COVID-19 Lung Microvascular and Parenchymal Sequelae (Lung-MaPS)

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The long-term health impact of COVID-19 remains uncertain. We are already providing post-hospitalization care for thousands of COVID-19 survivors at Columbia University Irving Medical Center (CUIMC) in New York City. This study is designed to help our and other medical centers care for COVID-19 survivors by using gold- standard imaging approaches to describe the major sequelae of severe COVID-19. The possibility of significant vascular and parenchymal sequelae of severe COVID-19 is suggested by the prominent Alverolar- arterial gradients observed clinically, plus histopathology confirming substantial endothelial and epithelial damage. Nonetheless, precise assessments of vascular and parenchymal sequelae in vivo have been limited, especially for the vasculature, and long-term follow-up to assess recovery or progression is lacking. Our investigative team has developed and refined a dual-energy computed tomography (CT) protocol to provide direct measures of the pulmonary vasculature, including pulmonary parenchymal perfused blood volume (PBV); and, detailed phenotyping of the parenchyma, including ground glass opacity (GGO) textures, which we have identified by an adaptive multiple features model (AMFM) approach in preliminary work among COVID-19 survivors. In multiethnic cohort studies, we have associated these CT measures with development and progression of chronic lung diseases. To strengthen our investigation into potential microvascular mechanisms of COVID-19 lung injury, this application will also test if PBV is associated with biomarkers of inflammation, hypercoagulability, and complement activation. We will randomly sample 200 adults without a prior diagnosis of chronic lung disease who were hospitalized for COVID-19 at CUIMC and did not require intubation, plus 100 seronegative controls matched on age, sex, race, ethnicity, body mass index, and neighborhood. All participants will undergo contrast-enhanced dual-energy CT, diffusing capacity of the lung for carbon monoxide, spirometry, questionnaires, and phlebotomy for SARS-CoV-2 antibodies and biomarkers. These measures will be performed 3-12 months and 27-36 months post-COVID hospital discharge to accomplish three specific aims. Aim 1 is to define lung microvascular sequelae of COVID-19. We hypothesize that PBV in COVID-19 survivors will be lower and more heterogeneous, and that these abnormalities will be associated with levels of IL-6, CRP, d-dimer, C5a, MBL, and MASP-2. Aim 2 is to define lung parenchymal sequelae of COVID-19. We hypothesize that there will be greater GGO texture patterns in COVID-19 survivors. Aim 3 is to explore if COVID-related differences in lung structure and procoagulant biomarkers are maintained up to 3 years after acute illness. We hypothesize that two years following the baseline study visit, parenchymal and biomarker abnormalities will normalize, but vascular abnormalities will progress. Accomplishment of the Aims will guide post-COVID care and risk stratification, suggest targets for therapeutic interventions, and inform policies for risk mitigation and public health in the COVID-19 era.