Lessons from Two COVID-19 Autopsies

By Sanjay Mukhopadhyay, MD

Physicians are faced with many challenges during the COVID-19 pandemic, one of which is accurate determination of cause of death. While the cause of death may seem obvious in individuals who test positive for SARS-CoV-2 and die after a febrile illness that evolves into respiratory failure, not all cases fit this stereotype. Since many patients with COVID-19 are elderly and have underlying medical conditions, other possibilities must be considered. When such individuals die with atypical symptoms or are not tested for SARS-CoV-2 prior to death, assessment of cause of death can be complicated.

The key question then becomes: did the patient die from COVID-19 or with COVID-19? In other words, did COVID-19 cause death, or was it contributory or even incidental? My colleagues and I recently published observations germane to this issue in the first report of complete COVID-19 autopsies in an English-language peer-reviewed journal. These cases offer insights into the underlying pathology of COVID-19 and illustrate how autopsies can clarify the cause of death in some cases.

Two COVID-19 cases, two different causes of death

The two autopsies discussed in this report — published in the American Journal of Clinical Pathology — were performed by forensic pathologists Eric Duval, DO, and Edana Stroberg, DO, at the Office of the Chief Medical Examiner, Oklahoma City, Okla. In both cases, the medical examiner’s office assumed jurisdiction because the decedents were not under the care of a physician at the time of death. Neither individual was known to have COVID-19 during life, and neither one had any known exposure to an individual known to have COVID-19.

The first individual was a 77-year-old man with fever and chills for six days. He was scheduled to see a physician the following week. On the day of his demise, he had been feeling extremely weak and had become increasingly short of breath. He was emergently transported to a hospital, but unfortunately suffered a cardiac arrest during transport and died soon after reaching the hospital. He was never ventilated. His history included hypertension, remote deep vein thrombosis and remote splenectomy. At the time of autopsy, the forensic pathologist performed a postmortem nasopharyngeal swab and lung swab, both of which were positive for SARS–CoV–2. Testing for influenza was negative. Autopsy revealed microscopic findings typical of severe viral infection, including diffuse alveolar damage (DAD, below) and chronic airway inflammation (feature image). We concluded that the cause of death was COVID-19.

The second case involved a 42-year-old man with a history of myotonic dystrophy for many years. He died after a short illness that was interpreted clinically as “community-acquired pneumonia.” Postmortem nasopharyngeal swabs taken at the time of autopsy were positive for SARS-CoV-2, but bilateral lung parenchymal swabs were negative. Microscopic examination of his lungs revealed acute bronchopneumonia with aspirated food particles. There was no evidence of DAD. His liver was cirrhotic. In this case, we concluded that the patient died with COVID-19, not of COVID-19.

Complete autopsy key to accurate reporting

In both cases, the diagnosis of COVID-19 would have been missed without an autopsy. Indeed, it is possible that many individuals dying during this pandemic have never been tested for COVID-19, precluding a definitive diagnosis. The second case discussed above highlights an even more nuanced issue: that patients testing positive for COVID-19 might occasionally die of other disease processes. If the forensic pathologists had stopped at viral testing and had not obtained lung tissue for microscopic examination, the diagnosis of aspiration pneumonia would have been missed. These complete autopsies were therefore critical for confirming viral infection as well as for distinguishing true virus-related pathology from potential confounders.

While it is impossible to draw broader conclusions on the basis of two cases, we believe that our report offers the first clear glimpse into the tissue reaction in COVID-19. Postmortem examination offers insights into disease processes, enables greater accuracy in cause of death reporting and enables collection of tissue for more sophisticated analyses. We look forward to further insights to build on these observations as the findings of complete autopsies are reported from other parts of the world.

Dr. Mukhopadhyay is Director of Pulmonary Pathology in the Department of Anatomic Pathology in the Pathology and Laboratory Medicine Institute at Cleveland Clinic.