Determinants of RSV epidemiology following suppression through pandemic contact restrictions

Introduction COVID-19 related non-pharmaceutical interventions (NPIs) led to a suppression of RSV circulation in winter 2020/21 throughout Europe and an off-season resurgence in Summer 2021 in several European countries. We explore how such temporary interruption may shape future RSV epidemiology and what factors drive the associated uncertainty. Methods We developed an age-structured dynamic transmission model to simulate pre-pandemic RSV infections and hospitalisations. We sampled parameters governing RSV seasonality, immunity acquisition and duration of post-infection immunity and retained those simulations that qualitatively fit the UK's pre-pandemic epidemiology. From Spring 2020 to Summer 2021 we assumed a 50% reduced contact frequency, returning to pre-pandemic levels from mid-May 2021. We simulated transmission forwards until 2023 and evaluated the impact of the sampled parameters on the projected trajectories of RSV hospitalisations. Results Following a lifting of contact restrictions in summer 2021 the model replicated an out-of-season resurgence of RSV. If unmitigated, paediatric RSV hospitalisation incidence in the 2021/22 season was projected to increase by 32% to 67% compared to pre-pandemic levels. The size of the increase depended most on whether infection risk was primarily determined by immunity acquired from previous exposure or general immune maturation. While infants were less affected, the increase in seasonal hospitalisation incidence exceeded 100% in 1-2 year old children and 275% in 2-5 year old children, respectively, in some simulations where immunity from previous exposure dominated. Consequently, the average age of a case increased by 1 to 5 months, most markedly if there was strong immunity acquisition from previous exposure. If immunity to infection was largely determined by age rather than previous exposure, the 2021/22 season started earlier and lasted longer but with a peak incidence lower or similar to pre-pandemic levels. For subsequent seasons, simulations suggested a quick return to pre-pandemic epidemiology, with some slight oscillating behaviour possible depending on the strength of post-exposure immunity. Conclusion COVID-19 mitigation measures stopped RSV circulation in the 2020/21 season and generated immunity debt that will likely lead to a temporary increase in RSV burden in the season following the lifting of restrictions, particularly in 1 to 5 year old children. A more accurate understanding of immunity drivers for RSV is needed to better predict the size of such an increase and plan a potential expansion of pharmaceutical and non-pharmaceutical mitigation measures.

Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study

Introduction The rise of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTI) threatens antiretroviral therapy's long-term success (ART). NNRTIs will remain an essential drug for the management of HIV-1 due to safety concerns associated with integrase inhibitors. We fitted a dynamic transmission model to historical data from 2000 to 2018 in nine countries of southern Africa to understand the mechanisms that have shaped the HIV-1 epidemic and the rise of pretreatment NNRTI resistance. Methods We included data on HIV-1 prevalence, ART coverage, HIV-related mortality, and survey data on pretreatment NNRTI resistance from nine southern Africa countries from a systematic review, UNAIDS and World Bank. Using a Bayesian hierarchical framework, we developed a dynamic transmission model linking data on the HIV-1 epidemic to survey data on NNRTI drug resistance in each country. We estimated the proportion of resistance attributable to unregulated, off-programme use of ART. We examined each national ART programme's vulnerability to NNRTI resistance by defining a fragility index: the ratio of the rate of NNRTI resistance emergence during first-line ART over the rate of switching to second-line ART. We explored associations between fragility and characteristics of the health system of each country. Results The model reliably described the dynamics of the HIV-1 epidemic and NNRTI resistance in each country. Predicted levels of resistance in 2018 ranged between 3.3% (95% credible interval 1.9–7.1) in Mozambique and 25.3% (17.9–33.8) in Eswatini. The proportion of pretreatment NNRTI resistance attributable to unregulated antiretroviral use ranged from 6% (2–14) in Eswatini to 64% (26–85) in Mozambique. The fragility index was low in Botswana (0.01; 0.0–0.11) but high in Namibia (0.48; 0.16–10.17), Eswatini (0.64; 0.23–11.8) and South Africa (1.21; 0.83–9.84). The combination of high fragility of ART programmes and high ART coverage levels was associated with a sharp increase in pretreatment NNRTI resistance. Conclusions This comparison of nine countries shows that pretreatment NNRTI resistance can be controlled despite high ART coverage levels. This was the case in Botswana, Mozambique, and Zambia, most likely because of better HIV care delivery, including rapid switching to second-line ART of patients failing first-line ART.

MITIGATING THE 4th WAVE OF THE COVID-19 PANDEMIC IN ONTARIO

Background: The goal of this study was to project the number of COVID-19 cases and demand for acute hospital resources for Fall of 2021 in a representative mid-sized community in southwestern Ontario. We sought to evaluate whether current levels of vaccine coverage and contact reduction could mitigate a potential 4th wave fueled by the Delta variant, or whether the reinstitution of more intense public health measures will be required. Methods: We developed an age-stratified dynamic transmission model of COVID-19 in a mid-sized city (population 500,000) currently experiencing a relatively low, but increasing, infection rate in Step 3 of Ontario's Wave 3 recovery. We parameterized the model using the medical literature, grey literature, and government reports. We estimated the current level of contact reduction by model calibration to cases and hospitalizations. We projected the number of infections, number of hospitalizations, and the time to re-instate high intensity public health measures over the fall of 2021 under different levels of vaccine coverage and contact reduction. Results: Maintaining contact reductions at the current level, estimated to be a 17% reduction compared to pre-pandemic contact levels, results in COVID-related admissions exceeding 20% of pre-pandemic critical care capacity by late October, leading to cancellation of elective surgeries and other non-COVID health services. At high levels of vaccination and relatively high levels of mask wearing, a moderate additional effort to reduce contacts (30% reduction compared to pre-pandemic contact levels), is necessary to avoid re-instating intensive public health measures. Compared to prior waves, the age distribution of both cases and hospitalizations shifts younger and the estimated number of pediatric critical care hospitalizations may substantially exceed 20% of capacity. Discussion: High rates of vaccination coverage in people over the age of 12 and mask wearing in public settings will not be sufficient to prevent an overwhelming resurgence of COVID-19 in the Fall of 2021. Our analysis indicates that immediate moderate public health measures can prevent the necessity for more intense and disruptive measures later.

Multi-objective optimization of hydro-viscous flexible drive for dynamic characteristics using genetic algorithm

Purpose The purpose of this study is to investigate the flexible dynamic characteristics about hydro-viscous drive providing meaningful insights into the credible speed-regulating behavior during the soft-start. Design/methodology/approach A comprehensive dynamic transmission model is proposed to investigate the effects of key parameters on the dynamic characteristics. To achieve a trade-off between the transmission efficiency and time proportion of hydrodynamic and mixed lubrication, a multi-objective optimization of friction pair system by genetic algorithm is presented to obtain the optimal combination of design parameters. Findings Decreasing the engagement pressure or the ratio of inner and outer radius, increasing the lubricating oil viscosity or the outer radius will result in the increase of time proportion of hydrodynamic and mixed lubrication, as well as the transmission efficiency and its maximum value. After optimization, main dynamic parameters including the oil film thickness, angular velocity of the driven disk, viscous torque and total torque show remarkable flexible transmission characteristics. Originality/value Both the dynamic transmission model and multi-objective optimization model are established to analyze the effects of main design parameters on the dynamic characteristics of hydro-viscous flexible drive.

Determining The Age Priority in Universal Vaccination Using Economic Evidence: Case From US Based On Dynamic Transmission Model

Background: Currently, increasing regions have realized that universal vaccination are necessary to prevent COVID-19. However many of them are facing problems associated with insufficient supply or chaotic allocation of vaccines. This study selected the United States population as an example and explored prioritization strategies of COVID-19 vaccination for different age groups to achieve the highest economic efficiency.Methods: We built a dynamic transmission model to predict the incidence of SARS-CoV-2 infections under the prioritization strategies of vaccination for different ages within a 180-day simulation period. Quality-adjusted life year (QALY) was selected as the outcome. Medical costs included direct medical cost and vaccine cost based on a healthcare system perspective. Data on SARS-CoV-2 epidemiology, vaccine efficacy, and medical costs were derived from publicly available databases and previously published literature. Different COVID-19 vaccines were included in scenario analysis. The robustness of the study results was evaluated by one-way sensitivity analysis and probabilistic sensitivity analysis.Results: COVID-19 vaccination is economical compared with no vaccination. Priority vaccination for adults aged 25–59 years saves $31,664.2 million and that for adults over 60 years old saves $30,082.9 million in medical costs compared with no vaccine intervention. Additionally, priority vaccination for adults aged 25–59 years vs. over 60 years old saves $1,581.3 million. In contrast, priority vaccination for adults aged over 60 years vs. 25–59 years old gains 0.001 QALYs and costs $4.7 per capita, with an incremental cost-effectiveness ratio of $4,829.3/QALY, and it is economical when taking gross domestic product per capita of the United States in 2020 as the willingness-to-pay threshold. The results of sensitivity analysis indicate that the base-case results are robust.Conclusions: From a healthcare system perspective, it is most economical to prioritize adults aged over 60 years for COVID-19 vaccination in the United States, thereby achieving effective resource allocation and saving the government costs.

Analysis and Evaluation of Non-Pharmaceutical Interventions on Prevention and Control of COVID-19: A Case Study of Wuhan City

As the threat of COVID-19 increases, many countries have carried out various non-pharmaceutical interventions. Although many studies have evaluated the impact of these interventions, there is a lack of mapping between model parameters and actual geographic areas. In this study, a non-pharmaceutical intervention model of COVID-19 based on a discrete grid is proposed from the perspective of geography. This model can provide more direct and effective information for the formulation of prevention and control policies. First, a multi-level grid was introduced to divide the geographical space, and the properties of the grid boundary were used to describe the quarantine status and intensity in these different spaces; this was also combined with the model of hospital isolation and self-protection. Then, a process for the spatiotemporal evolution of the early COVID-19 spread is proposed that integrated the characteristics of residents’ daily activities. Finally, the effect of the interventions was quantitatively analyzed by the dynamic transmission model of COVID-19. The results showed that quarantining is the most effective intervention, especially for infectious diseases with a high infectivity. The introduction of a quarantine could effectively reduce the number of infected humans, advance the peak of the maximum infected number of people, and shorten the duration of the pandemic. However, quarantines only function properly when employed at sufficient intensity; hospital isolation and self-protection measures can effectively slow the spread of COVID-19, thus providing more time for the relevant departments to prepare, but an outbreak will occur again when the hospital reaches full capacity. Moreover, medical resources should be concentrated in places where there is the most urgent need under a strict quarantine measure.

Clinical and economic impact of universal varicella vaccination in Norway: A modeling study

Background Norway has not implemented universal varicella vaccination, despite the considerable clinical and economic burden of varicella disease. Methods An existing dynamic transmission model of varicella infection was calibrated to age-specific seroprevalence rates in Norway. Six two-dose vaccination strategies were considered, consisting of combinations of two formulations each of a monovalent varicella vaccine (Varivax® or Varilrix®) and a quadrivalent vaccine against measles-mumps-rubella-varicella (ProQuad® or PriorixTetra®), with the first dose given with a monovalent vaccine at age 15 months, and the second dose with either a monovalent or quadrivalent vaccine at either 18 months, 7 or 11 years. Costs were considered from the perspectives of both the health care system and society. Quality-adjusted life-years saved and incremental cost-effectiveness ratios relative to no vaccination were calculated. A one-way sensitivity analysis was conducted to assess the impact of vaccine efficacy, price, the costs of a lost workday and of inpatient and outpatient care, vaccination coverage, and discount rate. Results In the absence of varicella vaccination, the annual incidence of natural varicella is estimated to be 1,359 per 100,000 population, and the cumulative numbers of varicella outpatient cases, hospitalizations, and deaths over 50 years are projected to be 1.81 million, 10,161, and 61, respectively. Universal varicella vaccination is projected to reduce the natural varicella incidence rate to 48–59 per 100,000 population, depending on the vaccination strategy, and to reduce varicella outpatient cases, hospitalizations, and deaths by 75–85%, 67–79%, and 75–79%, respectively. All strategies were cost-saving, with the most cost-saving as two doses of Varivax® at 15 months and 7 years (payer perspective) and two doses of Varivax® at 15 months and 18 months (societal perspective). Conclusions All modeled two-dose varicella vaccination strategies are projected to lead to substantial reductions in varicella disease and to be cost saving compared to no vaccination in Norway.

Dependence of COVID-19 Policies on End-of-Year Holiday Contacts in Mexico City Metropolitan Area: A Modeling Study

Background. Mexico City Metropolitan Area (MCMA) has the largest number of COVID-19 (coronavirus disease 2019) cases in Mexico and is at risk of exceeding its hospital capacity in early 2021. Methods. We used the Stanford-CIDE Coronavirus Simulation Model (SC-COSMO), a dynamic transmission model of COVID-19, to evaluate the effect of policies considering increased contacts during the end-of-year holidays, intensification of physical distancing, and school reopening on projected confirmed cases and deaths, hospital demand, and hospital capacity exceedance. Model parameters were derived from primary data, literature, and calibrated. Results. Following high levels of holiday contacts even with no in-person schooling, MCMA will have 0.9 million (95% prediction interval 0.3–1.6) additional COVID-19 cases between December 7, 2020, and March 7, 2021, and hospitalizations will peak at 26,000 (8,300–54,500) on January 25, 2021, with a 97% chance of exceeding COVID-19-specific capacity (9,667 beds). If MCMA were to control holiday contacts, the city could reopen in-person schools, provided they increase physical distancing with 0.5 million (0.2–0.9) additional cases and hospitalizations peaking at 12,000 (3,700–27,000) on January 19, 2021 (60% chance of exceedance). Conclusion. MCMA must increase COVID-19 hospital capacity under all scenarios considered. MCMA’s ability to reopen schools in early 2021 depends on sustaining physical distancing and on controlling contacts during the end-of-year holiday.

Quantifying the potential for dominant spread of SARS-CoV-2 variant B.1.351 in the United States

Recent evidence suggests that the SARS-CoV-2 variant B.1.351 exhibits partial immune evasion to antibodies generated by natural infection or vaccination. We used a dynamic transmission model to evaluate whether this variant could become dominant in the United States given mounting vaccination coverage and other circulating variants. In the presence of the B.1.1.7 variant, we show that B.1.351 is unlikely to become dominant even when all fully vaccinated individuals return to their pre-pandemic behavior. However, an improved selection advantage of B.1.351 arising from a combination of increased transmission and immune escape could drive this variant to dominance as early as July 2021 and fuel a resurgence of cases and hospitalizations. Our study underscores the urgency for continued rollout of the current generation of vaccines despite the emergence of immune escape variants.