Projecting the COVID-19 immune landscape in Japan in the presence of waning immunity and booster vaccination

Abstract

Coronavirus disease 2019 (COVID-19) booster vaccination has been implemented globally in the midst of surges in infection due to the Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of the present study was to present a framework to estimate the proportion of the population that is immune to symptomatic SARS-CoV-2 infection with the Omicron variant (immune proportion) in Japan, considering the waning of immunity resulting from vaccination and naturally acquired infection. We quantified the decay rate of immunity against symptomatic infection with Omicron conferred by the second and third doses of COVID-19 vaccine. We estimated the current and future vaccination coverage for the second and third vaccine doses from February 17, 2021 to August 1, 2022 and used data on the confirmed COVID-19 incidence from February 17, 2021 to April 10, 2022. From this information, we estimated the age-specific immune proportion over the period from February 17, 2021 to August 1, 2022. Vaccine-induced immunity, conferred by the second vaccine dose in particular, was estimated to rapidly wane. There were substantial variations in the estimated immune proportion by age group because each age cohort experienced different vaccination rollout timing and speed as well as a different infection risk. Such variations collectively contributed to heterogeneous immune landscape trajectories over time and age. The resulting prediction of the proportion of the population that is immune to symptomatic SARS-CoV-2 infection could aid decision-making on when and for whom another round of booster vaccination should be considered. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

Keywords: Mathematical model; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Statistical model; Vaccine effectiveness; Waning immunity.

Fig. 1

The age-specific number of confirmed COVID-19 cases and second vaccine dose coverage in Japan from February 17, 2021 to April 10, 2022. (A–F) The black bars show the confirmed COVID-19 incidence among people aged 20–29 (A), 30–39 (B), 40–49 (C), 50–59 (D), 60–69 (E), and ≥ 70 (F) years. The blue line represents the estimated second vaccine dose coverage; it should be noted that the age grouping of COVID-19 vaccination is slightly different from that of COVID-19 incidence, i.e., aged 15–24 (A), 25–34 (B), 35–44 (C), 45–54 (D), 55–64 (E), and ≥ 65 (F) years. The methods applied for estimating the second vaccine dose coverage are described elsewhere (Sasanami et al., 2022b), and we estimated the coverage until March 13, 2022, when the daily proportion of the population that was newly vaccinated in each age group became lower than 0.01% of the age-specific population and the coverage was deemed to have plateaued.

Fig. 2

Estimated waning of vaccine-induced protection against symptomatic infection with the Omicron variant after the second (left) and third (right) vaccine doses. The blue lines show the estimated protected fraction, with the shaded area representing their 95% confidence intervals (CIs) derived by parametric bootstrapping. The points represent the empirically reported vaccine effectiveness against symptomatic infection, with error bars displaying their 95% CIs, according to a published study (Andrews et al., 2022).

Fig. 3

Reported and predicted booster vaccination coverage stratified by age group for December 1, 2021 to August 1, 2022. (A–F) The dark blue lines show the reported booster vaccination coverage until April 10, 2022, and the light blue dash-dotted line represents the projected booster vaccination coverage among people aged from 20 to 29 (A), 30–39 (B), 40–49 (C), 50–59 (D), 60–69 (E), and ≥ 70 (F) years.

Fig. 4

Age-specific proportion of the population immune to symptomatic SARS-CoV-2 infection from February 17, 2021 to August 1, 2022. (A–F) The lines show the time-dependent proportion of people immune to symptomatic SARS-CoV-2 infection among those aged from 20 to 29 (A), 30–39 (B), 40–49 (C), 50–59 (D), 60–69 (E), and ≥ 70 (F) years, and the shaded areas are their 95% confidence intervals (CIs), computed via the bootstrapping method. The red lines reflect the scenarios in which the immunity from natural infection as well as the immunity from the second and third vaccine doses are considered, whereas the light blue lines reflect the scenarios in which only the immunity from the second and third vaccine doses is taken into account. The projection was performed on April 10, 2022, and the estimates afterward are from a model-based projection.

Fig. 5

Predicted proportion of individuals susceptible to symptomatic SARS-CoV-2 infection on 10 April, 1 June 1, and August 1, 2022. The bars represent the proportion of individuals susceptible to symptomatic SARS-CoV-2 infection over time, according to the age groups 20–29, 30–39, 40–49, 50–59, 60–69, and ≥ 70 years, presented from left to right. The projection was performed on April 10, 2022, and the estimates afterward are from a model-based projection.

Fig. 6

The prefecture-specific immune proportion according to the trend of infection with SARS-CoV-2. The box-plot shows the estimated immune proportion on April 10, 2022 among the prefectures that had decreasing and increasing risks of infection on the left and right, respectively, from February 7 to April 10, 2022. Each dot represents the estimated fraction immune in a single prefecture, and there are in total 47 prefectures in Japan. Grouping each prefecture as decreasing or increasing in its incidence was judged by the growth rate of incidence as on April 10, 2022 taking negative or positive values, respectively. The lines inside the box represent the median, and lower and upper box boundaries are the first and third quantiles, respectively. The whiskers indicate $1.5\times$ the interquartile range from the first and third quantiles.