Introduction

Covid-19 vaccination was effective against SARS-CoV-2 infection and severe outcomes; however, vaccine effectiveness waned over time, and repeated booster vaccination was required to enhance immunity [1-3]. The United States government alone has spent more than $30 billion on Covid-19 vaccines, and the prices of the updated bivalent vaccines are expected to rise sharply after the end of the federal COVID-19 Public Health Emergency declaration [4]. A question naturally arises: what are the cost-benefit ratios of the bivalent vaccines?

Methods

To answer this question, we considered surveillance data on the administration of the Moderna and Pfizer-BioNTech bivalent vaccines and clinical outcomes from September 1, 2022 to February 10, 2023 for North Carolina residents 12 years of age or older [3]. Of the 6,306,311 participants who had been previously vaccinated or boosted, 1,279,802 received the bivalent vaccines as a booster dose. A total of 154,581 SARS-CoV-2 infections, 2,208 Covid-19-related hospitalizations, and 867 Covid-19-related deaths were reported over this 23-week period [3].

We estimated the effectiveness (one minus relative risk) of one booster dose under a proportional hazards model for hospitalization (or death) and a proportional rates model for recurrent infection, while adjusting for baseline characteristics [3]. Using the fitted models, we predicted the cumulative frequency of infection and the cumulative incidences of hospitalization and death when none of the participants received a bivalent booster versus when every participant received a bivalent booster on September 1, 2022. We then calculated the differences between the two sets of predicted values and multiplied them by 1 million to estimate the numbers of infections, hospitalizations, and deaths that would be prevented by administering 1 million doses of bivalent vaccines, which would cost $120 million at the price of $120 per dose. We obtained the confidence intervals by the bootstrap method.

Results

The results are shown in column A of Table 1. For individuals 65 years of age or older, 1 million doses would prevent 3,010 (95% CI, 2,737 to 3,283) infections, 489 (95% CI, 362 to 616) hospitalizations, and 179 (95% CI, 117 to 242) deaths. For individuals 12–64 years of age, 1 million doses would prevent 2,379 (95% CI, 2,168 to 2,590) infections, 55 (95% CI, 41 to 68) hospitalizations, and 10 (95% CI, 6 to 14) deaths. The number of infections prevented would be much higher than the numbers of hospitalization and death prevented, and the numbers of hospitalizations and deaths prevented would be much higher in the older age group than in the younger age group. The impact of bivalent boosters on the study cohort is shown in Table 2.

The number of prevented events depends on the duration of follow-up. The above results pertain to a duration of 23 weeks after booster administration. Because of the rapid waning of booster effectiveness against infection [3], no additional infections would be prevented after 23 weeks. Booster effectiveness against hospitalization and death also waned over time but was 34% and 38%, respectively, at 23 weeks [3], such that the numbers of hospitalizations and deaths to be eventually prevented would be greater than what are shown in column A of Table 1.

The surveillance system did not fully capture clinical outcomes, especially infections and hospitalizations, such that the actual numbers of infections and hospitalizations prevented would be greater than what are shown in column A of Table 1. More importantly, the transmissibility and lethality of the virus vary over time. Thus, we performed sensitivity analyses by assuming that the background risks of infection, hospitalization, and death are two times or half of the levels observed in our study while booster effectiveness remains the same. The results are shown in the last two columns of Table 1. Unsurprisingly, the number of prevented events increases (or decreases) as the disease incidence rises (or drops).

Table 1: Number of Covid-19 Events Prevented by One Million Doses of Bivalent Vaccines.

Table 2: Numbers of events that would have been prevented (95% CI) if all non-booster participants had received boosters on September 1, 2022 and additional numbers of events that would have occurred (95% CI) if booster recipients had not received boosters during the period of September 1, 2022—February 19, 2023 among North Carolina residents 12 years of age or older who were eligible to receive bivalent boosters.

Discussion

Booster vaccination was much more beneficial for people 65 years of age or older than for people 12–64 years of age, mainly because the risks of hospitalization and death were much higher in the older age group. The cost-benefit ratio of a vaccination program will depend on vaccine effectiveness, the background risks of infection and severe outcomes, the prices of the vaccines, as well as the costs associated with hospitalization and years of life lost.

References

1. Lin DY, Gu Y, Wheeler B, et al. Effectiveness of Covid-19 vaccines over a 9-month period in North Carolina. N Engl J Med 386 (2022): 933-941.
2. Lin DY, Gu Y, Xu Y, et al. Association of primary and booster vaccination and prior infection with SARS-CoV-2 infection and severe COVID-19 outcomes. JAMA 328 (2022): 1415-1426.
3. Lin DY, Xu Y, Gu Y, et al. Durability of bivalent boosters against omicron subvariants. N Engl J Med 388 (2023): 1818-1820.
4. Kates J, Cox C, Michaud J. How much could Covid-19 vaccines cost the U.S. after commercialization?