Breakthrough SARS-CoV-2 infections in people who have been vaccinated are a growing concern. A new study offers some valuable information on who is most at risk of hospitalization and death in that situation, based on a predictive tool.

University of Oxford–led researchers focused on determining who among the vaccinated are at the greatest risk from severe CoVID-19 leading to hospitalization or death from 14 days after the second-dose vaccination when protective immunity should exist.

The article in the British Medical Journal discusses how the updated QCovid tool, originally developed in 2020, was used to make those predictions. The authors point out that the tool had a strong influence on UK policy in February 2021, putting an additional 1.5 million Britons in February on the list of people who most needed to be protected from risk of hospitalization or death from COVID-19.

"The UK was the first place to implement a vaccination program and has some of the best clinical research data in the world," explained Julia Hippisley-Cox, MB ChB MD. "We have developed this new tool using the QResearch database, to help the NHS identify which patients are at highest risk of serious outcomes despite vaccination for targeted intervention. This new tool can also inform discussions between doctors and patients about the level of risk to aid shared decision making."

To construct a sample of more than 6.9 million adults to analyze, researchers used national linked datasets from general practice, national immunization and SARS-COV-2 testing, death registry and hospital episode data. In that sample, about 5.2 million had received both vaccines doses, which was representative of the UK population as a whole.

Of those patients, 2,031 had died of COVID-19 and there were 1,929 COVID-19 related hospital admissions. Of those, 81 deaths and 71 admissions occurred 14 or more days after the second vaccine dose.

Cumulative risk scores used to calculate people's risk of hospitalization or death from COVID-19 following one or two vaccination doses suggest the following are at most elevated risk for breakthrough infection: Those who are immunosuppressed as a result of chemotherapy, a recent bone marrow or solid organ transplant, or HIV/AIDS; people with neurological disorders, including dementia and Parkinson's disease; and nursing home residents and those with chronic disorders, including Down's Syndrome

The researchers point out that there were relatively few COVID-19 related hospitalizations or deaths in those who had received the second dose of any vaccine. That means the study lacked the statistical power to determine if the groups listed as being at higher risk would be better protected after a second dose compared with the first.

Coauthor Aziz Sheikh, OBE, BSc, MBBS, MSc, MD, professor at The University of Edinburgh, suggests that the calculator can help predict who would benefit from "interventions such as vaccine booster doses or new treatments such as monoclonal antibodies, which can help reduce the risk of progression of SARS-CoV-2 infection to serious COVID-19 outcomes."

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