Association of COVID-19 and Influenza Vaccinations and Cardiovascular Pharmacotherapy with Hospitalisation and Mortality in People with COVID-19 and Long COVID: 2-Year Follow-Up of Over 17 Million People in England

Abstract

Background: Identifying highest-risk subgroups for COVID-19 and Long COVID(LC), particularly in the context of influenza and cardiovascular disease(CVD), may inform policy decisions.

Methods: Using national, linked electronic health records for England(NHS England Secure Data Environment via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals(of all ages) with COVID-19 and LC from January 2020 to February 2023. We compared all-cause hospitalisation and mortality in unmatched and matched cohort analyses, by prior CVD, high CVD risk(by QRISK2), COVID-19 and influenza vaccination status, and prescription of CVD prevention therapies. We investigated potential impact of targeted vaccination and CVD prevention strategies on mortality and hospitalisations using population preventable fractions.

Findings: We identified 17,373,850 individuals with COVID-19 [54.4% female; mean age 38.8 years; COVID-19 vaccination ≥2 doses:50.0%, influenza vaccination (≥1 dose):27.8%; mean follow-up 1.28 years] and 301,115 with LC [61.8% female; mean age 46.0 years; COVID-19 vaccination ≥2 doses:66.4%, influenza vaccination:33.1%; mean follow-up 1.1 years]. Hospitalisation and mortality rates were 15.3% and 2.0% in COVID-19 (LC rate 1.3%) and 16.8% and 1.4% in LC, respectively. Adjusted risk of mortality and hospitalisation were reduced with COVID-19 vaccination ≥2 doses (COVID-19: HR 0.36 and 0.69; LC:0.44 and 0.90). With influenza vaccination, mortality was reduced, but not hospitalisation (COVID-19: 0.86 and 1.01, and LC: 0.72, and 1.05). Combined influenza and COVID-19 vaccination was associated with reduced mortality(0.35) and hospitalisation(0.62) in individuals with COVID-19. In LC, it was associated with reduced mortality(0.37) and hospitalisation(0.43). Mortality and hospitalisation were also reduced by CVD prevention in those with CVD e.g. anticoagulants- COVID-19: 0.69 and 0.92; LC: 0.59, and 0.88. COVID-19 vaccination averted 245044 of 321383 and 7586 of 8738 preventable deaths after COVID-19 and LC, respectively.

Interpretation: Prior CVD and high CVD risk are associated with increased hospitalisation and mortality in COVID-19 and LC. Targeted improvement in COVID-19 vaccination and CVD prevention should be priority interventions during pandemics.

Funding: This work was funded by HDR UK (HDRUK2022.0317) and NIHR (COV-LT2-0043). The British Heart Foundation Data Science Centre (grant No SP/19/3/34678, awarded to Health Data Research (HDR) UK) funded co-development (with NHS England) of the Secure Data Environment service for England, provision of linked datasets, data access, user software licences, computational usage, and data management and wrangling support, with additional contributions from the HDR UK Data and Connectivity component of the UK Government Chief Scientific Adviser’s National Core Studies programme to coordinate national COVID-19 priority research. Consortium partner organisations funded the time of contributing data analysts, biostatisticians, epidemiologists, and clinicians.

Declaration of Interest: KK is chair of the ethnicity subgroup of the UK Scientific Advisory Group for Emergencies (SAGE) and is a member of SAGE. KK (Chair) and AB are members of the LC Research Group that reports to the Chief Medical Officer for England. All other authors declare no competing interests.

Ethical Approval: Data were accessed in NHS England’s Secure Data Environment (SDE) service for England and made available via the British Heart Foundation (BHF) Data Science Centre’s CVD-COVID-UK/COVID- IMPACT Consortium, as previously published with ethical approval by the North East- Newcastle and North Tyneside 2 research ethics committee (REC No 20/NE/0161)(17,18).

Keywords: COVID-19, Long COVID, cardiovascular disease, vaccination, high-risk