Detection and Kinetics of Subgenomic Severe Acute Respiratory Syndrome Coronavirus 2 RNA Viral Load in Longitudinal Diagnostic RNA-Positive Samples

Meagan E Deming; Tracy Q Dong; Vaidehi Agrawal; Margaret G Mills; Meei Li W Huang; Alexander L Greninger; Keith R Jerome; Mark H Wener; Michael K Paasche-Orlow; Patricia Kissinger; Alfred Luk; Risa M Hoffman; Jenell Stewart; Angelica C Kottkamp; Anna Bershteyn; Helen Y Chu; Helen C Stankiewicz Karita; Christine M Johnston; Anna Wald; Ruanne Barnabas; Elizabeth R Brown; Kathleen M Neuzil

doi:10.1093/infdis/jiac048

Detection and Kinetics of Subgenomic Severe Acute Respiratory Syndrome Coronavirus 2 RNA Viral Load in Longitudinal Diagnostic RNA-Positive Samples

J Infect Dis. 2022 Sep 13;226(5):788-796. doi: 10.1093/infdis/jiac048.

Authors

Meagan E Deming¹, Tracy Q Dong², Vaidehi Agrawal¹, Margaret G Mills³, Meei Li W Huang³, Alexander L Greninger^{2

3}, Keith R Jerome^{2

3}, Mark H Wener^{3

4}, Michael K Paasche-Orlow⁵, Patricia Kissinger⁶, Alfred Luk⁷, Risa M Hoffman⁸, Jenell Stewart^{9

10}, Angelica C Kottkamp¹¹, Anna Bershteyn¹², Helen Y Chu^{10

13}, Helen C Stankiewicz Karita¹³, Christine M Johnston^{2

3

10}, Anna Wald^{2

3

10

12}, Ruanne Barnabas^{14

10

12}, Elizabeth R Brown^{2

13

15}, Kathleen M Neuzil¹

Affiliations

¹ The Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
² Vaccine and Infectious Disease Division, Fred Hutchinson, Cancer Research Center, Seattle, Washington, USA.
³ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
⁴ Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington, USA.
⁵ Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USA.
⁶ Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine.
⁷ Section of Infectious Diseases, John W. Deming, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
⁸ Division of Infectious Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California, USA.
⁹ Department of Medicine, University of Washington, Seattle, Washington, USA.
¹⁰ Division of Infectious Diseases & Immunology, Department of Medicine, New York University Grossman, School of Medicine, New York, New York, USA.
¹¹ Department of Population Health; New York University, Grossman School of Medicine, New York, New York, USA.
¹² Department of Epidemiology, University of Washington, Seattle, Washington, USA.
¹³ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
¹⁴ Department of Global Health, University of Washington, Seattle, Washington, USA.
¹⁵ Department of Biostatistics, University of Washington, Seattle, Washington, USA.

Abstract

While detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by diagnostic reverse-transcription polymerase chain reaction (RT-PCR) is highly sensitive for viral RNA, the nucleic acid amplification of subgenomic RNAs (sgRNAs) that are the product of viral replication may more accurately identify replication. We characterized the diagnostic RNA and sgRNA detection by RT-PCR from nasal swab samples collected daily by participants in postexposure prophylaxis or treatment studies for SARS-CoV-2. Among 1932 RT-PCR-positive swab samples with sgRNA tests, 40% (767) had detectable sgRNA. Above a diagnostic RNA viral load (VL) threshold of 5.1 log10 copies/mL, 96% of samples had detectable sgRNA with VLs that followed a linear trend. The trajectories of diagnostic RNA and sgRNA VLs differed, with 80% peaking on the same day but duration of sgRNA detection being shorter (8 vs 14 days). With a large sample of daily swab samples we provide comparative sgRNA kinetics and a diagnostic RNA threshold that correlates with replicating virus independent of symptoms or duration of illness.

Keywords: COVID-19; SARS-CoV-2; detection; kinetics; subgenomic RNA; viral load.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19 Testing
COVID-19* / diagnosis
Humans
Kinetics
RNA, Viral / analysis
RNA, Viral / genetics
SARS-CoV-2* / genetics
Viral Load

Substances

RNA, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding