Improving vaccination coverage and offering vaccine to all school-age children will allow uninterrupted in-person schooling in King County, WA: Modeling analysis

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 are restored. The impact of improving overall vaccination coverage among 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-old 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 are expected to decrease the overall cumulative hospitalizations by 2% and 4% respectively and youth’s 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.

Key results figure

Overall hospitalizations expected under different scenarios of school reopening and extended vaccine eligibility. A) The maximum number of people hospitalized with COVID at any given time over the school year and B) Overall per capita cumulative hospitalizations by vaccination status. Boxes represent interquartile range while whiskers extend to the most extreme data point which is no more than 1.5 times the interquartile range. Red line indicates 10% of the hospital bed capacity in King County used as a metric for public-health decisions.

Citation

Chloe Bracis, Mia Moore, David A. Swan, Laura Matrajt, Larissa Anderson, Daniel B. Reeves, Eileen Burns, Joshua T. Schiffer, Dobromir Dimitrov, Bracis C, Moore M, Swan DA, Matrajt L, Anderson L, Reeves DB, Schiffer JT, Dimitrov D. Improving vaccination coverage and offering vaccine to all school-age children will allow uninterrupted in-person schooling in King County, WA: Modeling analysis. medRxiv(2021).

Published article

Rapid vaccination and partial lockdown minimize 4th waves from emerging highly contagious SARS-CoV-2 variants

Original Medrxiv article

Rapid vaccination and early reactive partial lockdown will minimize deaths from emerging highly contagious SARS-CoV-2 variants.

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.

Key results figure

Increasing vaccination rate minimizes infections, hospitalizations and deaths, as well as total numbers of days under lockdown. a. Spearman correlations for input variables related to vaccination rate and efficacy. Increasing vaccination rate reduces infections, hospitalizations and deaths, and time under partial lockdown. Increasing vaccine efficacy against infection (VE_SUSC) results in uniform benefit for all health-related outcomes and slight reduction in days at maximal social distancing. Increasing vaccine efficacy against symptoms given infection (VE_SYMP) results in decreases in hospitalizations and deaths. Increasing vaccine efficacy against infectivity given infection (VE_INF) results in slight reduction in numbers of diagnosed cases and infections. b-e. Impact of vaccination rate on relevant outcomes assuming different efficacy. b. VE_SUSC=90% / VE_SYMP=10% / VE_INF=10%, c. VE_SUSC=50% / VE_SYMP=10% / VE_INF=10%, d. VE_SUSC=10% / VE_SYMP=90% / VE_INF=10%, e. VE_SUSC=10% / VE_SYMP=50% / VE_INF=10%. All simulations Cmax =350 cases per 100,000 (2-week average), Cmin =25 cases per 100,000 (2-week average) and σmin =0.2. Black dashed vertical line is the end of model calibration. Orange dashed vertical line is the time at which vaccination is initiated. f. Proportion of prevalent infections in b. due to new variants.

Citations

Published article

Reeves DB, Bracis C, Swan DA, Burns E, Moore M, Dimitrov D, Schiffer JT. Rapid vaccination and partial lockdown minimize 4th waves from emerging highly contagious SARS-CoV-2 variants. Med (2021).

Original Medrxiv article

Reeves DB, Bracis C, Swan DA, Moore M, Dimitrov D, Schiffer JT. Rapid vaccination and early reactive partial lockdown will minimize deaths from emerging highly contagious SARS-CoV-2 variants. medRxiv (2021).

Mathematical Modeling of Vaccines That Prevent SARS-CoV-2 Transmission

Abstract

SARS-CoV-2 vaccine clinical trials assess efficacy against disease (VEDIS), the ability to block symptomatic COVID-19. They only partially discriminate whether VEDIS is mediated by preventing infection completely, which is defined as detection of virus in the airways (VESUSC), or by preventing symptoms despite infection (VESYMP). Vaccine efficacy against transmissibility given infection (VEINF), the decrease in secondary transmissions from infected vaccine recipients, is also not measured. Using mathematical modeling of data from King County Washington, we demonstrate that if the Moderna (mRNA-1273QS) and Pfizer-BioNTech (BNT162b2) vaccines, which demonstrated VEDIS > 90% in clinical trials, mediate VEDIS by VESUSC, then a limited fourth epidemic wave of infections with the highly infectious B.1.1.7 variant would have been predicted in spring 2021 assuming rapid vaccine roll out. If high VEDIS is explained by VESYMP, then high VEINF would have also been necessary to limit the extent of this fourth wave. Vaccines which completely protect against infection or secondary transmission also substantially lower the number of people who must be vaccinated before the herd immunity threshold is reached. The limited extent of the fourth wave suggests that the vaccines have either high VESUSC or both high VESYMP and high VEINF against B.1.1.7. Finally, using a separate intra-host mathematical model of viral kinetics, we demonstrate that a 0.6 log vaccine-mediated reduction in average peak viral load might be sufficient to achieve 50% VEINF, which suggests that human challenge studies with a relatively low number of infected participants could be employed to estimate all three vaccine efficacy metrics.

Key results figure

High VE_SUSC or high VE_INF alone can effectively limit cases and deaths with initial vaccine prioritization to the elderly. For unvaccinated (black lines) and each vaccine cohort red lines, legend), we project a. infections, b. diagnosed cases, c. hospitalizations and d. deaths, as well as e. social distancing relative to pre-pandemic levels and f. the effective reproductive number. The first four columns (a-d) are organized by row: top = daily incidence, middle = cumulative, bottom = reduction since day of vaccination. Waves of infection are numbered 1-4. Nine combinations of VE_SUSC and VE_INF are considered while VE_SYMP is fixed at 10%. High VE_SUSC (90%) simulations are blue and have similar outcomes to one another. Moderate VE_SUSC (50%) simulations are green. Low VE_SUSC (10%) simulations are red / pink. Dark lines are high VE_INF (90%) and have similar outcomes to one another. Moderate darkness are medium VE_INF (50%). Light lines are low VE_INF (10%). The largest reduction in cases is associated with either high VE_SUSC or VE_INF. 5000 vaccines are given per day starting January 21 (yellow square) until 50% are vaccinated. Case threshold for reinstituting physical distancing to 0.6 is 300 per 100,000 and for relaxation is 100 per 100,000. 80% of vaccines are initially allocated to the elderly with the remaining 20% to middle-aged cohorts.

Citation

Swan DA, Goyal A, Bracis C, Moore M, Krantz E, Brown E, Cardozo-Ojeda F, Reeves DB, Gao F, Gilbert PB, Corey L, Cohen MS, Janes H, Dimitrov D, Schiffer JT. Mathematical Modeling of Vaccines That Prevent SARS-CoV-2 Transmission. Viruses. 2021 Sep 24;13(10):1921. doi: 10.3390/v13101921. PMID: 34696352; PMCID: PMC8539635.

COVID-19 vaccines that reduce symptoms but do not block infection need higher coverage and faster rollout to achieve population impact

Abstract

Background. Trial results for two COVID-19 vaccines suggest at least 90% efficacy against symptomatic disease (VE_DIS). It remains unknown whether this efficacy is mediated by lowering SARS-CoV-2 infection susceptibility (VE_SUSC) or development of symptoms after infection (VE_SYMP). We aim to assess and compare the population impact of vaccines with different efficacy profiles (VE_SYMP and VE_SUSC) satisfying licensure criteria.

Methods. We developed a mathematical model of SARS-CoV-2 transmission, calibrated to data from King County, Washington. Rollout scenarios starting December 2020 were simulated with combinations of VE_SUSC and VE_SYMP resulting in up to 100% VE_DIS. We assumed no reduction of infectivity upon infection conditional on presence of symptoms. Proportions of cumulative infections, hospitalizations and deaths prevented over 1 year from vaccination start are reported.

Findings. Rollouts of 1M vaccinations (5,000 daily) using vaccines with 50% VE_DIS are projected to prevent 30%-58% of infections and 38%-58% of deaths over one year. In comparison, vaccines with 90% VE_DIS are projected to prevent 47%-78% of infections and 58%-77% of deaths over one year. In both cases, there is a greater reduction if VE_DIS is mediated mostly by VE_SUSC. The use of a “symptom reducing” vaccine will require twice as many people vaccinated than a “susceptibility reducing” vaccine with the same 90% VE_DIS to prevent 50% of the infections and death over one year. Delaying the start of the vaccination by 3 months decreases the expected population impact by approximately 40%.

Conclusions. Vaccines which prevent COVID-19 disease but not SARS-CoV-2 infection, and thereby shift symptomatic infections to asymptomatic infections, will prevent fewer infections and require larger and faster vaccination rollouts to have population impact, compared to vaccines that reduce susceptibility to infection. If uncontrolled transmission across the U.S. continues, then expected vaccination in Spring 2021 will provide only limited benefit.

Key results figure

Projected vaccine effectiveness under various vaccine efficacy profiles. Contour plots of the proportions of: A) cumulative infections prevented and B) cumulative deaths prevented over 1 year after the start of vaccine rollout by vaccines with different effects on susceptibility (VE_SUSC) and the risk to develop symptoms (VE_SYMP). Rollout assumes 5,000 vaccinated daily till 1,000,000 vaccinations are reached. Thick lines represent VE profiles resulting in 50% and 90% reduction in symptomatic disease (VE_DIS).

Citation

Swan DA, Bracis C, Janes H, Moore M, Matrajt L, Reeves DB, Burns E, Donnell D, Cohen MS, Schiffer JT, Dimitrov D. COVID-19 vaccines that reduce symptoms but do not block infection need higher coverage and faster rollout to achieve population impact. Scientific Reports (2021).

Widespread testing, case isolation and contact tracing may allow safe school reopening with continued moderate physical distancing: a modeling analysis of King County, WA data

Abstract

Background. In late March 2020, a “Stay Home, Stay Healthy” order was issued in Washington State in response to the COVID-19 pandemic. On May 1, a 4-phase reopening plan began. We investigated whether adjunctive prevention strategies would allow less restrictive physical distancing to avoid second epidemic waves and secure safe school reopening.

Methods. We developed a mathematical model, stratifying the population by age, infection status and treatment status to project SARS-CoV-2 transmission during and after the reopening period. The model was parameterized with demographic and contact data from King County, WA and calibrated to confirmed cases, deaths and epidemic peak timing. Adjunctive prevention interventions were simulated assuming different levels of pre-COVID physical interactions (pC_PI) restored.

Results. The best model fit estimated ~35% pC_PI under the lockdown which prevented ~17,000 deaths by May 15. Gradually restoring 75% pC_PI for all age groups between May 15-July 15 would have resulted in ~350 daily deaths by early September 2020. Maintaining <45% pC_PI was required with current testing practices to ensure low levels of daily infections and deaths. Increased testing, isolation of symptomatic infections, and contact tracing permitted 60% pC_PI without significant increases in daily deaths before November and allowed opening of schools with <15 daily deaths. Inpatient antiviral treatment was predicted to reduce deaths significantly without lowering cases or hospitalizations.

Conclusions . We predict that widespread testing, contact tracing and case isolation would allow relaxation of physical distancing, as well as opening of schools, without a surge in local cases and deaths.

Citation

Bracis C, Burns E, Moore M, Swan D, Reeves DB, Schiffer JT, Dimitrov DT. Widespread testing, case isolation and contact tracing may allow safe school reopening with continued moderate physical distancing: a modeling analysis of King County, WA data. Infectious Disease Modelling, 6: 24-35 (2021).