Back to Search
Start Over
Sensitive tracking of circulating viral RNA through all stages of SARS-CoV-2 infection
- Source :
- J Clin Invest
- Publication Year :
- 2021
- Publisher :
- American Society for Clinical Investigation, 2021.
-
Abstract
- BACKGROUND: Circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA may represent a more reliable indicator of infection than nasal RNA, but quantitative reverse transcription PCR (RT-qPCR) lacks diagnostic sensitivity for blood samples. METHODS: A CRISPR-augmented RT-PCR assay that sensitively detects SARS-CoV-2 RNA was employed to analyze viral RNA kinetics in longitudinal plasma samples from nonhuman primates (NHPs) after virus exposure; to evaluate the utility of blood SARS-CoV-2 RNA detection for coronavirus disease 2019 (COVID-19) diagnosis in adults cases confirmed by nasal/nasopharyngeal swab RT-PCR results; and to identify suspected COVID-19 cases in pediatric and at-risk adult populations with negative nasal swab RT-qPCR results. All blood samples were analyzed by RT-qPCR to allow direct comparisons. RESULTS: CRISPR-augmented RT-PCR consistently detected SARS-CoV-2 RNA in the plasma of experimentally infected NHPs from 1 to 28 days after infection, and these increases preceded and correlated with rectal swab viral RNA increases. In a patient cohort (n = 159), this blood-based assay demonstrated 91.2% diagnostic sensitivity and 99.2% diagnostic specificity versus a comparator RT-qPCR nasal/nasopharyngeal test, whereas RT-qPCR exhibited 44.1% diagnostic sensitivity and 100% specificity for the same blood samples. This CRISPR-augmented RT-PCR assay also accurately identified patients with COVID-19 using one or more negative nasal swab RT-qPCR results. CONCLUSION: Results of this study indicate that sensitive detection of SARS-CoV-2 RNA in blood by CRISPR-augmented RT-PCR permits accurate COVID-19 diagnosis, and can detect COVID-19 cases with transient or negative nasal swab RT-qPCR results, suggesting that this approach could improve COVID-19 diagnosis and the evaluation of SARS-CoV-2 infection clearance, and predict the severity of infection. TRIAL REGISTRATION: ClinicalTrials.gov. NCT04358211. FUNDING: Department of Defense, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, and the National Center for Research Resources.
- Subjects :
- 0301 basic medicine
Adult
Male
Allergy
Time Factors
Coronavirus disease 2019 (COVID-19)
Adolescent
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Sensitivity and Specificity
Child health
Virus
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Humans
Viral rna
Longitudinal Studies
Child
Pandemics
Aged
business.industry
SARS-CoV-2
RNA
COVID-19
Infant
General Medicine
Middle Aged
medicine.disease
Virology
Macaca mulatta
Disease Models, Animal
030104 developmental biology
Nasal Swab
030220 oncology & carcinogenesis
COVID-19 Nucleic Acid Testing
Child, Preschool
RNA, Viral
Female
Clinical Medicine
CRISPR-Cas Systems
business
Cell-Free Nucleic Acids
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- J Clin Invest
- Accession number :
- edsair.doi.dedup.....b306b06d4af65c32befeeee6e0bab1e5