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1.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.05.08.23289679

ABSTRACT

Marginalized racial and ethnic groups in the United States were disproportionally affected by the COVID-19 pandemic. To study these disparities, we construct an age-and-race-stratified mathematical model of SARS-CoV-2 transmission fitted to age-and-race-stratified data from 2020 in Oregon and analyze counterfactual vaccination strategies in early 2021. We consider two racial groups: non-Hispanic White persons and persons belonging to BIPOC groups (including non-Hispanic Black persons, non-Hispanic Asian persons, non-Hispanic American Indian or Alaska Native persons, and Hispanic or Latino persons). We allocate a limited amount of vaccine to minimize overall disease burden (deaths or years of life lost), inequity in disease outcomes between racial groups (measured with five different metrics), or both. We find that, when allocating small amounts of vaccine (10% coverage), there is a trade-off between minimizing disease burden and minimizing inequity. Older age groups, who are at a greater risk of severe disease and death, are prioritized when minimizing measures of disease burden, and younger BIPOC groups, who face the most inequities, are prioritized when minimizing measures of inequity. The allocation strategies that minimize combinations of measures can produce middle-ground solutions that similarly improve both disease burden and inequity, but the trade-off can only be mitigated by increasing the vaccine supply. With enough resources to vaccinate 20% of the population the trade-off lessens, and with 30% coverage, we can optimize both equity and mortality. Our goal is to provide a race-conscious framework to quantify and minimize inequity that can be used for future pandemics and other public health interventions.


Subject(s)
COVID-19 , Death
2.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.11.10.21266139

ABSTRACT

Despite the development of safe and effective vaccines, effective treatments for COVID-19 disease are still desperately needed. Recently, two antiviral drugs have shown to be effective in reducing hospitalizations in clinical trials. In the present work, we use an agent-based mathematical model to assess the potential population impact of the use of antiviral treatments in four countries, corresponding to four current levels of vaccination coverage: Kenya, Mexico, United States (US) and Belgium, with 1.5, 38, 57 and 74% of their populations vaccinated. For each location, we varied antiviral coverage and antiviral effect in reducing viral load (25, 50, 75 or 100% reduction). Irrespective of location, widespread antiviral treatment of symptomatic infections ([≥]50% coverage) is expected to prevent the majority of COVID-19 deaths. Furthermore, even treating 20% of adult symptomatic infections, is expected to reduce mortality by a third in all countries, irrespective of the assumed treatment efficacy in reducing viral load. Our results suggest that early antiviral treatment is needed to mitigate transmission, with early treatment (within two days of symptoms) preventing 50% more infections compared to late treatment (started on days 3 to 5 after developing symptoms). Our results highlight the synergistic effect of vaccination and antiviral treatment: as vaccination rate increased, antiviral treatment had a bigger impact on overall transmission. These results suggest that antiviral treatments can become a strategic tool that, in combination with vaccination, can significantly control SASRS-CoV-2 transmission and reduce COVID-19 hospitalizations and deaths.


Subject(s)
COVID-19
3.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.10.01.21264426

ABSTRACT

Background The mass rollout of COVID vaccination in early 2021 allowed local and state authorities to relax mobility and social interaction regulations in spring 2021 including lifting all restrictions for vaccinated people and restoring in-person schooling. However, the emergence and rapid spread of highly transmissible variants combined with slowing down the pace of vaccination created uncertainty around the future trajectory of the epidemic. In this study we analyze the expected benefits of offering vaccination to children age 5-11 under differing conditions for in-person schooling. Methods We adapted a mathematical model of SARS-CoV-2 transmission, calibrated to data from King County, Washington, to handle multiple variants with increased transmissibility and virulence as well as differential vaccine efficacies against each variant. Reactive social distancing is implemented driven by fluctuations in the number of hospitalizations in the county. We simulate scenarios offering vaccination to children aged 5-11 with different starting dates and different proportions of physical interactions (PPI) in schools being restored. The impact of improving overall vaccination coverage among the eligible population is also explored. Cumulative hospitalizations, percentage reduction of hospitalizations and proportion of time at maximum social distancing over the 2021-2022 school year are reported. Findings In the base-case scenario with 85% vaccination coverage of 12+ year-olds, our model projects 4945 (median, IQR 4622-5341) total COVID-19 hospitalizations and 325 (median, IQR 264-400) pediatric hospitalizations if physical contacts at schools are fully restored (100% PPI) for the entire school year compared to 3675 (median, IQR 2311-4725) and 163 (median, IQR 95-226) if schools remained closed. Reducing contacts in schools to 75% PPI or 50% PPI through masking, ventilation and distancing is expected to decrease the overall cumulative hospitalizations by 2% and 4% respectively and youth hospitalizations by 8% and 23% respectively. Offering early vaccination to children aged 5-11 with 75% PPI is expected to prevent 756 (median, IQR 301-1434) hospitalizations and cut hospitalizations in the youngest age group in half compared to no vaccination. It will largely reduce the need of additional social distancing over the school year. If, in addition, 90% overall vaccination coverage is reached, 60% of remaining hospitalizations will be averted and the need of extra mitigation measures almost certainly avoided. Conclusions Our work highlights that in-person schooling is possible if reasonable precaution measures are taken at schools to reduced infectious contacts. Rapid vaccination of all school-aged children will provide meaningful reduction of the COVID health burden over this school year but only if implemented early. Finally, it remains critical to vaccinate as many people as possible to limit the morbidity and mortality associated with the current surge in Delta variant cases.


Subject(s)
COVID-19
4.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.02.02.21250985

ABSTRACT

The goals of SARS-CoV-2 vaccination programs are to maximally reduce cases and deaths, and to limit the amount of time required under lockdown. Using a mathematical model calibrated to data from King County Washington but generalizable across states, we simulated multiple scenarios with different vaccine efficacy profiles, vaccination rates, and case thresholds for triggering and relaxing partial lockdowns. We assumed that a contagious variant is currently present at low levels. In all scenarios, it rapidly becomes dominant by early summer. Low case thresholds for triggering partial lockdowns during current and future waves of infection strongly predict lower total numbers of COVID-19 infections, hospitalizations and deaths in 2021. However, in regions with relatively higher current seroprevalence, there is a predicted delay in onset of a subsequent surge in new variant infections. For all vaccine efficacy profiles, increasing vaccination rate lowers the total number of infections and deaths, as well as the total number of days under partial lockdown. Due to variable current estimates of emerging variant infectiousness, vaccine efficacy against these variants, vaccine refusal, and future adherence to masking and physical distancing, we project considerable uncertainty regarding the timing and intensity of subsequent waves of infection. Nevertheless, under all plausible scenarios, rapid vaccination and early implementation of partial lockdown are the two most critical variables to save the greatest number of lives.


Subject(s)
COVID-19
5.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.12.31.20249099

ABSTRACT

Most of the COVID-19 vaccines require two doses, at least 3 weeks apart. In the first few months of vaccine deployment, vaccine shortages will be inevitable. Current vaccine prioritization guidelines for COVID-19 vaccines all assume two-dose vaccine deployment. However, vaccinating twice as many people with a single dose of vaccine might be a better use of resources. Utilizing an age-stratified mathematical model combined with optimization algorithms, we determined the optimal vaccine allocation with one and two doses of vaccine to minimize five key metrics of disease burden (total infections, symptomatic infections, deaths, peak non-ICU and ICU hospitalizations) under a variety of assumptions (different levels of social distancing, vaccine availability, mode of action of vaccines, vaccination rate). Our results suggest that maintaining current social distancing interventions and speedy vaccine deployment are key for successful vaccination campaigns. Further, we show that the optimal allocation of vaccine critically depends on the single-dose efficacy (SDE). If the SDE is high, then under the majority of scenarios considered, single-dose vaccination is the optimal use of vaccine, preventing up to 48% more deaths than a strategy allocating vaccine to the high-risk (older age groups in our model) first. If the SDE is low or medium, then our results suggest that mixed vaccination campaigns with one and two doses of vaccine are best. Our work suggests that it is an absolute imperative to quickly and fully determine the efficacy of single-dose vaccines, as single-dose vaccinations can put an end to this pandemic much more quickly.


Subject(s)
COVID-19
6.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.12.13.20248120

ABSTRACT

Ongoing SARS-CoV-2 vaccine trials assess vaccine efficacy against disease (VEDIS), the ability of a vaccine to block symptomatic COVID-19. They will only partially discriminate whether VEDIS is mediated by preventing infection as defined by the detection of virus in the airways (vaccine efficacy against infection defined as VESUSC), or by preventing symptoms despite breakthrough infection (vaccine efficacy against symptoms or VESYMP). Vaccine efficacy against infectiousness (VEINF), defined as the decrease in secondary transmissions from infected vaccine recipients versus from infected placebo recipients, is also not being measured. Using mathematical modeling of data from King County Washington, we demonstrate that if the Moderna and Pfizer vaccines, which have observed VEDIS>90%, mediate VEDIS predominately by complete protection against infection, then prevention of a fourth epidemic wave in the spring of 2021, and associated reduction of subsequent cases and deaths by 60%, is likely to occur assuming rapid enough vaccine roll out. If high VEDIS is explained primarily by reduction in symptoms, then VEINF>50% will be necessary to prevent or limit the extent of this fourth epidemic wave. The potential added benefits of high VEINF would be evident regardless of vaccine allocation strategy and would be enhanced if vaccine roll out rate is low or if available vaccines demonstrate waning immunity. Finally, we demonstrate that a 1.0 log vaccine-mediated reduction in average peak viral load might be sufficient to achieve VEINF=60% and that human challenge studies with 104 infected participants, or clinical trials in a university student population could estimate VESUSC, VESYMP and VEINF using viral load metrics.


Subject(s)
COVID-19
7.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.10.30.20222893

ABSTRACT

BackgroundDuring the COVID-19 pandemic, gay and other men who have sex with men (MSM) in the United States (US) report similar or fewer sexual partners and reduced HIV testing and care access. Pre-exposure prophylaxis (PrEP) use has declined. We estimated the potential impact of COVID-19 on HIV incidence and mortality among US MSM. MethodsWe used a calibrated HIV transmission model for MSM in Baltimore, Maryland, and available data on COVID-19-related disruptions to predict impacts of data-driven reductions in sexual partners(0%,25%,50%), condom use(5%), HIV testing(20%), viral suppression(10%), PrEP initiations(72%), PrEP use(9%) and ART initiations(50%), exploring different disruption durations and magnitudes. We estimated the median (95% credible interval) change in cumulative new HIV infections and deaths among MSM over one and five years, compared with a scenario without COVID-19-related disruptions. FindingsA six-month 25% reduction in sexual partners among Baltimore MSM, without HIV service changes, could reduce new HIV infections by 12{middle dot}2%(11{middle dot}7,12{middle dot}8%) and 3{middle dot}0%(2{middle dot}6,3{middle dot}4%) over one and five years, respectively. In the absence of changes in sexual behaviour, the six-month data-driven disruptions to condom use, testing, viral suppression, PrEP initiations, PrEP use and ART initiations combined were predicted to increase new HIV infections by 10{middle dot}5%(5{middle dot}8,16{middle dot}5%) over one year, and by 3{middle dot}5%(2{middle dot}1,5{middle dot}4%) over five years. A 25% reduction in partnerships offsets the negative impact of these combined service disruptions on new HIV infections (overall reduction 3{middle dot}9%(-1{middle dot}0,7{middle dot}4%), 0{middle dot}0%(-1{middle dot}4,0{middle dot}9%) over one, five years, respectively), but not on HIV deaths (corresponding increases 11{middle dot}0%(6{middle dot}2,17{middle dot}7%), 2{middle dot}6%(1{middle dot}5,4{middle dot}3%)). The predicted impacts of reductions in partnerships or viral suppression doubled if they lasted 12 months or if disruptions were twice as large. InterpretationMaintaining access to ART and adherence support is of the utmost importance to minimise excess HIV-related mortality due to COVID-19 restrictions in the US, even if accompanied by reductions in sexual partnerships. FundingNIH Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe COVID-19 pandemic and responses to it have disrupted HIV prevention and treatment services and led to changes in sexual risk behaviour in the United States, but the overall potential impact on HIV transmission and HIV-related mortality is not known. We searched PubMed for articles documenting COVID-related disruptions to HIV prevention and treatment and changes in sexual risk behaviour in the United States, published between 1st January and 7th October 2020, with no language restrictions, using the terms COVID* AND (HIV OR AIDS) AND ("United States" OR US). We identified three cross-sectional surveys assessing changes in sexual risk behaviour among men who have sex with men (MSM) in the United States, one finding a reduction, one a slight increase, and one no change in partner numbers during COVID-19 restrictions. Two of these studies also found reductions in reported HIV testing, HIV care and/or access to pre-exposure prophylaxis (PrEP) among MSM due to COVID-19. A separate study from a San Francisco clinic found declines in viral suppression among its clients during lockdown. We searched PubMed for articles estimating the impact of COVID-related disruptions on HIV transmission and mortality published between 1st January 2020 and 12th October 2020, with no language restrictions, using the following terms: COVID* AND model* AND (HIV OR AIDS). We identified two published studies which had used mathematical modelling to estimate the impact of hypothetical COVID-19-related disruptions to HIV programmes on HIV-related deaths and/or new HIV infections in Africa, another published study using modelling to estimate the impact of COVID-19-related disruptions and linked HIV and SARS-CoV-2 testing on new HIV infections in six cities in the United States, and a pre-print reporting modelling of the impact of COVID-19-related disruptions on HIV incidence among men who have sex with men in Atlanta, United States. None of these studies were informed by data on the size of these disruptions. The two African studies and the Atlanta study assessed the impact of disruptions to different healthcare disruptions separately, and all found that the greatest negative impacts on new HIV infections and/or deaths would arise from interruptions to antiretroviral therapy. They all found smaller effects on HIV-related mortality and/or incidence from other healthcare disruptions, including HIV testing, PrEP use and condom supplies. The United States study assessing the impact of linked HIV and SARS-CoV-2 testing estimated that this could substantially reduce HIV incidence. Added value of this studyWe used mathematical modelling to derive estimates of the potential impact of the COVID-19 pandemic and associated restrictions on HIV incidence and mortality among MSM in the United States, directly informed by data from the United States on disruptions to HIV testing, antiretroviral therapy and pre-exposure prophylaxis services and reported changes in sexual risk behaviour during the COVID-19 pandemic. We also assessed the impact of an HIV testing campaign during COVID-19 lockdown. Implications of all the available evidenceIn the United States, maintaining access to antiretroviral therapy and adherence support for both existing and new users will be crucial to minimize excess HIV-related deaths arising from the COVID-19 pandemic among men who have sex with men. While reductions in sexual risk behaviour may offset increases in new HIV infections arising from disruptions to HIV prevention and treatment services, this will not offset the additional HIV-related deaths which are also predicted to occur. There are mixed findings on the impact of an HIV testing campaign among US MSM during COVID-19 lockdown. Together, these studies highlight the importance of maintaining effective HIV treatment provision during the COVID-19 pandemic.


Subject(s)
COVID-19
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