Four coronaviruses are endemic in humans (human coronavirus NL63 (HCoV-NL63), HCoV-229E, HCoV-OC43 and HCoV-HKU1) and typically infect the upper respiratory tract, causing common-cold symptoms. Finally, we highlight how these findings may aid the development of new therapeutic interventions against COVID-19.Ĭoronaviruses (family Coronaviridae) are common pathogens of humans and animals. 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. We describe how SARS-CoV-2 may infect the lower respiratory tract and cause alveolar damage as a result of dysfunctional immune responses. 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. 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. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating pandemic.
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