Long-term angiogenic and thromboinflammatory signatures in post-COVID-19 syndrome

Abstract

Post-COVID-19 syndrome is a major long-term sequela of severe SARS-CoV-2 infection, potentially involving persistent angiogenic and thromboinflammatory dysfunction, though long-term biomarker behavior remains unclear. To evaluate the evolution of angiogenic and thromboinflammatory biomarkers in post-COVID-19 syndrome patients. This ambispective cohort study was conducted at the National Institute of Respiratory Diseases in Mexico City. Thirty-two adults hospitalized for severe or critical COVID-19 in 2020 were followed for three and a half years. Paired plasma samples were collected during hospitalization and at long-term follow-up. Endothelial dysfunction markers included soluble P-selectin, vascular endothelial growth factor receptor 2, vascular endothelial growth factor D, and angiopoietin-1. Hemostasis was assessed by prothrombin time. Acute-phase proteins alpha-2-macroglobulin and haptoglobin were measured via immunoassay. Persistent symptoms were documented at follow-up. At three and a half years, persistent symptoms were common: fatigue in sixty-five point 6%, dyspnea in sixty-two point 5%, and concentration difficulties in sixty-five point 6%. Vascular endothelial growth factor D and angiopoietin-1 remained elevated. Alpha-2-macroglobulin stayed high, and prothrombin time was prolonged in a subset of patients. Severe COVID-19 survivors show sustained angiogenic dysregulation and thromboinflammatory imbalance. Elevated vascular endothelial growth factor D and angiopoietin-1 indicate ongoing angiogenic perturbations, while increased alpha-2-macroglobulin and prolonged prothrombin time reflect persistent coagulation disturbances. These biomarkers may help identify long-term vascular alterations in post-COVID-19 syndrome.