The Study Looks at the Prevalence of Severe Covid-19 in High-risk, Fully Vaccinated and Boosted Populations

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


While studies have shown that complete primary vaccinations in combination with booster doses are effective in reducing the number and severity of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declining immunity and the emergence of SARS-CoV-2 variants have been linked to an increased risk of outbreak infections, particularly in high-risk populations.

To maintain good protection, the US Centers for Disease Control and Prevention now recommends decreasing the period between first immunizations and boosters to three months rather than five months. While studies have demonstrated that booster vaccines with COVID-19 avoid adverse clinical outcomes, the efficacy of primary immunizations and boosters in protecting immunocompromised and high-risk persons has not been investigated.

Concerning the research

The current investigation included a cohort of patients from US Veterans Health Administration hospitals who had received primary and booster immunizations with combinations of BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines. The study has 1,610,719 participants and took place between July 1, 2021, and May 30, 2022.

The exposure factors were the combinations of main and booster vaccination. The three outcomes were symptomatic COVID-19 breakthrough cases, hospitalization with or death from COVID-19 symptoms or pneumonia within 30 days of infection, and hospitalization with or death from severe COVID-19 pneumonia within 30 days of infection.

COVID-19 pneumonia was defined using ICD-10 codes from the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. ICD-10 classifications and the need for mechanical ventilation were used to identify severe COVID-19 pneumonia.

A significant number of covariates were considered in the analyses, including demographic factors such as age, gender, race, geographic area, and marital status, as well as metrics such as body mass index and a range of co-morbidities.

The study covered a complete list of comorbidities such as cardiovascular, renal, pulmonary, vertebral, and immune system problems, as well as cancer. Behavioral factors such as smoking and alcohol consumption were also taken into account.


The results showed that participants who had primary and booster vaccination had a decreased incidence of COVID-19-related hospitalization and death. The observation period of the study coincided with the preponderance of the Delta variation and several Omicron subvariants, implying that the vaccines provided excellent protection against the developing variants, despite evidence of immunological escape by some of the subvariants.

Despite the fact that all trial participants were from high-risk populations due to age (65 years or older) or significant comorbidities, the authors highlighted that severe symptoms and an increased rate of infection were related to immunocompromised persons.

Hospital admissions differed significantly amongst these groups, with 1.9, 6.7, and 39.6 hospital admissions per 10,000 people aged 65 and older, high-risk comorbid, and immunocompromised, respectively.

The authors believe that their assessment of COVID-9 severity, focused particularly on pneumonia as an endpoint, enhanced the study by removing any misclassifications of symptoms or severity.

The study did, however, have several shortcomings. In addition to not accounting for COVID-19 exposure behavior, nursing facilities were excluded, despite the fact that a major section of the population is at risk. Although the study included women, Latinos, and African Americans, the majority of participants were white men, making the extrapolation of the findings challenging.


In conclusion, all combinations of Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen/Johnson & Johnson (Ad26.COV2.S) vaccines for initial immunization and one booster dose were beneficial in lowering the risk. COVID-19-related hospitalization and death among high-risk community members in the United States

Except for immunocompromised people, main and single booster vaccines appeared to protect high-risk populations with comorbidities against even developing variants including Delta and Omicron BA.1, BA.2, and BA.2.12.1. The authors concluded that further booster doses would have benefitted only the immunocompromised individuals during the research period.

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