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SARS-CoV-2 RNA and nucleocapsid antigen are blood biomarkers associated with severe disease outcomes that improve in response to remdesivir

  1. Author:
    Singh, Kanal [ORCID]
    Rubenstein,Kevin
    Callier,Viviane
    Shaw-Saliba, Katy
    Rupert,Adam
    Dewar,Robin
    Laverdure,Sylvain
    Highbarger,Helene
    Lallemand,Perrine
    Huang, Meei-Li
    Jerome, Keith R [ORCID]
    Sampoleo, Reigran
    Mills, Margaret G
    Greninger, Alexander L
    Juneja, Kavita
    Porter, Danielle
    Benson, Constance A
    Dempsey, Walla
    El Sahly, Hana M
    Focht, Chris
    Jilg, Nikolaus [ORCID]
    Paules, Catharine I
    Rapaka, Rekha R
    Uyeki, Timothy M
    Lane, H Clifford
    Beigel, John [ORCID]
    Dodd, Lori E

  2. Author Address

    National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA., Fred Hutchinson Cancer Center, Seattle, WA, USA., Gilead Sciences, Inc., Foster City, CA, USA., University of California San Diego, San Diego, CA, USA., Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA., The Emmes Company, Rockville, MD, USA., Massachusetts General Hospital and Brigham and Women 39;s Hospital, Harvard Medical School, Boston, MA, USA., Division of Infectious Diseases, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA., Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA., Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.,
    1. Year: 2024
    2. Date: Sep 23
    3. Epub Date: 2024 04 24
  2. Journal: The Journal of Infectious Diseases
    1. 230
    2. 3
    3. Pages: 624-634
  4. Type of Article: Article
  1. Abstract:

    Background: Although antivirals remain important for the treatment COVID-19, methods to assess treatment efficacy are lacking. Here, we investigated the impact of remdesivir on viral dynamics and their contribution to understanding antiviral efficacy in the multicenter ACTT-1 clinical trial that randomized patients to remdesivir or placebo. Methods: Longitudinal specimens collected during hospitalization from a substudy of 642 COVID-19 patients were measured for viral RNA (upper respiratory tract and plasma), viral nucleocapsid antigen (serum), and host immunologic markers. Associations with clinical outcomes and response to therapy were assessed. Results: Higher baseline plasma viral loads were associated with poorer clinical outcomes, and decreases in viral RNA and antigen in blood but not the upper respiratory tract correlated with enhanced benefit from remdesivir. The treatment effect of remdesivir was most pronounced in patients with elevated baseline nucleocapsid antigen levels: the recovery rate ratio was 1.95 (95%CI 1.40-2.71) for levels >245 pg/ml vs 1.04 (95%CI 0.76-1.42) for levels < 245 pg/ml. Remdesivir also accelerated the rate of viral RNA and antigen clearance in blood, and patients whose blood levels decreased were more likely to recover and survive.

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External Sources

  1. View Full Text
  2. DOI: 10.1093/infdis/jiae198
  3. PMID: 38657001
  4. PMCID: PMC11420797
  5. View record in Web of Science®
  6. WOS: 001318772300001
  7. PII : 7657712

Library Notes

  1. Fiscal Year: FY2024-2025
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