The COVID-19 pandemic has undoubtedly transformed routine clinical practice. The challenges imposed on healthcare systems are unprecedented, and medical operations worldwide are crippled. Nevertheless, the need for remote pathological evaluation and disease diagnosis amidst the COVID-19 pandemic has brought digital pathology into the spotlight, and the speed of clinical adoption of digital pathology technologies is increasing at an unprecedented rate. In addition to enabling pathologists to remotely review, share, and annotate digital slides from the comfort—and safety—of their homes,^1,2 digital pathology platforms are proving useful in the fight against COVID-19.

The role of tissue biopsies in COVID-19 research

Despite the rapid increase in the global COVID-19 death toll, most hospitals and clinics lack appropriate facilities and equipment to collect tissues from patients infected with SARS-CoV-2 or from those who succumb to the disease.³ Tissues from biopsies and autopsies are paramount for investigating the pathophysiology of COVID-19 and for developing effective treatments against SARS-CoV-2.⁴

SARS-CoV-2 has been shown to infect many other tissues and organs other than the lungs, including the kidneys, liver, and heart.⁵ Although SARS-CoV-2 is known to cause extensive tissue damage in the lungs,^6,7 the immediate and long-term pathologic effects of SARS-CoV-2 infection on other organs remain elusive as pathology data are scarce.

In an effort to describe the histopathological features of COVID-19, Deshmukh et al. conducted a systematic review of the available literature. They reported that, although COVID-19 primarily affected the structure and function of the lungs, SARS-CoV-2 infection also caused profound histopathological changes to the heart, kidneys, brain, intestine, and testes. The authors also noted that the elderly were more likely to develop multi-systemic pathology due to SARS-CoV-2 infection.⁸

Consistently, two recent post-mortem pathological studies in a small number of patients who died of COVID-19 revealed that the disease had caused varying degrees of histological changes in the lungs, liver, and heart.^9,10

Biopsies from patients with COVID-19 can help elucidate the effects of the virus on the structure and function of tissues and organs, as well as guide the development of strategies to prevent or mitigate these effects. Therefore, establishing widely accessible and well-annotated repositories of whole slide biopsy images from patients with COVID-19 can dramatically accelerate global research efforts to prevent the further spread of COVID-19.

COVID digital pathology repositories

Indica Labs, a leading provider of digital pathology software and services, has joined forces with the information technology consulting companies Octo and Axle Informatics and the National Institutes of Health (NIH) to develop an online collection of high-resolution histopathology images of tissues from COVID-19 patients using Indica’s HALO Link platform. The online COVID Digital Pathology Repository (COVID-DPR) is a centralized, secure, cloud-based repository of digital whole slide images. COVID-DPR is already available to researchers throughout the world, with datasets from the US, Canada, Australia, and Europe. The repository contains images of lung, heart, liver, and kidney tissues from patients with SARS-CoV-2, thereby fostering international collaboration and supporting research efforts to combat the COVID-19 pandemic.

This unique resource also provides a histopathology database for analysis of the histopathology of COVID-19 using machine learning and artificial intelligence. Such collaborative efforts are key to understanding the effects of COVID-19 on the human body and developing effective therapeutics. Furthermore, COVID-DPR contains histopathology images from patients infected with related coronaviruses (e.g., SARS-CoV and MERS-CoV) or H1N1 to enable the conduction of comparative analyses.

In addition to assessing the histopathological characteristics of COVID-19, researchers can use the COVID-DPR to follow the natural history of SARS-CoV-2 infection, assess the efficacy of drug candidates, and identify risk factors associated with COVID-19 severity and mortality.

“To better understand the ravaging effects of COVID-19 on the human body and to make progress in alleviating those effects, researchers need to have timely access to clinical and imaging data,” said Susan Gregurick, Associate Director for Data Science and Director of the Office of Data Science Strategy at the NIH.¹¹ “The COVID-19 digital pathology repository is a significant step in this direction. This resource provides all investigators a platform to access important reference datasets, and in the next iteration, to support clinical trials research and provide datasets for computational studies based on imaging analysis and artificial intelligence, which are essential capabilities for defeating COVID-19.”

COVID-DPR employs HALO Link, a software developed by Indica Labs to allow secure sharing of digital pathology data among collaborators. Through the COVID-DPR, investigators can employ the HALO Link application and use integrated machine learning and artificial intelligence tools to view, analyze, annotate, and share whole slide images merely using a web browser.

“The entire Indica Labs team takes great pride in working with NIH and Octo to deliver a much-needed global integration for COVID-19 pathology and a framework for the implementation of further cutting-edge technologies,” said Steven Hashagen, CEO of Indica Labs.¹¹ “Deployment of the HALO Link platform will provide data availability and allow real-time collaboration between the world’s leading clinical institutions at this critical time in our battle against the novel coronavirus.”

In collaboration with the World Health Organization (WHO), the Royal College of Pathologists (RCPath) has developed a COVID-19 post-mortem portal containing anonymized digital pathology images from patients who underwent post-mortem COVID-19 testing. The portal was launched with the aim of supporting COVID-19 research and efforts to develop effective countermeasures.

In a similar effort, The Alliance for Digital Pathology is currently in the process of developing the COVID-19 Worldwide Digital Repository, a central histopathological repository of digital whole slide images of post-mortem lung specimens from patients with COVID-19. The overarching goal of this initiative is to enhance our understanding of the pathobiological characteristics of the disease and identify factors predicting COVID-19 severity. The Alliance also aims to establish standardized specimen preparation guidelines, as well as international guidelines to standardize the communication and interpretation of COVID-related digital images.

Perspectives

Despite the rapid increase which has been observed in the number of people succumbing to COVID-19, the histopathological changes associated with SARS-CoV-2 infection remain largely unknown. However, elucidating the histopathological features of COVID-19 can provide key insight into the pathology of this novel disease, which is imperative to developing effective countermeasures.

As data from post-mortem biopsies are scarce, digital pathology repositories have come to the forefront of international collaborative efforts to better understand this novel disease and the factors associated with COVID-19 severity and mortality. However, the speed of development of such repositories has been somewhat slow.

In addition to the lack of appropriate facilities for autopsies of patients dying of COVID-19, several challenges hinder the establishment of international COVID digital pathology repositories. Significant obstacles include logistical and financial burdens of integrating digital pathology platforms in hospitals and diagnostic labs, regulatory requirements associated with the use of artificial intelligence algorithms to analyze and share pathology data, and the lack of standardized guidelines for sample preparation and interpretation of COVID-related digital images.

Addressing these challenges is of high urgency, as it will allow scientists to harness the many benefits and potentials of digital pathology to finally put an end to this global health crisis.

References

1. Browning L, Colling R, Rakha E, et al. Digital pathology and artificial intelligence will be key to supporting clinical and academic cellular pathology through COVID-19 and future crises: The PathLAKE consortium perspective. J Clin Pathol. 2020:1-5. doi:10.1136/jclinpath-2020-206854
2. Cimadamore A, Lopez-Beltran A, Scarpelli M, Cheng L, Montironi R. Digital pathology and COVID-19 and future crises: pathologists can safely diagnose cases from home using a consumer monitor and a mini PC. J Clin Pathol. 2020;73(11):695 LP – 696. doi:10.1136/jclinpath-2020-206943
3. Salerno M, Sessa F, Piscopo A, et al. No Autopsies on COVID-19 Deaths: A Missed Opportunity and the Lockdown of Science. J Clin Med. 2020;9(5):1472. doi:10.3390/jcm9051472
4. Williams BJ, Fraggetta F, Hanna MG, et al. The Future of Pathology: What can we Learn from the COVID-19 Pandemic? J Pathol Inform. 2020;11:15. doi:10.4103/jpi.jpi_29_20
5. Lindner D, Fitzek A, Bräuninger H, et al. Association of Cardiac Infection with SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases. JAMA Cardiol. 2020;5(11):1281-1285. doi:10.1001/jamacardio.2020.3551
6. Wu J, Yu J, Zhou S, et al. What can we learn from a COVID-19 lung biopsy? Int J Infect Dis IJID  Off Publ  Int Soc Infect Dis. 2020;99:410-413. doi:10.1016/j.ijid.2020.07.067
7. Huilan Z, Zhou P, Wei Y, et al. Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19. Ann Intern Med. 2020;172(9):629-632. doi:10.7326/M20-0533
8. Deshmukh V, Motwani R, Kumar A, Kumari C, Raza K. Histopathological observations in COVID-19: A systematic review. J Clin Pathol. 2020:76-83. doi:10.1136/jclinpath-2020-206995
9. Tian S, Xiong Y, Liu H, et al. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. Mod Pathol. 2020;33(6):1007-1014. doi:10.1038/s41379-020-0536-x
10. Beigmohammadi MT, Jahanbin B, Safaei M, et al. Pathological Findings of Postmortem Biopsies From Lung, Heart, and Liver of 7 Deceased COVID-19 Patients. Int J Surg Pathol. 2020:1-11. doi:10.1177/1066896920935195
11. Indica Labs, Octo and Axle work with NIH to launch a global COVID-19 digital pathology repository. Indica Labs. 2020.