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

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.