Can Hyperperfusion of Nonaerated Lung Explain COVID-19 Hypoxia?

Herrmann, Jacob; Mori, Vitor; Bates, Jason H. T.; Suki, Bélâ

doi:10.21203/rs.3.rs-32949/v1

Cited by 5 publications

(8 citation statements)

References 26 publications

(57 reference statements)

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“…The hypoxic events in COVID-19 patients have been a mystery to medical caretakers and physicians. This is due to the fact that the patients display minimal visible distress, although clinical oxygen levels are remarkably low ( 99 ). Its presentation defies its pathophysiology, which initially led to its description of “Happy Hypoxia” ( 100 ).…”

Section: The Hypoxic Responsementioning

confidence: 99%

The Notch Pathway: A Link Between COVID-19 Pathophysiology and Its Cardiovascular Complications

Breikaa

Lilly

2021

Front. Cardiovasc. Med.

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COVID-19 is associated with a large number of cardiovascular sequelae, including dysrhythmias, myocardial injury, myocarditis and thrombosis. The Notch pathway is one likely culprit leading to these complications due to its direct role in viral entry, inflammation and coagulation processes, all shown to be key parts of COVID-19 pathogenesis. This review highlights links between the pathophysiology of SARS-CoV2 and the Notch signaling pathway that serve as primary drivers of the cardiovascular complications seen in COVID-19 patients.

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Section: The Hypoxic Responsementioning

confidence: 99%

The Notch Pathway: A Link Between COVID-19 Pathophysiology and Its Cardiovascular Complications

Breikaa

Lilly

2021

Front. Cardiovasc. Med.

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“…The presence of normal or high pulmonary blood flow in non-aerated lung areas is probably caused by the relative failure of the hypoxic pulmonary vasoconstriction mechanism in COVID-19 pneumonia [13,18]. Mathematical modeling has also confirmed that the amount of pulmonary shunt observed in patients with early stage severe COVID-19 is not plausible without hyperperfusion of the injured lung [19].…”

Section: Discussionmentioning

confidence: 94%

Unusual perfusion patterns on perfusion-only SPECT/CT scans in COVID-19 patients

Farkas

Képes

Barna³

et al. 2022

Ann Nucl Med

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Purpose We aimed at examining both the incidence and extent of different lung perfusion abnormalities as well as the relationship between them on Tc-99m macroaggregated albumin (MAA) perfusion-only SPECT/CT scans in COVID-19 patients. Methods Ninety-one patients (71.4 ± 13.9 years; range: 29–98 years, median age: 74 years; 45 female and 46 male) with confirmed SARS-CoV-2 virus infection were included in this retrospective study. After performing perfusion-only Tc-99m MAA SPECT/CT scans, visual, semi-quantitative assessment of the subsequent perfusion abnormalities was carried out: mismatch lesions (MM; activity defects on SPECT images identical to apparently healthy parenchyma on CT images), matched lesions (MA; activity defects with corresponding parenchymal lesions on CT scans), and reverse mismatch lesions (RM; parenchymal lesions with preserved or increased tracer uptake). Lesion-based and patient-based analysis were performed to evaluate the extent, severity, and incidence of each perfusion abnormality. Statistical tests were applied to investigate the association between the experienced perfusion impairments. Results Moderately severe parenchymal lesions were detected in 87 (95.6%) patients. Although, 50 (54.95%) patients were depicted to have MM lesions, the whole patient cohort was mildly affected by this abnormality. MA lesions of average moderate severity were seen in most of the patients (89.01%). In 65 (71.43%) patients RM lesions were found with mild severity on average. Positive association was detected between total CT score and total RM score and between total CT score and total MA score. Significantly higher total CT scores were experienced in the subgroup, where RM lesions were present. Conclusions Heterogeneous perfusion abnormalities were found in most of COVID-19 patients: parenchymal lesions with normal, decreased or increased perfusion and perfusion defects in healthy lung areas. These phenomena may be explained by the failure of the hypoxic pulmonary vasoconstriction mechanism and presence of pulmonary thrombosis and embolism.

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“…the fraction of lung affected in this way is often surprisingly low given the severity of the associated hypoxia and estimated shunt fractions (average 50%). If one assumes that ground-glass opacification represents lung that is nonventilated, these CT studies imply abnormally high ratios of shunt fraction to nonaerated lung fraction of 3.0 for COVID-19 compared to 1.3 for ARDS Herrmann et al, 2020. Their model finds that truly vast increases in diameter of pulmonary arterioles would be necessary to explain such a vast decrease in vascular resistance, opening of pulmonary vessels, and delivery of blood to non-aerated lung tissue, concluding only that 'Approximating vascular resistance using the Hagen-Poiseuille equation, this change in resistance corresponds to an increase in vascular diameter of 26 to 35%.…”

Section: Rush To Attribute Early Covid-19 Hypoxemia To Vascular Mecha...mentioning

confidence: 99%

Pulmonary surfactant and COVID-19: A new synthesis

2022

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Chapter 1: COVID-19 pathogenesis poses paradoxes difficult to explain with traditional physiology. For instance, since type II pneumocytes are considered the primary cellular target of SARS-CoV-2; as these produce pulmonary surfactant (PS), the possibility that insufficient PS plays a role in COVID-19 pathogenesis has been raised. However, the opposite of predicted high alveolar surface tension is found in many early COVID-19 patients: paradoxically normal lung volumes and high compliance occur, with profound hypoxemia. That ‘COVID anomaly’ was quickly rationalised by invoking traditional vascular mechanisms–mainly because of surprisingly preserved alveolar surface in early hypoxemic cases. However, that quick rejection of alveolar damage only occurred because the actual mechanism of gas exchange has long been presumed to be non-problematic, due to diffusion through the alveolar surface. On the contrary, we provide physical chemical evidence that gas exchange occurs by an process of expansion and contraction of the three-dimensional structures of PS and its associated proteins. This view explains anomalous observations from the level of cryo-TEM to whole individuals. It encompasses results from premature infants to the deepest diving seals. Once understood, the COVID anomaly dissolves and is straightforwardly explained as covert viral damage to the 3D structure of PS, with direct treatment implications. As a natural experiment, the SARS-CoV-2 virus itself has helped us to simplify and clarify not only the nature of dyspnea and its relationship to pulmonary compliance, but also the fine detail of the PS including such features as water channels which had heretofore been entirely unexpected.

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Can Hyperperfusion of Nonaerated Lung Explain COVID-19 Hypoxia?

Cited by 5 publications

References 26 publications

The Notch Pathway: A Link Between COVID-19 Pathophysiology and Its Cardiovascular Complications

The Notch Pathway: A Link Between COVID-19 Pathophysiology and Its Cardiovascular Complications

Unusual perfusion patterns on perfusion-only SPECT/CT scans in COVID-19 patients

Pulmonary surfactant and COVID-19: A new synthesis

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