Learning from death to help the living
Dr Michael Osborn, President Elect and Chair of the Death Investigations Committee, and his colleague Dr Brian Hanley, cellular pathologist at Imperial College Healthcare NHS Trust, explain the value of post mortems. Their work will help inform the treatment of patients with COVID-19, improve understanding of the most severe complications and advance the ways patients are monitored and treated. Longer term, their findings will feed into research about the disease.
All were conducted according to our College guidelines. Consent was obtained in all cases in line with the Human Tissue Authority 2009 codes of practice and we recognise the generosity of those who gave their consent for our work.
The coronavirus disease 2019 (COVID-19) pandemic has presented a challenge for autopsy practice in the UK. There was a large peak in the number of COVID-19-related deaths during March, April and May 2020 in England and it would have been beneficial to have established a national COVID-19 autopsy network. This would have enabled pathologists to assess the pathological features of COVID-19 on a wider scale. Because of existing strains on the autopsy service nationally, a reduction in hospital autopsies in recent decades and the speed with which COVID-19 spread globally, only a handful of centres across the UK were able to perform autopsies on these cases. At our centre (Imperial College Healthcare NHS Trust), we performed ten hospital autopsies on patients who died from COVID-19. Nine of these were standard full autopsies and one was a needle biopsy-based examination. All were conducted according to our College guidelines. Consent was obtained in all cases in line with the Human Tissue Authority 2009 codes of practice and we recognise the generosity of those who gave their consent for our work.
In the cases we reviewed, we found evidence of acute damage to the lungs (consistent with many reports in medical literature). We also found thrombosis (blood clots) in at least one major organ in all cases where we were able to carry out a full post mortem. Thrombosis prevents blood from flowing normally and can lead to strokes and heart attacks among other things. The patients also had evidence of T-lymphocyte depletion in the spleen and lymph nodes. This showed that there had been an alteration in the patients’ immune systems and how they respond to infection. Haemophagocytosis (in which infection-fighting cells eat each other) was another consistent finding in this group, showing that there had been an extreme over-reaction by the immune system to infection. One of the ten patients was found to have developed a secondary fungal infection (mucormycosis, an infection that spreads through the bloodstream to affect other parts of the body). This finding was unexpected, and this infection was, ultimately, the direct cause of death in this patient.
This increased knowledge of the way the virus infects and multiples within the body through the course of the disease is vital to understanding the disease process.
Through collaboration with our colleagues in the Department of Virology (Prof Wendy Barclay), we were able to demonstrate the presence of viral RNA in a range of organs using laboratory tests. We discovered the presence of active viral replication outside the respiratory tract. It was also possible using this data to show the persistence of low-level viral replication late in the disease process.
This increased knowledge of the way the virus infects and multiples within the body through the course of the disease is vital to understanding the disease process. It helps determine what treatment is best suited to patients at different times in the course of their disease. By working with our neuropathology colleagues, it has been possible to describe the ways in which severe COVID-19 affects the central nervous system, which goes some way to help explain the central effects of COVID-19 that some patients suffer, such as loss of smell and respiratory depression.
Only a few centres around the UK were able to conduct consented hospital autopsies on COVID-19 patients in a similar way to us, meaning the entire cohort of such cases in the country is around just 30 cases.
Another extremely worthwhile aspect to these post-mortem examinations was the ability to provide tissue samples for research. We worked closely with Imperial College Healthcare Tissue Bank (ICHTB) from an early stage in this project. They were able to help us create a sub-collection of tissue from our COVID-19 autopsy cases for research purposes. They also provided ethical oversight and helped with the significant governance issues related to the use of this archived tissue. To date, we have worked with and provided tissue to more than 20 research groups, both nationally and internationally. This resource has proved invaluable to the national and international fight against COVID-19 as very little tissue of this nature is available globally.
Only a few centres around the UK were able to conduct consented hospital autopsies on COVID-19 patients in a similar way to us, meaning the entire cohort of such cases in the country is around just 30 cases. In response to the low autopsy rate and following requests from clinical colleagues eager to learn as much as possible about this new disease, the College set up a COVID-19 post-mortem portal. Any autopsy conducted on a known or suspected COVID-19 patient, whether it was a consented hospital post mortem or a post mortem conducted for the coroner, can be submitted through the portal. The information from these reports is then added to the College COVID-19 database and made available to doctors and scientists to support their work. The portal has been widely promoted and a significant number of the COVID-19 autopsies conducted in the country have been submitted. It is a valuable data resource and suitable case studies will be submitted to the World Health Organization to facilitate research and learning. The College, with the help of a £40,000 grant from Pfizer, is working to further analyse the data to provide more information about the disease to help fight the pandemic. We hope our work will lead to better treatments and fewer deaths.