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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Publication Details

Journal
Nature Communications
Published
2026-09-30
DOI
https://doi.org/10.1038/s41467-026-77925-y
Primary Topic
Long-Term Effects of COVID-19
Type
article
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article

SARS-CoV-2-specific monoclonal antibody AER002 in Long COVID: an exploratory randomized phase 2a mechanistic trial

Matthew S. Durstenfeld, Ma Somsouk, Leonard H. Calabrese, Louise L. Hansen et al.
Nature Communications
Long-Term Effects of COVID-19
article

SARS-CoV-2-specific monoclonal antibody AER002 in Long COVID: an exploratory randomized phase 2a mechanistic trial

Matthew S. Durstenfeld, Ma Somsouk, Leonard H. Calabrese, Louise L. Hansen, Timothy J. Henrich, Jeffrey N. Martin, Mark M. Painter, Antonio E. Rodríguez, Steven E. Bellan, David V. Glidden, Thomas Dalhuisen, Zoe Swank, Emilio De Narvaez, Amelia N. Deitchman, Michael J. Peluso, Joanna Vinden, Emily A. Fehrman, Dylan Ryder, Yoshinori Fukazawa, Beatrice Huang, E. John Wherry, Josephat Asiago, Steven G. Deeks, John Daniel Kelly, Prakash K. Bhuyan, Robert R. Flavell, David R. Walt, Kofi A. Asare, Brian H. LaFranchi, Mohammad Sofiqur Rahman, Peter W. Hunt, Anisha Sekar, Danny Hoi Tsun Chu, Rajeev Venkayya, Priscilla Y. Hsue, Meghann C. Williams, Kathleen Bellon Pizarro, Henry VanBrocklin, Holly Tieu, Rebecca Hoh
article en

Abstract

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.

Nature Communications
Brigham and Women's Hospital (US), Cleveland Clinic (US), Harvard University (US), University of California, Los Angeles (US), University of California, San Francisco (US), Patient-Led Research Collaborative, University of Pennsylvania (US)
Good health and well-being
Openalex Percentile: Top 12%
Long-Term Effects of COVID-19
DOIOpen Access PDFOpenAlex
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