SARS-CoV-2-specific monoclonal antibody AER002 in Long COVID: an exploratory randomized phase 2a mechanistic trial
Abstract
Persistence of SARS-CoV-2 has been proposed as a biological driver of Long COVID, a disabling chronic illness with no proven treatments. We conducted an exploratory, placebo-controlled, double-blind, 2:1 randomized mechanistic trial (NCT05877508) of the SARS-CoV-2-specific monoclonal antibody AER002 in 36 participants who met the World Health Organization case definition of Long COVID. After baseline characterization, participants received a single infusion and were followed for 360 days. The primary endpoint was the PROMIS-29 Physical Health Summary Score (PHSS) at 90 days; secondary and exploratory endpoints included patient-reported and objective measures of physical and neurocognitive function as well as blood-, imaging-, and tissue-based biomarkers. While AER002 was safe and well tolerated, no significant differences in physical health, quality of life, objective measures of physical function or cognition, or blood-based biomarkers were demonstrated between the treatment and control arms. In a post-hoc analysis, participants with a lower baseline SARS-CoV-2 antibody level and higher drug exposure were more likely to perceive treatment benefit based on the Patient Global Impression of Change scale ( p < 0.05 for anti-S, S1, and RBD). Although AER002 was not efficacious in this proof-of-concept study, our findings could inform future trials using monoclonal antibodies to target viral persistence in Long COVID.
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BibTeX
@article{peluso2026sarscov2specific,
title = {{SARS-CoV-2-specific monoclonal antibody AER002 in Long COVID: an exploratory randomized phase 2a mechanistic trial}},
author = {Michael J. Peluso and Dylan Ryder and Thomas Dalhuisen and Danny Hoi Tsun Chu and Meghann C. Williams and Antonio E. Rodriguez and Brian H. LaFranchi and Joanna Vinden and Emily A. Fehrman and Beatrice Huang and Rebecca Hoh and Kofi A. Asare and Kathleen Bellon Pizarro and Mohammad Sofiqur Rahman and Emilio de Narvaez and Mark M. Painter and E. John Wherry and Zoe N. Swank and Louise L. Hansen and David R. Walt and Yoshinori Fukazawa and Anisha Sekar and Steven E. Bellan and Holly Tieu and Josephat Asiago and Prakash Bhuyan and Rajeev Venkayya and Robert R. Flavell and Henry VanBrocklin and J. Daniel Kelly and Priscilla Y. Hsue and Matthew S. Durstenfeld and Peter W. Hunt and Leonard Calabrese and Ma Somsouk and Jeffrey N. Martin and David V. Glidden and Amelia N. Deitchman and Timothy J. Henrich and Steven G. Deeks},
journal = {Nature Communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77925-y},
url = {https://www.nature.com/articles/s41467-026-77925-y},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - SARS-CoV-2-specific monoclonal antibody AER002 in Long COVID: an exploratory randomized phase 2a mechanistic trial
AU - Michael J. Peluso
AU - Dylan Ryder
AU - Thomas Dalhuisen
AU - Danny Hoi Tsun Chu
AU - Meghann C. Williams
AU - Antonio E. Rodriguez
AU - Brian H. LaFranchi
AU - Joanna Vinden
AU - Emily A. Fehrman
AU - Beatrice Huang
AU - Rebecca Hoh
AU - Kofi A. Asare
AU - Kathleen Bellon Pizarro
AU - Mohammad Sofiqur Rahman
AU - Emilio de Narvaez
AU - Mark M. Painter
AU - E. John Wherry
AU - Zoe N. Swank
AU - Louise L. Hansen
AU - David R. Walt
AU - Yoshinori Fukazawa
AU - Anisha Sekar
AU - Steven E. Bellan
AU - Holly Tieu
AU - Josephat Asiago
AU - Prakash Bhuyan
AU - Rajeev Venkayya
AU - Robert R. Flavell
AU - Henry VanBrocklin
AU - J. Daniel Kelly
AU - Priscilla Y. Hsue
AU - Matthew S. Durstenfeld
AU - Peter W. Hunt
AU - Leonard Calabrese
AU - Ma Somsouk
AU - Jeffrey N. Martin
AU - David V. Glidden
AU - Amelia N. Deitchman
AU - Timothy J. Henrich
AU - Steven G. Deeks
PY - 2026
DA - 2026/09/30
JO - Nature Communications
DO - 10.1038/s41467-026-77925-y
UR - https://www.nature.com/articles/s41467-026-77925-y
AB - Persistence of SARS-CoV-2 has been proposed as a biological driver of Long COVID, a disabling chronic illness with no proven treatments. We conducted an exploratory, placebo-controlled, double-blind, 2:1 randomized mechanistic trial (NCT05877508) of the SARS-CoV-2-specific monoclonal antibody AER002 in 36 participants who met the World Health Organization case definition of Long COVID. After baseline characterization, participants received a single infusion and were followed for 360 days. The primary endpoint was the PROMIS-29 Physical Health Summary Score (PHSS) at 90 days; secondary and exploratory endpoints included patient-reported and objective measures of physical and neurocognitive function as well as blood-, imaging-, and tissue-based biomarkers. While AER002 was safe and well tolerated, no significant differences in physical health, quality of life, objective measures of physical function or cognition, or blood-based biomarkers were demonstrated between the treatment and control arms. In a post-hoc analysis, participants with a lower baseline SARS-CoV-2 antibody level and higher drug exposure were more likely to perceive treatment benefit based on the Patient Global Impression of Change scale ( p < 0.05 for anti-S, S1, and RBD). Although AER002 was not efficacious in this proof-of-concept study, our findings could inform future trials using monoclonal antibodies to target viral persistence in Long COVID.
SN - 2041-1723
ER -