Extension of Collagen Deposition in COVID-19 Post Mortem Lung Samples and Computed Tomography Analysis Findings

Abstract

Lung fibrosis has specific computed tomography (CT) findings and represents a common finding in advanced COVID-19 pneumonia whose reversibility has been poorly investigated. The aim of this study was to quantify the extension of collagen deposition and aeration in postmortem cryobiopsies of critically ill COVID-19 patients and to describe the correlations with qualitative and quantitative analyses of lung CT. Postmortem transbronchial cryobiopsy samples were obtained, formalin fixed, paraffin embedded and stained with Sirius red to quantify collagen deposition, defining fibrotic samples as those with collagen deposition above 10%. Lung CT images were analyzed qualitatively with a radiographic score and quantitatively with computer-based analysis at the lobe level. Thirty samples from 10 patients with COVID-19 pneumonia deceased during invasive mechanical ventilation were included in this study. The median [interquartile range] percent collagen extension was 6.8% (4.6–16.2%). In fibrotic compared to nonfibrotic samples, the qualitative score was higher (260 (250–290) vs. 190 (120–270), p = 0.036) while the gas fraction was lower (0.46 (0.32–0.47) vs. 0.59 (0.37–0.68), p = 0.047). A radiographic score above 230 had 100% sensitivity (95% confidence interval, CI: 66.4% to 100%) and 66.7% specificity (95% CI: 41.0% to 92.3%) to detect fibrotic samples, while a gas fraction below 0.57 had 100% sensitivity (95% CI: 66.4% to 100%) and 57.1% specificity (95% CI: 26.3% to 88.0%). In COVID-19 pneumonia, qualitative and quantitative analyses of lung CT images have high sensitivity but moderate to low specificity to detect histopathological fibrosis. Pseudofibrotic CT findings do not always correspond to increased collagen deposition.

Covid-19 and Pulmonary Fibrosis: A Literature Review

“…Six months after infection, the ground-glass pattern resolved, but there was persistence or development of changes suggestive of pulmonary fibrosis, such as reticulation with or without a distortion of the lung parenchyma . Another, more recent analysis with 118 infected patients diagnosed with moderate or severe pneumonia by SARS-CoV-2, adopting a stricter definition of fibrotic changes, found fibrotic-like changes in 72% of cases (SOLOMON, 2021) (BALL, 2021).…”

Different Methods to Improve the Monitoring of Noninvasive Respiratory Support of Patients with Severe Pneumonia/ARDS Due to COVID-19: An Update

“…Both COVID-19 and non-COVID-19 ARDS are characterized by severe refractory hypoxemia and high mortality [ 3 , 4 ]. However, despite several pathophysiological similarities existing between COVID-19 and non-COVID-19 ARDS, some substantial differences should be discussed ( Figure 1 and Figure 2 ).…”

“…Usually, three histopathological phases are described in traditional ARDS: (1) acute early exudative (1–7 days) with intra-alveolar edema, interstitial widening, formation of hyaline membranes, epithelial disruption, and alveolar distortion; (2) subacute proliferative phase (1–3 weeks) with myofibroblast proliferation and hyperplasia of the epithelial lining; and (3) late fibrotic phase (>3 weeks) characterized by collagen deposition, progressive obliteration of alveolar spaces, and interstitial fibrosis [ 4 ]. Associated thrombi can result as expression of an altered coagulation cascade, which is common in COVID-19 [ 3 ] ( Table 1 ).…”

Understanding the pathophysiology of typical acute respiratory distress syndrome and severe COVID-19

“…Severe COVID-19 pneumonia often requires invasive mechanical ventilation and appears to be a specific phenotype of ARDS (ARDSp), with a distinct histological pattern compared with ARDSexp. Autopsy studies on COVID-19 have reported diffuse alveolar damage, alveolar flooding with the presence of fibrin and hyaluran [ 41 ], intense remodeling [ 42 ], platelet–fibrin microthrombi [ 43 ], and early fibrotic evolution [ 44 ], with variable deposition of collagen fibers [ 45 ]. Despite several similarities with conventional ARDSp, which is characterized by normal endothelium, COVID-19 pneumonia, despite being a pulmonary ARDS, presents in the early stages with endothelial injury and dysfunction induced by direct viral action and host inflammatory response [ 46 ].…”