TY - JOUR
T1 - Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19
AU - Jensen, Tomas O
AU - Grandits, Greg A
AU - Jain, Mamta K
AU - Murray, Thomas A
AU - Grund, Birgit
AU - Shaw-Saliba, Kathryn
AU - Matthay, Michael A
AU - Abassi, Mahsa
AU - Ardelt, Magdalena
AU - Baker, Jason V
AU - Chen, Peter
AU - Dewar, Robin L
AU - Goodman, Anna L
AU - Hatlen, Timothy J
AU - Highbarger, Helene C
AU - Holodniy, Mark
AU - Lallemand, Perrine
AU - Laverdure, Sylvain
AU - Leshnower, Bradley G
AU - Looney, David
AU - Moschopoulos, Charalampos D
AU - Mugerwa, Henry
AU - Murray, Daniel D
AU - Mylonakis, Eleftherios
AU - Nagy-Agren, Stephanie
AU - Rehman, M Tauseef
AU - Rupert, Adam
AU - Stevens, Randy A
AU - Turville, Stuart
AU - Weintrob, Amy
AU - Wick, Katherine
AU - Lundgren, Jens
AU - Ko, Emily R
AU - ACTIV-3/TICO Study Group
A2 - Søborg, Christian
A2 - Pedersen, Thomas Ingemann
A2 - Lindegaard Madsen, Birgitte
A2 - Harboe, ZItta Barrella
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PY - 2024/3/14
Y1 - 2024/3/14
N2 - BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood.METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and d-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models.RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P < .001), and a steeper rate of decline through the first 5 days (P < .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale.CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed.CLINICAL TRIALS REGISTRATION: NCT04501978.
AB - BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood.METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and d-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models.RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P < .001), and a steeper rate of decline through the first 5 days (P < .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale.CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed.CLINICAL TRIALS REGISTRATION: NCT04501978.
UR - https://www.scopus.com/pages/publications/85187928457
U2 - 10.1093/infdis/jiad446
DO - 10.1093/infdis/jiad446
M3 - Journal article
C2 - 37948759
SN - 0022-1899
VL - 229
SP - 671
EP - 679
JO - The Journal of infectious diseases
JF - The Journal of infectious diseases
IS - 3
ER -