Diffuse Alveolar Damage (DAD) from Coronavirus Disease 2019 Infection is Morphologically Indistinguishable from Other Causes of DAD

Konopka, Kristine E.; Nguyen, Teresa; Jentzen, Jeffrey M.; Rayes, Omar; Schmidt, Carl J.; Wilson, Allecia M.; Farver, Carol F.; Myers, Jeffrey L.

AIMS: Diffuse alveolar damage (DAD) is a ubiquitous finding in inpatient coronavirus disease 2019 (COVID‐19)‐related deaths, but recent reports also describe additional atypical findings, including vascular changes. Here, we assess lung autopsy findings in COVID‐19 inpatients and untreated, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐positive individuals who died in the community to understand the relative impact of medical intervention on lung histology. Additionally, we investigate if COVID‐19 represents a unique histologic variant of DAD by comparing the pathologic findings to uninfected control patients. METHODS AND RESULTS: Lung sections from autopsy cases were reviewed by three pulmonary pathologists, including two who were blinded to patient cohort. The cohorts included 4 COVID‐19 inpatients, 4 cases with post‐mortem SARS‐CoV‐2 diagnoses who died in the community, and 8 SARS‐CoV‐2‐negative control cases. DAD was present in all but one SARS‐CoV‐2‐positive patient who was asymptomatic and died in the community. Although SARS‐CoV‐2‐positive patients were noted to have more focal perivascular inflammation/endothelialitis than control patients, there were no significant differences in the presence of hyaline membranes, fibrin thrombi, airspace organization, and “acute fibrinous and organizing pneumonia”‐like intraalveolar fibrin deposition between the cohorts. Fibrinoid vessel wall necrosis, hemorrhage, and capillaritis were not features of COVID‐19‐related DAD. CONCLUSIONS: DAD is the primary histologic manifestation of severe lung disease in COVID‐19 patients who die both in the hospital and in the community, suggesting no contribution of hyperoxemic mechanical ventilation to the histologic changes. There are no distinctive morphologic features to confidently differentiate COVID‐19‐related DAD from DAD due to other causes.