Proadrenomedullin in the Management of COVID-19 Critically Ill Patients in Intensive Care Unit: A Systematic Review and Meta-Analysis of Evidence and Uncertainties in Existing Literature

Mid-regional proadrenomedullin (MR-proADM) is a new biomarker of endothelial damage and its clinical use is increasing in sepsis and respiratory infections and recently in SARS-CoV-2 infection. We conducted a systematic review and meta-analysis to clarify the use of MR-proADM in severe COVID-19 disease. After Pubmed, Embase, and Scopus search, registries, and gray literature, deduplication, and selection of full-texts, we found 21 studies addressing the use of proadrenomedullin in COVID-19. All the studies were published between 2020 and 2022 from European countries. A total of 9 studies enrolled Intensive Care Unit (ICU) patients, 4 were conducted in the Emergency Department, and 8 had mixed populations. Regarding the ICU critically ill patients, 4 studies evaluating survival as primary outcome were available, of which 3 reported completed data. Combining the selected studies in a meta-analysis, a total of 252 patients were enrolled; of these, 182 were survivors and 70 were non-survivors. At the admission to the ICU, the average MR-proADM level in survivor patients was 1.01 versus 1.64 in non-survivor patients. The mean differences of MR-proADM values in survivors vs. non-survivors was -0.96 (95% CI from -1.26, to -0.65). Test for overall effect: Z = 6.19 (p < 0.00001) and heterogeneity was I2 = 0%. MR-proADM ICU admission levels seem to predict mortality among the critical COVID-19 population. Further, prospective studies, focused on critically ill patients and investigating a reliable MR-proADM cut-off, are needed to provide adequate guidance to its use in severe COVID-19.