Patients who died from coronavirus disease 2019 (COVID-19) presented mainly with pulmonary disease involving diffuse alveolar damage that led to acute respiratory insufficiency, with pulmonary arterial thrombosis identified as the possible cause of death, according to the results of a clinicopathologic autopsy case series published in the Annals of Internal Medicine.

The pathologic bases for many of the severe COVID-19 clinical phenotypes remain largely unclear, with clinicians still lacking a full understanding of the associated patterns of multi-organ damage and failure. Investigators sought to examine post-mortem gross and microscopic findings with clinical presentations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

In this single-center, prospective study conducted at a single academic medical center, autopsies were performed on 11 individuals who died from COVID-19 (mean age, 80.55 years; age range, 66-91 years; 72.7% men; mean COVID-19 duration, 8.5 days; 10 randomly chosen and 1 referred). Despite a lack of clinical suspicion of venous thromboembolism, 10 of the 11 patients were treated prophylactically with anticoagulant or antiaggregant therapy (or a combination of both). Histopathologic, macroscopic and viral analyses (via real-time polymerase chain reaction testing for SARS-CoV-2 RNA) were conducted systematically on all individuals, and results were correlated with clinicopathologic features, which included patient comorbidities, laboratory values and medication regimens.


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Bilateral diffuse alveolar damage at various stages was observed in all patients, with hyaline membranes, edema and fibroblast and pneumocyte proliferation. Nine patients also had hypostasis and massive bilateral congestion, and unilateral or bilateral pneumonia was observed in 8 of 9 chest radiographies. Common laboratory findings included lymphopenia and reduced hemoglobin, hematocrit, erythrocytes, monocytes and eosinophils, along with increases in the levels of liver enzymes, lactate dehydrogenase, ferritin, C-reactive protein, procalcitonin, D-dimer, and fibrinogen.

All 11 patients had multiple segmental and subsegmental pulmonary arterial thrombosis with partial neutrophilic infiltration of vessel walls, which was associated with bronchopneumonia and infarction in 6 and 8 patients, respectively.

There were 8 individuals with chronic hepatic congestion, and all patients had proliferation of Kupffer cells. Other liver changes observed in some patients included portal fibrosis, steatosis, acute hepatocyte necrosis, lobular cholestasis, and ductular proliferation and lymphocytic infiltrates, as well as central vein thrombosis. Focal pancreatitis, renal proximal tubular injury, adrenocortical hyperplasia, bilateral ventricular myocardial hypertrophy, and splenic and lymph node lymphocyte depletion were among other frequent findings.

Viral RNA was detected in samples from the mucosal surfaces in the pharynx, bronchi and colon, but not bile.

The only study limitation noted was the small sample size.

“Strict thrombosis prophylaxis, close laboratory and imaging studies, and early anticoagulant therapy for suspected cases of pulmonary arterial thrombosis or venous thromboembolism should be considered,” noted the authors.

Funding and Conflicts of Interest Disclosures:

Dr Lax reports personal fees from Roche, Astra-Zeneca, Novartis, and Biogena outside the submitted work. Dr Koelblinger reports personal fees from CSL Behring and Eumedics outside the submitted work. Dr Trauner reports personal fees from BiomX, Boehringer Ingelheim, Genfit, Novartis, and Regulus; grants, personal fees, and other from Falk; grants, personal fees, and other from Gilead and Intercept; other from AbbVie and Shire; and grants from Cymabay and Takeda outside the submitted work.

Reference

Lax SF, Skok K, Zechner P, et al. Pulmonary arterial thrombosis in COVID-19 with fatal outcome: results from a prospective, single-center, clinicopathologic case series. Ann Intern Med. May 2020. doi:10.7326/m20-2566