Pooled analysis of mid-regional pro-adrenomedullin values in COVID-19 patients with critical illness

We performed a critical literature review and meta-analysis to explore as to whether MR-proADM assessment may help predicting unfavorable disease progression in COVID-9 patients. The electronic search carried out in accordance the above-mentioned criteria identified 34 documents after elimination of duplicates. Among these, 28 were excluded as they were review articles (n = 13), editorial material (n = 1) or correspondence without original data (n = 2), did not specifically deal with COVID-19 (n = 6), did not provide MR-proADM values (n = 2), lack of complete information on MR-proADM values (n = 1), or MR-proADM values were not stratified according to COVID-19 severity (n = 3). No significant disagreement emerged between the two reviewers. Six studies were thus finally included in pooled analysis, totaling 487 COVID-19 patients, 159 (32.6%) with critical illness. All included studies were cross sectional investigations, three conducted in Italy, while the others were located in Germany, Russia and Switzerland. The clinical endpoints used for characterizing critical illness of COVID-19 were cumulative mortality in two studies, as opposed to intensive care unit (ICU) admission or death, need for renal replacement therapy (RRT), death or intubation, and acute respiratory distress syndrome (ARDS) in the remaining investigations. A positive difference of MR-proADM values was found between patients with or without critical COVID-19 in each individual study. The WMD of MR-proADM values in COVID-19 patients with critical illness versus those without was 0.67 (95% CI 0.42–0.93) nmol/L in the quality effects model (with high heterogeneity, I2 = 81%), further increasing to 0.80 (95% CI 0.58–1.02) nmol/L in the random effects model. Overall, MR-proADM values were found to be increased by 74% (95% CI 46–103%) in COVID-19 patients with critical illness compared to those without.