Data on the pathology of COVID-19 are scarce; available studies show diffuse alveolar damage; however, there is scarce information on the chronologic evolution of COVID-19 lung lesions. The primary aim of the study is to describe the chronology of lung pathologic changes in COVID-19 by using a post-mortem transbronchial lung cryobiopsy approach. Our secondary aim is to correlate the histologic findings with computed tomography patterns. SARS-CoV-2-positive patients, who died while intubated and mechanically ventilated, were enrolled. The procedure was performed 30 min after death, and all lung lobes sampled. Histopathologic analysis was performed on thirty-nine adequate samples from eight patients: two patients (illness duration < 14 days) showed early/exudative phase diffuse alveolar damage, while the remaining 6 patients (median illness duration—32 days) showed progressive histologic patterns (3 with mid/proliferative phase; 3 with late/fibrotic phase diffuse alveolar damage, one of which with honeycombing). Immunohistochemistry for SARS-CoV-2 nucleocapsid protein was positive predominantly in early-phase lesions. Histologic patterns and tomography categories were correlated: early/exudative phase was associated with ground-glass opacity, mid/proliferative lesions with crazy paving, while late/fibrous phase correlated with the consolidation pattern, more frequently seen in the lower/middle lobes. This study uses an innovative cryobiopsy approach for the post-mortem sampling of lung tissues from COVID-19 patients demonstrating the progression of fibrosis in time and correlation with computed tomography features. These findings may prove to be useful in the correct staging of disease, and this could have implications for treatment and patient follow-up.

关于COVID-19病理的数据很少。现有研究表明弥漫性肺泡损伤；但是，关于COVID-19肺部病变的时间演变信息很少。这项研究的主要目的是通过验尸后经支气管肺冷冻检查法描述COVID-19的肺病理变化的时间顺序。我们的次要目标是将组织学发现与计算机断层扫描模式相关联。招募了在插管和机械通气时死亡的SARS-CoV-2阳性患者。该过程在死亡后30分钟进行，并取样所有肺叶。对来自八名患者的三十九份适当的样本进行了组织病理学分析：两名患者（病程<14天）显示早期/渗出期弥漫性肺泡损伤，其余6例患者（中位病程为32天）表现出进行性组织学模式（3例处于中期/增生期； 3例处于晚期/纤维化期弥漫性肺泡损伤，其中1例为蜂窝状）。SARS-CoV-2核衣壳蛋白的免疫组织化学主要在早期病变中呈阳性。组织学模式和断层扫描类别相关：早期/渗出期与玻璃杯混浊有关，中期/增生性病变伴有疯狂铺路，而晚期/纤维化阶段与固结模式有关，在下/中叶更常见。这项研究使用创新的冷冻活检方法对死于COVID-19患者的肺组织进行了事后采样，证明了纤维化的进展及时并与计算机断层扫描特征相关。