Inflammatory and Organ Injury Signatures Associated with Progression to Mechanical Ventilation and Extracorporeal Membrane Oxygenation in Hospitalized Patients with COVID-19

Background: ECMO is used in patients with refractory cardiopulmonary failure when conventional therapy fails; however, biomarker features associated with this clinical deterioration remain unclear. We investigated whether dynamic biomarker changes were associated with the escalation of respiratory support and subsequent end-organ injury in hospitalized patients with COVID-19. Methods: A total of 106 hospitalized patients with PCR-confirmed COVID-19 underwent serial blood sampling within 24 h (T1), 48 h (T2), 7 days (T3), and after 28 days (T4) when available. The patients were classified by respiratory support trajectory: no invasive mechanical ventilation (GrMin), invasive mechanical ventilation (GrMV), and ECMO (GrECMO). Plasma and urine inflammatory markers were profiled, together with selected coagulation, complement, neurological, and cardiovascular injury biomarkers. Clinical characteristics, severity scores, complications, and mortality were extracted from electronic records. Results: The patients in GrECMO were younger than those in GrMin and GrMV. The SOFA and APACHE scores were lowest in GrMin and similar between GrMV and GrECMO, while GCS was lower in GrECMO. GrECMO showed leukocytosis and elevated BLC, with increased CRP, PCT, and MCP-3 in both GrMV and GrECMO versus GrMin. IL6 and MUC-16 were selectively elevated in GrECMO, whereas PDL2 and PTN were reduced and MCP-4 increased; CAIX and TREM2 were elevated in GrMV. NCAM1 levels were numerically lower, whereas pTau181 levels were higher in GrECMO than in GrMin. Progression to ECMO was associated with leukocytosis, increased MCP-4, MUC-16, and TIE2, and reduced PDL2/PTN, while early elevations of HMGB1, CRP, PCT, and TREM2 were associated with the GrMin→MV trajectory. No differences were observed in coagulation or complement markers. Six-month mortality was higher in the MV and ECMO groups, and six-month stroke incidence was highest in the GrECMO group. Conclusions: The transition from MV to ECMO was associated with leukocytosis, increased MCP-4, TIE2, and MUC-16, and reduced PDL2/PTN, suggesting deterioration from profound multisystem stress, beyond an acute inflammatory surge.