tetano
Editor, Senior Moderator
Nat Commun
. 2026 Sep 30;17(1):11205.
doi: 10.1038/s41467-026-77925-y.
Michael J Peluso # 1 , Dylan Ryder # 2 , Thomas Dalhuisen 2 , Danny Hoi Tsun Chu 3 , Meghann C Williams 2 , Antonio E Rodriguez 2 , Brian H LaFranchi 4 , Joanna Vinden 4 , Emily A Fehrman 2 , Beatrice Huang 2 , Rebecca Hoh 2 , Kofi A Asare 2 , Kathleen Bellon Pizarro 2 , Mohammad Sofiqur Rahman 3 , Emilio de Narvaez 4 , Mark M Painter 5 , E John Wherry 5 , Zoe N Swank 6 , Louise L Hansen 6 , David R Walt 6 , Yoshinori Fukazawa 4 , Anisha Sekar 7 , Steven E Bellan 7 , Holly Tieu 8 , Josephat Asiago 8 , Prakash Bhuyan 8 , Rajeev Venkayya 8 , Robert R Flavell 9 , Henry VanBrocklin 9 , J Daniel Kelly 10 , Priscilla Y Hsue 11 , Matthew S Durstenfeld 12 , Peter W Hunt 4 , Leonard Calabrese 13 , Ma Somsouk 14 , Jeffrey N Martin 10 , David V Glidden 10 , Amelia N Deitchman 3 , Timothy J Henrich 4 , Steven G Deeks 2
Affiliations Expand
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.
. 2026 Sep 30;17(1):11205.
doi: 10.1038/s41467-026-77925-y.
SARS-CoV-2-specific monoclonal antibody AER002 in Long COVID: an exploratory randomized phase 2a mechanistic trial
Michael J Peluso # 1 , Dylan Ryder # 2 , Thomas Dalhuisen 2 , Danny Hoi Tsun Chu 3 , Meghann C Williams 2 , Antonio E Rodriguez 2 , Brian H LaFranchi 4 , Joanna Vinden 4 , Emily A Fehrman 2 , Beatrice Huang 2 , Rebecca Hoh 2 , Kofi A Asare 2 , Kathleen Bellon Pizarro 2 , Mohammad Sofiqur Rahman 3 , Emilio de Narvaez 4 , Mark M Painter 5 , E John Wherry 5 , Zoe N Swank 6 , Louise L Hansen 6 , David R Walt 6 , Yoshinori Fukazawa 4 , Anisha Sekar 7 , Steven E Bellan 7 , Holly Tieu 8 , Josephat Asiago 8 , Prakash Bhuyan 8 , Rajeev Venkayya 8 , Robert R Flavell 9 , Henry VanBrocklin 9 , J Daniel Kelly 10 , Priscilla Y Hsue 11 , Matthew S Durstenfeld 12 , Peter W Hunt 4 , Leonard Calabrese 13 , Ma Somsouk 14 , Jeffrey N Martin 10 , David V Glidden 10 , Amelia N Deitchman 3 , Timothy J Henrich 4 , Steven G Deeks 2
Affiliations Expand
- PMID: 42957665
- PMCID: PMC13720204
- DOI: 10.1038/s41467-026-77925-y
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.