Breakthrough COVID-19: Who is most at risk?

  • According to a new study, although very few post-vaccination deaths or hospitalizations occurred in the United Kingdom, several groups were at higher risk than others.
  • A new tool identifies people at highest risk of severe outcomes from SARS-CoV-2 breakthrough infections. SARS-CoV-2 is the coronavirus that causes COVID-19.
  • The hope is that this information allows healthcare professionals and patients alike to make better-informed decisions regarding COVID-19 strategies.

Before the availability of vaccines, experts in the U.K. developed the QCOVID risk assessment tool to identify those with the highest risk of dying or being hospitalized with COVID-19. The tool resulted in the addition of 1.5 million people to the National Shielded Patient List and helped authorities prioritize vaccinations.

There remains, however, a residual risk of breakthrough infections for people who are fully or partially vaccinated. To identify people most at risk of breakthrough infections, researchers from the University of Oxford in the U.K. have published a paper presenting an updated QCOVID tool called QCOVID3.

The new QCOVID3 tool has identified several groups of vaccinated people who are at particular risk of dying or being hospitalized due to a SARS-CoV-2 infection.

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Paper co-author Dr. Julia Hippisley-Cox, a professor of clinical epidemiology and general practice at the University of Oxford, explains:

“The U.K. was the first place to implement a vaccination program and has some of the best clinical research data in the world. We have developed this new tool using the QResearch database to help the [National Health Service] identify which patients are at highest risk of serious outcomes despite vaccination for targeted intervention.”

Dr. Hippisley-Cox adds, “This new tool can also inform discussions between doctors and patients about the level of risk to aid shared decision making.”

The authors of the paper make clear that few vaccinated people have died or required hospitalization 14 days or more after vaccination. This is presumably time enough for immunity to develop.

Paper co-author Dr. Aziz Sheikh, a professor of primary care research and development and the director of the Usher Institute at the University of Edinburgh in the U.K., says:

“This enormous national study of over 5 million people vaccinated with [two] doses across the U.K. has found that a small minority of people remain at risk of COVID-19 hospitalization and death. Our risk calculator helps to identify those who remain most at risk post-vaccination.”

The paper now appears in the BMJ.

The groups most at risk

Dr. Sheikh says, “Our new QCOVID tool, developed with the help of experts from across the U.K., has been designed to identify those at high risk who may 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.”

Over 6 million datasets of vaccinated adults were studied using the QCOVID3 algorithm. Of these adults, more than 5 million had received both vaccine doses.

The datasets included 2,031 COVID-19-related deaths and 1,929 COVID-19-related hospital admissions, 4% and 3.7% of which, respectively, occurred 14 days after the second vaccination.

The QCOVID3 algorithm identified the following groups as being at highest risk, in descending order:

Vaccinated Pakistani and Indian individuals had a twofold higher risk than white individuals.

The authors of the paper surmise that this finding may reflect other, non-physiological factors beyond the scope of the research.

They say, “These ethnic disparities in COVID-19 outcomes may represent residual differential exposure (linked for example to behavior, lifestyle, household size, and occupation) more than differential susceptibility mechanisms, though we also acknowledge that being vaccinated may change behavior (and exposure) more in some groups than in others.”

Remaining questions

There were so few deaths or hospitalizations among people who had received two vaccine doses in the study that, the authors write, “most information about associations between predictors and mortality comes from individuals who have only received one dose.”

They feel that the numbers post-full vaccination were too small to draw any conclusions about the likelihood of acquiring a breakthrough infection after the second versus the first dose.

The researchers also draw no distinction between the different vaccines administered to the cohort, and they do not draw any associations between them and reported outcomes.

The authors cite a few other limitations as well. These include the short follow-up time after vaccination — up to 70 days — and the inclusion of many partially vaccinated individuals. During the study, they also did not consider outcomes associated with different SARS-CoV-2 variants due to insufficient data.

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