Risk of COVID-19 death in adults who received booster COVID-19 vaccinations in England – Nature.com

This national investigation has identified adults who remained at increased risk of COVID-19 death after receiving a second dose booster vaccination in England in Autumn 2022. Our results indicate that having learning disabilities or Downs syndrome, pulmonary hypertension or fibrosis, motor neuron disease, multiple sclerosis, myasthenia or Huntingtons disease, cancer of blood and bone marrow, Parkinsons disease, lung or oral cancer, dementia or liver cirrhosis were independently associated with a higher risk of COVID-19 related death. For cancer of blood or bone marrow, CKD, cystic fibrosis, pulmonary hypotension or fibrosis or rheumatoid arthritis or SLE the increase in the relative risk was greater for COVID-19 death than non-COVID-19 death. Our findings suggest individuals in those groups were particularly vulnerable to COVID-19 death relative to other causes of death. For instance, for people with rheumatoid arthritis or SLE, the risk of dying from non-COVID-19 causes was not significantly different from people without these diagnoses; however, the risk was higher for COVID-19 death. Importantly, this group was not identified as one of the listed health comorbidities with the highest overall risk of COVID-19 death, but our analysis highlights the importance of relative risk with individuals being more likely to die from COVID-19 in this group relative to other causes.

For many health conditions the increase in risk of COVID-19 death was similar to, or lower than, the increase in risk of non-COVID-19 deaths, suggesting that the increase in the risk of COVID-19 death was not different to the increase in the risk of death from other causes. Whilst we find that patients with asthma were at elevated risk of COVID-19 death after accounting for age, sex, ethnic group and region, we found that having asthma was not associated with the risk of COVID-19 death after adjusting for other comorbidities, suggesting that asthma was not directly increasing the risk of COVID-19 death.

Our findings support previous research which has assessed mortality outcomes following first dose COVID-19 booster vaccinations8. Overall, in the UK first dose booster vaccinations have been found to reduce severe outcomes (hospitalisation and death), with particular groups remaining at elevated risk2. Older adults (over 80 years of age), those with health comorbidities and specific conditions such as CKD were found to be at elevated risk. A study conducted in the United States reported that in patients who were immunocomproised, diabetic, had CKD or chronic lung disease there was a graded increase in risk of breakthrough COVID-19 infections positively associated with the number of comorbidities following two primary doses9. It is important to consider the results presented in our study may not reflect the differences in risk of COVID-19 death following infection. Our study looks at the risk of death since the time of having received a second booster dose, not since infection. It is possible that the risk of infection also differs by clinical risk factors, as patients who are the most vulnerable may maintain social isolation to protect themselves. It is also possible that some vulnerable patients may be at greater risk of infection because they live in communal establishments or have frequent contacts with carers or medical staff.

Critically, our work assesses the impact of the autumn 2022 booster vaccination on COVID-19, but additionally non-COVID-19 outcomes in adults in England. Our results provide strong evidence to inform JCVI about which groups should be prioritised for subsequent boosters and possibly subsequent boosters. It is critical to highlight the fact that some groups who do not have the overall highest risk of COVID-19 death, have an increased risk relative to non-COVID-19 causes and thus should remain a key priority.

Our study has several strengths. Firstly, we used population level data for England based on a unique linkage of the 2021 Census to electronic health records. Sociodemographic characteristics, including ethnic group, were derived from the 2021 Census, and were accurate and had low missingness, unlike in some electronic health records, where ethnic group is often missing and not always self-reported10. Second, we identified the clinical risk factors using primary care data. Third, we used information on the cause of death to define COVID-19 death and were also able to examine non-COVID-19 death as a comparator and identify which conditions were associated with a relative increased risk of larger for COVID-19 death than for non-COVID-19 death.

An important limitation of our study is the use of 2021 Census for our population means that people who did not respond to the Census were excluded. In addition, it also excluded Census respondents who could not be linked to the Personal Demographics Service (PDS). However, the data we used covered 96.0% of those who received a booster dose in England the autumn of 2022. One of the limitations of our work was the lack of data on COVID-19 hospital admissions11. In order to effectively manage resource and understand which groups are at the highest risk of hospitalisation, subsequent work with access to timely data should account for hospital admittance. Additionally, we are unable to account for behaviours which would be classified as health protective such as minimising social contact in the present study. Therefore, it is important to consider for some patients whose risk of hospitalisation or death was most pertinent following SARS-CoV-2 infection, they may be maintaining social isolation to protect themselves. Hence for groups of individuals where the risk was not higher for COVID-19 outcomes, but overall was greater for all-cause death we must maintain prioritisation of vaccination to these individuals. Subsequent research should explore common conditions (e.g., asthma) to understand if the interaction between having a common diagnosis in addition to another specific condition results in a particular susceptibility to adverse COVID-19 outcomes.

Our work investigates the risk of cause-specific COVID-19 death, as well as non-COVID-19 death in a cohort of adults who received a booster dose in the autumn of 2022. In order to effectively manage the COVID-19 risk, it is imperative that the most vulnerable groups of individuals are prioritised for COVID-19 booster vaccinations. We highlight that the risk of COVID-19 death, compared to all other cause death, remains particularly high in adults with learning disabilities or Down syndrome, pulmonary hypertension or fibrosis, motor neuron disease, multiple sclerosis, myasthenia or Huntingtons disease, cancer of blood and bone marrow, Parkinsons disease, lung or oral cancer, dementia, or liver cirrhosis. These groups of patients should be a key priority for subsequent vaccinations, therapeutics, and novel treatment. In addition, we highlight the risk associated with a range of health conditions and sociodemographic characteristics which should inform policy makers and researchers with key demographics of interest for subsequent research and vaccination.

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Risk of COVID-19 death in adults who received booster COVID-19 vaccinations in England - Nature.com