Early Insights from Statistical and Mathematical Modeling of Key Epidemiologic Parameters of COVID-19.
Ontology highlight
ABSTRACT:
SUBMITTER: Biggerstaff M
PROVIDER: S-EPMC7588530 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In the last decades, developmental origins of health and disease (DOHaD) has emerged as a central framework for studying early-life effects, that is, the impact of fetal and early postnatal experience on adult functioning. Apace with empirical progress, theoreticians have built mathematical models that provide novel insights for DOHaD. This article focuses on three of these insights, which show the power of environmental noise (i.e., imperfect indicators of current and future conditions) in shaping development. Such noise can produce: (a) detrimental outcomes even in ontogenetically stable environments, (b) individual differences in sensitive periods, and (c) early-life effects tailored to predicted future somatic states. We argue that these insights extend DOHaD and offer new research directions.
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Project description:With the recent licensure of mRNA vaccines against COVID-19 in the 5- to 11-year-old age group, the public health impact of a childhood immunization campaign is of interest. Using a mathematical epidemiological model, we project that childhood vaccination carries minimal risk and yields modest public health benefits. These include large relative reductions in child morbidity and mortality, although the absolute reduction is small because these events are rare. Furthermore, the model predicts "altruistic" absolute reductions in adult cases, hospitalizations, and mortality. However, vaccinating children to benefit adults should be considered from an ethical as well as a public health perspective. From a global health perspective, an additional ethical consideration is the justice of giving priority to children in high-income settings at low risk of severe disease while vaccines have not been made available to vulnerable adults in low-income settings. IMPORTANCE Countries have recently begun implementation of childhood vaccination against SARS-CoV-2 with the Pfizer/BioNTech mRNA vaccine in children 5 to 11 years of age. Because SARS-CoV-2 disease severity is remarkably age dependent, vaccinating children may have modest public health benefits, relative to the unequivocal benefit of vaccinating vulnerable older adults. Furthermore, vaccinating children to "altruistically" increase herd immunity should be considered from an ethical as well as a public health perspective. An additional question is related to global social justice: should priority be given to vaccinating children in high-income settings while older adult populations in low-resource settings have limited access to vaccine? To address the risks and benefits of childhood vaccination, we provide a balanced commentary, supported by a mathematical epidemiological model, using Australia and Alberta, Canada, as case studies. We give highlights of the modeling findings in the commentary and include details in the supplemental materials for interested readers.
| S-EPMC8764932 | biostudies-literature
Project description:In this study, we examined various forms of mathematical models that are relevant for the containment, risk analysis, and features of COVID-19. Greater emphasis was laid on the extension of the Susceptible-Infectious-Recovered (SIR) models for policy relevance in the time of COVID-19. These mathematical models play a significant role in the understanding of COVID-19 transmission mechanisms, structures, and features. Considering that the disease has spread sporadically around the world, causing large scale socioeconomic disruption unwitnessed in contemporary ages since World War II, researchers, stakeholders, government, and the society at large are actively engaged in finding ways to reduce the rate of infection until a cure or vaccination procedure is established. We advanced argument for the various forms of the mathematical model of epidemics and highlighted their relevance in the containment of COVID-19 at the present time. Mathematical models address the need for understanding the transmission dynamics and other significant factors of the disease that would aid policymakers to make accurate decisions and reduce the rate of transmission of the disease.
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Project description:BackgroundUganda has a unique set up comprised of resource-constrained economy, social-economic challenges, politically diverse regional neighborhood and home to long-standing refuge crisis that comes from long and protracted conflicts of the great lakes. The devastation of the on-going global pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be escalated by these circumstances with expectations of the impact of the disease being severe.Materials and methodsIn this study, we formulate a mathematical model that incorporates the currently known disease characteristics and tracks various intervention measures that the government of Uganda has implemented since the reporting of the first case in March 2020. We then evaluate these measures to understand levels of responsiveness and adherence to standard operating procedures and quantify their impact on the disease burden. Novel in this model was the unique aspect of modeling the trace-and-isolate protocol in which some of the latently infected individuals tested positive while in strict isolation centers thereby reducing their infectious period.ResultsThe study findings show that even with elimination of all imported cases at any given time it would take up to nine months to rid Uganda of the disease. The findings also show that the optimal timing of easing of lockdowns while mitigating the possibility of re-emergence of a second epidemic wave requires avoiding the scenario of releasing too-many-too-soon. It is even more worrying that enhancing contact tracing would only affect the magnitude and timing of the second wave but cannot prevent it altogether.ConclusionWe conclude that, given the prevailing circumstances, a phased-out lifting of lockdown measures, minimization of COVID-19 transmissibility within hospital settings, elimination of recruitment of infected individuals as well as enhanced contact tracing would be key to preventing overwhelming of the healthcare system that would come with dire consequences.
| S-EPMC7899325 | biostudies-literature
Project description:Prior to vaccination or drug treatment, non-pharmaceutical interventions were almost the only way to control the coronavirus disease 2019 (COVID-19) epidemic. After vaccines were developed, effective vaccination strategies became important. The prolonged COVID-19 pandemic has caused enormous economic losses worldwide. As such, it is necessary to estimate the economic effects of control policies, including non-pharmaceutical interventions and vaccination strategies. We estimated the costs associated with COVID-19 according to different vaccination rollout speeds and social distancing levels and investigated effective control strategies for cost minimization. Age-structured mathematical models were developed and used to study disease transmission epidemiology. Using these models, we estimated the actual costs due to COVID-19, considering costs associated with medical care, lost wages, death, vaccination, and gross domestic product (GDP) losses due to social distancing. The lower the social distancing (SD) level, the more important the vaccination rollout speed. SD level 1 was cost-effective under fast rollout speeds, but SD level 2 was more effective for slow rollout speeds. If the vaccine rollout rate is fast enough, even implementing SD level 1 will be cost effective and can control the number of critically ill patients and deaths. If social distancing is maintained at level 2 at the beginning and then relaxed when sufficient vaccinations have been administered, economic costs can be reduced while maintaining the number of patients with severe symptoms below the intensive care unit (ICU) capacity. Korea has wellequipped medical facilities and infrastructure for rapid vaccination, and the public's desire for vaccination is high. In this case, the speed of vaccine supply is an important factor in controlling the COVID-19 epidemic. If the speed of vaccination is fast, it is possible to maintain a low level of social distancing without a significant increase in the number of deaths and hospitalized patients with severe symptoms, and the corresponding costs can be reduced.
| S-EPMC9512395 | biostudies-literature
Project description:34,354,966 active cases and 460,787 deaths because of COVID-19 pandemic were recorded on November 06, 2021, in India. To end this ongoing global COVID-19 pandemic, there is an urgent need to implement multiple population-wide policies like social distancing, testing more people and contact tracing. To predict the course of the pandemic and come up with a strategy to control it effectively, a compartmental model has been established. The following six stages of infection are taken into consideration: susceptible (S), asymptomatic infected (A), clinically ill or symptomatic infected (I), quarantine (Q), isolation (J) and recovered (R), collectively termed as SAIQJR. The qualitative behavior of the model and the stability of biologically realistic equilibrium points are investigated in terms of the basic reproduction number. We performed sensitivity analysis with respect to the basic reproduction number and obtained that the disease transmission rate has an impact in mitigating the spread of diseases. Moreover, considering the non-pharmaceutical and pharmaceutical intervention strategies as control functions, an optimal control problem is implemented to mitigate the disease fatality. To reduce the infected individuals and to minimize the cost of the controls, an objective functional has been constructed and solved with the aid of Pontryagin's maximum principle. The implementation of optimal control strategy at the start of a pandemic tends to decrease the intensity of epidemic peaks, spreading the maximal impact of an epidemic over an extended time period. Extensive numerical simulations show that the implementation of intervention strategy has an impact in controlling the transmission dynamics of COVID-19 epidemic. Further, our numerical solutions exhibit that the combination of three controls are more influential when compared with the combination of two controls as well as single control. Therefore, the implementation of all the three control strategies may help to mitigate novel coronavirus disease transmission at this present epidemic scenario.Supplementary informationThe online version supplementary material available at 10.1007/s11071-022-07235-7.
| S-EPMC8801045 | biostudies-literature
Project description:Trypanosome RNA polymerase II transcription is polycistronic, individual mRNAs being excised by trans splicing and polyadenylation. In this study, we refined the previously published mathematical model for bloodstream form parasites and extended it to the procyclic form. We used the model, together with known mRNA half-lives, to predict the abundances of individual mRNAs, assuming rapid, unregulated mRNA processing; then we compared the results with measured mRNA abundances. Remarkably, the abundances of most mRNAs in procyclic forms are predicted quite well by the model, being largely explained by variations in mRNA decay rates and length. In bloodstream forms substantially more mRNAs are less abundant than predicted. We list mRNAs that are likely to show particularly slow or inefficient processing, either in both forms or with developmental regulation. We also measured ribosome occupancies of all mRNAs in trypanosomes grown in the same conditions as were used to measure mRNA turnover. In procyclic forms there was a weak positive correlation between ribosome density and mRNA half-life, suggesting cross-talk between translation and mRNA decay; ribosome density was related to the proportion of the mRNA on polysomes, indicating control of translation initiation. Ribosomal protein mRNAs in procyclics appeared to be exceptionally rapidly processed but poorly translated. Through this study, we conclude that lLevels of mRNAs in procyclic form trypanosomes are determined mainly by length and mRNA decay, with some control of precursor processing. In bloodstream forms variations in nuclear events play a larger role in transcriptome regulation, suggesting acquisition of new control mechanisms during adaptation to mammalian parasitism. Ribosome profiling and mRNA libraries were constructed in triplicate from in vitro PCF and in duplicate from in vitro T. brucei Lister427, to understand global differntial gene transcription.
2016-03-16 | E-GEOD-79208 | biostudies-arrayexpress
Project description:BackgroundAn increase in the average age of dengue hemorrhagic fever (DHF) cases has been reported in Thailand. The cause of this increase is not known. Possible explanations include a reduction in transmission due to declining mosquito populations, declining contact between human and mosquito, and changes in reporting. We propose that a demographic shift toward lower birth and death rates has reduced dengue transmission and lengthened the interval between large epidemics.Methods and findingsUsing data from each of the 72 provinces of Thailand, we looked for associations between force of infection (a measure of hazard, defined as the rate per capita at which susceptible individuals become infected) and demographic and climactic variables. We estimated the force of infection from the age distribution of cases from 1985 to 2005. We find that the force of infection has declined by 2% each year since a peak in the late 1970s and early 1980s. Contrary to recent findings suggesting that the incidence of DHF has increased in Thailand, we find a small but statistically significant decline in DHF incidence since 1985 in a majority of provinces. The strongest predictor of the change in force of infection and the mean force of infection is the median age of the population. Using mathematical simulations of dengue transmission we show that a reduced birth rate and a shift in the population's age structure can explain the shift in the age distribution of cases, reduction of the force of infection, and increase in the periodicity of multiannual oscillations of DHF incidence in the absence of other changes.ConclusionsLower birth and death rates decrease the flow of susceptible individuals into the population and increase the longevity of immune individuals. The increase in the proportion of the population that is immune increases the likelihood that an infectious mosquito will feed on an immune individual, reducing the force of infection. Though the force of infection has decreased by half, we find that the critical vaccination fraction has not changed significantly, declining from an average of 85% to 80%. Clinical guidelines should consider the impact of continued increases in the age of dengue cases in Thailand. Countries in the region lagging behind Thailand in the demographic transition may experience the same increase as their population ages. The impact of demographic changes on the force of infection has been hypothesized for other diseases, but, to our knowledge, this is the first observation of this phenomenon. Please see later in the article for the Editors' Summary.
| S-EPMC2726436 | biostudies-literature
Project description:COVID-19 is affecting healthcare resources worldwide, with lower and middle-income countries being particularly disadvantaged to mitigate the challenges imposed by the disease, including the availability of a sufficient number of infirmary/ICU hospital beds, ventilators, and medical supplies. Here, we use mathematical modelling to study the dynamics of COVID-19 in Bahia, a state in northeastern Brazil, considering the influences of asymptomatic/non-detected cases, hospitalizations, and mortality. The impacts of policies on the transmission rate were also examined. Our results underscore the difficulties in maintaining a fully operational health infrastructure amidst the pandemic. Lowering the transmission rate is paramount to this objective, but current local efforts, leading to a 36% decrease, remain insufficient to prevent systemic collapse at peak demand, which could be accomplished using periodic interventions. Non-detected cases contribute to a ∽55% increase in R0. Finally, we discuss our results in light of epidemiological data that became available after the initial analyses.
| S-EPMC7803757 | biostudies-literature
Project description:The antiviral remdesivir has been approved by regulatory bodies such as the European Medicines Agency (EMA) and the US Food and Drug administration (FDA) for the treatment of COVID-19. However, its efficacy is debated and toxicity concerns might limit the therapeutic range of this drug. Computational models that aid in balancing efficacy and toxicity would be of great help. Parametrizing models is difficult because the prodrug remdesivir is metabolized to its active form (RDV-TP) upon cell entry, which complicates dose-activity relationships. Here, we employ a computational model that allows drug efficacy predictions based on the binding affinity of RDV-TP for its target polymerase in SARS-CoV-2. We identify an optimal infusion rate to maximize remdesivir efficacy. We also assess drug efficacy in suppressing both wild-type and resistant strains, and thereby describe a drug regimen that may select for resistance. Our results differ from predictions using prodrug dose-response curves (pseudo-EC50s). We expect that reaching 90% inhibition (EC90) is insufficient to suppress SARS-CoV-2 in the lungs. While standard dosing mildly inhibits viral polymerase and therefore likely reduces morbidity, we also expect selection for resistant mutants for most realistic parameter ranges. To increase efficacy and safeguard against resistance, we recommend more clinical trials with dosing regimens that substantially increase the levels of RDV-TP and/or pair remdesivir with companion antivirals.
| S-EPMC8400702 | biostudies-literature