VEGF-A plasma levels are associated with impaired DLCO and radiological sequelae in long COVID patients

Background Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is characterized by persistent clinical symptoms following COVID-19. Objective To correlate biomarkers of endothelial dysfunction with persistent clinical symptoms and pulmonary function defects at distance from COVID-19. Methods Consecutive patients with long COVID-19 suspicion were enrolled. A panel of endothelial biomarkers was measured in each patient during clinical evaluation and pulmonary function test (PFT). Results The study included 137 PASC patients, mostly male (68%), with a median age of 55 years. A total of 194 PFTs were performed between months 3 and 24 after an episode of SARS-CoV-2 infection. We compared biomarkers evaluated in PASC patients with 20 healthy volunteers (HVs) and acute hospitalized COVID-19 patients ( n = 88). The study found that angiogenesis-related biomarkers and von Willebrand factor (VWF) levels were increased in PASC patients compared to HVs without increased inflammatory or platelet activation markers. Moreover, VEGF-A and VWF were associated with persistent lung CT scan lesions and impaired diffusing capacity of the lungs for carbon monoxide (DLCO) measurement. By employing a Cox proportional hazards model adjusted for age, sex, and body mass index, we further confirmed the accuracy of VEGF-A and VWF. Following adjustment, VEGF-A emerged as the most significant predictive factor associated with persistent lung CT scan lesions and impaired DLCO measurement. Conclusion VEGF-A is a relevant predictive factor for DLCO impairment and radiological sequelae in PASC. Beyond being a biomarker, we hypothesize that the persistence of angiogenic disorders may contribute to long COVID symptoms.