Nano-scale morphological and chemical characterization of cardiac, coronary and carotid macro-/micro-thrombi in COVID-19 positive and negati

This project aims at gaining novel insight in two pathological mechanisms observed in the vascular system supplying the heart and brain of COVID-19 patients as an adverse consequence of a SARS-CoV-2 infection, i.e. the development of 1) macroscopic thrombi (MTs) in epicardial coronary and carotid arteries and 2) peripheral microscopic thrombi (µTs) in myocardial and brain microvasculature. Few pathology studies have been conducted thus far and a precise mechanistic understanding is still needed. We propose the use of a combination of different synchrotron analysis techniques (X-ray micro- & nano-CT, fluorescence & SAXS/WAXS) for the characterization of the morphology, composition and structure of the MTs and µTs. In this specific experiment, we will apply X-ray nano-holotomography and fluorescence microscopy to obtain an unprecedented morphological and chemical characterization of the MTs and µTs at the level of individual thrombi, endothelial cells and possibly SARS-CoV-2 virions.

本研究旨在深入解析新型冠状病毒（SARS-CoV-2）感染所致不良后果中，新冠肺炎患者心脑血管供血系统出现的两类病理机制：其一为心外膜冠状动脉与颈动脉内的宏观血栓（macroscopic thrombi, MTs）形成，其二为心肌与脑微血管内的外周微观血栓（microscopic thrombi, µTs）形成。迄今为止相关病理研究较为匮乏，对其精确的机制学认知仍有待完善。我们提出联合应用多种同步辐射分析技术——涵盖X射线显微与纳米CT、荧光成像以及小角X射线散射/广角X射线散射（SAXS/WAXS）——以表征两类血栓的形态、组成及结构。在本次特定实验中，我们将采用X射线纳米断层扫描（X-ray nano-holotomography）与荧光显微镜成像技术，实现在单个血栓、内皮细胞乃至可能的SARS-CoV-2病毒颗粒层面，对两类血栓开展前所未有的形态学与化学特征解析。