When the coronavirus pandemic slammed into the city of Bergamo, Italy, starting in February, the Papa Giovanni XXIII Hospital there was quickly overwhelmed. Clinicians raced to dedicate the hospital, one of the largest in the region, to the care of people with COVID-19.
Soon, however, pathologist Andrea Gianatti and his colleagues began to shift their attention to a less visible priority: autopsies. “The need arose to understand how the disease affects the various organs,” Gianatti says. “And the most effective way was performing autopsy.”
Autopsies are painstaking work under normal conditions; during an infectious-disease outbreak, the added risk calls for safety precautions that make them even more arduous. Since 16 March, Gianatti’s team has performed 80 autopsies of people who tested positive for the coronavirus. The group typically handles only 150 autopsies in a year. Few hospitals in Italy have the safety equipment and resources to launch a similar undertaking, Gianatti says.
Researchers around the world have flocked to study COVID-19, a disease that mainly attacks the lungs, but also has bewildering effects on the heart, kidneys and brain. The raging pandemic and accompanying lockdowns have complicated efforts to collect the tissue samples that researchers need to understand how the new coronavirus wreaks such havoc. Now, pathologists are looking for ways to collect such samples systematically and share the results.
“We need those tissues to determine what is killing patients affected by COVID-19,” says pathologist Roberto Salgado of the GZA-ZNA Hospitals in Antwerp, Belgium. “Is it pneumonia? Is it blood clots? Why do they develop kidney failure? We have no clue.”
A pandemic is a difficult time to focus on tissue collection for research. Health-care systems are overwhelmed, essentials including personal protective equipment and lab reagents are in short supply, and health-care workers are already taking on tremendous personal risk to care for their patients. To go the extra step to collect blood and tissue samples can feel like a diversion in the face of so much acute need, says pathologist Andrew Connolly of the University of California, San Francisco.
On top of that are complications from lockdowns and isolation procedures. People who are severely ill with COVID-19 are sometimes unconscious and on a ventilator; often, their families are not allowed to visit them in hospital. As a result, seeking consent from the patient to donate their body for research might be impossible, and to do so from their families can be fraught, without a bond of trust between families and hospital staff. “A death has occurred, and now someone they’ve never heard of before is asking for an autopsy,” says Connolly.
The strict lockdown in San Francisco has also made it hard for Connolly to share samples with colleagues at other institutions, because of the difficulty getting the required forms and signatures needed to transfer potentially infectious material when so many people are confined to their homes.
As researchers struggle to understand the many effects of COVID-19 on the human body, they are clamouring for access to patient samples. The demand ramped up quickly in the early days of the outbreak in the United Kingdom, says Phil Quinlan, director of the UK Clinical Research Collaboration Tissue Directory and Coordination Centre at the University of Nottingham.
Requests are now are a daily occurrence, but Quinlan still has few options. The UK National Biosample Centre in Milton Keynes, for example, has been converted into a COVID-19 test-processing centre. Even clinical samples like blood from COVID-19 patients are hard to come by. "If you don’t have a direct connection to a physician involved in a clinical-trial programme, you’re almost certainly not going to get samples right now,” says Quinlan.
Even in the middle of the outbreak, some centres have found ways to collect data. In Brazil, pathologist Marisa Dolhnikoff at the University of São Paulo and her colleagues have been using minimally invasive autopsies to take tissue samples. Rather than using the standard procedure, which can require the removal of whole organs, Dolhnikoff’s team takes needle biopsies from various locations in the body, using ultrasound as a guide.
The technique is considered safer than a normal autopsy, which exposes the pathologist to infectious agents and so must often be done in a dedicated room with airflow that minimizes risk — a set-up that few hospitals in Brazil have, says Dolhnikoff. Her team has analysed dozens of samples from the lungs, heart, kidney, liver, spleen, skin and brain, and is trying to understand why blood clots are common in people with severe COVID-191.
To determine what is happening in those organs, researchers need large numbers of samples, says Matthew Leavitt, chief medical officer at Lumea, a digital-pathology company in Lehi, Utah. “In a normal environment, autopsy answers questions about one patient,” he says. “In the instance of a newly emerging disease, autopsy is critical to all of humanity.”
Pathologist Peter Boor of RWTH Aachen University in Germany has set up a database of COVID-19 autopsies so that researchers can share their data, stripped of identifying information. He would like to share internationally, but quickly found that even within Germany, it posed an enormous logistical challenge. Each county has different legal requirements governing autopsies and patient privacy: “Honestly, it was quite overwhelming,” Boor says.
Salgado, Leavitt and a team of pathologists are taking up the challenge of creating an international COVID-19 pathology repository. They are working with the World Health Organization, whose International Agency for Research on Cancer maintains a tumour pathology database and has experience juggling legal requirements. And they are putting together guidelines for the safe collection of autopsy samples and a standardized way of recording the results.
So far, researchers from 25 countries have said that they are interested in participating, although such a repository will probably take months to complete, says Amanda Lowe, a managing director at the digital-pathology company Visiopharm in Westminster, Colorado. “Everybody who steps forward and has access to tissue even from one patient is highly valuable.”