Lasting Protection Against COVID-19

Effectiveness of Booster Vaccination and Prior Infection in Reducing the Risk of SARS-CoV-2 Infection, Hospitalization, or Death Among Primary Vaccinated Participants

Summary

Importance

Data on the association of COVID-19 vaccination and prior SARS-CoV-2 infection with the risk of SARS-CoV-2 infection and severe COVID-19 outcomes may guide prevention strategies.

Aim

To estimate the time-varying association of primary and booster COVID-19 vaccination and prior SARS-CoV-2 infection with subsequent SARS-CoV-2 infection, hospitalization, and death.

Design, environment and participants

Cohort study of 10.6 million North Carolina residents from March 2, 2020 to June 3, 2022.

Exhibitions

COVID-19 primary vaccine series and boosters and prior SARS-CoV-2 infection.

Main results and measures

Rate ratio (RR) of SARS-CoV-2 infection and risk ratio (HR) of hospitalization and death related to COVID-19.

Results

The median age among the 10.6 million participants was 39 years; 51.3% were women, 71.5% were white, and 9.9% were Hispanic. As of June 3, 2022, 67% of participants had been vaccinated.

There were 2,771,364 SARS-CoV-2 infections, with a hospitalization rate of 6.3% and a mortality rate of 1.4%. The adjusted RR of the primary vaccine series compared with not being vaccinated against infection became 0.53 (95% CI, 0.52-0.53) for BNT162b2, 0.52 (95% CI, 0.52). 51-0.53) for mRNA-1273 and 0.51 (95% CI, 0.52-0.53). 0.50-0.53) for Ad26.COV2.S 10 months after the first dose, but the adjusted HR for hospitalization remained at 0.29 (95% CI, 0.24-0.35) for BNT162b2, 0.27 (95% CI, 0.23-0.32) for -1273 mRNA and 0.35 (95% CI, 0.29-0.42) for Ad26.COV2.S and the adjusted HR of death remained at 0.23 (95% CI, 0.17-0.29) for BNT162b2, 0.15 (95% CI, 0.11-0.20) for mRNA-1273, and 0.24 (95% CI, 0.11-0.29) for 95%, 0.19-0.31) for Ad26.COV2.S.

For the BNT162b2 primary series, boosting in December 2021 with BNT162b2 had an adjusted RR relative to the primary series of 0.39 (95% CI, 0.38-0.40) and boosting with mRNA-1273 had a Adjusted RR of 0.32 (95% CI, 0.30-0.34) against infection after 1 month and boosting with BNT162b2 had an adjusted RR of 0.84 (95% CI, 0.82-0.34). .86) and boosting with mRNA-1273 had an adjusted RR of 0.60 (95% CI, 0.57-0.62) after 3 months.

Among all participants, the adjusted RR of Omicron infection compared with no prior infection was estimated to be 0.23 (95% CI, 0.22-0.24) versus infection, and the adjusted HRs were 0.10 (95% CI, 0.07-0.14) against hospitalization and 0.11 (95% CI, 0.08-0.15) against death at 4 months.

Conclusions and relevance

Receipt of the primary series of COVID-19 vaccines compared to no vaccination, receipt of boosters compared to primary vaccination, and prior infection compared to no prior infection were significantly associated with a lower risk of COVID-19 infection. SARS-CoV-2 (including Omicron) and subsequent hospitalization and death. The associated protection decreased over time, especially against infection.

Comments

A new study of more than 10 million North Carolinians, published in the Journal of the American Medical Association (JAMA), highlights how effective COVID-19 vaccines, boosters and prior infection can be, both for reduce the risk of future infection and prevent hospitalization and death.

The study provides a clearer picture of the separate protections that vaccination and prior infection could provide, and compares the effectiveness of vaccines and boosters between those who have and those who have not had a previous case of COVID-19.

In addition, it demonstrates the effectiveness of the primary series of vaccines against COVID-19 a year and a half after its administration. The findings also suggest that Omicron infection may protect against reinfection with Omicron, although the level of protection decreases over time.

"Our study provides the most comprehensive characterizations of the effectiveness of primary and booster vaccination and prior infection in the United States," said Danyu Lin, PhD, principal investigator of the study and Dennis Gillings Distinguished Professor of Biostatistics at the Gillings School of UNC Global Public Health.

 The researchers found that those who received the primary series of vaccines were less likely to become infected or experience severe outcomes from the infection than those who were not vaccinated, even after a year and a half. Those who received a booster dose had greater protection than those who received only the primary series.

The results also show that booster injection to those not previously infected conferred strong protection, especially against hospitalization and death, while booster injection also provided additional protection to previously infected people.

The data, captured between March 2020 and June 2022, comprises several SARS-CoV-2 variants, including Omicron and its more recent subvariants. While the effectiveness of both the vaccines and prior infection decreased over time, especially against infection with the Omicron variant, protection against hospitalization and death remained strong.

Lin says the rapid decline in protection of boosters and pre-infection against post-infection during the omicron period points to the need for bivalent (omicron) boosters. He hopes the new boosters, which are now available for ages 12 and up, will be similar to boosters in the original variety.

In future studies, the research team aims to investigate the effectiveness of second reinforcers and the effectiveness of new bivalent reinforcers.

Additional researchers on the study include Yu Gu, Yangjianchen Xu, and Professor Donglin Zeng, PhD, of the Gillings School; Bradford Wheeler, MPH, Hayley Young, MPH, and Zack Moore, MD, of the North Carolina Department of Health and Human Services (NCDHHS); and Shadia Khan Sunny, MD, PhD, of the CDC Foundation at NCDHHS.

This group of authors also published a paper on the effects of vaccination and prior infection on omicron infection in children in the New England Journal of Medicine (NEJM) earlier this month. The current JAMA paper focuses on adults and adolescents.

"Dr. Lin’s research over the past year has been vital to advancing our understanding of the protection that vaccines and boosters provide against COVID-19," said Lisa LaVange, PhD, professor and chair of biostatistics at the School Gillings. "This new article in JAMA and the articles previously published in NEJM represent a very successful collaboration between the UNC biostatistics department and scientists at NCDHHS. The combination of the statistical expertise of Dr. Lin and his colleagues and the foundation "NCDHHS’ comprehensive data collection sheds important light on the question of how long the effects of vaccines and boosters last. These insights, in turn, inform important health policy decisions."

LaVange believes this collaboration represents the profound impact that applying cutting-edge statistics can have to address important public health problems today. “I am extremely proud of all of our faculty and graduate students in their contributions to public health research, and this example is just one more instance of their continued success,” she said.