SARS-CoV-2 RNA and nucleocapsid antigen are blood biomarkers associated with severe disease outcomes that improve in response to remdesivir.
COVID-19
SARS-CoV-2
antiviral efficacy
clinical trial
remdesivir
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
24 Apr 2024
24 Apr 2024
Historique:
received:
19
10
2023
revised:
09
04
2024
accepted:
12
04
2024
medline:
24
4
2024
pubmed:
24
4
2024
entrez:
24
4
2024
Statut:
aheadofprint
Résumé
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. 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. 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. Reductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy.
Sections du résumé
BACKGROUND
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
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
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.
CONCLUSIONS
CONCLUSIONS
Reductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy.
Identifiants
pubmed: 38657001
pii: 7657712
doi: 10.1093/infdis/jiae198
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
Aneesh K Mehta
(AK)
Nadine G Rouphael
(NG)
Jessica J Traenkner
(JJ)
Valeria D Cantos
(VD)
Ghina Alaaeddine
(G)
Barry S Zingman
(BS)
Robert Grossberg
(R)
Paul F Riska
(PF)
Elizabeth Hohmann
(E)
Mariam Torres-Soto
(M)
Nikolaus Jilg
(N)
Helen Y Chu
(HY)
Anna Wald
(A)
Margaret Green
(M)
Annie Luetkemeyer
(A)
Pierre-Cedric B Crouch
(PB)
Hannah Jang
(H)
Susan Kline
(S)
Joanne Billings
(J)
Brooke Noren
(B)
Diego Lopez de Castilla
(DL)
Jason W Van Winkle
(JW)
Francis X Riedo
(FX)
Robert W Finberg
(RW)
Jennifer P Wang
(JP)
Mireya Wessolossky
(M)
Kerry Dierberg
(K)
Benjamin Eckhardt
(B)
Henry J Neumann
(HJ)
Victor Tapson
(V)
Jonathan Grein
(J)
Fayyaz Sutterwala
(F)
Lanny Hsieh
(L)
Alpesh N Amin
(AN)
Thomas F Patterson
(TF)
Heta Javeri
(H)
Trung Vu
(T)
Roger Paredes
(R)
Lourdes Mateu
(L)
Daniel A Sweeney
(DA)
Constance A Benson
(CA)
Farhana Ali
(F)
William R Short
(WR)
Pablo Tebas
(P)
Jessie Torgersen
(J)
Giota Touloumi
(G)
Vicky Gioukari
(V)
David Chien Lye
(DC)
Sean W X Ong
(SWX)
Norio Ohmagari
(N)
Ayako Mikami
(A)
Gerd Fätkenheuer
(G)
Jakob J Malin
(JJ)
Philipp Koehler
(P)
Andre C Kalil
(AC)
LuAnn Larson
(L)
Angela Hewlett
(A)
Mark G Kortepeter
(MG)
C Buddy Creech
(CB)
Isaac Thomsen
(I)
Todd W Rice
(TW)
Babafemi Taiwo
(B)
Karen Krueger
(K)
Stuart H Cohen
(SH)
George R Thompson
(GR)
Cameron Wolfe
(C)
Emmanuel B Walter
(EB)
Maria Frank
(M)
Heather Young
(H)
Ann R Falsey
(AR)
Angela R Branche
(AR)
Paul Goepfert
(P)
Nathaniel Erdmann
(N)
Otto O Yang
(OO)
Jenny Ahn
(J)
Anna Goodman
(A)
Blair Merrick
(B)
Richard M Novak
(RM)
Andrea Wendrow
(A)
Henry Arguinchona
(H)
Christa Arguinchona
(C)
Sarah L George
(SL)
Janice Tennant
(J)
Robert L Atmar
(RL)
Hana M El Sahly
(HM)
Jennifer Whitaker
(J)
D Ashley Price
(DA)
Christopher J A Duncan
(CJA)
Simeon Metallidis
(S)
Theofilos Chrysanthidis
(T)
F McLellan
(F)
Myoung-Don Oh
(MD)
Wan Beom Park
(WB)
Eu Suk Kim
(ES)
Jongtak Jung
(J)
Justin R Ortiz
(JR)
Karen L Kotloff
(KL)
Brian Angus
(B)
Jack David Germain Seymour
(JD)
Noreen A Hynes
(NA)
Lauren M Sauer
(LM)
Neera Ahuja
(N)
Kari Nadeau
(K)
Patrick E H Jackson
(PEH)
Taison D Bell
(TD)
Anastasia Antoniadou
(A)
Konstantinos Protopapas
(K)
Richard T Davey
(RT)
Jocelyn D Voell
(JD)
Jose Muñoz
(J)
Montserrat Roldan
(M)
Ioannis Kalomenidis
(I)
Spyros G Zakynthinos
(SG)
Catharine I Paules
(CI)
Fiona McGill
(F)
Jane Minton
(J)
Nikolaos Koulouris
(N)
Zafeiria Barmparessou
(Z)
Edwin Swiatlo
(E)
Kyle Widmer
(K)
Nikhil Huprikar
(N)
Anuradha Ganesan
(A)
Guillermo M Ruiz-Palacios
(GM)
Alfredo Ponce de León
(AP)
Sandra Rajme
(S)
Justino Regalado Pineda
(JR)
José Arturo Martinez-Orozco
(JA)
Mark Holodniy
(M)
Aarthi Chary
(A)
Timo Wolf
(T)
Christoph Stephan
(C)
Jan-Christian Wasmuth
(JC)
Christoph Boesecke
(C)
Martin Llewelyn
(M)
Barbara Philips
(B)
Christopher J Colombo
(CJ)
Rhonda E Colombo
(RE)
David A Lindholm
(DA)
Katrin Mende
(K)
Tida Lee
(T)
Tahaniyat Lalani
(T)
Ryan C Maves
(RC)
Gregory C Utz
(GC)
Jens Lundgren
(J)
Marie Helleberg
(M)
Jan Gerstoft
(J)
Thomas Benfield
(T)
Tomas Jensen
(T)
Birgitte Lindegaard
(B)
Lothar Weise
(L)
Lene Knudsen
(L)
Isik Johansen
(I)
Lone W Madsen
(LW)
Lars Østergaard
(L)
Nina Stærke
(N)
Henrik Nielsen
(H)
Timothy H Burgess
(TH)
Michelle Green
(M)
Mat Makowski
(M)
Jennifer L Ferreira
(JL)
Michael R Wierzbicki
(MR)
Tyler Bonnett
(T)
Nikki Gettinger
(N)
Theresa Engel
(T)
Jing Wang
(J)
John H Beigel
(JH)
Kay M Tomashek
(KM)
Seema Nayak
(S)
Lori E Dodd
(LE)
Walla Dempsey
(W)
Effie Nomicos
(E)
Marina Lee
(M)
Peter Wolff
(P)
Rhonda Pikaart-Tautges
(R)
Mohamed Elsafy
(M)
Robert Jurao
(R)
Hyung Koo
(H)
Michael Proschan
(M)
Dean Follmann
(D)
H Clifford Lane
(HC)
Informations de copyright
Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.