transmission by pre-symptomatic and asymptomatic viral carriers rendered intervention and containment of the disease extremely challenging. Based on reported infection case studies, we construct an epidemiological model that focuses on transmission around the symptom onset. The model is calibrated against incubation period and pairwise transmission statistics during the initial outbreaks of the pandemic outside Wuhan with minimal non-pharmaceutical interventions. Mathematical treatment of the model yields explicit express…
We develop a variable population age-structured ODE model to investigate the role of Intermittent Preventive Treatment (IPT) in averting malaria-induced mortalities in children, as well as its related cost in promoting the spread of anti-malarial drug resistance. IPT, a malaria control strategy in which a full curative dose of an antimalarial medication is administered to vulnerable asymptomatic individuals at specified intervals, has been shown to have a positive impact on reducing malaria transmission and deaths in children and pregnant women. However, it can also promote drug resistance spr…
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…
In the night of February 20, 2020, the first case of novel coronavirus disease (COVID-19) was confirmed in the Lombardy Region, Italy. In the week that followed, Lombardy experienced a very rapid increase in the number of cases. We analyzed the first 5,830 laboratory-confirmed cases to provide the first epidemiological characterization of a COVID-19 outbreak in a Western Country. Epidemiological data were collected through standardized interviews of confirmed cases and their close contacts. We collected demographic backgrounds, dates of symptom onset, clinical features, respiratory tract speci…
We present a System Dynamics (SD) model of the Covid-19 pandemic spread in India. The detailed age-structured compartment-based model endogenously captures various disease transmission pathways, expanding significantly from the standard SEIR model. The model is customized for India by using the appropriate population pyramid, contact rate matrices, external arrivals (as per actual data), and a few other calibrated fractions based on the reported cases of Covid-19 in India. Also, we have explicitly modeled, using independent time-variant levers, the effects of testing, contact tracing, isolatin…
In this study, we address three important challenges related to disease transmissions such as the COVID-19 pandemic, namely, (a) providing an early warning to likely exposed individuals, (b) identifying individuals who are asymptomatic, and (c) prescription of optimal testing when testing capacity is limited. First, we present a dynamic-graph based SEIR epidemiological model in order to describe the dynamics of the disease propagation. Our model considers a dynamic network that accounts for the interactions between individuals over time, such as the ones obtained by manual or automated contact…
Solid estimates describing the clinical course of SARS-CoV-2 infections are still lacking due to under-ascertainment of asymptomatic and mild-disease cases. In this work, we quantify age-specific probabilities of transitions between stages defining the natural history of SARS-CoV-2 infection from 1,965 SARS-CoV-2 positive individuals identified in Italy between March and April 2020 among contacts of confirmed cases. Infected contacts of cases were confirmed via RT-PCR tests as part of contact tracing activities or retrospectively via IgG serological tests and followed-up for symptoms and clini…
The recent outbreak of COVID-19 in Mainland China is characterized by a distinctive algebraic, sub-exponential increase of confirmed cases during the early phase of the epidemic, contrasting an initial exponential growth expected for an unconstrained outbreak with sufficiently large reproduction rate. Although case counts vary significantly between affected provinces in Mainland China, the scaling law $t^μ$ is surprisingly universal, with a range of exponents $μ=2.1\pm0.3$. The universality of this behavior indicates that despite social, regional, demographical, geographical, and socio-economi…
To increase situational awareness and support evidence-based policy-making, we formulated two types of mathematical models for COVID-19 transmission within a regional population. One is a fitting function that can be calibrated to reproduce an epidemic curve with two timescales (e.g., fast growth and slow decay). The other is a compartmental model that accounts for quarantine, self-isolation, social distancing, a non-exponentially distributed incubation period, asymptomatic individuals, and mild and severe forms of symptomatic disease. Using Bayesian inference, we have been calibrating our mod…
In this article, we investigate the importance of demographic and contact patterns in determining the spread of COVID-19 and to the effectiveness of social distancing policies. We investigate these questions proposing an augmented epidemiological model with an age-structured model, with the population divided into susceptible (S), exposed (E), infected and asymptomatic (A), hospitalized (H), infected and symptomatic (I), and recovered individuals (R), to simulate COVID-19 dissemination. The simulations were carried out using six combinations of four types of isolation policies (work restrictio…
In this article, we consider a dynamic epidemiology model for the spread of the COVID-19 infection. Starting from the classical SEIR model, the model is modified so as to better describe characteristic features of the underlying pathogen and its infectious modes. In line with the large number of secondary infections not related to contact with documented infectious individuals, the model includes a cohort of asymptomatic or oligosymptomatic infectious individuals, not accounted for in the data of new daily counts of infections. A Bayesian particle filtering algorithm is used to update dynamica…
We introduce a system of differential equations to assess the impact of (self-)quarantine of symptomatic infectious individuals on disease dynamics. To this end we depart from using the classic bilinear infection process, but remain still within the framework of the mass-action assumption. From the mathematical point of view our model is interesting due to the lack of continuous differentiability at disease free steady states, which implies also that the basic reproductive number cannot be computed following established approaches for certain parameter values. However, we parametrise our mathe…
We propose a time-fractional compartmental model (SEI$_A$I$_S$HRD) comprising of the susceptible, exposed, infected (asymptomatic and symptomatic), hospitalized, recovered and dead population for the Covid-19 pandemic. We study the properties and dynamics of the proposed model. The conditions under which the disease-free and endemic equilibrium points are asymptotically stable are discussed. Furthermore, we study the sensitivity of the parameters and use the data from Tennessee state (as a case study) to discuss identifiability of the parameters of the model. The non-negative parameters in the…
We demonstrate the ability of statistical data assimilation to identify the measurements required for accurate state and parameter estimation in an epidemiological model for the novel coronavirus disease COVID-19. Our context is an effort to inform policy regarding social behavior, to mitigate strain on hospital capacity. The model unknowns are taken to be: the time-varying transmission rate, the fraction of exposed cases that require hospitalization, and the time-varying detection probabilities of new asymptomatic and symptomatic cases. In simulations, we obtain accurate estimates of undetect…
The COVID-19 epidemic is the last of a long list of pandemics that have affected humankind in the last century. In this paper, we propose a novel mathematical epidemiological model named SUIHTER from the names of the seven compartments that it comprises: susceptible uninfected individuals (S), undetected (both asymptomatic and symptomatic) infected (U), isolated (I), hospitalized (H), threatened (T), extinct (E), and recovered (R). A suitable parameter calibration that is based on the combined use of least squares method and Markov Chain Monte Carlo (MCMC) method is proposed with the aim of re…
During the current Covid-19 pandemic in Italy, official data are collected with medical swabs following a pure convenience criterion which, at least in an early phase, has privileged the exam of patients showing evident symptoms. However, there are evidences of a very high proportion of asymptomatic patients (e. g. Aguilar et al., 2020; Chugthai et al, 2020; Li, et al., 2020; Mizumoto et al., 2020a, 2020b and Yelin et al., 2020). In this situation, in order to estimate the real number of infected (and to estimate the lethality rate), it should be necessary to run a properly designed sample sur…
Imported COVID-19 cases, if unchecked, can jeopardize the effort of domestic containment. We aim to find out what sustainable border control options for different entities (e.g., countries, states) exist during the reopening phases, given their own choice of domestic control measures and new technologies such as contact tracing. We propose a SUIHR model, which represents an extension to the discrete time SIR models. The model focuses on studying the spreading of virus predominantly by asymptomatic and pre-symptomatic patients. Imported risk and (1-tier) contact tracing are both built into the …
The COVID-19 pandemic has caused major disturbance to human life. An important reason behind the widespread social anxiety is the huge uncertainty about the pandemic. A fundamental uncertainty is how many or what percentage of people have been infected. There are published and frequently updated data on various statistics of the pandemic, at local, country or global level. However, due to various reasons, many cases were not included in those reported numbers. We propose a structured approach for the estimation of the number of unreported cases, where we distinguish cases that arrive late in t…
In an earlier paper we proposed a recursive model for epidemics; in the present paper we generalize this model to include the asymptomatic or unrecorded symptomatic people, which we call {\em dark people} (dark sector). We call this the SEPAR$_d$-model. A delay differential equation version of the model is added; it allows a better comparison to other models. We carry this out by a comparison with the classical SIR model and indicate why we believe that the SEPAR$_d$ model may work better for Covid-19 than other approaches. In the second part of the paper we explain how to deal with the data p…
The quarantine of identified close contacts has been vital to reducing transmission rates and averting secondary infection risk before symptom onset and by asymptomatic cases. The effectiveness of this contact tracing strategy to mitigate transmission is sensitive to the adherence to quarantines, which may be lower for longer quarantine periods or in vaccinated populations (where perceptions of risk are reduced). This study develops a simulation model to evaluate contact tracing strategies based on the sequential testing of identified contacts after exposure as an alternative to quarantines, i…
Risk mapping for COVID-19 outbreaks in Australia using mobility data
The University of Melbourne（墨尔本大学）；The University of Adelaide（阿德莱德大学）；Victorian Department of Health and Human Services, Government of Victoria（维多利亚州卫生与人类服务部）；Department of Infectious Diseases, The Alfred and Central Clinical School, Monash University（蒙纳士大学阿尔弗雷德医院与中央临床学院传染病系）；University of New South Wales（新南威尔士大学）；Melbourne School of Engineering（墨尔本工程学院）；The Peter Doherty Institute for Infection and Immunity, The Royal Melbourne Hospital and The University of Melbourne（彼得·多赫蒂感染与免疫研究所、皇家墨尔本医院和墨尔本大学）
