Risk of Developing Severe Breakthrough Infection From COVID-19 May Increase Over 50 Years of Age


The risk of severe COVID-19 breakthrough infection was stronger with age and some comorbidities—the findings can inform antiviral distribution to prevent death or respiratory failure.

The strongest associative risk for severe COVID-19 after vaccination was age, according to new research—after age 50, the adjusted odds ratio for severity increased every 5 years. Those who were immunocompromised with severe comorbidities also had a similar risk.

“Improving identification of patients at high risk for progression is important for informing clinical practice and directing distribution of antivirals to those most likely to benefit,” wrote study authors in a recent report.

Breakthrough infections from the COVID-19 vaccines have been happening since the vaccine was made available. Omicron is now the predominant variant in circulation, and breakthrough cases are on the rise. Researchers believe that identifying patients at risk of severe breakthrough infection could promote booster vaccinations and increase the direction of antiviral drugs.

In a national, retrospective cohort study, researchers aimed to identify risk factors that could increase COVID-19 severity after vaccination in US veterans. They identified 110,760 predominantly male US veterans who had infections after vaccination.

The primary outcome was identified as severe breakthrough infection, resulting in death within 28 days or hospitalization from respiratory failure or hypoxia. Secondary aims looked at quantifiable subgroup risk factors and evaluating the risk of severe infection between the time of receiving a primary dose and a first booster dose.

Among participants, 9.6% experienced severe infection—it was determined that age was the biggest risk factor.

“However, age was so much stronger as a risk factor for severe outcomes that the magnitudes of risk associated with any source of immunocompromise, or the most important comorbidities, were similar to the difference in risk between vaccinated persons aged 60 vs 50 years,” study authors wrote in the report.

Preexisting organ disease, such as heart failure, and globally tenuous (or frail) states, like low BMI, were comorbidities that still were a strong risk factor associated with severe breakthrough disease—this is compared to risk factors that may lead to future organ dysfunction, such as hypertension.

Many immunocompromised individuals were on drugs to reduce comorbidities associated with their condition, and it was found that risk of severe outcomes from breakthrough infection were greater if the patient were on immunosuppressive drugs while getting vaccinated (and subsequently afterwards).

“These data suggest that many patients receiving immunosuppressive medications at the time of vaccine develop durable protection, and the causal risk factor is immune status at the time of exposure,” study authors wrote in the report.

However, researchers identified factors that could mildly reduce the risk of severe outcome—these include a booster vaccine or previous infection before vaccination.

Important study limitations include a lack of generalizability for female and younger patients with comorbidities. Additionally, data could be missing and affect results of those with prior infections or boosting.

“These results could be used to bolster guidelines for administration of preexposure prophylaxis and to identify patients most likely to benefit from antiviral therapy,” study authors wrote in the report.


Vo A, La J, Wu J, et al. Factors Associated With Severe COVID-19 Among Vaccinated Adults Treated in US Veterans Affairs Hospitals. JAMA Netw Open. 2022;5(10):e2240037. doi:10.1001/jamanetworkopen.2022.40037

Related Videos
Mid-section portrait of unrecognizable woman during last months of pregnancy holding her big belly gently standing against wall in blue room - Image credit: pressmaster | stock.adobe.com
palliative and hospice care/ Image Credits: © David Pereiras - stock.adobe.com
multiple myeloma clinical trial daratumumab/ Image Credits: © Dragana Gordic - stock.adobe.com
multiple myeloma clinical trial/Image Credits: © Studio Romantic - stock.adobe.com
Medicine tablets on counting tray with counting spatula at pharmacy | Image Credit: sutlafk - stock.adobe.com
pharmacy oncology, Image Credit: © Konstantin Yuganov - stock.adobe.com
Mayo Clinic oncology pharmacy
Testicular cancer and prostate cancer concept. | Image Credit: kenchiro168 - stock.adobe.com
Medicine tablets on counting tray with counting spatula at pharmacy | Image Credit: sutlafk - stock.adobe.com
© 2024 MJH Life Sciences

All rights reserved.