Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists

Abstract

Since its initial recognition in December 2019, Coronavirus disease 19 (COVID-19) has quickly spread to a pandemic infectious disease. The causative agent has been recognized as a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affecting the respiratory tract. To date, no vaccines are available nor any specific treatment. To limit the number of infections, strict directives have been issued by governments that have been translated into equally rigorous guidelines notably for post-mortem examinations by international and national scientific societies. The recommendations for biosafety control required during specimen collection and handling have strongly limited the practice of autopsies of the COVID-19 patients to a few adequate laboratories. A full pathological examination has always been considered an important tool to better understand the pathophysiology of diseases, especially when the knowledge of an emerging disorder is limited and the impact on the healthcare system is significant. The first evidence of diffuse alveolar damage in the context of an acute respiratory distress syndrome has now been joined by the latest findings that report a more complex scenario in COVID-19, including a vascular involvement and a wide spectrum of associated pathologies. Ancillary tools such as electron microscopy and molecular biology used on autoptic tissue samples from autopsy are also significantly contributing to confirm and/or identify new aspects useful for a deeper knowledge of the pathogenetic mechanisms. This article will review and summarize the pathological findings described in COVID-19 until now, chiefly focusing on the respiratory tract, highlighting the importance of autopsy towards a better knowledge of this disease.

Keywords: Autopsy; COVID-19; Lung; Pandemic; SARS-CoV-2.

Fig. 1

a Padova protocol for lung gross examination after sagittal section of lungs: three specimens/lobe (two peripheral and one central) are sampled. When there are other evident lesions or pleural effusions, additional sampling is performed. Transversal section of the trachea and small fragments for cultural, molecular, and ultrastructural analyses are collected. b Video frame of the right lung captured during the autopsy in a COVID-19 patient (69-year-old women). A marbled appearance of the lung with bloody pleural effusion was evident. c Cut surface of the same lung after formalin fixation. The parenchyma showed patchy areas of consolidation and congestion

Fig. 2

Timeline of autopsy studies focusing on lung lesions in COVID-19 patients. Since the end of March, the increased number of full autopsies has led to a better knowledge of the pathophysiology of the disease. Together with the features of acute lung injury, vascular involvement has been reported. a, b Acute lung injury: hyaline membrane in alveolar space (hematoxylin and eosin stain, original magnification a × 100; b × 200). c, d Vascular damage: two microthrombi in lung small vessels (hematoxylin and eosin stain, original magnification × 200), capillary inflammation (hematoxylin and eosin stain, original magnification × 200). e Airway inflammation: tracheal section showing a polymorphous inflammatory infiltrate of the submucosal layers (hematoxylin and eosin stain, original magnification × 200)

Fig. 3

Cyto-block preparation of pleural effusion fluid. Aggregates of dysmorphic mesothelial cells with enlarged nuclei (a hematoxylin and eosin, original magnification × 600) and multinucleated syncytial cell (b hematoxylin and eosin, original magnification × 400). These features suggest viral infection, as was confirmed by the positivity of RT-PCR for SARS-CoV-2 on the cytological specimen

Fig. 4

Cytoplasm of type II pneumocyte from a post-mortem lung sample of a COVID-19 patient. The molecular test RT-PCR for SARS-CoV-2 was positive on lung tissue. Post-mortem autolytic phenomena prevent a precise visualization of sub-cellular compartments. There are several spherical particles outlined with electron-dense dots that could mimic coronavirus-like virions. Most probably, some of these particles are clathrin-coated intracytoplasmic vesicles (arrowheads) or cross-sections of the rough endoplasmic reticulum. Immunogold labeling would be desirable to verify the nature of these putative viral particles. A microvesicular body/autophagosome was also evident (arrow) (transmission electron microscopy, original magnification × 30,000)