Uptake, effectiveness and safety of COVID-19 vaccines in individuals at clinical risk due to immunosuppressive drug therapy or transplantation procedures: a population-based cohort study in England

Abstract

Background: Immunocompromised individuals are at increased risk of severe COVID-19 outcomes, underscoring the importance of COVID-19 vaccination in this population. The lack of comprehensive real-world data on vaccine uptake, effectiveness and safety in these individuals presents a critical knowledge gap, highlighting the urgency to better understand and address the unique challenges faced by immunocompromised individuals in the context of COVID-19 vaccination.

Methods: We analysed data from 12,274,946 people in the UK aged > 12 years from 01/12/2020 to 11/04/2022. Of these, 583,541 (4.8%) were immunocompromised due to immunosuppressive drugs, organ transplants, dialysis or chemotherapy. We undertook a cohort analysis to determine COVID-19 vaccine uptake, nested case-control analyses adjusted for comorbidities and sociodemographic characteristics to determine effectiveness of vaccination against COVID-19 hospitalisation, ICU admission and death, and a self-controlled case series assessing vaccine safety for pre-specified adverse events of interest.

Results: Overall, 93.7% of immunocompromised individuals received at least one COVID-19 vaccine dose, with 80.4% having received three or more doses. Uptake reduced with increasing deprivation (hazard ratio [HR] 0.78 [95%CI 0.77-0.79] in the most deprived quintile compared to the least deprived quintile for the first dose). Estimated vaccine effectiveness against COVID-19 hospitalisation 2-6 weeks after the second and third doses compared to unvaccinated was 78% (95%CI 72-83) and 91% (95%CI 88-93) in the immunocompromised population, versus 85% (95%CI 83-86) and 86% (95%CI 85-89), respectively, for the general population. Results showed COVID-19 vaccines were protective against intensive care unit (ICU) admission and death in both populations, with effectiveness of over 92% against COVID-19-related death and up to 95% in reducing ICU admissions for both populations following the third dose. COVID-19 vaccines were generally safe for immunocompromised individuals, though specific doses of ChAdOx1, mRNA-1273 and BNT162b2 raised risks of specific cardiovascular/neurological conditions.

Conclusions: COVID-19 vaccine uptake is high in immunocompromised individuals on immunosuppressive drug therapy or who have undergone transplantation procedures, with documented disparities by deprivation. Findings suggest that COVID-19 vaccines are protective against severe COVID-19 outcomes in this vulnerable population, and show a similar safety profile in immunocompromised individuals and the general population, despite some increased risk of adverse events. These results underscore the importance of ongoing vaccination prioritisation for this clinically at-risk population to maximise protection against severe COVID-19 outcomes.

Keywords: COVID-19; COVID-19 vaccination; Immunocompromised; Population-based; Vaccine effectiveness; Vaccine safety; Vaccine uptake.

Fig. 1

Diagram of the data sources, study methods and objectives. Note: * immunocompromised due to immunosuppressive drugs, organ transplantation, undergoing dialysis or receiving chemotherapy; ǂ mainly, ChAdOx1 [AstraZeneca/Oxford], BNT162b2 [Pfizer–BioNTech] and mRNA1273 [Moderna]

Fig. 2

Forest plot of the multivariable Cox regression analyses of COVID-19 vaccine uptake in the immunocompromised population*. Note: * immunocompromised due to immunosuppressive drugs, organ transplantation, undergoing dialysis or receiving chemotherapy; Q1 to Q5 indicates quintiles of Townsend, from the most affluent (Q1) to the most deprived (Q5); models were adjusted for age, sex, BMI, region of England and QCOVID comorbidities

Fig. 3

Adjusted vaccine effectiveness against COVID-19-related hospitalisation, intensive care unit (ICU) admission and death in the study population. Note: Vaccine effectiveness reported was estimated relative to the unvaccinated in both the immunocompromised and the general population; modelling was conducted separately for both populations and was further adjusted for ethnicity, Townsend, prior-COVID-19 infection, BMI, region and QCOVID comorbidities. VE: vaccine effectiveness = (1 − odds ratio)*100

Fig. 4

Risk of serious outcomes following any COVID-19 vaccination in immunocompromised people*. Note: * immunocompromised due to immunosuppressive drugs, organ transplantation, undergoing dialysis or receiving chemotherapy; N = number of events in the 1–28 days following each dose in immunocompromised people; incidence rate ratios (IRR 99%CI) in the 1–28 days following vaccination compared to the baseline period are presented for pre-specified outcomes only where there were at least five events following a first, second or third dose in immunocompromised people. ITP, idiopathic or immune thrombocytopenic purpura; TIA, transient ischaemic attack; ICU, intensive care unit