TY - JOUR
T1 - Liposome-mediated detection of SARS-CoV-2 RNA-positive extracellular vesicles in plasma
AU - Ning, Bo
AU - Huang, Zhen
AU - Youngquist, Brady M.
AU - Scott, John W.
AU - Niu, Alex
AU - Bojanowski, Christine M.
AU - Zwezdaryk, Kevin J.
AU - Saba, Nakhle S.
AU - Fan, Jia
AU - Yin, Xiao Ming
AU - Cao, Jing
AU - Lyon, Christopher J.
AU - Li, Chen zhong
AU - Roy, Chad J.
AU - Hu, Tony Y.
N1 - Funding Information:
This study was supported by grants R01AI113725, R01AI122932, 1R03AI140977-01 and R21Al126361 from the National Institute of Allergy and Infectious Diseases (NIAID), grant R01HD090927 from the National Institute of Child Health and Human Development, grant 1U01CA252965-01 from the National Cancer Institute and grant W8IXWH1910926 from the Department of Defense. The work at the Tulane National Primate Research Center (TNPRC) was supported in part by NIAID contract no. HHSN272201700033I (C.J.R.) and grant OD011104 from the NIH Office of Research Infrastructure Programs. T.Y.H. also acknowledges the generous support of the Weatherhead Presidential Endowment fund.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/9
Y1 - 2021/9
N2 - Plasma SARS-CoV-2 RNA may represent a viable diagnostic alternative to respiratory RNA levels, which rapidly decline after infection. Quantitative PCR with reverse transcription (RT–qPCR) reference assays exhibit poor performance with plasma, probably reflecting the dilution and degradation of viral RNA released into the circulation, but these issues could be addressed by analysing viral RNA packaged into extracellular vesicles. Here we describe an assay approach in which extracellular vesicles directly captured from plasma are fused with reagent-loaded liposomes to sensitively amplify and detect a SARS-CoV-2 gene target. This approach accurately identified patients with COVID-19, including challenging cases missed by RT–qPCR. SARS-CoV-2-positive extracellular vesicles were detected at day 1 post-infection, and plateaued from day 6 to the day 28 endpoint in a non-human primate model, while signal durations for 20–60 days were observed in young children. This nanotechnology approach uses a non-infectious sample and extends virus detection windows, offering a tool to support COVID-19 diagnosis in patients without SARS-CoV-2 RNA detectable in the respiratory tract.
AB - Plasma SARS-CoV-2 RNA may represent a viable diagnostic alternative to respiratory RNA levels, which rapidly decline after infection. Quantitative PCR with reverse transcription (RT–qPCR) reference assays exhibit poor performance with plasma, probably reflecting the dilution and degradation of viral RNA released into the circulation, but these issues could be addressed by analysing viral RNA packaged into extracellular vesicles. Here we describe an assay approach in which extracellular vesicles directly captured from plasma are fused with reagent-loaded liposomes to sensitively amplify and detect a SARS-CoV-2 gene target. This approach accurately identified patients with COVID-19, including challenging cases missed by RT–qPCR. SARS-CoV-2-positive extracellular vesicles were detected at day 1 post-infection, and plateaued from day 6 to the day 28 endpoint in a non-human primate model, while signal durations for 20–60 days were observed in young children. This nanotechnology approach uses a non-infectious sample and extends virus detection windows, offering a tool to support COVID-19 diagnosis in patients without SARS-CoV-2 RNA detectable in the respiratory tract.
UR - http://www.scopus.com/inward/record.url?scp=85111167441&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111167441&partnerID=8YFLogxK
U2 - 10.1038/s41565-021-00939-8
DO - 10.1038/s41565-021-00939-8
M3 - Article
C2 - 34294909
AN - SCOPUS:85111167441
SN - 1748-3387
VL - 16
SP - 1039
EP - 1044
JO - Nature Nanotechnology
JF - Nature Nanotechnology
IS - 9
ER -