Virchows Archiv : an international journal of pathology
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The lung is the main affected organ in severe coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2, and lung damage is the leading cause of death in the vast majority of patients. Mainly based on results obtained by autopsies, the seminal features of fatal COVID-19 have been described by many groups worldwide. Early changes encompass edema, epithelial damage, and capillaritis/endothelialitis, frequently combined with microthrombosis. ⋯ These features, however, are not specific for COVID-19 and can be found in other disorders including viral infections. Clinically, the early disease stage of severe COVID-19 is characterized by high viral load, lymphopenia, massive secretion of pro-inflammatory cytokines and hypercoagulability, documented by elevated D-dimers and an increased frequency of thrombotic and thromboembolic events, whereas virus loads and cytokine levels tend to decrease in late disease stages, when tissue repair including angiogenesis prevails. The present review describes the spectrum of lung pathology based on the current literature and the authors' personal experience derived from clinical autopsies, and tries to summarize our current understanding and open questions of the pathophysiology of severe pulmonary COVID-19.
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Review
Predictive biomarkers for response to immune checkpoint inhibitors in lung cancer: PD-L1 and beyond.
Immune checkpoint inhibitor (ICI) therapies, including the programmed cell death protein 1 (PD-1) axis blockade, are considered a major oncological breakthrough of the early twenty-first century and have led to remarkable response rates and survival in a subset of patients with non-small cell lung cancer (NSCLC). However, the available therapies work only for one in five unselected, advanced NSCLC patients; thus, patient selection needs to be performed with the use of efficient biomarkers. ⋯ In addition, given the lack of robust sensitivity and specificity of PD-L1 IHC for predicting response to ICIs, other biomarkers including tumor mutation burden (TMB) are under investigation. In this review, issues associated with PD-L1 IHC and TMB estimations will be discussed, and other promising biomarkers for predicting response to ICIs will be briefly introduced.