key: cord-0712278-6g0cd9r1
authors: Ackermann, Maximilian; Tafforeau, Paul; Wagner, Willi L.; Walsh, Claire L.; Werlein, Christopher; Kühnel, Mark P.; Länger, Florian P.; Disney, Catherine; Bodey, Andrew J.; Bellier, Alexandre; Verleden, Stijn E.; Lee, Peter D.; Mentzer, Steven J.; Jonigk, Danny D.
title: The Bronchial Circulation in COVID-19 Pneumonia
date: 2021-08-31
journal: Am. j. respir. crit. care med
DOI: 10.1164/rccm.202103-0594im
sha: 2b5aae94d99aa0c95f6f2ba2eb91161d58ea6bcb
doc_id: 712278
cord_uid: 6g0cd9r1

nan

The primary life-limiting pulmonary morbidity of severe coronavirus disease (COVID-19) is characterized by pulmonary endothelialitis, microangiopathy, and aberrant angiogenesis (1) . Although numerous studies have highlighted the pronounced microangiopathy in pulmonary circulation, the impact of the bronchial vascular system has not been fully elucidated. Therefore, we comprehensively analyzed complete lung lobes from three male patients (age, 63.7 6 14.2 years; hospitalization time, 22 6 1 days, mechanically ventilated) who succumbed to severe COVID-19 using conventional computed tomography, histology, microvascular corrosion casting, and hierarchical phase-contrast tomography (2) . We used three control lungs from body donors (age, 78.3 6 13.6 yr; nonventilated, two females and one male died from cerebral stroke or uterine carcinoma).

In pulmonary computed tomography angiography, we found the previously reported pulmonary sequelae of COVID-19 lung injury in the form of bilateral peripheral ground-glass opacities, peribronchial consolidations, and peripheral macrovascular congestion (3) (Figures 1A and 1B) . Peribronchial and perivascular microvessels (vasa vasorum) were distinctly dilated ( Figures  1C-1F ). This intrapulmonary shunting by the bronchial circulation ( Figure 2A ) accounts for the continued perfusion in a variety of airway conditions, such as inflammation, acute respiratory distress syndrome, and chronic thromboembolism (3). In severe COVID-19 pneumonia, the microvascular architecture of the peribronchial vessels showed a microvascular architecture with densely packed aberrant bundles of blood vessels ( Figures 2B-2E ). The expansion of the peribronchial plexus is mainly driven by intussusceptive angiogenesis as evidenced by the appearance of transluminal endothelial tissue pillars ( Figures 2B-2D ) (1, 4, 5) .

A spatial analysis of peribronchial vessels in COVID-19 pneumonia by hierarchical phase-contrast tomography demonstrated the expansion of peribronchial and perivascular arteriovenous anastomoses and a recruitment of "Sperrarterien" 

Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19

Imaging intact human organs with local resolution of cellular structures using hierarchical phase-contrast tomography

The bronchial circulation-worth a closer look: a review of the relationship between the bronchial vasculature and airway inflammation

Angiogenesis in the lung

Inflammation and intussusceptive angiogenesis in COVID-19: everything in and out of flow

the online supplement). This intralobular shunting is accompanied by different spots of glomerouid-like vascular expansion ( Figures  3C and 3D) .Here, we show the first insight into the complex three-dimensional phenomenon of bronchiopulmonary shunting in COVID-19. However, the sequelae of this excessive neovascularization, the actual remodeling that may account for intralesional hyperperfusion and long-term implications, have so far not been understood.Author disclosures are available with the text of this article at www.atsjournals.org.