Plasma bioactive adrenomedullin predicts mortality and need for dialysis in critical COVID-19

COVID-19 is a severe respiratory disease affecting millions worldwide, causing significant morbidity and mortality. Adrenomedullin (bio-ADM) is a vasoactive hormone regulating the endothelial barrier and has been associated with COVID-19 mortality and other adverse events. This prospective cohort pilot study included 119 consecutive patients with verified SARS-CoV-2 infection admitted to two intensive care units (ICUs) in Southern Sweden. Bio-ADM was retrospectively analysed from plasma on ICU admission, and days 2 and 7. Information on comorbidities, adverse events and mortality was collected. The primary outcome was 90-day mortality, and secondary outcomes were markers of disease severity. The association between bio-ADM and outcomes was analysed using survival analysis and logistic regression. Bio-ADM on admission, day 2, and day 7 only moderately predicted 90-day mortality in univariate and multivariate Cox regression. The relative change in bio-ADM between sample times predicted 90-day mortality better even when adjusting for the SAPS3 score, with an HR of 1.09 (95% CI 1.04-1.15) and a C-index of 0.82 (95% CI 0.72-0.92) for relative change between day 2 and day 7. Bio-ADM had a good prediction of the need for renal replacement therapy in multivariate Cox regression adjusting for creatinine, where day 2 bio-ADM had an HR of 3.18 (95% CI 1.21-8.36) and C-index of 0.91 (95% CI 0.87-0.96). Relative changes did not perform better, possibly due to a small sample size. Admission and day 2 bio-ADM was associated with early acute kidney injury (AKI). Bio-ADM on ICU admission, day 2 and day 7 predicted 90-day mortality and dialysis needs, highlighting bio-ADM's importance in COVID-19 pathophysiology. Bio-ADM could be used to triage patients with a risk of adverse outcomes and as a potential target for clinical interventions.