Photomicrograph of the lung of a patient with fatal COVID-19 pneumonia showing diffuse alveolar damage with hyaline membranes.

In an effort to continue fighting the global COVID-19 pandemic, a team of pathologists from McGovern Medical School has documented the pathological findings from 23 autopsy patients with the disease in an upcoming issue of Cardiovascular Pathology, now published on line and available on ScienceDirect.

The paper titled “The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID-19): Report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities,” aims to collate and summarize the findings of autopsy studies around the United States to provide correlation with clinical information and create discussion on the best treatment strategies to fight the pandemic.

Initially, conflicting guidance and rigorous standards from several regulatory agencies in the United States hampered the process of autopsies around the country. Thanks in part to a statement from American Medical Association President Patricia Harris, MD, MA, scientific and health care professionals have persisted to perform autopsies at a number of sites across the United States, including Houston.

“As the pandemic spread resulting in major morbidity and mortality, it became crystal clear that autopsy of deceased victims of the disease was of paramount importance for gaining knowledge of its pathogenesis and pathophysiology,” the writers said.

COVID-19 is a viral disease that results in patients usually presenting with acute respiratory illness known as Acute Respiratory Distress Syndrome (ARDS) early in the disease, most commonly with cough or shortness of breath, fever, and chills.  However, through autopsy, researchers have found that the disease is systematic, attacking not only the lungs producing a pattern of injury know as Diffuse Alveolar Damage (DAD), but the heart and other organs as well.

“The virus infects endothelial cells that line the blood vessels of the body, starting with the endothelial cells lining the capillaries in the lungs,” said L. Maximilian Buja, MD, professor of pathology and laboratory medicine and the corresponding author of the paper. “This sets off a chain reaction leading to activation of the blood clotting system, including activation of platelets and precipitation of fibrin. There is also activation of the innate and acquired immune systems, leading to the release of powerful cytokines.”

This reaction can lead to an unnecessary activation of the coagulation system which can cause hypercoagulation and clotting of major veins and arteries and lead to fatal pulmonary emboli in the lungs.

According to the writers, viruses like the SARS-CoV-2 virus, which affect endothelial and perivascular cells in the heart, can indirectly damage the muscle cells in the heart, which can cause symptoms that mimic a heart attack.

“We were one of the first groups, along with colleagues at LSU in New Orleans to identify and document this thrombotic microangiopathy starting in the lungs and leading to a state of general hypercoagulation and risk of major blood clotting and embolization,” Buja said. “Endothelial infection with endothelialitis is a key initiating event. In a real sense, COVID-19 is a blood vessel disease and hematologic disease with major target organ effects on the lungs and heart.”

Early treatment for severely ill COVID-19 patients often has involved mechanical ventilation; however, this can lead to potential counterproductive effects and should be used cautiously, in the opinion of the authors. With the research gathered through autopsy, physicians can plan a broader scope of treatment which can be tailored to the needs of an individual patient. Early in treatment, supplemental oxygen, with or without intubation, as well as anticoagulation and antiplatelet therapy can be given to patients presenting with the virus. From there, different approaches can be taken using anti-inflammatory therapy (corticosteroids), anti-cytokine therapy (anti-IL-6 agents), anti-viral agents (Remdesivir), COVID-19 convalescent plasma, extracorporeal membrane oxygenation (ECMO) treatment as needed for respiratory or cardiopulmonary failure, and cardiovascular medications such as statins, ACE inhibitors and ARBs, beta blockers, and calcium channel blockers.  Treatment for each patient needs to be planned and individualized.

Buja and his team will continue to work with clinical colleagues to perform autopsies and have joined a national autopsy consortium led by Alex Williamson, MD, anatomic/clinical pathologist at Northwell Health on Long Island to contribute to a case study which will collate more than 100 cases across the nation.

Co-authors include Department of Pathology and Laboratory Medicine faculty and staff Bihong Zhao, MD, PhD, assistant professor; Michelle McDonald, DO, resident; Laura C. Lelenwa, MD, assistant professor; and Noah Reilly, DO, resident. Other McGovern faculty co-authors include Daniel Ocazionez-Trujillo, MD, assistant professor of diagnostic and interventional imaging; and Department of Internal Medicine faculty Bindu Akkanti, MD, CMQ, FCCP, associate professor; Gabriel M. Aisenberg, MD, assistant professor; Mohammad Madjid, MD, MS, FACC, assistant professor; and Biswajit Kar, MD, professor.

Dwayne A. Wolf, MD, PhD; Giulia Ottaviani, MD, PhD; and M. Tarek Elghetany, MD; also contributed to the paper.