tetano
Editor, Senior Moderator
J Infect Dis
. 2023 Nov 9:jiad446.
doi: 10.1093/infdis/jiad446. Online ahead of print. Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19
Tomas O Jensen[SUP] 1 [/SUP], Greg A Grandits[SUP] 2 [/SUP], Mamta K Jain[SUP] 3 [/SUP], Thomas A Murray[SUP] 2 [/SUP], Birgit Grund[SUP] 4 [/SUP], Kathryn Shaw-Saliba[SUP] 5 [/SUP], Michael A Matthay[SUP] 6 [/SUP], Mahsa Abassi[SUP] 7 [/SUP], Magdalena Ardelt[SUP] 6 [/SUP], Jason V Baker[SUP] 7 8 [/SUP], Peter Chen[SUP] 9 [/SUP], Robin L Dewar[SUP] 10 [/SUP], Anna L Goodman[SUP] 11 12 [/SUP], Timothy J Hatlen[SUP] 13 [/SUP], Helene C Highbarger[SUP] 10 [/SUP], Mark Holodniy[SUP] 14 15 [/SUP], Perrine Lallemand[SUP] 10 [/SUP], Sylvain Laverdure[SUP] 16 [/SUP], Bradley G Leshnower[SUP] 17 [/SUP], David Looney[SUP] 18 [/SUP], Charalampos D Moschopoulos[SUP] 19 [/SUP], Henry Mugerwa[SUP] 20 [/SUP], Daniel D Murray[SUP] 1 [/SUP], Eleftherios Mylonakis[SUP] 21 [/SUP], Stephanie Nagy-Agren[SUP] 22 23 [/SUP], M Tauseef Rehman[SUP] 10 [/SUP], Adam Rupert[SUP] 10 [/SUP], Randy A Stevens[SUP] 10 [/SUP], Stuart Turville[SUP] 24 [/SUP], Amy Weintrob[SUP] 25 [/SUP], Katherine Wick[SUP] 26 [/SUP], Jens Lundgren[SUP] 1 [/SUP], Emily R Ko[SUP] 27 [/SUP]; ACTIV-3/TICO Study Group
Collaborators, Affiliations
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.
Keywords: COVID-19; anti-nucleocapsid antibody; inflammatory biomarkers; neutralizing monoclonal antibody; plasma nucleocapsid antigen.
. 2023 Nov 9:jiad446.
doi: 10.1093/infdis/jiad446. Online ahead of print. Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19
Tomas O Jensen[SUP] 1 [/SUP], Greg A Grandits[SUP] 2 [/SUP], Mamta K Jain[SUP] 3 [/SUP], Thomas A Murray[SUP] 2 [/SUP], Birgit Grund[SUP] 4 [/SUP], Kathryn Shaw-Saliba[SUP] 5 [/SUP], Michael A Matthay[SUP] 6 [/SUP], Mahsa Abassi[SUP] 7 [/SUP], Magdalena Ardelt[SUP] 6 [/SUP], Jason V Baker[SUP] 7 8 [/SUP], Peter Chen[SUP] 9 [/SUP], Robin L Dewar[SUP] 10 [/SUP], Anna L Goodman[SUP] 11 12 [/SUP], Timothy J Hatlen[SUP] 13 [/SUP], Helene C Highbarger[SUP] 10 [/SUP], Mark Holodniy[SUP] 14 15 [/SUP], Perrine Lallemand[SUP] 10 [/SUP], Sylvain Laverdure[SUP] 16 [/SUP], Bradley G Leshnower[SUP] 17 [/SUP], David Looney[SUP] 18 [/SUP], Charalampos D Moschopoulos[SUP] 19 [/SUP], Henry Mugerwa[SUP] 20 [/SUP], Daniel D Murray[SUP] 1 [/SUP], Eleftherios Mylonakis[SUP] 21 [/SUP], Stephanie Nagy-Agren[SUP] 22 23 [/SUP], M Tauseef Rehman[SUP] 10 [/SUP], Adam Rupert[SUP] 10 [/SUP], Randy A Stevens[SUP] 10 [/SUP], Stuart Turville[SUP] 24 [/SUP], Amy Weintrob[SUP] 25 [/SUP], Katherine Wick[SUP] 26 [/SUP], Jens Lundgren[SUP] 1 [/SUP], Emily R Ko[SUP] 27 [/SUP]; ACTIV-3/TICO Study Group
Collaborators, Affiliations
- PMID: 37948759
- DOI: 10.1093/infdis/jiad446
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.
Keywords: COVID-19; anti-nucleocapsid antibody; inflammatory biomarkers; neutralizing monoclonal antibody; plasma nucleocapsid antigen.