Could widespread use of antiviral treatment curb the COVID-19 pandemic? A modeling study.

BACKGROUND: Despite the development of safe and effective vaccines, effective treatments for COVID-19 disease are still urgently needed. Several antiviral drugs have shown to be effective in reducing progression of COVID-19 disease. METHODS: 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 with different demographic structure and current levels of vaccination coverage: Kenya, Mexico, United States (US) and Belgium. We analyzed antiviral effects on reducing hospitalization and death, and potential antiviral effects on reducing transmission. For each country, we varied daily treatment initiation rate (DTIR) and antiviral effect in reducing transmission (AVT). RESULTS: Irrespective of location and AVT, widespread antiviral treatment of symptomatic adult infections (20% DTIR) prevented the majority of COVID-19 deaths, and recruiting 6% of all adult symptomatic infections daily reduced mortality by over 20% in all countries. Furthermore, our model projected that targeting antiviral treatment to the oldest age group (65 years old and older, DTIR of 20%) can prevent over 30% of deaths. Our results suggest that early antiviral treatment (as soon as possible after inception of infection) is needed to mitigate transmission, preventing 50% more infections compared to late treatment (started 3 to 5 days after symptoms onset). Our results highlight the synergistic effect of vaccination and antiviral treatment: as the vaccination rate increases, antivirals have a larger relative impact on population transmission. Finally, our model projects that even in highly vaccinated populations, adding antiviral treatment can be extremely helpful to mitigate COVID-19 deaths. CONCLUSIONS: These results suggest that antiviral treatments can become a strategic tool that, in combination with vaccination, can significantly reduce COVID-19 hospitalizations and deaths and can help control SARS-CoV-2 transmission.

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

The rapid spread of highly transmissible SARS-CoV-2 variants combined with slowing pace of vaccination in Fall 2021 created uncertainty around the future trajectory of the epidemic in King County, Washington, USA. We analyzed the benefits of offering vaccination to children ages 5-11 and expanding the overall vaccination coverage using mathematical modeling. We adapted a mathematical model of SARS-CoV-2 transmission, calibrated to data from King County, Washington, to simulate scenarios of vaccinating children aged 5-11 with different starting dates and different proportions of physical interactions (PPI) in schools being restored. Dynamic social distancing was implemented in response to changes in weekly hospitalizations. Reduction of hospitalizations and estimated time under additional social distancing measures are reported over the 2021-2022 school year. In the scenario with 85% vaccination coverage of 12+ year-olds, offering early vaccination to children aged 5-11 with 75% PPI was predicted to prevent 756 (median, IQR 301-1434) hospitalizations cutting youth hospitalizations in half compared to no vaccination and largely reducing the need for additional social distancing measures over the school year. If, in addition, 90% overall vaccination coverage was reached, 60% of remaining hospitalizations would be averted and the need for increased social distancing would almost certainly be avoided. Our work suggests that uninterrupted in-person schooling in King County was partly possible because reasonable precaution measures were taken at schools to reduce infectious contacts. Rapid vaccination of all school-aged children provides meaningful reduction of the COVID-19 health burden over this school year but only if implemented early. It remains critical to vaccinate as many people as possible to limit the morbidity and mortality associated with future epidemic waves.

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.

Quantifying the Impact of Lifting Community Nonpharmaceutical Interventions for COVID-19 During Vaccination Rollout in the United States.

Using a mathematical model, we estimated the potential impact on mortality and total infections of completely lifting community nonpharmaceutical interventions when only a small proportion of the population has been fully vaccinated in 2 states in the United States. Lifting all community nonpharmaceutical interventions immediately is predicted to result in twice as many deaths over the next 6 months as a more moderate reopening allowing 70% of prepandemic contacts.

Optimizing vaccine allocation for COVID-19 vaccines shows the potential role of single-dose vaccination.

Most COVID-19 vaccines require two doses, however with limited vaccine supply, policymakers are considering single-dose vaccination as an alternative strategy. Using a mathematical model combined with optimization algorithms, we determined optimal allocation strategies with one and two doses of vaccine under various degrees of viral transmission. Under low transmission, we show that the optimal allocation of vaccine vitally depends on the single-dose efficacy. With high single-dose efficacy, single-dose vaccination is optimal, preventing up to 22% more deaths than a strategy prioritizing two-dose vaccination for older adults. With low or moderate single-dose efficacy, mixed vaccination campaigns with complete coverage of older adults are optimal. However, with modest or high transmission, vaccinating older adults first with two doses is best, preventing up to 41% more deaths than a single-dose vaccination given across all adult populations. Our work suggests that it is imperative to determine the efficacy and durability of single-dose vaccines, as mixed or single-dose vaccination campaigns may have the potential to contain the pandemic much more quickly.

Vaccine optimization for COVID-19: Who to vaccinate first?

Vaccines, when available, will likely become our best tool to control the COVID-19 pandemic. Even in the most optimistic scenarios, vaccine shortages will likely occur. Using an age-stratified mathematical model paired with optimization algorithms, we determined optimal vaccine allocation for four different metrics (deaths, symptomatic infections, and maximum non-ICU and ICU hospitalizations) under many scenarios. We find that a vaccine with effectiveness ≥50% would be enough to substantially mitigate the ongoing pandemic, provided that a high percentage of the population is optimally vaccinated. When minimizing deaths, we find that for low vaccine effectiveness, irrespective of vaccination coverage, it is optimal to allocate vaccine to high-risk (older) age groups first. In contrast, for higher vaccine effectiveness, there is a switch to allocate vaccine to high-transmission (younger) age groups first for high vaccination coverage. While there are other societal and ethical considerations, this work can provide an evidence-based rationale for vaccine prioritization.

Evaluating the Effectiveness of Social Distancing Interventions to Delay or Flatten the Epidemic Curve of Coronavirus Disease.

By April 2, 2020, >1 million persons worldwide were infected with severe acute respiratory syndrome coronavirus 2. We used a mathematical model to investigate the effectiveness of social distancing interventions in a mid-sized city. Interventions reduced contacts of adults >60 years of age, adults 20-59 years of age, and children <19 years of age for 6 weeks. Our results suggest interventions started earlier in the epidemic delay the epidemic curve and interventions started later flatten the epidemic curve. We noted that, while social distancing interventions were in place, most new cases, hospitalizations, and deaths were averted, even with modest reductions in contact among adults. However, when interventions ended, the epidemic rebounded. Our models suggest that social distancing can provide crucial time to increase healthcare capacity but must occur in conjunction with testing and contact tracing of all suspected cases to mitigate virus transmission.