Introduction: The main objective of this study was to evaluate the impact of hemoadsorption on the elimination of inflammatory mediators. Methods: A prospective, bicenter, observational cohort study was conducted between March 2020 and February 2022 to explore the immunomodulatory response, demographic and clinical characteristics of individuals with COVID-19 admitted to the ICU with severe acute respiratory failure and in need of CRRT with Oxiris® with or without AKI. Results: Sixty-four patients were analyzed. Statistically significant differences were observed between exposed and unexposed groups, in relation to the reduction in D-dimer levels −15,614 (24,848.9) versus −4,136.5 (9,913.47) (p 0.031, d: 1.59, 95% CI: −21,830, −1,126). An increase in PCT was observed 0.47 (2.08) versus −0.75 (2.3) (p 0.044 95% CI: 0.03, 2.44). No differences were found in a decrease in CRP −4.21 (7.29) versus −1.6 (9.02) (p 0.22) nor in the rest of inflammatory parameters fibrinogen, IL-6, ferritin, lymphocytes, and neutrophils. Subgroup analysis in patients exposed to therapy also showed a significant decrease in D-dimer of 55% from baseline: 6,000 (1,984.5–27,750) pre-therapy versus 2,700 (2,119.5–6,145) (95% CI: −23,000, −2,489) post-therapy with a strong effect size (p 0.001, d: 0.65). Conclusion: The hemoadsorptive therapy in COVID-19 was associated with a significant decrease in D-dimer parameters without showing decreases in the rest of the clinical, inflammatory parameters and severity scales analyzed.

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