Risk of COVID-19 death in adults who received booster COVID-19 vaccinations: national retrospective cohort study on 14.6 million people in England

Importance The emergence of the COVID-19 vaccination has been critical in changing the course of the COVID-19 pandemic, with estimates suggesting vaccinations have prevented millions of deaths worldwide. To ensure protection remains high in vulnerable groups booster vaccinations in the UK have been targeted based on age and clinical vulnerabilities. Objective We sought to identify adults who had received a booster vaccination as part of the autumn 2022 campaign in England yet remained at increased risk of postbooster COVID-19 death and compared to non-COVID-19 risk. Design, Setting, and Participants We undertook a national retrospective cohort study using data from the 2021 Census linked to electronic health records. We fitted cause-specific Cox models to examine the association between health conditions and the risk of COVID-19 death and all-other-cause death for adults aged 50-100-years in England vaccinated with a booster in autumn 2022. Our total population was 14,644,570 people; there were 6,800 COVID-19 deaths and 150,075 non-COVID-19 deaths. Exposure Sociodemographic characteristics (sex, age, ethnic group, region), disability, body mass index, and diagnosis of a health condition defined from QCovid2. Main Outcomes and Measures The primary outcome of this study was COVID-19 death. The secondary outcome was all-cause non-COVID-19 deaths. Results Having learning disabilities or Down Syndrome (hazard ratio=5.07;95% confidence interval=3.69-6.98), pulmonary hypertension or fibrosis (2.88;2.43-3.40), motor neuron disease, multiple sclerosis, myasthenia or Huntington’s disease (2.94, 1.82-4.74), cancer of blood and bone marrow (3.11;2.72-3.56), Parkinson’s disease (2.74;2.34-3.20), lung or oral cancer (2.57;2.04 to 3.24), dementia (2.64;2.46 to 2.83) or liver cirrhosis (2.65;1.95 to 3.59) was associated with an increased risk of COVID-19 death. Individuals with cancer of the blood or bone marrow, chronic kidney disease, cystic fibrosis, pulmonary hypotension or fibrosis, or rheumatoid arthritis or systemic lupus erythematosus had a significantly higher risk of COVID-19 death relative to other causes of death compared with individuals who did not have diagnoses. Conclusions, and Relevance We identify groups who are at increased risk of postbooster COVID-19 death relative to non-COVID-19 deaths. Policy makers should continue to priorities vulnerable groups for subsequent COVID-19 booster doses to minimise the risk of COVID-19 death. Funding National Core Studies–Immunity, National Core Studies–Data and Connectivity, Health Data Research UK, and the Medical Research Council . Key Points Question: What health conditions are associated with increased risk of postbooster COVID-19 death in adults who received a COVID-19 vaccination in autumn 2022? Findings: Certain groups were found to be at overall higher risk of postbooster COVID-19 death (e.g., learning disability or Down Syndrome) and certain groups were found to have significantly higher relative risk of COVID-19 death compared to other non-COVID-19 causes (e.g., cancer of the blood or bone marrow). Meaning: This work has implications for prioritisation of vaccination booster doses worldwide. We highlight which groups with health conditions are at elevated risk of postbooster COVID-19 death. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement National Core Studies Immunity, National Core Studies Data and Connectivity, Health Data Research UK, and the Medical Research Council. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from the National Statistician's Data Ethics Advisory Committee. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data used in this study cannot be shared. It is available to accredited government researchers in a secure environment.