Title | Vasculopathy and Increased Vascular Congestion in Fatal COVID-19 and Acute Respiratory Distress Syndrome. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Villalba JA, Hilburn CF, Garlin MA, Elliott GA, Li Y, Kunitoki K, Poli S, Alba GA, Madrigal E, Taso M, Price MC, Aviles AJ, Araujo-Medina M, Bonanno L, Boyraz B, Champion SN, Harris CK, Helland TL, Hutchison B, Jobbagy S, Marshall MS, Shepherd DJ, Barth JL, Hung YP, Ly A, Hariri LP, Turbett SE, Pierce VM, Branda JA, Rosenberg ES, Mendez-Pena J, Chebib I, Rosales IA, Smith RN, Miller MA, Rosas IO, Hardin CC, Baden LR, Medoff BD, Colvin RB, Little BP, Stone JR, Mino-Kenudson M, Shih AR |
Journal | Am J Respir Crit Care Med |
Volume | 206 |
Issue | 7 |
Pagination | 857-873 |
Date Published | 2022 Oct 01 |
ISSN | 1535-4970 |
Keywords | COVID-19, Humans, Lung, Pneumonia, Pulmonary Alveoli, Respiratory Distress Syndrome, Vascular Diseases |
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. |
DOI | 10.1164/rccm.202109-2150OC |
Alternate Journal | Am J Respir Crit Care Med |
PubMed ID | 35671465 |
PubMed Central ID | PMC9799276 |
Grant List | DP2 CA259675 / CA / NCI NIH HHS / United States |
Related Faculty:
Baris Boyraz, M.D., Ph.D.