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Randomized Controlled Trial
. 2024 Mar 14;229(3):671-679.
doi: 10.1093/infdis/jiad446.

Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19

Tomas O Jensen  1 , Greg A Grandits  2 , Mamta K Jain  3 , Thomas A Murray  2 , Birgit Grund  4 , Kathryn Shaw-Saliba  5 , Michael A Matthay  6 , Mahsa Abassi  7 , Magdalena Ardelt  6 , Jason V Baker  7   8 , Peter Chen  9 , Robin L Dewar  10 , Anna L Goodman  11   12 , Timothy J Hatlen  13 , Helene C Highbarger  10 , Mark Holodniy  14   15 , Perrine Lallemand  10 , Sylvain Laverdure  16 , Bradley G Leshnower  17 , David Looney  18 , Charalampos D Moschopoulos  19 , Henry Mugerwa  20 , Daniel D Murray  1 , Eleftherios Mylonakis  21 , Stephanie Nagy-Agren  22   23 , M Tauseef Rehman  10 , Adam Rupert  10 , Randy A Stevens  10 , Stuart Turville  24 , Amy Weintrob  25 , Katherine Wick  26 , Jens Lundgren  1 , Emily R Ko  27 ; ACTIV-3/TICO Study Group
Collaborators, Affiliations
Randomized Controlled Trial

Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19

Tomas O Jensen et al. J Infect Dis. .

Abstract

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.

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Conflict of interest statement

Potential conflicts of interest. A. L. G. reports receiving institutional funding from Novavax, insititutaional partnership with Astra Zeneca, and reports being personally named as inventor on a patent used by Astra Zeneca. D. D. M. reports receiving grant from the Danish National research Foundation. E. M. reports payments to his institution received from SciClone Pharmaceuticals, Regeneron Pharmaceuticals, Pfizer, Chemic Labs/KODA Therapeutics, Cidara, and Leidos Biomedical Research Inc; E. M. also reports being on an advisory board for Basilea. K. W. reports receiving a honorarium for international ARDS conference and travel support from UCSF. M. A. reports a grant from NINDS. M. A. M. reports institutional grants from NHLBI/NIAID, the department of defence, California Institute of Regeneration, Roche-Genentech, and Quantum Health. M. A. M. has also received personal consulting fees from Novartis, Pliant Therapeutics, Johnson and Johnson, Gilead, and Citius Pharmaceuticals. M. K. J. reports institutional grants from Gilead, Laurent, and Regeneron; personal consulting fees from Gilead; and personal honoraria from Cooper Clinic. S. T. is funded by grants from the Australian Medical Foundation and New South Wales Health. The remaining authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Line plots of mean biomarker levels (with 95% confidence intervals) over time by neutralizing monoclonal antibody treatment and placebo groups. A, D, E, and F, Levels as geometric means; these biomarkers were analyzed on the log scale and back transformed. B and C, Levels as means analyzed on the original scale.
Figure 2.
Figure 2.
Subgroup analysis of baseline factors affected by neutralizing monoclonal antibody treatment on nucleocapsid antigen, C-reactive protein, and pulmonary ordinal outcome on day 5. Black circles represent the geometric mean ratio (plasma N-Ag, C-reactive protein) and odds ratio (pulmonary ordinal outcome) between nmAb and placebo groups with 95% CIs. Abbreviations: Anti-N, anti-nucleocapsid; Anti-S, anti-spike; CI, confidence interval; HFNO, high-flow nasal oxygen; HIV, human immunodeficiency virus; N-Ag, nucleocapsid antigen; NIV, non-invasive ventilation; nmAb, neutralizing monoclonal antibody; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. aFully vaccinated indicates full course completed, symptoms started at least 14 days after the last dose.
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