/pdf/clinical-characteristics-and-day-90-outcomes-of-4244-6bpmow2brz.pdf

Clinical characteristics and day-90 outcomes of 4244 ctritically ill adults with COVID-19: a prospective cohort study

The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating pandemic. Although most people infected with SARS-CoV-2 develop a mild to moderate disease with virus replication restricted mainly to the upper airways, some progress to having a life-threatening pneumonia. In this Review, we explore recent clinical and experimental advances regarding SARS-CoV-2 pathophysiology and discuss potential mechanisms behind SARS-CoV-2-associated acute respiratory distress syndrome (ARDS), specifically focusing on new insights obtained using novel technologies such as single-cell omics, organoid infection models and CRISPR screens. We describe how SARS-CoV-2 may infect the lower respiratory tract and cause alveolar damage as a result of dysfunctional immune responses. We discuss how this may lead to the induction of a 'leaky state' of both the epithelium and the endothelium, promoting inflammation and coagulation, while an influx of immune cells leads to overexuberant inflammatory responses and immunopathology. Finally, we highlight how these findings may aid the development of new therapeutic interventions against COVID-19. 

/pdf/sars-cov-2-pathogenesis-1tieifc2.pdf

SARS-CoV-2 pathogenesis

Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study.

Recent studies have provided insights into the pathology of and immune response to COVID-191–8 However, a thorough investigation of the interplay between infected cells and the immune system at sites of infection has been lacking Here we use high-parameter imaging mass cytometry9 that targets the expression of 36 proteins to investigate the cellular composition and spatial architecture of acute lung injury in humans (including injuries derived from SARS-CoV-2 infection) at single-cell resolution These spatially resolved single-cell data unravel the disordered structure of the infected and injured lung, alongside the distribution of extensive immune infiltration Neutrophil and macrophage infiltration are hallmarks of bacterial pneumonia and COVID-19, respectively We provide evidence that SARS-CoV-2 infects predominantly alveolar epithelial cells and induces a localized hyperinflammatory cell state that is associated with lung damage We leverage the temporal range of fatal outcomes of COVID-19 in relation to the onset of symptoms, which reveals increased macrophage extravasation and increased numbers of mesenchymal cells and fibroblasts concomitant with increased proximity between these cell types as the disease progresses—possibly as a result of attempts to repair the damaged lung tissue Our data enable us to develop a biologically interpretable landscape of lung pathology from a structural, immunological and clinical standpoint We use this landscape to characterize the pathophysiology of the human lung from its macroscopic presentation to the single-cell level, which provides an important basis for understanding COVID-19 and lung pathology in general Imaging mass cytometry of the human lung reveals the cellular composition and spatial architecture during COVID-19 and other acute injuries, enabling the characterization of lung pathophysiology from structural, immunological and clinical perspectives

/pdf/the-spatial-landscape-of-lung-pathology-during-covid-19-4j3f6i0dpf.pdf

Marco Di Laudo

Papers

Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study.