Customize your JAMA Network experience by selecting one or more topics from the list below.
Using the adjusted incidence rate ratio data presented in the table, I calculated vaccine effectiveness relative to the primary doses to compare the homologous and heterologous booster groups as follows.
Relative risk reduction (RRR) is 73% (1 minus 0.272) for homologous Pfizer vaccination ("P-P-P"), and 82% (1 minus 0.177) for heterologous vaccination ("P-P-Moderna"). The two CIs do not overlap so the difference in vaccine effectiveness (VE) appears statistically significant.
Relative risk reduction (RRR) is 95% (1 minus 0.047) for homologous Pfizer vaccination and 92%(1 minus 0.078) for heterologous. Their
Tan SHX, Pung R, Wang L, et al. Association of Homologous and Heterologous Vaccine Boosters With COVID-19 Incidence and Severity in Singapore. JAMA. 2022;327(12):1181–1182. doi:10.1001/jama.2022.1922
Reports of waning antibody levels and breakthrough infections among vaccinated individuals1 have prompted the recommendation for vaccine boosters to prevent SARS-CoV-2 infections. Despite more than 80% of the population in Singapore having received 2 doses of a COVID-19 vaccine, cases surged in September 2021 with the relaxation of social distancing and quarantine measures. In response, adults aged 60 years and older who completed their primary vaccination series at least 6 months prior were invited to receive a booster injection and given a choice of either 30-μg BNT162b2 (Pfizer-BioNTech) or 50-μg mRNA-1273 (Moderna). We estimated SARS-CoV-2 infections and disease severity with the receipt of a booster and by type of booster.
This study was carried out under the Infectious Diseases Act for policy decision-making and exempted from ethical review and informed consent by the Singapore Ministry of Health.
Rates and severity of SARS-CoV-2 infections between September 15 and October 31, 2021, among those eligible to receive vaccine boosters between September 15 and October 15, 2021, were analyzed based on official data reported to the Singapore Ministry of Health. Cases were identified through testing of symptomatic individuals and nonsymptomatic high-risk workers and close contacts. Outcomes included polymerase chain reaction–confirmed infections and severe disease (requiring oxygen supplementation, intensive care admission, or death due to COVID-19). Individuals were classified under the booster group 12 days after receiving a vaccine booster and under the nonbooster group otherwise to account for time required for antibody levels to rise.2 Person-days at risk were reported because individuals could contribute observations to both the nonbooster and booster groups. Using a Poisson regression, we estimated the incidence rate ratio (IRR) of confirmed infections and severe disease between booster and nonbooster groups by type of vaccine received for the primary series (BNT162b2 or mRNA-1273). Covariates included sex, race (4 official racial categories reported in Singapore are Chinese, Malay, Indian, and others and registered at birth according to children’s parents’ race), housing type as a marker of socioeconomic status, age group, date of second vaccine dose to account for possible waning of immunity, and individual dummy variables for calendar date to adjust for the varying force of infection over the study period (eMethods in the Supplement). We obtained IRRs for individuals receiving the same vaccine as a booster (homologous boosted) and those receiving a different vaccine (heterologous boosted). Data analysis was carried out in Stata version 17.0 (StataCorp LLC), and a 2-sided P < .05 was considered statistically significant.
Among 703 209 eligible individuals during the study period, 576 132 received boosters. The study included 22 643 521 and 9 339 981 person-days among the nonbooster and booster groups, respectively. By person-days, 59% were aged 60 to 69 years, 29% were aged 70 to 79 years, and 11% were aged 80 years and older, with 53% being female.
Among individuals who received BNT162b2 for their primary series, the incidences (per million person-days) of confirmed and severe infections were 227.9 and 1.4 for homologous-boosted compared with 600.4 and 20.5 for nonboosted individuals. The IRRs were 0.272 (95% CI, 0.258-0.286) for the confirmed cases among homologous-boosted individuals and 0.047 (95% CI, 0.026-0.084) for severe cases (Table). For heterologous-boosted individuals, the incidences of confirmed and severe infections were 147.9 and 2.3 cases per million person-days, respectively, with IRRs of 0.177 (95% CI, 0.138-0.227) and 0.078 (95% CI, 0.011-0.560).
For individuals who received mRNA-1273 for their primary series, the incidence of confirmed infections for homologous-boosted individuals was 133.9 cases per million person-days (IRR, 0.198 [95% CI, 0.144-0.271]). For heterologous-boosted individuals, the incidence of confirmed infections was 100.6 per million person-days (IRR, 0.140 [95% CI, 0.052-0.376]). The number of severe infections among individuals receiving mRNA-1273 for their primary series was too small to assess IRRs.
Heterologous boosting was associated with lower SARS-CoV-2 incidence rates than homologous boosting. Severe infections were lower among those receiving a booster after BNT162b2 as the primary series compared with nonboosted individuals, regardless of the type of booster.
Limitations of the study include potential confounding from unobservable individual characteristics that may influence individuals’ choice of booster, a short follow-up period, small numbers of infections after mRNA-1273 administration, and lack of data from younger age groups. The study results support recommendations for vaccine boosters and suggest that heterologous boosting may provide greater protection against COVID-19.
Accepted for Publication: January 31, 2022.
Published Online: February 11, 2022. doi:10.1001/jama.2022.1922
Corresponding Author: Sharon Hui Xuan Tan, MPH, Tahir Foundation Bldg, National University of Singapore, 12 Science Dr 2, #10-01, Singapore 117549 (email@example.com).
Author Contributions: Dr K. B. Tan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Pung, Lye, Ong, K. B. Tan.
Acquisition, analysis, or interpretation of data: S. H. X. Tan, Wang, Cook, K. B. Tan.
Drafting of the manuscript: S. H. X. Tan, Wang, K. B. Tan.
Critical revision of the manuscript for important intellectual content: Pung, Wang, Lye, Ong, Cook, K. B. Tan.
Statistical analysis: Pung, Cook, K. B. Tan.
Administrative, technical, or material support: S. H. X. Tan, Wang.
Supervision: Lye, Ong.
Conflict of Interest Disclosures: Dr Wang reported having a patent for a test for SARS-CoV-2 neutralizing antibodies licensed to GenScript and commercialized as cPass Neutralization Antibody Detection Kit. No other disclosures were reported.
Additional Contributions: We thank Derrick Heng, MPH, for advice on the design and interpretation of the study. We thank Vernon Lee, PhD, and Marc Ho, MPH, for oversight of the public health management and contact tracing activities for the identification of COVID-19–positive cases. We thank Joon Kiat Chua, BSocSci, Shannen Ho, MSc, Yong Kai Lim, BEng, Yi Ding Lim, MSc, Darren Chan, BEng, and Jing Jie Ong, BSc, for assisting with data collation and database management. All are employees of the Singapore Ministry of Health. No compensation was received for their contributions to this work.