Introduction This study aims to explore the impact of COVID-19 vaccination on critical care by examining associations between vaccination and admission to critical care with COVID-19 during England's Delta wave, by age group, dose, and over time. Methods We used linked routinely-collected data to conduct a population cohort study of patients admitted to adult critical care in England for management of COVID-19 between 1 May and 15 December 2021. Included participants were the whole population of England aged 18 years or over (44.7 million), including 10,141 patients admitted to critical care with COVID-19. The intervention was vaccination with one, two, or a booster/three doses of any COVID-19 vaccine. Results Compared with unvaccinated patients, vaccinated patients were older (median 64 years for patients receiving two or more doses versus 50 years for unvaccinated), with higher levels of severe comorbidity (20.3% versus 3.9%) and immunocompromise (15.0% versus 2.3%). Compared with patients who were unvaccinated, those vaccinated with two doses had a relative risk reduction (RRR) of between 90.1% (patients aged 18-29, 95% CI, 86.8% to 92.7%) and 95.9% (patients aged 60-69, 95% CI, 95.5% to 96.2%). Waning was only observed for those aged 70+, for whom the RRR reduced from 97.3% (91.0% to 99.2%) to 86.7% (85.3% to 90.1%) between May and December but increased again to 98.3% (97.6% to 98.8%) with a booster/third dose. Conclusion Important demographic and clinical differences exist between vaccinated and unvaccinated patients admitted to critical care with COVID-19. While not a causal analysis, our findings are consistent with a substantial and sustained impact of vaccination on reducing admissions to critical care during England's Delta wave, with evidence of waning predominantly restricted to those aged 70+.

DAH, PJW, JCD, PRM, MP, CACC, PH-C and KMR report grant funding to their institutions from UK Research and Innovation related to the current work. The following authors declare competing interests not related to the current work: DAH, JCD, PRM and KMR report grant funding to their institution from Wellcome and the National Institute for Health Research. PJW reports grant funding to his institution from Wellcome and Sensyne Health, stock or stock options from Sensyne Health and that he was previously Chief Medical Officer to Sensyne Health. MS-H reports a career development fellowship from the National Institute for Health Research. MP, CACC and JH-C report grant funding to their institutions from Wellcome, the Medical Research Council, the National Institute for Health Research and other research charities. JH-C reports that she is Chair of the Risk Stratification Subgroup of NERVTAG, a member of a SAGE subcommittee and shareholder in ClinRisk Ltd, and that the QResearch database is jointly owned by the University of Oxford and EMIS (commercial supplier of IT systems in the NHS).

https://www.qresearch.org/research/approved-research-programs-and-projects/uptake-and-comparative-safety-of-new-covid-19-therapeutics/

This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office For National Statistics and funded by UK Research and Innovation (grant ref. MC_PC_20029). MSH is supported by the National Institute for Health Research Clinician Scientist Award (NIHR-CS-2016-16-011).

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:

NHS Research Ethics Committee approval was obtained from East Midlands-Derby Research Ethics Committee (ref 04/03/2021)

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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

The data that support the findings of this study are not publicly available because they are based on de-identified national clinical records. Due to national and organisational data privacy regulations, individual-level data such as those used for this study cannot be shared openly.