Microvascular Shunts in COVID-19 Pneumonia

To the Editor:

Throughout the coronavirus disease (COVID-19) pandemic, clinicians and scientists have attempted to understand mechanisms underlying severe hypoxia in individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be disproportionate to changes in lung mechanics (1). Pathophysiologic mechanisms leading to hypoxia in SARS-CoV-2 are incompletely understood but may include the recruitment of intrapulmonary shunt vessels. Past work has noted the presence of prominent intrapulmonary bronchopulmonary anastomoses (IBA), which represent connections between the pulmonary and bronchial circulations, in severe SARS-CoV-2 (2, 3). Prominent IBA have been previously observed by lung histology and three-dimensional reconstruction from patients dying with SARS-CoV-2, proposing that these vessels contribute to intrapulmonary shunt (2). IBA have previously been identified in several diseases characterized by severe hypoxemia with extensive pulmonary vascular disease, including developmental lung diseases, and in idiopathic pulmonary arterial hypertension (4, 5).

In patients with SARS-CoV-2, Reynolds and colleagues performed studies using contrast-enhanced transcranial Doppler imaging of the bilateral middle cerebral arteries (3). These investigators demonstrated that 83% of the study participants had clear evidence of shunting of agitated saline bubbles into the middle cerebral arteries, which bypassed the pulmonary capillaries (3). Furthermore, the Pa_O2-to-Fi_O2 ratio was inversely correlated with the number of microbubbles observed (Pearson’s r = −0.55; P = 0.02), suggesting that the larger the shunt, the greater the degree of hypoxemia. With these findings, this group proposed that shunt vessels may further contribute to the pathophysiology and severity of hypoxemia in SARS-CoV-2.

This recent publication by Ackermann and colleagues (6) supports these past observations describing IBA in COVID-19 lungs at autopsy. However, their findings would be further strengthened with more details regarding how vascular types and connections were determined by their extensive imaging methods. The histologic terms that were used, such as describing vessels as “angiomatoid” or “plexiform”, are more typically used to describe histologic features of plexiform lesions in severe pulmonary arterial hypertension, observations that were not made in this case series. Both current and past work (7) by this team suggests that neovascularization takes place in severe COVID-19 pneumonia via intussusceptive angiogenesis at capillary levels. This proposal markedly depends on the demonstration of increased numbers of holes within capillary networks from corrosion casts. Production of such tiny and fragile casts is very difficult with highly variable outcomes, and interpretation may be subject to sampling bias. Thorough quantification and cast comparison to other pulmonary disease controls would be helpful. Our view is that the observed microvessels appear dilated and congested and are detectable owing to increased recruitment through enhanced blood flow, which reflects intrapulmonary shunting (2). In fact, alveolar and bronchial capillary abundance due to pathologic congestion is frequently seen in histologic sections of autopsy material in the presence of right heart failure.

Over the years, vascular connections between the pulmonary and bronchial circulations have been given a variety of names, including bronchopulmonary, pulmobronchial, supernumerary vessels, or “Sperrarterien”, but their roles during development or in disease have been uncertain. Advances in our understanding of the role of these vessels through comprehensive studies including histology, three-dimensional reconstruction, hemodynamics, and now, advanced imaging provide tools to stimulate future work to better understand their potential contributions to disease. We have proposed the term IBA to describe microvascular pulmonary and bronchial connections that allow for pulmonary arterial blood to bypass alveolar capillaries. Further characterization of mechanisms underlying the developmental basis for and physiologic regulation of IBA may provide insights leading to the development of novel diagnostic and therapeutic strategies to better address the many challenges of severe respiratory failure in patients with SARS-CoV-2, as well as potential roles in “long COVID” during follow-up in survivors.