As the world was shutting down in the face of the COVID-19 pandemic, Digital Pathology was thrust to the forefront as a vital option for not only completing existing projects, but more importantly in understanding the disease of COVID-19. Characterizing the mechanisms by which the novel coronavirus attacks the human body, and also understanding the immune system’s response to the disease are critical to guiding treatment and influencing outcomes. Researchers around the world utilized the HALO suite of products to share rare digital pathology slides, collect quantitative pathological data from translational models, characterize gene expression in immune response, and integrate transcriptional data with tissue-based immunoprofiling. This workshop will present some insight on how HALO has been used by researchers at 3 different global institutions to study and characterize COVID-19.
Assistant Professor/Research Pathologist
Department of Pathology and Laboratory Medicine, Tulane University School of Medicine
Division of Comparative Pathology, Tulane National Primate Research Center
Using Digital Image Analysis to Characterize Primate Models of COVID-19
The COVID-19 pandemic has necessitated a rapid response by the research community to study pathogenic mechanisms and test vaccine candidates for SARS-CoV-2. Nonhuman primates are ideally suited to model respiratory viral infections due to their similarities to human anatomy and immunologic responses compared to other animal species. In order to develop and characterize nonhuman primate models to study SARS-CoV-2, we utilized digital image analysis with the HALO software platform to generate quantitative pathologic data to objectively compare results across species.
Robert Blair is a veterinary, research pathologist at the Tulane National Primate Research Center. He is an Assistant Professor in the Division of Comparative Pathology and has been the lead pathologist on their COVID-19 model development studies.
Prof. Dr. med. Viktor Koelzer
Attending Pathologist, Institute of Pathology and Molecular Pathology, University Hospital Zürich
Assistant Professor and Lead for Digital Pathology, University of Zürich
Honorary Senior Clinical Researcher, Department of Oncology, University of Oxford
Understanding COVID-19 lung disease – an integrated digital and molecular pathology perspective
Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Therefore we conducted transcriptomic, histologic and cellular profiling of post mortem COVID-19 (n=34 tissues from 16 patients) and normal lung tissues (n=9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 were identified. One pattern showed high local expression of interferon stimulated genes (ISGhigh) and cytokines, high viral loads and limited pulmonary damage, the other pattern showed severely damaged lungs, low ISGs (ISGlow), low viral loads and abundant infiltrating activated CD8+ T cells and macrophages. ISGhigh patients died significantly earlier after hospitalization than ISGlow patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment.
Prof. Viktor Kölzer holds the first professorship for digital pathology in Switzerland with the key strategic aim in digitalization of clinical pathology diagnostics and research at the University Hospital Zurich. He aims to improve patient care through implementation of high quality, science driven computational image analysis approaches with a focus on gastrointestinal disease, immunology and immunotherapy. His research work has been recognized by national and international awards from the European Society of Pathology, the US and Canadian Academy of Pathology, the British Division of the International Academy of Pathology and the Pfizer Award in Oncology 2019. Prof. Koelzer holds an honorary position as senior clinical researcher at the University of Oxford with the key aim to drive forward collaboration in the field of digital pathology and artificial intelligence. His translational work is complemented by his clinical work at the Institute of Pathology and Molecular Pathology at the University Hospital Zurich.
Linda Nieman, PhD
Massachusetts General Hospital
The importance of contextual spatial information provided by digital image analysis in SARS-CoV-2 research
Digital image analysis provides contextual spatial information needed to shed light on the complex biology of SARS-CoV-2 infection. Coupled with orthogonal RNA and protein analytical techniques, spatial profiling of 24 autopsy samples from patients who succumbed to SARS-CoV-2 infection showed temporal spatial heterogeneity of immune response. A spectrum of high and low virus cases was associated with duration of disease and activation of interferon pathway genes. Further, the virus corresponded to distinct spatial expression of interferon response genes and immune checkpoint genes. These results have implications for the timing of therapeutics and points toward the importance of capturing geographical relationships of cells in tissue in order to gain a fuller understanding of disease biology.
Halo topics to cover:
- Area vs phenotype analysis
- Phenotype analysis provides more specificity
- More useful for focal positivity (see heatmaps)
- Sequential tissue section
- Transfer of annotated regions
- High vs low virus regions
- Value of heat maps
- Can guide GeoMX platform
- Clusters of SARS-CoV-2 high positive cells
- Compare to negative regions
- Can guide GeoMX platform
Linda Nieman, PhD is a senior scientist at MGH Cancer Center and is Technical Director of Microscopy and Imaging for the Biomarker Discovery Center. She has formal training in physics and extensive experience in optical approaches to understand disease processes. She has trained a broad range of researchers from experimental biologists to clinical oncologists to use advanced imagers and has worked closely with them to develop sophisticated image analysis algorithms. Dr. Nieman is dedicated to realizing the full potential of imaging technologies with her colleagues to understand basic biology and develop novel assays for the clinic.
Director of Life Science Applications
Indica Labs, Inc.
Adam earned a BS in Biology from Ursinus College in 2004. He began his professional career as a biologist in the Safety Assessment department of Merck Research Laboratories in the fall of 2004. During his time at Merck he developed skills in the pathology labs from necropsy to immunohistochemistry. In 2006, Adam worked as part of a team at Merck to implement and perform a GLP validation of their digital pathology system, connecting pathologists at multiple global sites. He worked as the digital pathology lead for Merck’s Safety Assessment group, and developed image analysis protocols that have aided in establishing the safety profiles of several compounds. In 2015, Adam joined Indica Labs as an application scientist, providing training and workflow support to customers world-wide.