Vasculopathy and Increased Vascular Congestion in Fatal COVID-19 and Acute Respiratory Distress Syndrome
Julian A Villalba1,2, Caroline F Hilburn1,2, Michelle A Garlin3,4
1James Homer Wright Pathology Laboratories.
Insights
Fatal COVID-19 pneumonia involves distinct lung vascular changes and congestion, differing from other causes of diffuse alveolar damage (DAD). These vascular alterations impact acute respiratory distress syndrome (ARDS) outcomes.
Area of Science:
- Pulmonary Pathology
- Vascular Biology
- Infectious Disease
Background:
- Severe COVID-19 pneumonia frequently leads to acute respiratory distress syndrome (ARDS) and diffuse alveolar damage (DAD).
- The distinct pathological features of DAD in fatal COVID-19 compared to other causes remain unclear.
Purpose of the Study:
- To compare lung parenchymal and vascular alterations in fatal COVID-19 pneumonia versus other DAD etiologies.
- To investigate the role of vascular changes in ARDS and clinical outcomes.
Main Methods:
- Autopsy cohort study comparing COVID-19 pneumonia (n=20) with non-COVID-19 DAD (n=21).
- Analysis included premortem CT scans for vascular changes, postmortem histopathology, and machine-learning-based morphometric analysis of microvasculature (C_Vasc).
- Longitudinal evaluation of respiratory mechanics and gas exchange in ARDS patients.
Main Results:
- COVID-19 cases showed more dilated vasculature on CT and distinct histopathological findings like hemangiomatosis-like changes, thromboemboli, infarcts, and perivascular inflammation.
- Machine learning quantified greater vascular congestion (C_Vasc) in COVID-19.
- Alveolar-septal congestion correlated with shorter survival, hospital stay, and increased ventilatory ratio (V) in ARDS.
Conclusions:
- Severe COVID-19 pneumonia is characterized by significant vasculopathy and alveolar-septal congestion.
- These vascular alterations are key features distinguishing COVID-19 DAD.
- Vascular changes likely play a critical role in ARDS pathophysiology and clinical outcomes.
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 (V); 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 V and clinical outcomes in ARDS in general.
More Related Videos
07:56Monitoring Changes in Human Umbilical Vein Endothelial Cells upon Viral Infection Using Impedance-Based Real-Time Cell Analysis
Published on: May 5, 2023
08:05Lung CT Segmentation to Identify Consolidations and Ground Glass Areas for Quantitative Assesment of SARS-CoV Pneumonia
Published on: December 19, 2020
Related Concept Videos
01:26Heart Failure III: Clinical Manifestations
01:26Imbalances in Cardiac Output
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
01:21Acute Respiratory Failure-II
The underlying physiological abnormalities that contribute to hypoxemic respiratory failure include:
01:30Acute Respiratory Failure-III
01:30Cardiomyopathy II: Dilated Cardiomyopathy
01:23Rheumatic Heart Disease I: Introduction