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 <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. 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).
| Original language | English |
|---|---|
| Pages (from-to) | 624-634 |
| Number of pages | 11 |
| Journal | Journal of Infectious Diseases |
| Volume | 230 |
| Issue number | 3 |
| DOIs | |
| State | Published - 15 Sep 2024 |
Keywords
- COVID-19
- SARS-CoV-2
- antiviral efficacy
- clinical trial
- remdesivir
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In: Journal of Infectious Diseases, Vol. 230, No. 3, 15.09.2024, p. 624-634.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - SARS-CoV-2 RNA and Nucleocapsid Antigen Are Blood Biomarkers Associated With Severe Disease Outcomes That Improve in Response to Remdesivir
AU - Singh, Kanal
AU - Rubenstein, Kevin
AU - Callier, Viviane
AU - Shaw-Saliba, Katy
AU - Rupert, Adam
AU - Dewar, Robin
AU - Laverdure, Sylvain
AU - Highbarger, Helene
AU - Lallemand, Perrine
AU - Huang, Meei Li
AU - Jerome, Keith R.
AU - Sampoleo, Reigran
AU - Mills, Margaret G.
AU - Greninger, Alexander L.
AU - Juneja, Kavita
AU - Porter, Danielle
AU - Benson, Constance A.
AU - Dempsey, Walla
AU - El Sahly, Hana M.
AU - Focht, Chris
AU - Jilg, Nikolaus
AU - Paules, Catharine I.
AU - Rapaka, Rekha R.
AU - Uyeki, Timothy M.
AU - Clifford Lane, H.
AU - Beigel, John
AU - Dodd, Lori E.
AU - Mehta, Aneesh K.
AU - Rouphael, Nadine G.
AU - Traenkner, Jessica J.
AU - Cantos, Valeria D.
AU - Alaaeddine, Ghina
AU - Zingman, Barry S.
AU - Grossberg, Robert
AU - Riska, Paul F.
AU - Hohmann, Elizabeth
AU - Torres-Soto, Mariam
AU - Jilg, Nikolaus
AU - Chu, Helen Y.
AU - Wald, Anna
AU - Green, Margaret
AU - Luetkemeyer, Annie
AU - Crouch, Pierre Cedric B.
AU - Jang, Hannah
AU - Kline, Susan
AU - Billings, Joanne
AU - Noren, Brooke
AU - Lopez De Castilla, Diego
AU - Van Winkle, Jason W.
AU - Riedo, Francis X.
AU - Finberg, Robert W.
AU - Wang, Jennifer P.
AU - Wessolossky, Mireya
AU - Dierberg, Kerry
AU - Eckhardt, Benjamin
AU - Neumann, Henry J.
AU - Tapson, Victor
AU - Grein, Jonathan
AU - Sutterwala, Fayyaz
AU - Hsieh, Lanny
AU - Amin, Alpesh N.
AU - Patterson, Thomas F.
AU - Javeri, Heta
AU - Vu, Trung
AU - Paredes, Roger
AU - Mateu, Lourdes
AU - Sweeney, Daniel A.
AU - Benson, Constance A.
AU - Ali, Farhana
AU - Short, William R.
AU - Tebas, Pablo
AU - Torgersen, Jessie
AU - Touloumi, Giota
AU - Gioukari, Vicky
AU - Lye, David Chien
AU - Ong, Sean W.X.
AU - Ohmagari, Norio
AU - Mikami, Ayako
AU - Fätkenheuer, Gerd
AU - Malin, Jakob J.
AU - Koehler, Philipp
AU - Kalil, Andre C.
AU - Larson, Lu Ann
AU - Hewlett, Angela
AU - Kortepeter, Mark G.
AU - Creech, C. Buddy
AU - Thomsen, Isaac
AU - Rice, Todd W.
AU - Taiwo, Babafemi
AU - Krueger, Karen
AU - Cohen, Stuart H.
AU - Thompson, George R.
AU - Wolfe, Cameron
AU - Walter, Emmanuel B.
AU - Frank, Maria
AU - Young, Heather
AU - Falsey, Ann R.
AU - Branche, Angela R.
AU - Goepfert, Paul
AU - Erdmann, Nathaniel
AU - Yang, Otto O.
AU - Ahn, Jenny
AU - Goodman, Anna
AU - Merrick, Blair
AU - Novak, Richard M.
AU - Wendrow, Andrea
AU - Arguinchona, Henry
AU - Arguinchona, Christa
AU - George, Sarah L.
AU - Tennant, Janice
AU - Atmar, Robert L.
AU - El Sahly, Hana M.
AU - Whitaker, Jennifer
AU - Price, D. Ashley
AU - Duncan, Christopher J.A.
AU - Metallidis, Simeon
AU - Chrysanthidis, Theofilos
AU - Mclellan, F.
AU - Oh, Myoung Don
AU - Park, Wan Beom
AU - Kim, Eu Suk
AU - Jung, Jongtak
AU - Ortiz, Justin R.
AU - Kotloff, Karen L.
AU - Angus, Brian
AU - Germain Seymour, Jack David
AU - Hynes, Noreen A.
AU - Sauer, Lauren M.
AU - Ahuja, Neera
AU - Nadeau, Kari
AU - Jackson, Patrick E.H.
AU - Bell, Taison D.
AU - Antoniadou, Anastasia
AU - Protopapas, Konstantinos
AU - Davey, Richard T.
AU - Voell, Jocelyn D.
AU - Muñoz, Jose
AU - Roldan, Montserrat
AU - Kalomenidis, Ioannis
AU - Zakynthinos, Spyros G.
AU - Paules, Catharine I.
AU - Mcgill, Fiona
AU - Minton, Jane
AU - Koulouris, Nikolaos
AU - Barmparessou, Zafeiria
AU - Swiatlo, Edwin
AU - Widmer, Kyle
AU - Huprikar, Nikhil
AU - Ganesan, Anuradha
AU - Ruiz-Palacios, Guillermo M.
AU - De León, Alfredo Ponce
AU - Rajme, Sandra
AU - Pineda, Justino Regalado
AU - Martinez-Orozco, José Arturo
AU - Holodniy, Mark
AU - Chary, Aarthi
AU - Wolf, Timo
AU - Stephan, Christoph
AU - Wasmuth, Jan Christian
AU - Boesecke, Christoph
AU - Llewelyn, Martin
AU - Philips, Barbara
AU - Colombo, Christopher J.
AU - Colombo, Rhonda E.
AU - Lindholm, David A.
AU - Mende, Katrin
AU - Lee, Tida
AU - Lalani, Tahaniyat
AU - Maves, Ryan C.
AU - Utz, Gregory C.
AU - Lundgren, Jens
AU - Helleberg, Marie
AU - Gerstoft, Jan
AU - Benfield, Thomas
AU - Jensen, Tomas
AU - Lindegaard, Birgitte
AU - Weise, Lothar
AU - Knudsen, Lene
AU - Johansen, Isik
AU - Madsen, Lone W.
AU - Østergaard, Lars
AU - Stærke, Nina
AU - Nielsen, Henrik
AU - Burgess, Timothy H.
AU - Green, Michelle
AU - Makowski, Mat
AU - Ferreira, Jennifer L.
AU - Wierzbicki, Michael R.
AU - Bonnett, Tyler
AU - Gettinger, Nikki
AU - Engel, Theresa
AU - Wang, Jing
AU - Beigel, John H.
AU - Tomashek, Kay M.
AU - Nayak, Seema
AU - Dodd, Lori E.
AU - Dempsey, Walla
AU - Nomicos, Effie
AU - Lee, Marina
AU - Wolff, Peter
AU - Pikaart-Tautges, Rhonda
AU - Elsafy, Mohamed
AU - Jurao, Robert
AU - Koo, Hyung
AU - Proschan, Michael
AU - Follmann, Dean
AU - Lane, H. Clifford
N1 - Publisher Copyright: © 2024 Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PY - 2024/9/15
Y1 - 2024/9/15
N2 - 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 <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. 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).
AB - 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 <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. 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).
KW - COVID-19
KW - SARS-CoV-2
KW - antiviral efficacy
KW - clinical trial
KW - remdesivir
UR - http://www.scopus.com/inward/record.url?scp=85204819223&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiae198
DO - 10.1093/infdis/jiae198
M3 - Article
C2 - 38657001
AN - SCOPUS:85204819223
SN - 0022-1899
VL - 230
SP - 624
EP - 634
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -