Study examines the incidence of severe COVID-19 in fully vaccinated and boosted high-risk populations

In a recent study published in the Journal of the American Medical Association, a team of researchers studied a cohort of patients at the United States (U.S) Veterans Health Administration facilities to determine the incidence of severe coronavirus disease 2019 (COVID-19) outcomes among individuals with primary and booster doses of any combination of BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines.

Study: Incidence of Severe COVID-19 Illness Following Vaccination and Booster With BNT162b2, mRNA-1273, and Ad26.COV2.S Vaccines. Image Credit: Treecha/Shutterstock


While studies have shown that complete primary vaccinations combined with booster doses have been effective in limiting the number as well as the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, waning immunity and the emergence of SARS-CoV-2 variants have been associated with the risk of breakthrough infections, especially in high-risk populations.

The U.S. Centers for Disease Control and Prevention has now recommended that the interval between the primary vaccinations and the booster be shortened to three months from five months to maintain effective immunity. Although studies have shown that booster vaccinations prevent severe COVID-19 clinical outcomes, the efficacy of primary vaccinations and boosters in protecting immunocompromised and high-risk individuals has not been studied.

About the study

The present study used a cohort of participants from the U.S. Veterans Health Administration facilities who had received combinations of BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines for their primary and booster vaccinations. The study was conducted between July 1, 2021, and May 30, 2022, and consisted of 1,610,719 participants.

The primary and booster vaccination combinations were considered the exposure variables. The three measured outcomes were symptomatic breakthrough cases of COVID-19, hospitalization with or death due to any COVID-19 symptoms or pneumonia in the 30 days from breakthrough infection, and hospitalization or death due to severe COVID-19 pneumonia within 30 days of infection.

COVID-19 pneumonia was defined based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes. Severe COVID-19 pneumonia was defined based on ICD-10 codes and the need for mechanical ventilation.

A large number of covariates were considered in the analyses, including demographic factors such as age, sex, race, geographic location, and marital status, as well as parameters such as body mass index and a variety of comorbidities. A comprehensive list of comorbidities spanning cardiovascular, renal, respiratory, vertebral, and immune system-related conditions and cancer were included in the study. Behavioral risks such as smoking and alcohol use were also considered.


The results showed that the risk of COVID-19-related hospitalization and death was lower in individuals with primary and booster vaccine coverage. The observation period of the study overlapped the predominance of the Delta variant and multiple Omicron subvariants, which suggested that the vaccines provided effective protection against the emergent variants, despite evidence of immune escape by some of the subvariants.

While all the participants in the study belonged to high-risk populations based on age (65 years or older) or serious comorbidities, the authors noted that the severe symptoms and increased incidence of infection were associated with immunocompromised individuals. Hospitalizations varied greatly among these groups, with 1.9, 6.7, and 39.6 hospitalizations per 10,000 people for 65 years or older, high-risk comorbid, and immunocompromised individuals, respectively.

The authors believe that their assessment of COVID-9 severity based specifically on pneumonia as an outcome strengthened the study by eliminating potential misclassifications of symptoms or severity.

The study, however, had several limitations. Apart from not accounting for COVID-19 exposure behaviors, it excluded nursing homes, which have a substantial portion of the high-risk population. While the study did include female, Latino, and African American individuals, the participants were mostly White men, making the generalization of the results difficult.


To summarize, the findings suggested that all combinations of Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen/Johnson & Johnson (Ad26.COV2.S) vaccines for the primary vaccination and one booster dose were effective in lowering the risk of COVID-19-associated hospitalization and death among high-risk community-dwelling populations in the U.S. 

Except for immunocompromised individuals, the primary and single booster vaccinations seemed to protect the high-risk groups with comorbidities against even the emergent variants such as Delta and Omicron BA.1, BA.2, and BA.2.12.1. The authors concluded that additional booster doses during the study period would have been of benefit only to the immunocompromised patients.

Journal reference:
  • Kelly, J. D., Leonard, S., Hoggatt, K. J., Boscardin, W. J., Lum, E. N., Moss-Vazquez, T. A., Andino, R., Wong, J. K., Byers, A., Bravata, D. M., Tien, P. C., & Keyhani, S. (2022). Incidence of Severe COVID-19 Illness Following Vaccination and Booster With BNT162b2, mRNA-1273, and Ad26.COV2.S Vaccines. JAMA. doi:

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

Tags: Alcohol, Body Mass Index, Cancer, Coronavirus, Coronavirus Disease COVID-19, covid-19, Efficacy, Immune System, immunity, Nursing, Omicron, Pneumonia, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Smoking, 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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