Ultrasound assessment of pulmonary fibroproliferative changes in severe COVID-19: a quantitative correlation study with histopathological findings

Abstract

Purpose: This study was designed to evaluate the usefulness of lung ultrasound (LUS) imaging to characterize the progression and severity of lung damage in cases of COVID-19.

Methods: We employed a set of combined ultrasound parameters and histopathological images obtained simultaneously in 28 patients (15 women, 0.6-83 years) with fatal COVID-19 submitted to minimally invasive autopsies, with different times of disease evolution from initial symptoms to death (3-37 days, median 18 days). For each patient, we analysed eight post-mortem LUS parameters and the proportion of three histological patterns (normal lung, exudative diffuse alveolar damage [DAD] and fibroproliferative DAD) in eight different lung regions. The relationship between histopathological and post-mortem ultrasonographic findings was assessed using various statistical approaches.

Results: Statistically significant positive correlations were observed between fibroproliferative DAD and peripheral consolidation (coefficient 0.43, p = 0.02) and pulmonary consolidation (coefficient 0.51, p = 0.005). A model combining age, time of evolution, sex and ultrasound score predicted reasonably well (r = 0.66) the proportion of pulmonary parenchyma with fibroproliferative DAD.

Conclusion: The present study adds information to previous studies related to the use of LUS as a tool to assess the severity of acute pulmonary damage. We provide a histological background that supports the concept that LUS can be used to characterize the progression and severity of lung damage in severe COVID-19.

Keywords: Acute lung injury; Autopsy; COVID-19; Diffuse alveolar damage; Lung ultrasound; Minimally invasive autopsy; Pathology.

Fig. 1

Histological patterns associated to ultrasound scores. a Normal lung: preserved architecture, without inflammation, oedema or exudates. b Exudative diffuse alveolar damage: acute pulmonary injury with hyaline membranes, interstitial oedema and inflammation and pneumocyte hyperplasia. c Fibroproliferative diffuse alveolar damage: interstitial and intra-alveolar fibroblastic proliferation, collagen deposition, mild inflammatory cell infiltration, and small remnants of hyaline membranes

Fig. 2

The several patterns of LUS in COVID-19 patients: a normal pleural line (arrows) and A lines (arrowheads). b normal pleural line (arrowhead), spaced B lines (asterisks), and fragmented pleural line (arrow). c irregular pleural line (arrow) and confluent B lines (asterisks). d normal pleural line (arrows) and white lung (asterisks). e irregular pleural line (arrow), peripheral consolidation (arrowhead), and white lung (asterisk). f normal pleural line (arrow) and pulmonary consolidation with air bronchogram (arrowhead)

Fig. 3

Box plots represent the variation of the proportion (%) of normal alveolar parenchyma, exudative diffuse alveolar damage (DAD) and fibroproliferative DAD among the 28 patients, disaggregated by LUSCORE tertiles