Association of COVID-19 and influenza vaccinations and cardiovascular drugs with hospitalisation and mortality in COVID-19 and Long COVID: 2-year follow-up of 17 million individuals in England

Abstract Introduction For COVID-19 and Long COVID, determining the highest-risk subgroups, particularly in the context of compound pressures such as influenza and cardiovascular disease (CVD), may identify effective interventions to prevent adverse health outcomes, and inform public health and 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 with COVID-19 and Long COVID 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 preventive therapies. We investigated potential impact of targeted vaccination and CVD prevention strategies on mortality and hospitalisations by calculating population preventable fractions. Results 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 Long Covid [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 (Long COVID rate 1.3%) and 16.8% and 1.4% in Long COVID, respectively. Adjusted risk of mortality and hospitalisation were reduced with COVID-19 vaccination ≥2 doses (COVID-19:HR 0.36, 95% CI 0.34-0.38 and 0.69, 0.68-0.69; Long COVID:0.44, 0.42-0.47 and 0.90, 0.89-0.91). With influenza vaccination, mortality was reduced, but not hospitalisation (COVID-19: 0.86, 0.85-0.86 and HR 1.01, 1.01-1.01, and Long COVID: 0.72, 0.67-0.76, and 1.05, 1.03-1.07), with greatest effect in those with prior CVD and high CVD risk. Mortality and hospitalisation were also reduced by CVD prevention in those with CVD, e.g. anticoagulants- COVID-19: 0.69, 0.69-0.70 and 0.92, 0.91-0.93; Long Covid: 0.59, 0.54-0.64, and 0.88, 0.84-0.92. COVID-19 vaccination, influenza vaccination and CVD drugs (Anticoagulants) averted 101117 of 193598, 2138 of 4017 and 16573 of 36847 preventable deaths among individuals after COVID-19, and 875 of 1189, 65 of 127 and 507 of 1007 preventable deaths among those with Long COVID, particularly in people with CVD. Conclusions Prior CVD and high CVD risk are associated with increased hospitalisation and mortality risk in people with COVID-19 and Long COVID. Targeted improvement in COVID-19 vaccination and CVD prevention, especially in those with CVD are priority interventions in pandemics to avoid excess hospitalisation and mortality.Baseline Characteristics and OutcomesHospitalisation/mortality by COVID vaccn