TY - JOUR
T1 - Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19
AU - ACTIV-3/TICO Study Group
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 - Group, ACTIV-3/TICO Study
AU - Mishra, Biswajit
PY - 2023/11/1
Y1 - 2023/11/1
N2 - 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.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.Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20\Ag compared with placebo (95\ 12\27\ P \lt; .001), and a steeper rate of decline through the first 5 days (P \lt; .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.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.NCT04501978.
AB - 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.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.Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20\Ag compared with placebo (95\ 12\27\ P \lt; .001), and a steeper rate of decline through the first 5 days (P \lt; .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.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.NCT04501978.
U2 - 10.1093/infdis/jiad446
DO - 10.1093/infdis/jiad446
M3 - Article
SN - 0022-1899
SP - jiad446
JO - The Journal of infectious diseases
JF - The Journal of infectious diseases
ER -