Citations 1
Vasculopathy and Increased Vascular Congestion in Fatal COVID-19 and Acute Respiratory Distress Syndrome
Villalba, Julian A. , Hilburn, Caroline F., Garlin, Michelle A., Elliott, Grant A., Li, Yijia , Kunitoki, Keiko , Poli, Sergio , Alba, George A. , Taso, Manuel , Price, Melissa C. , Aviles, Alexis J., Araujo-Medina, Milagros, Bonanno, Liana, Boyraz, Bariş , Champion, Samantha N. , Harris, Cynthia K. , Helland, T. Leif , Hutchison, Bailey , Jobbagy, Soma , Shepherd, Daniel , Barth, Jaimie L., Hung, Yin P. , Ly, Amy , Turbett, Sarah E. , Pierce, Virginia , Branda, John A. , Rosenberg, Eric , Mendez-Pena, Javier E., Chebib, Ivan , Rosales, Ivy A. , Smith, R. Neal , Miller, Miles A. , Rosas, Iván O. , Hardin, C. Corey , Baden, Lindsey R. , Stone, James R. , Shih, Angela , Politis, Michelle Garlin , Little, Brent P. , Hung, Yin P , Miller, Miles A , Garlin Politis, Michelle , Madrigal, Emilio , Marshall, Michael S. , Hariri, Lida P. , Medoff, Benjamin D. , Colvin, Robert B. , Mino-Kenudson, Mari A. , Shih, Angela
American Journal of Respiratory and Critical Care Medicine | June 7, 2022 | Volume: 206 | Issue: 7 | Pages: 857-873
Abstract 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 nonviral 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 In premortem CT, patients with COVID-19 showed more dilated vasculature when all lung segments were evaluated (P = 0.001) compared with controls with DAD. 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.