Prolonged Viral Shedding in Three Young Adult Cases of COVID-19

Severe acute respiratory syndrome coronavirus-2 infection is usually self-limited, with a short duration for viral shedding within several weeks. However, prolonged viral shedding has been observed in severe or immune-compromised coronavirus disease 2019 (COVID-19) cases. Here, we reported that three young adult cases of COVID-19 patients, who were either immunosuppressed nor severe, showed prolonged viral RNA shedding from the upper respiratory tract for 58, 81, and 137 days since initial diagnosis. To our knowledge, this is the longest duration of viral shedding reported to date in young adult patients. Further studies on factors relevant to prolonged viral positivity, as well as the correlation between viral positivity and transmission risk are needed for the optimal management of COVID-19 patients with prolonged nucleic acid positive.

A multi-omics investigation of the composition and function of extracellular vesicles along the temporal trajectory of COVID-19.

Exosomes represent a subtype of extracellular vesicle that is released through retrograde transport and fusion of multivesicular bodies with the plasma membrane1. Although no perfect methodologies currently exist for the high-throughput, unbiased isolation of pure plasma exosomes2,3, investigation of exosome-enriched plasma fractions of extracellular vesicles can confer a glimpse into the endocytic pathway on a systems level. Here we conduct high-coverage lipidomics with an emphasis on sterols and oxysterols, and proteomic analyses of exosome-enriched extracellular vesicles (EVs hereafter) from patients at different temporal stages of COVID-19, including the presymptomatic, hyperinflammatory, resolution and convalescent phases. Our study highlights dysregulated raft lipid metabolism that underlies changes in EV lipid membrane anisotropy that alter the exosomal localization of presenilin-1 (PS-1) in the hyperinflammatory phase. We also show in vitro that EVs from different temporal phases trigger distinct metabolic and transcriptional responses in recipient cells, including in alveolar epithelial cells, which denote the primary site of infection, and liver hepatocytes, which represent a distal secondary site. In comparison to the hyperinflammatory phase, EVs from the resolution phase induce opposing effects on eukaryotic translation and Notch signalling. Our results provide insights into cellular lipid metabolism and inter-tissue crosstalk at different stages of COVID-19 and are a resource to increase our understanding of metabolic dysregulation in COVID-19.