Primary vaccinations and boosters effective in reducing COVID-19 severity during Delta and Omicron predominance

In a recent study published in the Journal of the American Medical Association, researchers analyzed coronavirus disease 2019 (COVID-19) vaccination and surveillance data to understand the effect of primary vaccinations, boosters, and prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on severe COVID-19 outcomes and subsequent infections.

Study: Association of Primary and Booster Vaccination and Prior Infection With SARS-CoV-2 Infection and Severe COVID-19 Outcomes. Image Credit: davide bonaldo/Shutterstock


Global vaccination efforts have been relatively successful in controlling the transmission and severity of COVID-19. However, the vaccine-induced humoral immunity is seen to fade over time, making booster doses essential to ensure continued protection against SARS-CoV-2.

Various studies have explored the effect of vaccinations, prior SARS-CoV-2 infections, and a combination of the two on the humoral immunity against emergent variants of SARS-CoV-2. Understanding the temporal aspects of vaccine- and previous infection-induced immunity against SARS-CoV-2 and the protection granted by this immunity against severe COVID-19 from emergent variants is very important in formulating prevention strategies.

About the study

In the present study, the researchers analyzed COVID-19 surveillance data from North Carolina between March 2 and June 3, 2022, which contained laboratory-reported polymerase chain reaction (PCR) and antigen test results, and information on demographics and clinical outcomes. The vaccination history data from December 11, 2020, to June 3, 2022, was procured from the COVID-19 vaccine management system records. The cohort study consisted of data for 10.6 million North Carolina residents.

The Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen/Johnson & Johnson (Ad26.COV2.S) vaccines and SARS-CoV-2 infections during the pre-Delta, Delta, and Omicron dominance periods were considered the exposure variables. Positive PCR and antigen test results were the primary outcomes, while severe COVID-19 manifestations such as hospitalization and death were considered secondary outcomes in the analyses.

The statistical analyses were divided into three parts to understand the effects of the exposure variables on the outcomes. In the first part, the association parameters for one and two doses of BNT162b2 and mRNA-1273, one dose of Ad26.COV2.S and prior infections were assessed simultaneously, and the effect of each exposure on each outcome was estimated by adjusting for the other exposure variables.

The second section of the analysis estimated booster effectivity in individuals with complete primary vaccinations. The waning effect of the booster vaccination on each outcome was calculated by incorporating the time elapsed since the booster vaccination into the analysis. The association of six common combinations of boosters and primary vaccines on COVID-19-related hospitalization and death was analyzed.

The last statistical analysis set explored the interaction between booster vaccines and prior infections in individuals with complete primary vaccinations. Demographic factors such as age, race and ethnicity, sex, and geographic region were included as covariates in all three sets of analyses to prevent individual and geographic characteristics from confounding the results.


The results indicated that all three vaccines tested in the study (BNT162b2, mRNA-1273, and Ad26.COV2.S) were effective in preventing hospitalization and mortality. The efficacy of the vaccines decreased with time, with reduced protection against SARS-CoV-2 Omicron infections but sustained protection against hospitalization and death.

Prior SARS-CoV-2 infections reduced the risk of reinfections, hospitalization, and death, but the protective effects diminished with time. Booster vaccines increased protection against infection and severe outcomes in primed individuals with and without previous infections.

The study found that booster efficacy waned over a four-to-six-month period, especially during the dominance period of the SARS-CoV-2 Omicron variant. Contrary to other studies from the United States (U.S.), the results of the present study suggested that heterologous messenger ribonucleic acid (mRNA) vaccine boosting granted greater protection than homologous booster shots.

The authors also discussed some limitations of the study, which included unmeasurable confounders and unreported or undiagnosed milder COVID-19 infections. Additionally, there were gaps in the hospitalization and mortality data, and with the availability of at-home testing, the information on infections also became unreliable. Lastly, the study did not consider factors like non-COVID-19-related deaths, migration, vaccination through federal departments, or multiple doses for immunocompromised individuals.


Overall, the findings of this cohort study showed that humoral immunity from primary vaccination series involving any of the three COVID-19 vaccines (BNT162b2, mRNA-1273, and Ad26.COV2.S), homologous boosters, and previous SARS-CoV-2 infections was effective in reducing the severity of subsequent SARS-CoV-2 infections, including the recent Omicron variant.

The protection granted by the boosters and prior infections diminished over time, increasing reinfection risk, especially during Omicron predominance. However, humoral immunity was still effective in reducing severe COVID-19 symptoms and associated hospitalization or death.

Journal reference:
  • Lin, D.-Y., Gu, Y., Xu, Y., Wheeler, B., Young, H., Sunny, S. K., Moore, Z., & Zeng, D. (2022). Association of Primary and Booster Vaccination and Prior Infection With SARS-CoV-2 Infection and Severe COVID-19 Outcomes. JAMA. doi:

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Antigen, Coronavirus, Coronavirus Disease COVID-19, covid-19, Efficacy, Homologous, immunity, Laboratory, Mortality, Omicron, Polymerase, Polymerase Chain Reaction, Respiratory, Ribonucleic Acid, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Vaccine

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Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.

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