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

Abstract

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. 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. Rollouts of 1 M vaccinations (5000 daily) using vaccines with 50% VE_DIS are projected to prevent 23-46% of infections and 31-46% of deaths over 1 year. In comparison, vaccines with 90% VE_DIS 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 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 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.

Figure 1

Schematic of the modeling analysis. (A) Diagram of the population transmission model with solid lines representing the flows of individuals between compartments and dotted lines indicating compartments which contribute to diagnosed cases; (B) mixing matrix between age groups showing proportions of contacts each group (row) has with the other groups (columns); (C) simplified diagram of the SARS-CoV2 transmission (red arrow) and the resulting force of infection (black arrow) in absence of vaccine and (D) the potential vaccine effects on the transmission and the force of infection.

Figure 2

Epidemic projections with different vaccine efficacy profiles. Comparison of (A) cumulative infections; (B) cumulative hospitalizations and (C) cumulative deaths over time simulated with different efficacy profiles assuming vaccination start date of Dec. 1, 2020 and rolled out with 5000 vaccinated daily until 1,000,000 vaccinations are reached. Vaccine 1 (10% VE_SUSC and 44.4% VE_SYMP) and Vaccine 2 (40% VE_SUSC and 16.7% VE_SYMP) result in 50% reduction in symptomatic disease (VE_DIS) while Vaccine 3 (10% VE_SUSC and 88.9% VE_SYMP) and Vaccine 4 (80% VE_SUSC and 50% VE_SYMP) result in 90% VE_DIS. All projections represent the mean value of epidemic simulations using 100 calibrated parameter sets.

Figure 3

Projected vaccine effectiveness. 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 5000 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).

Figure 4

Importance of the timing and the coverage achieved with the vaccine rollout. Comparison of the projected reductions in the number of: (A,D) cumulative infections; (B,E) cumulative hospitalizations and (C,F) cumulative deaths over 1 year due to the use of vaccines with different efficacy profiles compared to base-case scenarios without vaccination. (A–C) compare vaccine rollouts which start on Dec. 1, 2020 (white boxes), Sept. 1, 2020 (yellow boxes) or March 1, 2021 (gray boxes) assuming 5000 vaccinated daily till 1,000,000 vaccinations are reached. (D–F) show the impact of rollouts starting on Dec. 1, 2020 and reaching different number of total vaccinations over 200 days. Vaccine 1 (10% VE_SUSC and 44.4% VE_SYMP) and Vaccine 2 (40% VE_SUSC and 16.7% VE_SYMP) result in 50% reduction in symptomatic disease (VE_DIS) while Vaccine 3 (10% VE_SUSC and 88.9% VE_SYMP) and Vaccine 4 (80% VE_SUSC and 50% VE_SYMP) result in 90% VE_DIS. Lines represent the mean value while boxplots represent the uncertainty generated by 100 calibrated simulations.