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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

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Title: SARS-CoV-2 RNA and Nucleocapsid Antigen Are Blood Biomarkers Associated With Severe Disease Outcomes That Improve in Response to Remdesivir
Authors: Kanal Singh, Kevin Rubenstein, Viviane Callier, Katy Shaw-Saliba, Adam Rupert, Robin Dewar, Sylvain Laverdure, Helene Highbarger, Perrine Lallemand, Meei-Li Huang, Keith R Jerome, Reigran Sampoleo, Margaret G Mills, Alexander L Greninger, Kavita Juneja, Danielle Porter, Constance A Benson, Walla Dempsey, Hana M El Sahly, Chris Focht, Nikolaus Jilg, Catharine I Paules, Rekha R Rapaka, Timothy M Uyeki, H Clifford Lane, John Beigel, Lori E Dodd, Aneesh K Mehta, Nadine G Rouphael, Jessica J Traenkner, Valeria D Cantos, Ghina Alaaeddine, Barry S Zingman, Robert Grossberg, Paul F Riska, Elizabeth Hohmann, Mariam Torres-Soto, Helen Y Chu, Anna Wald, Margaret Green, Annie Luetkemeyer, Pierre-Cedric B Crouch, Hannah Jang, Susan Kline, Joanne Billings, Brooke Noren, Diego Lopez de Castilla, Jason W Van Winkle, Francis X Riedo, Robert W Finberg, Jennifer P Wang, Mireya Wessolossky, Kerry Dierberg, Benjamin Eckhardt, Henry J Neumann, Victor Tapson, Jonathan Grein, Fayyaz Sutterwala, Lanny Hsieh, Alpesh N Amin, Thomas F Patterson, Heta Javeri, Trung Vu, Roger Paredes, Lourdes Mateu, Daniel A Sweeney, Farhana Ali, William R Short, Pablo Tebas, Jessie Torgersen, Giota Touloumi, Vicky Gioukari, David Chien Lye, Sean W X Ong, Norio Ohmagari, Ayako Mikami, Gerd Fätkenheuer, Jakob J Malin, Philipp Koehler, Andre C Kalil, LuAnn Larson, Angela Hewlett, Mark G Kortepeter, C Buddy Creech, Isaac Thomsen, Todd W Rice, Babafemi Taiwo, Karen Krueger, Stuart H Cohen, George R Thompson, Cameron Wolfe, Emmanuel B Walter, Maria Frank, Heather Young, Ann R Falsey, Angela R Branche, Paul Goepfert, Nathaniel Erdmann, Otto O Yang, Jenny Ahn, Anna Goodman, Blair Merrick, Richard M Novak, Andrea Wendrow, Henry Arguinchona, Christa Arguinchona, Sarah L George, Janice Tennant, Robert L Atmar, Jennifer Whitaker, D Ashley Price, Christopher J A Duncan, Simeon Metallidis, Theofilos Chrysanthidis, F McLellan, Myoung-don Oh, Wan Beom Park, Eu Suk Kim, Jongtak Jung, Justin R Ortiz, Karen L Kotloff, Brian Angus, Jack David Germain Seymour, Noreen A Hynes, Lauren M Sauer, Neera Ahuja, Kari Nadeau, Patrick E H Jackson, Taison D Bell, Anastasia Antoniadou, Konstantinos Protopapas, Richard T Davey, Jocelyn D Voell, Jose Muñoz, Montserrat Roldan, Ioannis Kalomenidis, Spyros G Zakynthinos, Fiona McGill, Jane Minton, Nikolaos Koulouris, Zafeiria Barmparessou, Edwin Swiatlo, Kyle Widmer, Nikhil Huprikar, Anuradha Ganesan, Guillermo M Ruiz-Palacios, Alfredo Ponce de León, Sandra Rajme, Justino Regalado Pineda, José Arturo Martinez-Orozco, Mark Holodniy, Aarthi Chary, Timo Wolf, Christoph Stephan, Jan-Christian Wasmuth, Christoph Boesecke, Martin Llewelyn, Barbara Philips, Christopher J Colombo, Rhonda E Colombo, David A Lindholm, Katrin Mende, Tida Lee, Tahaniyat Lalani, Ryan C Maves, Gregory C Utz, Jens Lundgren, Marie Helleberg, Jan Gerstoft, Thomas Benfield, Tomas Jensen, Birgitte Lindegaard, Lothar Weise, Lene Knudsen, Isik Johansen, Lone W Madsen, Lars Østergaard, Nina Stærke, Henrik Nielsen, Timothy H Burgess, Michelle Green, Mat Makowski, Jennifer L Ferreira, Michael R Wierzbicki, Tyler Bonnett, Nikki Gettinger, Theresa Engel, Jing Wang, John H Beigel, Kay M Tomashek, Seema Nayak, Effie Nomicos, Marina Lee, Peter Wolff, Rhonda Pikaart-Tautges, Mohamed Elsafy, Robert Jurao, Hyung Koo, Michael Proschan, Dean Follmann
Contributors: Angus, B
Source: Singh, K, Rubenstein, K, Callier, V, Shaw-Saliba, K, Rupert, A, Dewar, R, Laverdure, S, Highbarger, H, Lallemand, P, Huang, M-L, Jerome, K R, Sampoleo, R, Mills, M G, Greninger, A L, Juneja, K, Porter, D, Benson, C A, Dempsey, W, El Sahly, H M, Focht, C, Jilg, N, Paules, C I, Rapaka, R R, Uyeki, T M, Lane, H C, Beigel, J, Dodd, L E, Adaptive COVID-19 Treatment Trial (ACTT-1) Study Group Members & Nielsen, H 2024, 'SARS-CoV-2 RNA and nucleocapsid antigen are blood biomarkers associated with severe disease outcomes that improve in response to remdesivir', The Journal of Infectious Diseases, vol. 230, no. 3, jiae198, pp. 624-634. https://doi.org/10.1093/infdis/jiae198
The Journal of Infectious Diseases, vol 230, iss 3
Singh, K, Rubenstein, K, Callier, V, Shaw-Saliba, K, Rupert, A, Dewar, R, Laverdure, S, Highbarger, H, Lallemand, P, Huang, M-L, Jerome, K R, Sampoleo, R, Mills, M G, Greninger, A L, Juneja, K, Porter, D, Benson, C A, Dempsey, W, El Sahly, H M, Focht, C, Jilg, N, Paules, C I, Rapaka, R R, Uyeki, T M, Lane, H C, Beigel, J, Dodd, L E & Adaptive COVID-19 Treatment Trial (ACTT-1) Study Group Members 2024, 'SARS-CoV-2 RNA and nucleocapsid antigen are blood biomarkers associated with severe disease outcomes that improve in response to remdesivir', The Journal of Infectious Diseases, vol. 230, no. 3, pp. 624-634. https://doi.org/10.1093/infdis/jiae198
Publisher Information: Oxford University Press (OUP), 2024.
Publication Year: 2024
Subject Terms: Male, Adult, 0301 basic medicine, COVID-19/blood, remdesivir, antiviral efficacy, Antiviral Agents, Adenosine Monophosphate/analogs & derivatives, Coronavirus Nucleocapsid Proteins/immunology, SARS-CoV-2/immunology, 03 medical and health sciences, 0302 clinical medicine, Humans, Coronavirus Nucleocapsid Proteins, Viral, RNA, Viral/blood, Antigens, Antigens, Viral, Aged, Antiviral Agents/therapeutic use, Alanine, SARS-CoV-2, COVID-19, clinical trial, Alanine/analogs & derivatives, antiviral efficacy, clinical trial, COVID-19, remdesivir, SARS-CoV-2, Middle Aged, Viral Load, Adenosine Monophosphate, COVID-19 Drug Treatment, 3. Good health, Antigens, Viral/blood, Treatment Outcome, RNA, RNA, Viral, Female, Biomarkers/blood, Biomarkers
Description: 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 Adaptive COVID-19 Treatment Trial 1, which randomized patients to remdesivir or placebo. Methods Longitudinal specimens collected during hospitalization from a substudy of 642 patients with COVID-19 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, .76–1.42) for levels Conclusions Reductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy. Clinical Trial Registration NCT04280705 (ClinicalTrials.gov).
Document Type: Article
File Description: application/pdf
Language: English
ISSN: 1537-6613
0022-1899
DOI: 10.1093/infdis/jiae198
Access URL: https://pubmed.ncbi.nlm.nih.gov/38657001
https://vbn.aau.dk/da/publications/848d0595-5d78-4048-abfa-86e65c031503
https://doi.org/10.1093/infdis/jiae198
http://www.scopus.com/inward/record.url?scp=85204819223&partnerID=8YFLogxK
https://vbn.aau.dk/ws/files/705491966/Singh_et_al._2024_._SARS-CoV-2_RNA_and_nucleocapsid_antigen_are_blood_biomarkers_associated_with_severe_disease_outcomes_that_improve_in_response_to_remdesivir.pdf
https://escholarship.org/content/qt2hf3r271/qt2hf3r271.pdf
https://escholarship.org/uc/item/2hf3r271
Accession Number: edsair.doi.dedup.....d57a469193da3c90ced0fe12677ab065
Database: OpenAIRE
Description
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 Adaptive COVID-19 Treatment Trial 1, which randomized patients to remdesivir or placebo. Methods Longitudinal specimens collected during hospitalization from a substudy of 642 patients with COVID-19 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, .76–1.42) for levels Conclusions Reductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy. Clinical Trial Registration NCT04280705 (ClinicalTrials.gov).
ISSN:15376613
00221899
DOI:10.1093/infdis/jiae198