Lessons From the Deceased to the Living and Back:

Investigation of SARS-CoV-2 Interactions with Human Cells, Tissues and Organs in a Unique Basel-region Cohort of Autoptically Examined COVID-19 Patients

Very little is known about the pathobiology of COVID-19, its effects on human tissues, the SARS-CoV-2 spread in the human body and its interactions with the immune system. The consortium will investigate in situ the interactions of SARS-CoV-2 with tissues and organs derived from deceased patients and patients suffering from severe COVID-19. The project will contribute valuable insights into the pathogenesis of COVID-19 and into the future design of medical interventions for this disease.

Many questions about how COVID-19 affects the body remain unanswered. The research community still has much to investigate about the pathobiology of COVID-19, its effects on human tissues, the progression of the disease in the human body, the SARS-CoV-2 spread and its interactions with the immune system. This gap in knowledge is partly explained by the relatively brief time period since the virus originated, but also by the fact that it is difficult to obtain tissues from affected patients because autopsies were and have not being routinely performed, especially at the beginning of the pandemic, since the procedure is considered a major risk.

This large consortium aims to bring together long-standing expertise in autopsy, histopathology, electron microscopy, gene expression analysis on fixated tissues, immunology and neurology to perform in situ exploration of the pathobiology of COVID-19 on material from deceased patients and materials from hospitalized patients suffering from severe disease. The material will be examined by accredited standard procedures, next to cutting-edge technologies to maximize the breadth of features and the depth of evidence obtainable from the samples to collect large quantities of data.

This project will enable direct correlations between pathological findings and clinical data in COVID-19, with the main aim to understand the interaction of SARS-CoV-2 with human tissues and the immune system. Overall, results will be very important for understanding the pathobiology of COVID-19 from a holistic perspective and will pave the way for future clinical management developments and specific therapies of the affected patients.

Banner image above: SARS-CoV-2 antigens in the alveolar wall.

Fluid-attenuated inversion recovery (FLAIR) - MRI images of some of the first COVID patients. They show interesting changes (lighter areas), which need to be further investigated. Image: Gregor Hutter, University Hospital Basel, Switzerland

Select markers from a CODEX multiplexed imaging experiment using more than 50 antibodies to stain lung autopsy samples from COVID-19 cases. Distribution of SARS-CoV-2 nucleoprotein (red) is shown alongside markers for host immune and lung tissue cells: CD163 (green), CD15 (blue), CD3 (magenta), CD34 (cyan), and MUC-1 (white). Tissue core with high viral load (left) is contrasted by a tissue core with low viral load (right). Images: Garry Nolan Lab, Stanford, 2020

Schematic representation of the pathomechanisms of diffuse alveolar damage with accompanying thromboinflammation, neutrophil extracellular traps, exudation and microangiopathy in COVID-19; upregulated genes in red, downregulated in green. Image: Alexandar Tzankov, Institute of Pathology, University Hospital Basel

SARS-CoV-2 antigens in the alveolar wall with a particular accentuation at the basal part of alveolar lining cells and in one capillary (upper right at 1 p.m.) as well as in isolated desquamated macrophages (intensively staining single cells). Image: Alexandar Tzankov, Institute of Pathology, University Hospital Basel

Additional Information

The consortium is led by investigators Prof Alexander Tzankov, Dr Matthias Matter and Prof Gregor Hutter.
Additional investigators and collaborators include Prof Stefano Bassetti, Prof Lukas Bubendorf, Prof Stephan Frank, Dr Jasmine Haslbauer, Dr Jügen Hench, Dr Sizun Jiang, Dr Johanna Lieb, Prof Kirsten Mertz, Dr David McIlwain, Dr Thomas Menter, Dr Ronny Nienhold, Prof Garry Nolan, Prof Hans Pargger, Dr Spasenija Savic, Dr Christian Schürch and Dr Ethan Taub.
More details on the CONSORTIUM WEBSITE
The University of Basel published a news article about the consortium's research.