The FLARE Four
- Acute lung injury can be associated with a variety of histologic patterns
- In COVID-19, the limited available histologic evidence predominantly reveals acute diffuse alveolar disease, the pattern of lung injury typically associated with acute respiratory distress syndrome
- Acute fibrinous and organizing pneumonia was described in one small case series, but definitive diagnosis may have been hampered by the sampling technique
Subscribe to the latest updates from Pulmonary & Critical Care Advances in Motion
It has been alleged that respiratory failure in COVID-19 represents a novel entity, despite case series showing moderate to severe hypoxemia and reduced compliance consistent with acute respiratory distress syndrome (ARDS). Nevertheless, the possibility remains that at a tissue level the lungs of patients with severe COVID-19 could reveal a new or unique pattern of injury.
In a fast literature update posted on May 1, 2020, Lida Hariri, MD, PhD, assistant pathologist in the Department of Pathology at Massachusetts General Hospital, reviews common histologic patterns of acute lung injury (ALI) and compares them with the available pathologic evidence in COVID-19.
Diffuse Alveolar Damage (DAD)
DAD lies on the severe end of the ALI spectrum and is the pattern typically associated with ARDS. Classic initial findings are intra-alveolar edema, alveolar wall thickening and—the hallmark—hyaline membranes. Vascular thrombosis and microthrombosis are also frequently observed in the acute phase.
Acute DAD is by far the most predominant histologic pattern observed in COVID-19. Some cases also have features of acute fibrinous and organizing pneumonia (AFOP).
Acute Fibrinous and Organizing Pneumonia
In AFOP, balls of fibrin form within alveoli. If hyaline membranes are present, though, the correct pathologic diagnosis is DAD.
A few autopsies of patients with COVID-19 have described fibrin balls within alveoli, but in most reports, hyaline membranes were also noted. A brief research letter described AFOP in six patients, but it's possible hyaline membranes went unobserved due to the sampling method.
Dr. Hariri noted a few gaps in past studies:
- Most reports of histologic findings after human SARS-CoV-2 infection rely on biopsy-based autopsies rather than full autopsies
- Other lung pathologic features, some pictured in the update, have been noted in post-mortem series, but reports are sparse
- So far, no histologic information is available from COVID-19 patients who recovered from severe ALI, had mild respiratory disease or had asymptomatic disease with radiologic findings
When considering COVID-19 pathology, it's important to remember that distinct histologic patterns may coexist within the same patient, for example, due to secondary infection.
View all COVID-19 updates
Learn more about the Division of Pulmonary and Critical Care Medicine