Pulmonary Vascular Dilatation Detected by Automated Transcranial Doppler in COVID-19 Pneumonia

Abstract

Some patients with coronavirus disease (COVID-19) pneumonia demonstrate severe hypoxemia despite having near normal lung compliance, a combination not commonly seen in typical acute respiratory distress syndrome (ARDS) (1). The disconnect between gas exchange and lung mechanics in COVID-19 pneumonia has raised the question of whether the mechanisms of hypoxemia in COVID-19 pneumonia differ from those in classical ARDS. Dual-energy computed tomographic imaging has demonstrated pulmonary vessel dilatation (2) and autopsies have shown pulmonary capillary deformation (3) in patients with COVID-19 pneumonia. Contrast-enhanced transcranial Doppler (TCD) of the bilateral middle cerebral arteries after the injection of agitated saline is an This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.

Modeling lung perfusion abnormalities to explain early COVID-19 hypoxemia

“…Whether this degree of vasodilation from baseline is physiologically plausible seems unlikely, given that maximal vasodilation using inhaled nitric oxide may decrease total pulmonary vascular resistance (PVR) by up to 50% 19,20 . Although speculative, it may be possible that COVID-19 interferes with the HPV feedback mechanism in such a way that pulmonary arterioles do not constrict, and may even dilate, in injured lung regions in which there is little or no oxygen transport into the blood 10,11,13,21,22 . Other evidence of vasodilation owing to COVID-19 includes recent discovery of cardiovascular complications reminiscent of vasodilatory shock and Kawasaki disease 23 , which is associated with weakened walls of the coronary artery.…”

“…It is uncertain to what degree the ratio F shu :F inj may vary in nonventilated patients compared to this reported value, as our modeling assumptions result from circumstantial evidence and small case series. A recent study using injected microbubbles suggests that vasodilation occurs in some mechanically ventilated patients with COVID-19 and is correlated with P a O 2 :F i O 2 , however the sample size is small and the measurement technique is nonspecific regarding the location of vascular enlargement and the possibility of intracardiac shunt 11 .…”

“…This gives a ratio of shunt to nonaerated lung of 3, which is large compared with values of 1.25 ± 0.8 reported for ARDS 1,9 . A possible interpretation of this finding is that a disproportionately large fraction of the pulmonary circulation in COVID-19 patients is being directed through poorly aerated or nonaerated lung 1,3,10 , which has led some to hypothesize an underlying impairment in hypoxic pulmonary vasoconstriction (HPV) 1,11 . That is, as HPV normally involves a local feedback mechanism whereby pulmonary arterioles constrict in response to poor regional oxygenation 12 , a failure of this response could potentially lead to a significant mismatch between ventilation and perfusion 13 .…”

Reply to Cherian et al.: Positive Bubble Study in Severe COVID-19 Indicates the Development of Anatomical Intrapulmonary Shunts in Response to Microvascular Occlusion

“…We appreciate Cherian and colleagues' interest in our research letter. 1 The medical community's knowledge of COVID-19 and its impact on the pulmonary system is evolving rapidly; we believe this kind of open, iterative dialogue is critical to informing our approach to patient care. In their letter, they suggest that transpulmonary bubble transit in hepatopulmonary syndrome (HPS) is solely due to abnormal pulmonary arteriovenous connections.…”

Immunological Mechanisms Explaining the Role of Vaccines, IgE, Mast Cells, Histamine, Elevating Ferritin, IL-6, D-dimer, VEGF Levels in COVID-19 and Dengue, Potential Treatments Such as Mast Cell Stabilizers, Antihistamines: Predictions and Confirmations

“…Histamine release results in increased vascular permeability and pulmonary vascular dilatation. Pulmonary vascular dilatation results in hypoxemia (Reynolds et al 2020), the most common symptom in COVID-19. An allergic immune response involving increase in multiple type 2 (anti-helminth) effectors, IgE, eosinophils, IL-13 and IL-5 has been reported in severe COVID-19 (Lucas et al 2020).…”