Forecasting Hepatitis C Virus Status for Children in the United States: A Modeling Study.

BACKGROUND: Virtually all cases of hepatitis C virus (HCV) infection in children in the United States occur through vertical transmission, but it is unknown how many children are infected. Cases of maternal HCV infection have increased in the United States, which may increase the number of children vertically infected with HCV. Infection has long-term consequences for a child's health, but treatment options are now available for children ≥3 years old. Reducing HCV infections in adults could decrease HCV infections in children. METHODS: Using a stochastic compartmental model, we forecasted incidence of HCV infections in children in the United States from 2022 through 2027. The model considered vertical transmission to children <13 years old and horizontal transmission among individuals 13-49 years old. We obtained model parameters and initial conditions from the literature and the Centers for Disease Control and Prevention's 2021 Viral Hepatitis Surveillance Report. RESULTS: Model simulations assuming direct-acting antiviral treatment for children forecasted that the number of acutely infected children would decrease slightly and the number of chronically infected children would decrease even more. Alone, treatment and early screening in individuals 13-49 years old reduced the number of forecasted cases in children and, together, these policy interventions were even more effective. CONCLUSIONS: Based on our simulations, acute and chronic cases of HCV infection are remaining constant or slightly decreasing in the United States. Improving early screening and increasing access to treatment in adults may be an effective strategy for reducing the number of HCV infected children in the United States.

A voltage-based Event-Timing-Dependent Plasticity rule accounts for LTP subthreshold and suprathreshold for dendritic spikes in CA1 pyramidal neurons.

Long-term potentiation (LTP) is a synaptic mechanism involved in learning and memory. Experiments have shown that dendritic sodium spikes (Na-dSpikes) are required for LTP in the distal apical dendrites of CA1 pyramidal cells. On the other hand, LTP in perisomatic dendrites can be induced by synaptic input patterns that can be both subthreshold and suprathreshold for Na-dSpikes. It is unclear whether these results can be explained by one unifying plasticity mechanism. Here, we show in biophysically and morphologically realistic compartmental models of the CA1 pyramidal cell that these forms of LTP can be fully accounted for by a simple plasticity rule. We call it the voltage-based Event-Timing-Dependent Plasticity (ETDP) rule. The presynaptic event is the presynaptic spike or release of glutamate. The postsynaptic event is the local depolarization that exceeds a certain plasticity threshold. Our model reproduced the experimentally observed LTP in a variety of protocols, including local pharmacological inhibition of dendritic spikes by tetrodotoxin (TTX). In summary, we have provided a validation of the voltage-based ETDP, suggesting that this simple plasticity rule can be used to model even complex spatiotemporal patterns of long-term synaptic plasticity in neuronal dendrites.

Predicting Drug-Drug Interactions Involving Rifampicin Using a Semi-mechanistic Hepatic Compartmental Model.

AIMS: To develop a semi-mechanistic hepatic compartmental model to predict the effects of rifampicin, a known inducer of CYP3A4 enzyme, on the metabolism of five drugs, in the hope of informing dose adjustments to avoid potential drug-drug interactions. METHODS: A search was conducted for DDI studies on the interactions between rifampicin and CYP substrates that met specific criteria, including the availability of plasma concentration-time profiles, physical and absorption parameters, pharmacokinetic parameters, and the use of healthy subjects at therapeutic doses. The semi-mechanistic model utilized in this study was improved from its predecessors, incorporating additional parameters such as population data (specifically for Chinese and Caucasians), virtual individuals, gender distribution, age range, dosing time points, and coefficients of variation. RESULTS: Optimal parameters were identified for our semi-mechanistic model by validating it with clinical data, resulting in a maximum difference of approximately 2-fold between simulated and observed values. PK data of healthy subjects were used for most CYP3A4 substrates, except for gilteritinib, which showed no significant difference between patients and healthy subjects. Dose adjustment of gilteritinib co-administered with rifampicin required a 3-fold increase of the initial dose, while other substrates were further tuned to achieve the desired drug exposure. CONCLUSIONS: The pharmacokinetic parameters AUCR and CmaxR of drugs metabolized by CYP3A4, when influenced by Rifampicin, were predicted by the semi-mechanistic model to be approximately twice the empirically observed values, which suggests that the semi-mechanistic model was able to reasonably simulate the effect. The doses of four drugs adjusted via simulation to reduce rifampicin interaction.

Distribution Clearance: Significance and Underlying Mechanisms.

PURPOSE: Evaluation of distribution kinetics is a neglected aspect of pharmacokinetics. This study examines the utility of the model-independent parameter whole body distribution clearance (CLD) in this respect. METHODS: Since mammillary compartmental models are widely used, CLD was calculated in terms of parameters of this model for 15 drugs. The underlying distribution processes were explored by assessment of relationships to pharmacokinetic parameters and covariates. RESULTS: The model-independence of the definition of the parameter CLD allowed a comparison of distributional properties of different drugs and provided physiological insight. Significant changes in CLD were observed as a result of drug-drug interactions, transporter polymorphisms and a diseased state. CONCLUSION: Total distribution clearance CLD is a useful parameter to evaluate distribution kinetics of drugs. Its estimation as an adjunct to the model-independent parameters clearance and steady-state volume of distribution is advocated.

The influence of gender and temephos exposure on community participation in dengue prevention: a compartmental mathematical model.

BACKGROUND: The use of temephos, the most common intervention for the chemical control of Aedes aegypti over the last half century, has disappointing results in control of the infection. The footprint of Aedes and the diseases it carries have spread relentlessly despite massive volumes of temephos. Recent advances in community participation show this might be more effective and sustainable for the control of the dengue vector. METHODS: Using data from the Camino Verde cluster randomized controlled trial, a compartmental mathematical model examines the dynamics of dengue infection with different levels of community participation, taking account of gender of respondent and exposure to temephos. RESULTS: Simulation of dengue endemicity showed community participation affected the basic reproductive number of infected people. The greatest short-term effect, in terms of people infected with the virus, was the combination of temephos intervention and community participation. There was no evidence of a protective effect of temephos 220 days after the onset of the spread of dengue. CONCLUSIONS: Male responses about community participation did not significantly affect modelled numbers of infected people and infectious mosquitoes. Our model suggests that, in the long term, community participation alone may have the best results. Adding temephos to community participation does not improve the effect of community participation alone.

Modelling respiratory syncytial virus age-specific risk of hospitalisation in term and preterm infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections in children worldwide. The highest incidence of severe disease is in the first 6 months of life, with infants born preterm at greatest risk for severe RSV infections. The licensure of new RSV therapeutics (a long-acting monoclonal antibody and a maternal vaccine) in Europe, USA, UK and most recently in Australia, has driven the need for strategic decision making on the implementation of RSV immunisation programs. Data driven approaches, considering the local RSV epidemiology, are critical to advise on the optimal use of these therapeutics for effective RSV control. METHODS: We developed a dynamic compartmental model of RSV transmission fitted to individually-linked population-based laboratory, perinatal and hospitalisation data for 2000-2012 from metropolitan Western Australia (WA), stratified by age and prior exposure. We account for the differential risk of RSV-hospitalisation in full-term and preterm infants (defined as < 37 weeks gestation). We formulated a function relating age, RSV exposure history, and preterm status to the risk of RSV-hospitalisation given infection. RESULTS: The age-to-risk function shows that risk of hospitalisation, given RSV infection, declines quickly in the first 12 months of life for all infants and is 2.6 times higher in preterm compared with term infants. The hospitalisation risk, given infection, declines to < 10% of the risk at birth by age 7 months for term infants and by 9 months for preterm infants. CONCLUSIONS: The dynamic model, using the age-to-risk function, characterises RSV epidemiology for metropolitan WA and can now be extended to predict the impact of prevention measures. The stratification of the model by preterm status will enable the comparative assessment of potential strategies in the extended model that target this RSV risk group relative to all-population approaches. Furthermore, the age-to-risk function developed in this work has wider relevance to the epidemiological characterisation of RSV.

Nonlinear compartmental modeling to monitor ovarian follicle population dynamics on the whole lifespan.

In this work, we introduce a compartmental model of ovarian follicle development all along lifespan, based on ordinary differential equations. The model predicts the changes in the follicle numbers in different maturation stages with aging. Ovarian follicles may either move forward to the next compartment (unidirectional migration) or degenerate and disappear (death). The migration from the first follicle compartment corresponds to the activation of quiescent follicles, which is responsible for the progressive exhaustion of the follicle reserve (ovarian aging) until cessation of reproductive activity. The model consists of a data-driven layer embedded into a more comprehensive, knowledge-driven layer encompassing the earliest events in follicle development. The data-driven layer is designed according to the most densely sampled experimental dataset available on follicle numbers in the mouse. Its salient feature is the nonlinear formulation of the activation rate, whose formulation includes a feedback term from growing follicles. The knowledge-based, coating layer accounts for cutting-edge studies on the initiation of follicle development around birth. Its salient feature is the co-existence of two follicle subpopulations of different embryonic origins. We then setup a complete estimation strategy, including the study of structural identifiability, the elaboration of a relevant optimization criterion combining different sources of data (the initial dataset on follicle numbers, together with data in conditions of perturbed activation, and data discriminating the subpopulations) with appropriate error models, and a model selection step. We finally illustrate the model potential for experimental design (suggestion of targeted new data acquisition) and in silico experiments.

Exploring the dynamics of the 2022 mpox outbreak in Canada.

The 2022 mpox outbreak predominantly impacted gay, bisexual, and other men who have sex with men (gbMSM). Two models were developed to support situational awareness and management decisions in Canada. A compartmental model characterized epidemic drivers at national/provincial levels, while an agent-based model (ABM) assessed municipal-level impacts of vaccination. The models were parameterized and calibrated using empirical case and vaccination data between 2022 and 2023. The compartmental model explored: (1) the epidemic trajectory through community transmission, (2) the potential for transmission among non-gbMSM, and (3) impacts of vaccination and the proportion of gbMSM contributing to disease transmission. The ABM incorporated sexual-contact data and modeled: (1) effects of vaccine uptake on disease dynamics, and (2) impacts of case importation on outbreak resurgence. The calibrated, compartmental model followed the trajectory of the epidemic, which peaked in July 2022, and died out in December 2022. Most cases occurred among gbMSM, and epidemic trajectories were not consistent with sustained transmission among non-gbMSM. The ABM suggested that unprioritized vaccination strategies could increase the outbreak size by 47%, and that consistent importation (≥5 cases per 10 000) is necessary for outbreak resurgence. These models can inform time-sensitive situational awareness and policy decisions for similar future outbreaks.

An individual level infectious disease model in the presence of uncertainty from multiple, imperfect diagnostic tests.

Bayesian compartmental infectious disease models yield important inference on disease transmission by appropriately accounting for the dynamics and uncertainty of infection processes. In addition to estimating transition probabilities and reproductive numbers, these statistical models allow researchers to assess the probability of disease risk and quantify the effectiveness of interventions. These infectious disease models rely on data collected from all individuals classified as positive based on various diagnostic tests. In infectious disease testing, however, such procedures produce both false-positives and false-negatives at varying rates depending on the sensitivity and specificity of the diagnostic tests being used. We propose a novel Bayesian spatio-temporal infectious disease modeling framework that accounts for the additional uncertainty in the diagnostic testing and classification process that provides estimates of the important transmission dynamics of interest to researchers. The method is applied to data on the 2006 mumps epidemic in Iowa, in which over 6,000 suspected mumps cases were tested using a buccal or oral swab specimen, a urine specimen, and/or a blood specimen. Although all procedures are believed to have high specificities, the sensitivities can be low and vary depending on the timing of the test as well as the vaccination status of the individual being tested.

Explaining transmission rate variations and forecasting epidemic spread in multiple regions with a semiparametric mixed effects SIR model.

The transmission rate is a central parameter in mathematical models of infectious disease. Its pivotal role in outbreak dynamics makes estimating the current transmission rate and uncovering its dependence on relevant covariates a core challenge in epidemiological research as well as public health policy evaluation. Here, we develop a method for flexibly inferring a time-varying transmission rate parameter, modeled as a function of covariates and a smooth Gaussian process (GP). The transmission rate model is further embedded in a hierarchy to allow information borrowing across parallel streams of regional incidence data. Crucially, the method makes use of optional vaccination data as a first step toward modeling of endemic infectious diseases. Computational techniques borrowed from the Bayesian spatial analysis literature enable fast and reliable posterior computation. Simulation studies reveal that the method recovers true covariate effects at nominal coverage levels. We analyze data from the COVID-19 pandemic and validate forecast intervals on held-out data. User-friendly software is provided to enable practitioners to easily deploy the method in public health research.

Epidemic Management via Imperfect Testing: A Multi-criterial Perspective.

Diagnostic testing may represent a key component in response to an ongoing epidemic, especially if coupled with containment measures, such as mandatory self-isolation, aimed to prevent infectious individuals from furthering onward transmission while allowing non-infected individuals to go about their lives. However, by its own nature as an imperfect binary classifier, testing can produce false negative or false positive results. Both types of misclassification are problematic: while the former may exacerbate the spread of disease, the latter may result in unnecessary isolation mandates and socioeconomic burden. As clearly shown by the COVID-19 pandemic, achieving adequate protection for both people and society is a crucial, yet highly challenging task that needs to be addressed in managing large-scale epidemic transmission. To explore the trade-offs imposed by diagnostic testing and mandatory isolation as tools for epidemic containment, here we present an extension of the classical Susceptible-Infected-Recovered model that accounts for an additional stratification of the population based on the results of diagnostic testing. We show that, under suitable epidemiological conditions, a careful assessment of testing and isolation protocols can contribute to epidemic containment, even in the presence of false negative/positive results. Also, using a multi-criterial framework, we identify simple, yet Pareto-efficient testing and isolation scenarios that can minimize case count, isolation time, or seek a trade-off solution for these often contrasting epidemic management objectives.

Quantitative Assessment of a Dual Epidemic Caused by Tuberculosis and HIV in the Philippines.

Tuberculosis (TB) and human immunodeficiency virus (HIV) are the two major public health emergencies in the Philippines. The country is ranked fourth worldwide in TB incidence cases despite national efforts and initiatives to mitigate the disease. Concurrently, the Philippines has the fastest-growing HIV epidemic in Asia and the Pacific region. The TB-HIV dual epidemic forms a lethal combination enhancing each other's progress, driving the deterioration of immune responses. In order to understand and describe the transmission dynamics and epidemiological patterns of the co-infection, a compartmental model for TB-HIV is developed. A class of people living with HIV (PLHIV) who did not know their HIV status is incorporated into the model. These unaware PLHIV who do not seek medical treatment are potential sources of new HIV infections that could significantly influence the disease transmission dynamics. Sensitivity analysis using the partial rank correlation coefficient is performed to assess model parameters that are influential to the output of interests. The model is calibrated using available Philippine data on TB, HIV, and TB-HIV. Parameters that are identified include TB and HIV transmission rates, progression rates from exposed to active TB, and from TB-latent with HIV to active infectious TB with HIV in the AIDS stage. Uncertainty analysis is performed to identify the degree of accuracy of the estimates. Simulations predict an alarming increase of 180% and 194% in new HIV and TB-HIV infections in 2025, respectively, relative to 2019 data. These projections underscore an ongoing health crisis in the Philippines that calls for a combined and collective effort by the government and the public to take action against the lethal combination of TB and HIV.

Effective population size in simple infectious disease models.

Almost all models used in analysis of infectious disease outbreaks contain some notion of population size, usually taken as the census population size of the community in question. In many settings, however, the census population is not equivalent to the population likely to be exposed, for example if there are population structures, outbreak controls or other heterogeneities. Although these factors may be taken into account in the model: adding compartments to a compartmental model, variable mixing rates and so on, this makes fitting more challenging, especially if the population complexities are not fully known. In this work we consider the concept of effective population size in outbreak modelling, which we define as the size of the population involved in an outbreak, as an alternative to use of more complex models. Effective population size is an important quantity in genetics for estimation of genetic diversity loss in populations, but it has not been widely applied in epidemiology. Through simulation studies and application to data from outbreaks of COVID-19 in China, we find that simple SIR models with effective population size can provide a good fit to data which are not themselves simple or SIR.

Dynamic Modeling of Carbon Dioxide Transport through the Skin Using a Capnometry Wristband.

The development of a capnometry wristband is of great interest for monitoring patients at home. We consider a new architecture in which a non-dispersive infrared (NDIR) optical measurement is located close to the skin surface and is combined with an open chamber principle with a continuous circulation of air flow in the collection cell. We propose a model for the temporal dynamics of the carbon dioxide exchange between the blood and the gas channel inside the device. The transport of carbon dioxide is modeled by convection-diffusion equations. We consider four compartments: blood, skin, the measurement cell and the collection cell. We introduce the state-space equations and the associated transition matrix associated with a Markovian model. We define an augmented system by combining a first-order autoregressive model describing the supply of carbon dioxide concentration in the blood compartment and its inertial resistance to change. We propose to use a Kalman filter to estimate the carbon dioxide concentration in the blood vessels recursively over time and thus monitor arterial carbon dioxide blood pressure in real time. Four performance factors with respect to the dynamic quantification of the CO2 blood concentration are considered, and a simulation is carried out based on data from a previous clinical study. These demonstrate the feasibility of such a technological concept.

Incorporating infectious duration-dependent transmission into Bayesian epidemic models.

Compartmental models are commonly used to describe the spread of infectious diseases by estimating the probabilities of transitions between important disease states. A significant challenge in fitting Bayesian compartmental models lies in the need to estimate the duration of the infectious period, based on limited data providing only symptom onset date or another proxy for the start of infectiousness. Commonly, the exponential distribution is used to describe the infectious duration, an overly simplistic approach, which is not biologically plausible. More flexible distributions can be used, but parameter identifiability and computational cost can worsen for moderately sized or large epidemics. In this article, we present a novel approach, which considers a curve of transmissibility over a fixed infectious duration. The incorporation of infectious duration-dependent (IDD) transmissibility, which decays to zero during the infectious period, is biologically reasonable for many viral infections and fixing the length of the infectious period eases computational complexity in model fitting. Through simulation, we evaluate different functional forms of IDD transmissibility curves and show that the proposed approach offers improved estimation of the time-varying reproductive number. We illustrate the benefit of our approach through a new analysis of the 1995 outbreak of Ebola Virus Disease in the Democratic Republic of the Congo.

A Stochastic Mobility-Driven Spatially Explicit SEIQRD covid-19 Model with VOCs, Seasonality, and Vaccines.

In this work, we extend our previously developed compartmental SEIQRD model for sars-cov-2 in Belgium. We introduce sars-cov-2 variants of concern, vaccines, and seasonality in our model, as their addition has proven necessary for modelling sars-cov-2 transmission dynamics during the 2020-2021 covid-19 pandemic in Belgium. The model is geographically stratified into eleven spatial patches (provinces), and a telecommunication dataset provided by Belgium's biggest operator is used to incorporate interprovincial mobility. We calibrate the model using the daily number of hospitalisations in each province and serological data. We find the model adequately describes these data, but the addition of interprovincial mobility was not necessary to obtain an accurate description of the 2020-2021 sars-cov-2 pandemic in Belgium. We further demonstrate how our model can be used to help policymakers decide on the optimal timing of the release of social restrictions.We find that adding spatial heterogeneity by geographically stratifying the model results in more uncertain model projections as compared to an equivalent nation-level model, which has both communicative advantages and disadvantages. We finally discuss the impact of imposing local mobility or social contact restrictions to contain an epidemic in a given province and find that lowering social contact is a more effective strategy than lowering mobility.

Analysis of the COVID-19 pandemic using a compartmental model with time-varying parameters fitted by a genetic algorithm.

Analyzing the COVID-19 pandemic is a critical factor in developing effective policies to deal with similar challenges in the future. However, many parameters (e.g., the actual number of infected people, the effectiveness of vaccination) are still subject to considerable debate because they are unobservable. To model a pandemic and estimate unobserved parameters, researchers use compartmental models. Most often, in such models, the transition rates are considered as constants, which allows simulating only one epidemiological wave. However, multiple waves have been reported for COVID-19 caused by different strains of the virus. This paper presents an approach based on the reconstruction of real distributions of transition rates using genetic algorithms, which makes it possible to create a model that describes several pandemic peaks. The model is fitted on registered COVID-19 cases in four countries with different pandemic control strategies (Germany, Sweden, UK, and US). Mean absolute percentage error (MAPE) was chosen as the objective function, the MAPE values of 2.168%, 2.096%, 1.208% and 1.703% were achieved for the listed countries, respectively. Simulation results are consistent with the empirical statistics of medical studies, which confirms the quality of the model. In addition to observables such as registered infected, the output of the model contains variables that cannot be measured directly. Among them are the proportion of the population protected by vaccines, the size of the exposed compartment, and the number of unregistered cases of COVID-19. According to the results, at the peak of the pandemic, between 14% (Sweden) and 25% (the UK) of the population were infected. At the same time, the number of unregistered cases exceeds the number of registered cases by 17 and 3.4 times, respectively. The average duration of the vaccine induced immune period is shorter than claimed by vaccine manufacturers, and the effectiveness of vaccination has declined sharply since the appearance of the Delta and Omicron strains. However, on average, vaccination reduces the risk of infection by about 65-70%.

Tracking the transmission dynamics of COVID-19 with a time-varying coefficient state-space model.

The spread of COVID-19 has been greatly impacted by regulatory policies and behavior patterns that vary across counties, states, and countries. Population-level dynamics of COVID-19 can generally be described using a set of ordinary differential equations, but these deterministic equations are insufficient for modeling the observed case rates, which can vary due to local testing and case reporting policies and nonhomogeneous behavior among individuals. To assess the impact of population mobility on the spread of COVID-19, we have developed a novel Bayesian time-varying coefficient state-space model for infectious disease transmission. The foundation of this model is a time-varying coefficient compartment model to recapitulate the dynamics among susceptible, exposed, undetected infectious, detected infectious, undetected removed, hospitalized, detected recovered, and detected deceased individuals. The infectiousness and detection parameters are modeled to vary by time, and the infectiousness component in the model incorporates information on multiple sources of population mobility. Along with this compartment model, a multiplicative process model is introduced to allow for deviation from the deterministic dynamics. We apply this model to observed COVID-19 cases and deaths in several U.S. states and Colorado counties. We find that population mobility measures are highly correlated with transmission rates and can explain complicated temporal variation in infectiousness in these regions. Additionally, the inferred connections between mobility and epidemiological parameters, varying across locations, have revealed the heterogeneous effects of different policies on the dynamics of COVID-19.

An eco-epidemiological modeling approach to investigate dilution effect in two different tick-borne pathosystems.

Disease (re)emergence appears to be driven by biodiversity decline and environmental change. As a result, it is increasingly important to study host-pathogen interactions within the context of their ecology and evolution. The dilution effect is the concept that higher biodiversity decreases pathogen transmission. It has been observed especially in zoonotic vector-borne pathosystems, yet evidence against it has been found. In particular, it is still debated how the community (dis)assembly assumptions and the degree of generalism of vectors and pathogens affect the direction of the biodiversity-pathogen transmission relationship. The aim of this study was to use empirical data and mechanistic models to investigate dilution mechanisms in two rodent-tick-pathogen systems differing in their vector degree of generalism. A community was assembled to include ecological interactions that expand from purely additive to purely substitutive. Such systems are excellent candidates to analyze the link between vector ecology, community (dis)assembly dynamics, and pathogen transmission. To base our mechanistic models on empirical data, rodent live-trapping, including tick sampling, was conducted in Wales across two seasons for three consecutive years. We have developed a deterministic single-vector, multi-host compartmental model that includes ecological relationships with non-host species, uniquely integrating theoretical and observational approaches. To describe pathogen transmission across a gradient of community diversity, the model was populated with parameters describing five different scenarios differing in ecological complexity; each based around one of the pathosystems: Ixodes ricinus (generalist tick)-Borrelia burgdorferi and I. trianguliceps (small mammals specialist tick)-Babesia microti. The results suggested that community composition and interspecific dynamics affected pathogen transmission with different dilution outcomes depending on the vector degree of generalism. The model provides evidence that dilution and amplification effects are not mutually exclusive in the same community but depend on vector ecology and the epidemiological output considered (i.e., the "risk" of interest). In our scenarios, more functionally diverse communities resulted in fewer infectious rodents, supporting the dilution effect. In the pathosystem with generalist vector we identified a hump shaped relationship between diversity and infections in hosts, while for that characterized by specialist tick, this relationship was more complex and more dependent upon specific parameter values.

Global prediction model for COVID-19 pandemic with the characteristics of the multiple peaks and local fluctuations.

BACKGROUND: With the spread of COVID-19, the time-series prediction of COVID-19 has become a research hotspot. Unlike previous epidemics, COVID-19 has a new pattern of long-time series, large fluctuations, and multiple peaks. Traditional dynamical models are limited to curves with short-time series, single peak, smoothness, and symmetry. Secondly, most of these models have unknown parameters, which bring greater ambiguity and uncertainty. There are still major shortcomings in the integration of multiple factors, such as human interventions, environmental factors, and transmission mechanisms. METHODS: A dynamical model with only infected humans and removed humans was established. Then the process of COVID-19 spread was segmented using a local smoother. The change of infection rate at different stages was quantified using the continuous and periodic Logistic growth function to quantitatively describe the comprehensive effects of natural and human factors. Then, a non-linear variable and NO2 concentrations were introduced to qualify the number of people who have been prevented from infection through human interventions. RESULTS: The experiments and analysis showed the R2 of fitting for the US, UK, India, Brazil, Russia, and Germany was 0.841, 0.977, 0.974, 0.659, 0.992, and 0.753, respectively. The prediction accuracy of the US, UK, India, Brazil, Russia, and Germany in October was 0.331, 0.127, 0.112, 0.376, 0.043, and 0.445, respectively. CONCLUSION: The model can not only better describe the effects of human interventions but also better simulate the temporal evolution of COVID-19 with local fluctuations and multiple peaks, which can provide valuable assistant decision-making information.