Journal article
SARS-CoV-2 Subgenomic RNA Kinetics in Longitudinal Clinical Samples
Open forum infectious diseases, Vol.8(7), p.ofab310
07/01/2021
DOI: 10.1093/ofid/ofab310
PMID: 34295944
Abstract
Background. Given the persistence of viral RNA in clinically recovered coronavirus disease 2019 (COVID-19) patients, subgenomic RNAs (sgRNAs) have been reported as potential molecular viability markers for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, few data are available on their longitudinal kinetics, compared with genomic RNA (gRNA), in clinical samples.
Methods. We analyzed 536 samples from 205 patients with COVID-19 from placebo-controlled, outpatient trials of peginterferon Lambda-1a (Lambda; n = 177) and favipiravir (n = 359). Nasal swabs were collected at 3 time points in the Lambda (days 1, 4, and 6) and favipiravir (days 1, 5, and 10) trials. N-gene gRNA and sgRNA were quantified by quantitative reverse transcription polymerase chain reaction. To investigate the decay kinetics in vitro, we measured gRNA and sgRNA in A549(ACE2+) cells infected with SARS-CoV-2, following treatment with remdesivir or dimethylsulfoxide control.
Results. At 6 days in the Lambda trial and 10 days in the favipiravir trial, sgRNA remained detectable in 51.6% (32/62) and 49.5% (51/106) of the samples, respectively. Cycle threshold (Ct) values for gRNA and sgRNA were highly linearly correlated (marginal R-2 = 0.83), and the rate of increase did not differ significantly in the Lambda trial (1.36 cycles/d vs 1.36 cycles/d; P =.97) or the favipiravir trial (1.03 cycles/d vs 0.94 cycles/d; P =.26). From samples collected 15-21 days after symptom onset, sgRNA was detectable in 48.1% (40/83) of participants. In SARS-CoV-2-infected A549(ACE2+) cells treated with remdesivir, the rate of Ct increase did not differ between gRNA and sgRNA.
Conclusions. In clinical samples and in vitro, sgRNA was highly correlated with gRNA and did not demonstrate different decay patterns to support its application as a viability marker.
Details
- Title: Subtitle
- SARS-CoV-2 Subgenomic RNA Kinetics in Longitudinal Clinical Samples
- Creators
- Renu Verma - Stanford MedicineEugene Kim - Stanford MedicineGiovanny Joel Martinez-Colon - Stanford MedicinePrasanna Jagannathan - Stanford MedicineArjun Rustagi - Stanford MedicineJulie Parsonnet - Stanford MedicineHector Bonilla - Stanford MedicineChaitan Khosla - Stanford UniversityMarisa Holubar - Stanford MedicineAruna Subramanian - Stanford MedicineUpinder Singh - Stanford MedicineYvonne Maldonado - Stanford MedicineCatherine A. Blish - Stanford MedicineJason R. Andrews - Stanford Medicine
- Resource Type
- Journal article
- Publication Details
- Open forum infectious diseases, Vol.8(7), p.ofab310
- DOI
- 10.1093/ofid/ofab310
- PMID
- 34295944
- NLM abbreviation
- Open Forum Infect Dis
- ISSN
- 2328-8957
- eISSN
- 2328-8957
- Publisher
- Oxford Univ Press
- Number of pages
- 10
- Grant note
- OPP1113682 / Bill and Melinda Gates Foundation; Bill & Melinda Gates Foundation 5T32AI007502 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA OPP1113682 / Bill Gates and Melinda Gates Foundation U01AI150741 / National Institute of Allergy and Infectious Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Language
- English
- Date published
- 07/01/2021
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985244541502771
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