Margaroli Camilla, Benson Paul, Gastanadui Maria G, Song Chunyan, Viera Liliana, Xing Dongqi, Wells J Michael, Patel Rakesh, Gaggar Amit, Payne Gregory A
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Program in Protease/Matrix Biology, University of Alabama at Birmingham, Birmingham, AL, United States.
Front Med (Lausanne). 2023 Mar 9;10:1118024. doi: 10.3389/fmed.2023.1118024. eCollection 2023.
Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well-established links to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this paradigm has sparked growing controversy. The significance of myocardial infection also remains unclear.
Autopsy-derived cardiac tissue from control ( = 4) and COVID-19 ( = 8) patients underwent spatial transcriptomic profiling to assess differential expression patterns in myocardial and coronary vascular tissue. Our approach enabled transcriptional profiling with preserved anatomy and unaltered local SARS-CoV-2 expression. In so doing, we examined the paracrine effect of SARS-CoV-2 infection in cardiac tissue.
We observed heterogeneous myocardial infection that tended to colocalize with CD31 positive cells within coronary capillaries. Despite these differences, COVID-19 patients displayed a uniform and unique myocardial transcriptional profile independent of local viral burden. Segmentation of tissues directly infected with SARS-CoV-2 showed unique, pro-inflammatory expression profiles including upregulated mediators of viral antigen presentation and immune regulation. Infected cell types appeared to primarily be capillary endothelial cells as differentially expressed genes included endothelial cell markers. However, there was limited differential expression within the endothelium of larger coronary vessels.
Our results highlight altered myocardial programming during severe COVID-19 that may in part be associated with capillary endothelial cells. However, similar patterns were not observed in larger vessels, diminishing endotheliitis, and endothelial activation as key drivers of cardiovascular events during COVID-19.
我们的目的是利用数字空间转录组学研究重症新型冠状病毒肺炎（COVID-19）患者的冠状动脉内皮和心肌编程。
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）与血栓形成和心血管事件有明确的关联。最初提出内皮细胞感染引发血管事件；然而，这一模式引发了越来越多的争议。心肌感染的意义也仍不清楚。
对来自对照（n = 4）和COVID-19（n = 8）患者的尸检心脏组织进行空间转录组分析，以评估心肌和冠状动脉血管组织中的差异表达模式。我们的方法能够在保留解剖结构和不改变局部SARS-CoV-2表达的情况下进行转录分析。通过这样做，我们研究了SARS-CoV-2感染在心脏组织中的旁分泌效应。
我们观察到异质性心肌感染，其倾向于与冠状动脉毛细血管内的CD31阳性细胞共定位。尽管存在这些差异，但COVID-19患者表现出与局部病毒载量无关的统一且独特的心肌转录谱。对直接感染SARS-CoV-2的组织进行分割显示出独特的促炎表达谱，包括病毒抗原呈递和免疫调节介质的上调。感染的细胞类型似乎主要是毛细血管内皮细胞，因为差异表达基因包括内皮细胞标志物。然而，较大冠状动脉内皮内的差异表达有限。
我们的结果突出了重症COVID-19期间心肌编程的改变，这可能部分与毛细血管内皮细胞有关。然而，在较大血管中未观察到类似模式，这削弱了内皮炎和内皮激活作为COVID-19期间心血管事件关键驱动因素的作用。
