Organ manifestations of COVID-19: what have we learned so far (not only) from autopsies?

Abstract

The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern analytical methods to understand the pathophysiology of COVID-19, the major pathological organ findings, limitations or current studies, and open questions. This article summarizes published literature and the consented experience of the nationwide network of clinical, neuro-, and forensic pathologists from 27 German autopsy centers with more than 1200 COVID-19 autopsies. The autopsy tissues revealed that SARS-CoV-2 can be found in virtually all human organs and tissues, and the majority of cells. Autopsies have revealed the organ and tissue tropism of SARS-CoV-2, and the morphological features of COVID-19. This is characterized by diffuse alveolar damage, combined with angiocentric disease, which in turn is characterized by endothelial dysfunction, vascular inflammation, (micro-) thrombosis, vasoconstriction, and intussusceptive angiogenesis. These findings explained the increased pulmonary resistance in COVID-19 and supported the recommendations for antithrombotic treatment in COVID-19. In contrast, in extra-respiratory organs, pathological changes are often nonspecific and unclear to which extent these changes are due to direct infection vs. indirect/secondary mechanisms of organ injury, or a combination thereof. Ongoing research using autopsies aims at answering questions on disease mechanisms, e.g., focusing on variants of concern, and future challenges, such as post-COVID conditions. Autopsies are an invaluable tool in medicine and national and international interdisciplinary collaborative autopsy-based research initiatives are essential.

Keywords: Acute kidney damage; Diffuse alveolar damage; Immune response; SARS-CoV-2.

Fig. 1

“Corpse journey” autopsy routine workflow and research applications in neuropathology, clinical pathology, and forensic pathology

Fig. 2

Radiographic images of pulmonary changes in COVID-19 over time: A Typical radiographic presentation of acute respiratory distress syndrome with bipulmonary infiltrates, so called “white lung”. B CT-image of a 39-year-old previously healthy man after 30 days of extracorporeal membrane oxygenation (ECMO) treatment displaying bipulmonary ground glass opacities and basal infiltrates in line with (prolonged) ARDS. C CT-image of a 62-year-old man showing interstitial fibrosis and cystic remodeling including subpleural areas after 3 weeks of ECMO treatment. D CT-image of 34-year-old woman after 70 days of ECMO treatment with advanced pulmonary remodeling

Fig. 3

Histologic findings in acute (panel A and B) and post-acute (panel C and D) COVID-19. A Acute COVID-19 pneumonia with diffuse alveolar damage (DAD) characterized by hyaline membranes (arrows), alveolar septae necrosis and lymphocytic inflammatory infiltrate. HE staining, Magnification 50×, scale bar 200 μm. B Acute COVID-19 pneumonia with a capillary hyaline microthrombus (arrow). HE staining, Magnification 600×, scale bar 10 μm. C, D Post-acute COVID-19 fibrotic remodeling with thickened alveolar septae and prominent type-II-pneumocyte hyperplasia. HE staining, panel C: magnification 20×, scale bar 500 μm, panel D: magnification 100×, scale bar 100 μm

Fig. 4

Respiratory tract morphology of COVID-19 patients with Hematoxylin & Eosin staining and SARS-CoV-2 RNA detection by fluorescence in situ hybridization, corresponding areas from consecutive slides. A Respiratory epithelial cells lining the tracheal mucosa with SARS-CoV-2 RNA (arrowhead, green signal). B Pulmonary alveolar capillary endothelial cells with detection of SARS-CoV-2 RNA (arrowheads, green signal). C Pulmonary intraalveolar detached pneumocytes (arrowheads, green signal) and intraalveolar macrophages (arrow, green signal) with SARS-CoV-2 RNA. Scale bars: left column, scale bars = 100 μm, center column, scale bars = 50 μm, right column, scale bars = 10 μm