The most severe alterations in Coronavirus disease 2019 (COVID-19) caused by the severe
acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection are seen in the lung.
However, other organs also are affected. Here, we report histopathologic findings
in the liver and detection of viral proteins and RNA in COVID-19 autopsies performed
at the Semmelweis University (Budapest, Hungary). Between March 2020 through March
2022, 150 autopsies on patients who died of COVID-19 were analyzed. Cause-of-death
categories were formed based on the association with SARS-CoV-2 as strong, contributive,
or weak. Samples for histopathologic study were obtained from all organs, fixed in
formalin, and embedded in paraffin (FFPE). Immunohistochemical study (IHC) to detect
SARS-CoV-2 spike protein and nucleocapsid protein (NP), CD31, claudin-5, factor VIII,
macrosialin (CD68), and cytokeratin 7, with reverse transcriptase polymerase chain
reaction (RT-PCR), and in situ hybridization (ISH, RNAscope®) for SARS-CoV-2 RNA were
conducted using FFPE samples of livers taken from 20 autopsies performed ≤ 2 days
postmortem. All glass slides were scanned; the digital images were evaluated by semiquantitative
scoring and scores were analyzed statistically. Steatosis, single-cell and focal/zonal
hepatocyte necrosis, portal fibrosis, and chronic inflammation were found in varying
percentages. Sinusoidal ectasia, endothelial cell disruption, and fibrin-filled sinusoids
were seen in all cases; these were assessed semiquantitatively for severity (SEF scored).
SEF scores did not correlate with cause-of-death categories ( p = 0.92) or with severity
of lung alterations ( p = 0.96). SARS-CoV-2 RNA was detected in 13/20 cases by PCR
and in 9/20 by ISH, with IHC demonstration of spike protein in 4/20 cases and NP in
15/20. Viral RNA and proteins were located in endothelial and Kupffer cells, and in
portal macrophages, but not in hepatocytes and cholangiocytes. In conclusion, endothelial
damage (SEF scores) was the most common alteration in the liver and was a characteristic,
but not specific alteration in COVID-19, suggesting an important role in the pathogenesis
of COVID-19-associated liver disease. Detection of SARS-CoV-2 RNA and viral proteins
in liver non-parenchymal cells suggests that while the most extended primary viral
cytotoxic effect occurs in the lung, viral components are present in other organs
too, as in the liver. The necrosis/apoptosis and endothelial damage associated with
viral infection in COVID-19 suggest that those patients who survive more severe COVID-19
may face prolonged liver repair and accordingly should be followed regularly in the
post-COVID period.
