oronaviruses are encapsulated, single-stranded RNA viruses that generally cause mild, coldlike illnesses in human beings (1). They can, however, cause life-threatening diseases such as severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS) (2, 3). Since late 2019, a new virus of this family, SARScoronavirus-2 (SARS-CoV-2), has caused a global pandemic (4). Persons infected with SARS-CoV-2 can become symptomatic with coronavirus disease 2019 (COVID-19), which usually presents at first with nonspecific symptoms such as fever, myalgia, and fatigue. Loss of the sense of taste is a not uncommon accompaniment (5). While most persons infected with the virus (about 80%) have only mild symptoms or none, some develop a clinically relevant disease necessitating hospitalization and, in some patients with SummaryBackground: The histomorphological changes of lung damage in severe coronavirus disease 2019 have not yet been adequately characterized. In this article, we describe the sequence of pathological changes in COVID-19 and discuss the implications for approaches to treatment. Methods: Standardized autopsies were performed on thirteen patients who had died of COVID-19. The findings were analyzed together with clinical data from the patients' medical records.Results: Most (77%) of the deceased patients were men. Their median age at death was 78 years (range, 41-90). Most of them had major pre-existing chronic diseases, most commonly arterial hypertension. The autopsies revealed characteristic COVID-19-induced pathological changes in the lungs, which were regarded as the cause of death in most patients. The main histological finding was sequential alveolar damage, apparently due in large measure to focal capillary microthrombus formation. Alveolar damage leads to the death of the patient either directly or by the induction of pulmonary parenchymal fibrosis. Diffuse lung damage was seen exclusively in invasively ventilated patients. Conclusion:Autopsies are crucial for the systematic assessment of new diseases such as COVID-19: they provide a basis for further investigations of disease mechanisms and for the devising of potentially effective modes of treatment. The autopsy findings suggest that focal damage of the microvascular pulmonary circulation is a main mechanism of lethal lung disease due to the SARS-CoV-2 virus. It may also be a cause of persistent lung damage in patients who recover from severe COVID-19.

Liver cancers, which are mostly hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are very aggressive tumors with poor prognosis. Therapeutic options with curative intent are largely limited to surgery and available systemic therapies show limited benefit. Signal transducer and activator of transcription 1 (STAT1) and 3 (STAT3) are key transcription factors activated by pro-inflammatory cytokines such as interferon-γ (IFN-γ) and interleukin-6 (IL-6). In this study, we combined in vitro cell culture experiments and immunohistochemical analyses of human HCC (N = 124) and CCA (N = 138) specimens. We observed that in the absence of STAT3, IL-6 induced the activation of STAT1 and its target genes suggesting that IL-6 derived from the tumor microenvironment may activate both STAT1 and STAT3 target genes in HCC tumor cells. In addition, STAT1 and STAT3 were highly activated in a subset of HCC, which exhibited a high degree of infiltrating CD8- and FOXP3-positive immune cells and PD-L1 expression. Our results demonstrate that STAT1 and STAT3 are expressed and activated in HCC and tumor infiltrating immune cells. In addition, HCC cases with high STAT1 and STAT3 expression also exhibited a high degree of immune cell infiltration, suggesting increased immunological tolerance.