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

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.

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

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.

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

Trial results for two COVID-19 vaccines suggest at least 90% efficacy against symptomatic disease (VEDIS). It remains unknown whether this efficacy is mediated by lowering SARS-CoV-2 infection susceptibility (VESUSC) or development of symptoms after infection (VESYMP). We aim to assess and compare the population impact of vaccines with different efficacy profiles (VESYMP and VESUSC) satisfying licensure criteria. 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 VESUSC and VESYMP resulting in up to 100% VEDIS. 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. Rollouts of 1 M vaccinations (5000 daily) using vaccines with 50% VEDIS are projected to prevent 23–46% of infections and 31–46% of deaths over 1 year. In comparison, vaccines with 90% VEDIS are projected to prevent 37–64% of infections and 46–64% of deaths over 1 year. In both cases, there is a greater reduction if VEDIS is mediated mostly by VESUSC. The use of a “symptom reducing” vaccine will require twice as many people vaccinated than a “susceptibility reducing” vaccine with the same 90% VEDIS to prevent 50% of the infections and death over 1 year. Delaying the start of the vaccination by 3 months decreases the expected population impact by more than 50%. 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.

Acute Hepatitis A Viral Infection in People Living with HIV with Previously Documented Hepatitis A Immunity or Appropriate Vaccination: A Case Series

We describe four people living with HIV (PLHIV) who acquired acute hepatitis A (HAV) infection during recent King County, WA outbreaks despite documented immunity and/or vaccination. HAV revaccination may be needed in PLHIV with risk factors for HAV infection regardless of pre-existing immunity.