Annexin A1 and Dexamethasone Treatment in Hospitalized COVID-19 Patients: Impact on Disease Recovery and Evidence for an Interplay Between Proresolving Mediators

Annexin A1 (ANXA1) is a proresolving protein regulated by glucocorticoids, the standard care for severe and critical COVID-19 patients. As part of a larger project including hospitalized COVID-19 patients, this study aimed at evaluating ANXA1 and its FPR2 receptor in these patients, focusing on longitudinal profiles and comparison across disease severities and outcomes, and exploring their correlations with inflammation, endotheliitis and other proresolving mediators. Blood was collected in “severe” (n = 27), “critical” (n = 17) and “critical on veno-venous extracorporeal membrane oxygenation” (n = 17) COVID-19 patients at admission, days 3–4, 5–8, and weekly thereafter, and in controls (n = 23) at a single time point. We quantified ANXA1, resolvin D1, resolvin E1 (RvE1) and endocan by ELISA, cytokines and other endothelial markers by multiplex immunoassays, and FPR2 and Chemerin1 receptors by RT-qPCR. Most patients underwent a 10-day dexamethasone regimen. Admission ANXA1 and FPR2 were significantly higher in all patient groups. Throughout hospitalization, ANXA1 increased mainly in “severe” patients and survivors, becoming higher at weeks 3 and 4 in survivors versus non-survivors. Variable cumulative dexamethasone doses did not differentially affect ANXA1 or FPR2. ANXA1 was associated with higher RvE1 during the dexamethasone effect period. Exploratory analyses showed that ANXA1 inversely correlated with RvE1 receptor and endotheliitis, whereas both ANXA1 and FPR2 positively correlated with inflammation. In conclusion, ANXA1 may be involved in COVID-19 recovery processes, and its interplay with RvE1 may ameliorate hyperinflammation.