Risks of major arterial and venous thrombotic diseases after hospitalisation for influenza, pneumonia, and COVID-19: A population-wide cohort in 2.6 million people in Wales
Spencer Keene a) b) c); Hoda Abbasizanjani d); Fatemeh Torabi d); Rochelle Knight e) f) g) h); Venexia Walker e) f) w); Elena Raffetti a b i); Genevieve Cezard a) b); Samantha Ip a) b) j) u); Alexia Sampri a) b); Thomas Bolton l); Rachel Denholm e) h) k); Kamlesh Khunti m); Ashley Akbari d); Jennifer Quint n); Spiros Denaxas l) o) p); Cathie Sudlow l); Emanuele Di Angelantonio a) b) c) q) r) s); Jonathan A.C. Sterne e) h) k); Angela Wood a) b) c) l) q) r) t) u); William N. Whiteley l) v)
a) British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
b) Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK
c) NIHR Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK
d) Population Data Science, Swansea University Medical School, Faculty of Medicine, Health, and Life Science, Swansea University, Swansea, UK
e) Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
f) MRC Integrative Epidemiology Unit, Bristol, UK
g) NIHR Applied Research Collaboration West, Bristol, UK
h) NIHR Bristol Biomedical Research Centre, Bristol, UK
i) Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
j) Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
k) Health Data Research UK South-West, Bristol, UK
l) British Heart Foundation Data Science Centre, Health Data Research UK, London, UK
m) Diabetes Research Centre, University of Leicester, UK
n) School of Public Health, Imperial College London, London, W12 0BZ, United Kingdom.
o) Institute of Health Informatics, University College London
p) University College London, Hospitals Biomedical Research Centre, University College London, UK
q) British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK
r) Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Hinxton, UK
s) Health Data Science Centre, Human Technopole, Milan, Italy
t) NIHR Cambridge Biomedical Research Centre, UK
u) Cambridge Centre for AI in Medicine, UK
v) Centre for Clinical Brain Sciences, University of Edinburgh, UK
w) Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
Abstract
Objective
Pneumonia, influenza, COVID-19, and other common infections might increase the risk of thrombotic events acutely through an interaction between inflammation and the thrombotic system. The long-term risks of arterial and venous thrombotic events following hospitalisation for COVID-19 and hospitalisation for pneumonia or influenza are unclear.
Materials and methods
In a population-wide cohort of linked Welsh health data of adults, we calculated the incidence of arterial and venous thrombosis after hospitalisation for COVID-19 (2020−2021). We then compared this post-hospitalisation incidence with the incidence prior to COVID-19 hospitalisation in the same individuals, and with the incidence in individuals who were never hospitalised for COVID-19. We then repeated this analysis for hospitalisation for pneumonia or influenza in a separate cohort (2016–2019). We estimated adjusted hazard ratios (aHRs) in separate time periods starting from the date of the first infection that resulted in hospitalisation (day 0, 1 to 7 days, 2 to 4 weeks, 5 to 16 weeks, and 17 to 75 weeks) using time-varying Cox regression. Confounders included age, sex, smoking status, obesity, deprivation (fifths of Welsh Index of Multiple Deprivation), rural or urban setting, care home attendance, Elixhauser comorbidity index, surgery in the last year, medications (e.g. lipid-lowering and antiplatelet/anticoagulant use), hypertension and/or hypertensive medication use, and past medical history of chronic kidney disease, diabetes, chronic obstructive pulmonary disease, dementia, cancer, or any CVD.
Results
For the first arterial thrombosis, the aHRs were 3.80 (95 % CI: 2.50–5.77) between days 1–7, 5.24 (4.21–6.51) between weeks 2–4, 2.12 (1.72–2.60) between weeks 5–16, and 1.60 (1.38–1.86) between weeks 17–75 after hospitalisation for COVID-19. The corresponding aHRs after hospitalisation for pneumonia/influenza were: 5.42 (4.35–6.75), 3.87 (3.32–4.49), 1.96 (1.74–2.21), and 1.41 (1.30–1.53).
For first venous thrombosis, aHRs were 7.47 (3.56–15.7) between days 1–7, 22.6 (17.5–29.1) between weeks 2–4, 6.58 (4.98–8.68) between weeks 5–16, and 2.25 (1.67–3.02) between weeks 17–75 after hospitalisation for COVID-19. The corresponding aHRs after hospitalisation for pneumonia/influenza were: 15.1 (10.3–22.0), 11.8 (9.23–15.1), 5.80 (4.75–7.08), and 1.89 (1.57–2.29).
Excess risk was highest in individuals aged ≥60 years, in whom we estimated 2,700 and 2,320 additional arterial and 1,270 and 840 additional venous events after 100,000 hospitalisations for COVID-19 and pneumonia/influenza, respectively.
Conclusions
Both hospitalisation for COVID-19 and pneumonia/influenza increase the risk of arterial and venous thrombosis. Preventative healthcare policies are needed for cardiovascular risk factor management, vaccination, and anticoagulation in high-risk patients with hospitalised or severe infections.