Microvascular injuries, secondary edema, and inconsistencies in lung vascularization between affected and nonaffected pulmonary segments of non-critically ill hospitalized COVID-19 patients presenting with clinical deterioration

Abstract

Purpose: We aimed to better understand the pathophysiology of SARS-CoV-2 pneumonia in non-critically ill hospitalized patients secondarily presenting with clinical deterioration and increase in oxygen requirement without any identified worsening factors.

Methods: We consecutively enrolled patients without clinical or biological evidence for superinfection, without left ventricular dysfunction and for whom a pulmonary embolism was discarded by computed tomography (CT) pulmonary angiography. We investigated lung ventilation and perfusion (LVP) by LVP scintigraphy, and, 24 h later, left and right ventricular function by Tc-99m-labeled albumin-gated blood-pool scintigraphy with late (60 mn) tomographic albumin images on the lungs to evaluate lung albumin retention that could indicate microvascular injuries with secondary edema.

Results: We included 20 patients with confirmed SARS-CoV-2 pneumonia. All had CT evidence of organizing pneumonia and normal left ventricular ejection fraction. No patient demonstrated preserved ventilation with perfusion defect (mismatch), which may discard a distal lung thrombosis. Patterns of ventilation and perfusion were heterogeneous in seven patients (35%) with healthy lung segments presenting a relative paradoxical hypoperfusion and hypoventilation compared with segments with organizing pneumonia presenting a relative enhancement in perfusion and preserved ventilation. Lung albumin retention in area of organizing pneumonia was observed in 12 patients (60%), indicating microvascular injuries, increase in vessel permeability, and secondary edema.

Conclusion: In hospitalized non-critically ill patients without evidence of superinfection, pulmonary embolism, or cardiac dysfunction, various types of damage may contribute to clinical deterioration including microvascular injuries and secondary edema, inconsistencies in lung segments vascularization suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others.

Summary statement: Microvascular injuries and dysregulation of the balance in perfusion between segments affected by COVID-19 and others are present in non-critically ill patients without other known aggravating factors.

Key results: In non-critically ill patients without evidence of superinfection, pulmonary embolism, macroscopic distal thrombosis or cardiac dysfunction, various types of damage may contribute to clinical deterioration including 1/ microvascular injuries and secondary edema, 2/ inconsistencies in lung segments vascularization with hypervascularization of consolidated segments contrasting with hypoperfusion of not affected segments, suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others.

Trial registration: ClinicalTrials.gov NCT04990505.

Keywords: SARS-CoV-2 pneumonia; microvascular injury; pulmonary embolism; secondary edema; vasoconstriction; vasodilation.

Figure 1.

Patients’ flow diagram. LVEF, left ventricular ejection fraction; SPECT, single photon emission computed tomography.

Figure 2.

Patient no. 2. Perfusion (a), ventilation (b), and CT scan (c). Blue arrow: non-COVID-19-involved area of the right Fowler lobe, with paradoxically matched hypoperfusion and hypoventilation, while the COVID-19-involved area of the right superior lobe just in front remains perfused with a slightly hyperperfused peripheral halo (red arrow).

Figure 3.

Patient no. 2. Albumin (a), CT (b), and fused CT + albumin scan (c). Green arrow: COVID-19 condensation of the right base with significant albumin uptake and moderate pleural effusion behind. There is also a moderate albumin uptake of the left inferior lobe. Albumin (d), CT (e), and fused CT + albumin scan (f). The moderate albumin uptake in the area of the peripheral halo of the COVID-19-involved area in the right superior lobe (red arrow) is related to the corresponding hyperperfusion displayed in Figure 2 (red arrow).

Figure 4.

Patient no. 7. Axial (a) and coronal CT slices (b). Corresponding perfusion (d, e) and ventilation (g, h) scans. Corresponding coronal (c), axial (f), and saggital (i) fused albumin and CT scans. Green arrow: non-COVID-19-involved segment of the right inferior lobe, with paradoxically matched hypoperfusion and hypoventilation, while the COVID-19-involved area just behind (red arrow) is normally ventilated and perfused. (c), (f), (i): Red arrow: significant albumin uptake in several COVID-19-related condensed areas.