Association of Interleukin-32 and Interleukin-34 with Cardiovascular Disease and Short-Term Mortality in COVID-19

Background: Excess cardiovascular (CV) morbidity and mortality has been observed in patients with COVID-19. Both interleukin-32 (IL-32) and interleukin-34 (IL-34) have been hypothesized to contribute to CV involvement in COVID-19. Methods: This prospective, observational study of patients with laboratory-confirmed COVID-19 infection was conducted from 6 June to 22 December 2020 in a tertiary care hospital in Vienna, Austria. IL-32 and IL-34 levels on admission were collected and tested for their association with CV disease and short-term mortality in patients with COVID-19. CV disease was defined by the presence of coronary artery disease, heart failure, stroke or atrial fibrillation and patients were stratified by CV disease burden. Results: A total of 245 eligible patients with COVID-19 were included, of whom 37 (15.1%) reached the primary endpoint of 28-day mortality. Of the total sample, 161 had no CV disease (65.7%), 69 had one or two CV diseases (28.2%) and 15 patients had ≥three CV diseases (6.1%). Median levels of IL-32 and IL-34 at admission were comparable across the three groups of CV disease burden. IL-32 and IL-34 failed to predict mortality upon both univariable and multivariable Cox regression analysis. The two CV disease groups, however, had a significantly higher risk of mortality within 28 days (one or two CV diseases: crude HR 4.085 (95% CI, 1.913–8.725), p < 0.001 and ≥three CV diseases: crude HR 13.173 (95% CI, 5.425–31.985), p < 0.001). This association persisted for those with ≥three CV diseases after adjustment for age, gender and CV risk factors (adjusted HR 3.942 (95% CI, 1.288–12.068), p = 0.016). Conclusion: In our study population of hospitalized patients with COVID-19, IL-32 and IL-34 did not show any associations with CV disease or 28-day mortality in the context of COVID-19. Patients with multiple CV diseases, however, had a significantly increased risk of short-term mortality.