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In American journal of respiratory and critical care medicine ; h5-index 108.0

Rationale The leading cause of death in coronavirus disease 2019(COVID-19) is severe pneumonia, with many patients developing acute respiratory distress syndrome(ARDS) and diffuse alveolar damage(DAD). Whether DAD in fatal COVID-19 is distinct from other causes of DAD remains unknown. Objective To compare lung parenchymal and vascular alterations between patients with fatal COVID-19 pneumonia and other DAD-causing etiologies using a multidimensional approach. Methods This autopsy cohort consisted of consecutive patients with COVID-19 pneumonia(n=20) and with respiratory failure and histologic DAD(n=21; non-COVID-19 viral and non-viral etiologies). Premortem chest computed tomography(CT) scans were evaluated for vascular changes. Postmortem lung tissues were compared using histopathological and computational analyses. Machine-learning-derived morphometric analysis of the microvasculature was performed, with a random forest classifier quantifying vascular congestion(CVasc) in different microscopic compartments. Respiratory-mechanics and gas-exchange parameters were evaluated longitudinally in patients with ARDS. Measurements and Main Results On premortem CT, COVID-19 patients showed more dilated vasculature when evaluating all lung segments (p=0.001) compared to DAD-controls. Histopathology revealed vasculopathic changes including hemangiomatosis-like-changes(p=0.043), thromboemboli(p=0.0038), pulmonary infarcts(p=0.047), and perivascular inflammation(p<0.001). Generalized estimating equations revealed significant regional differences in the lung microarchitecture among all DAD-causing entities. COVID-19 showed a larger overall CVasc-range(p=0.002). Alveolar-septal-congestion was associated with a significantly shorter time-to-death from symptom onset(p=0.03), length-of-hospital-stay(p=0.02), and increased ventilatory ratio[an estimate for pulmonary dead space fraction(Vd); p=0.043] in all cases of ARDS. Conclusions Severe COVID-19 pneumonia is characterized by significant vasculopathy and aberrant alveolar-septal-congestion. Our findings also highlight the role that vascular alterations may play in Vd and clinical outcomes in ARDS in general.

Villalba Julian A, Hilburn Caroline F, Garlin Michelle A, Elliott Grant A, Li Yijia, Kunitoki Keiko, Poli Sergio, Alba George A, Madrigal Emilio, Taso Manuel, Price Melissa C, Aviles Alexis J, Araujo-Medina Milagros, Bonanno Liana, Boyraz Baris, Champion Samantha N, Harris Cynthia K, Helland Timothy L, Hutchison Bailey, Jobbagy Soma, Marshall Michael S, Shepherd Daniel J, Barth Jaimie L, Hung Yin P, Ly Amy, Hariri Lida P, Turbett Sarah E, Pierce Virginia M, Branda John A, Rosenberg Eric S, Mendez-Pena Javier, Chebib Ivan, Rosales Ivy A, Smith Rex N, Miller Miles A, Rosas Ivan O, Hardin Charles C, Baden Lindsey R, Medoff Benjamin D, Colvin Robert B, Little Brent P, Stone James R, Mino-Kenudson Mari, Shih Angela R


ARDS, COVID-19, Vascular Congestion, Vasculopathy, Ventilatory ratio