Intrapulmonary shunt and alveolar dead space in a cohort of patients with acute COVID-19 pneumonitis and early recovery

Abstract

BackgroundPathological evidence suggests that COVID-19 pulmonary infection involves both alveolar damage (causing shunt) and diffuse micro-vascular thrombus formation (causing alveolar dead space). We propose that measuring respiratory gas exchange enables detection and quantification of these abnormalities. We aimed to measure shunt and alveolar deadspace in moderate COVID-19 during acute illness and recovery.MethodsWe studied 30 patients (22 males, age: 49.9±13.5 years) 3–15 days from symptom onset and again during recovery, 55±10 days later (n=17). Arterial blood (breathing ambient air) was collected while exhaled O2 and CO2 concentrations were measured, yielding alveolar-arterial differences for each gas (AaPO2, aAPCO2) from which shunt and alveolar dead space were computed.Measurements and Main ResultsFor acute COVID-19 patients, group mean (range) for AaPO2 was 41.4 (−3.5 to 69.3) mmHg; aAPCO2 was 6.0 (−2.3 to 13.4) mmHg. Both shunt (% cardiac output) at 10.4 (0 to 22.0)%, and alveolar dead space (% tidal volume) at 14.9 (0 to 32.3)% were elevated (normal: <5% and <10%, respectively), but not correlated (p=0.27). At recovery, shunt was 2.4 (0 to 6.1)% and alveolar dead space was 8.5 (0 to 22.4)% (both p<0.05 versus acute); shunt was marginally elevated for 2 patients, however, 5 (30%) had elevated alveolar dead space.ConclusionsWe speculate impaired pulmonary gas exchange in early COVID-19 pneumonitis arises from two concurrent, independent and variable processes (alveolar filling and pulmonary vascular obstruction). For most patients these resolve within weeks, however, high alveolar dead space in ∼30% of recovered patients suggests persistent pulmonary vascular pathology.

Comment on: Intrapulmonary shunt and alveolar dead space in a cohort of patients with acute COVID-19 pneumonitis and early recovery

“…In a recent study (2), we could demonstrate the involvement of the secondary pulmonary lobules in the fatal trajectory of COVID-19 using ultra-high resolution synchrotron radiation based hierarchical phase-contrast tomography (HiP-CT) (3) (Figure a-c). We observed a distinct, mosaic-like consolidation of individual secondary pulmonary lobules based on microvascular occlusion and secondary lobular microischemia, reflecting the increased alveolar dead space described by Harbut et al (1). Moreover, this septal microischemia was accompanied by a periseptal thickening (F) and pronounced dilatation and expansion of the bronchial circulation plexus by opening of intrapulmonary bronchopulmonary shunts and "Sperrarterien" (specialized blockade arteries of the bronchial circulation) (4,5) and an excessive blood vessel neoformation by intussusceptive angiogenesis, especially in the interlobular septae (2,6,7) (Figure d-g).…”

Novel gas exchange analysis in COVID-19 lung disease

“…The study by H arbut et al [ 1 ] reported in this issue of the European Respiratory Journal analyses gas exchange in patients with acute coronavirus disease 2019 (COVID-19) lung disease; arterial oxygen and carbon dioxide tension ( P O 2 and P CO 2 ) and the mean (or mixed) value for alveolar (A̅) P O 2 and P CO 2 (not an “ideal” [ 2 ] but the actual value) were measured, when patients (and healthy controls) were breathing air. From the mean alveolar to arterial P O 2 and arterial to mean alveolar P CO 2 gradients (A̅a P O 2 and aA̅ P CO 2 ), the authors computed intrapulmonary shunt and alveolar dead space using the classical three compartment model of R iley and C ournand [ 2 ] (but, with important differences: see later).…”

“…From the mean alveolar to arterial P O 2 and arterial to mean alveolar P CO 2 gradients (A̅a P O 2 and aA̅ P CO 2 ), the authors computed intrapulmonary shunt and alveolar dead space using the classical three compartment model of R iley and C ournand [ 2 ] (but, with important differences: see later). H arbut et al [ 1 ] argued that intrapulmonary shunt should be a marker for alveolar consolidation, as in lobar pneumonia, but at a more microscopic level; alveolar dead space, on the other hand, should be a surrogate for pulmonary microvascular obstruction and thrombosis, e.g. following severe endothelial injury.…”

“…30 patients were studied, initially 3–15 days from the start of COVID-19 symptoms, and subsequently during recovery [ 1 ]. They had mild to moderate hypoxaemia ( P aO 2 mean 68.3 mmHg, range 52–106 mmHg); 18 (60%) received supplemental oxygen.…”

“…At recovery, only two patients had continuing (but minimally elevated) shunt (down from 23), but eight still had high alveolar dead space (down from 21). The authors [ 1 ] claim that their method, which is applicable at the bedside, can distinguish intravascular pathology (most likely at a microvascular level) from alveolar and epithelial injury leading to airspace flooding/consolidation and intrapulmonary shunt.…”