A tricompartmental model of lung oxygenation disruption to explain pulmonary and systemic pathology in severe COVID-19

Abstract

The emergent 21st century betacoronaviruses, including SARS-CoV-2, lead to clinicopathological manifestations with unusual features, such as early-onset chest pain, pulmonary infarction, and pulmonary and systemic thromboembolism that is pathologically linked to extensive capillary, arteriolar, and venular thrombosis. Early ground glass opacities detected by CT, which are reminiscent of lung infarcts associated with pulmonary embolism, point to a novel vascular pathology in COVID-19. Under physiological conditions, normal parenchymal oxygenation is maintained by three sources: the alveolus itself and dual oxygen supply from the pulmonary and bronchial artery circulations. We propose a model in which these three components are disrupted in COVID-19 pneumonia, with severe viral alveolitis and concomitant immunothrombotic obstruction of the pulmonary and bronchiolar circulation. Tricompartmental disruption might have two main consequences: systemic clot embolisation from pulmonary vein territory immunothrombosis, and alveolar-capillary barrier disruption with systemic access of thrombogenic viral material. Our model encompasses the known pathological and clinical features of severe COVID-19, and has implications for understanding patient responses to immunomodulatory therapies, which might exert an anti-inflammatory effect within the vascular compartments.

Plasma Gradient of Soluble Urokinase-Type Plasminogen Activator Receptor Is Linked to Pathogenic Plasma Proteome and Immune Transcriptome and Stratifies Outcomes in Severe COVID-19

“…Thus, the present study identified soluble uPAR as a useful biomarker for the prognostic stratification of COVID-19 patients who have progressed to ARDS in an Indian cohort. The ARDS pathophysiology in COVID-19 is increasingly being appreciated in terms of alveolar inflammation-associated pulmonary intravascular coagulation (36,37). As uPAR-expressing myeloid cells are prevalent in both circulation and pulmonary tissue spaces, soluble uPAR may be a key link between the abnormally expanded circulating myeloid cell compartment in severe COVID-19 patients and the systemic hyper-inflammation and hypercoagulable state encountered in these patients, which warrants further mechanistic exploration.…”

Automated Quantitative Lung CT Improves Prognostication in Non-ICU COVID-19 Patients beyond Conventional Biomarkers of Disease

“…Recent theories on COVID-19 pathophysiology have focused on vasculitis-like anomalies or immune-mediated thrombosis in which viral alveolitis drives inflammation, endotheliopathy, and microvascular injury, leading to vascular tone dysregulation and pulmonary intravascular coagulopathy [5][6][7][8][9][10][11][12]. Postmortem reports and pathological specimens from COVID-19 patients showed DAD together with pulmonary infarction, small pulmonary vessel and capillary thrombosis, and hemorrhage [65,[67][68][69][70][71][72].…”

“…There are different reasons for clinical uncertainties and therapeutic failure in COVID-19. In fact, recent evidence has reconsidered the pathobiogenesis of COVID-19, shifting the attention from a dominant primary lung injury to all vasculitis-like anomalies and immune-mediated thrombosis [5][6][7][8][9][10][11][12].…”

Do you have COVID-19? An artificial intelligence-based screening tool for COVID-19 using acoustic parameters

“…The virus is often characterized by specific dysfunction in the respiratory physiology, including the diaphragm and other parts of the lower respiratory tract, thus affecting breathing patterns during inhalation and exhalation of air from the lungs ( WHO, 2020 ). According to many studies, including Osuchowski et al (2021) , McGonagle et al (2021) , and Gattinoni et al (2020) , COVID-19 has a special and distinct pathophysiology from influenza, other non-COVID-19-related acute respiratory distress syndrome (ARDS), and other coronavirus infections ( Gattinoni et al , 2020 ; McGonagle et al , 2021 ; Osuchowski et al , 2021 ).…”