Histopathologic Progression and Radiologic Correlation of COVID-19 Lung Parenchyma Using a Post-Mortem Mini-Invasive Transbronchial Lung Cryobiopsy Approach

Background: Data on the pathologic features in COVID-19 are scarce; the few available studies show diffuse alveolar damage (DAD) however no data on the chronologic evolution of COVID-19 lung lesions are available. The primary aim of the study was to describe the chronology of lung pathological changes in COVID-19 by using a post mortem transbronchial lung cryobiopsy approach (TBLC). Our secondary aim was to correlate the histologic findings with computed tomography (CT) patterns. Methods: SARS-Cov2 positive patients, with available CT scans, who died while intubated and mechanically ventilated, were enrolled. TBLC procedure was performed 30 minutes after death, and all lung lobes sampled. Histopathologic analysis was performed on all available tissue. Findings: Eight patients met criteria. Two patients (illness duration <14 days) showed early/exudative phase DAD while the remaining 6 patients (median illness duration - 32 days) showed progressive histologic patterns (3 with mid/proliferative phase; 3 with late/fibrous phase DAD one of which with honeycombing). Early phase lesions were more frequent in the upper lobes while mid/late phase lesions were more often seen in the lower/middle lobes. Histologic patterns and CT categories showed significant correlation (r s :0.84): early/exudative phase was associated with ground glass opacity, mid/proliferative lesions with crazy paving while late/fibrous phase correlated with the consolidation pattern. Interpretation: This study uses an innovative cryobiopsy approach for the post mortem sampling of lung tissues from COVID-19 patients. Information on histologic pattern progression and CT features may prove important in the follow-up of lung lesions in COVID-19 survivors. Funding Statement: Institutional financial support was provided to this study; funding played no significant role in study design, collection, analysis or data interpretation. Declaration of Interests: The authors have nothing to declare. Ethics Approval Statement: The protocol was approved by the regional ethics committee (reference number: CER Liguria: 144/2020-DB id 10460 on the 06/04/2020).