Abstract 16467: A Novel CT-derived Radiotranscriptomic Signature of Perivascular Adipose Tissue Stratifies COVID-19 Vascular Cytokine Burst and Predicts in Hospital Outcomes

Abstract

Introduction: COVID-19 is characterised by severe vascular inflammation. Perivascular adipose tissue (PVAT) has the ability to change its texture in response to vascular inflammation. Hypothesis: Computed Tomography Angiography (CTA)-based radiotranscriptomic phenotyping of PVAT may quantify COVID-19-induced vascular inflammation, predicting clinical outcomes. Methods: In Study 1, RNA sequencing of 60 internal mammary artery (IMA) biopsies from patients undergoing coronary bypass surgery was performed to build a transcriptomic fingerprint similar to that observed in COVID-19. This fingerprint was used to train an extreme gradient boosting algorithm, C19-RS, using CTA-derived radiomic features of PVAT around the IMA and descending thoracic aorta. In Study 2, C19-RS was validated in pulmonary artery CTAs from an independent cohort of 201 patients for COVID-19 detection and test its prognostic value in COVID-19. Results: Unsupervised hierarchical clustering of RNASeq data in Study 1 identified 2 clusters of vascular inflammation ( A ). Machine learning was used to train C19-RS to detect vascular inflammation based on 31 radiomic features. In study 2, 22 deaths and 32 ICU admissions were recorded. Patients with high C19-RS had an OR=3.11[95%CI:1.06-9.85] for COVID-19 adjusted for age, sex, risk factors, hsCRP, WBCC, COPD and CT tube voltage. C19-RS significantly improved the discrimination of a baseline model containing the above variables, for COVID-19 detection (delta[AUC]=0.03, p=0.008, B ). C19-RS was significantly associated with in-hospital death ( C ), and a composite endpoint of in-hospital death and ICU admission, with adjusted HR: 4.29 (95% CI: 1.48-13.52, p=0.009). Conclusion: COVID-19-induced vascular inflammation can be quantified by a radiotranscriptomic signature (C19-RS) derived from CT analysis of PVAT. C19-RS stratifies vascular inflammatory burden in COVID-19, and has striking prognostic value for in-hospital outcomes.