SARS-CoV-2-specific monoclonal antibody AER002 in Long COVID: an exploratory randomized phase 2a mechanistic trial
Nature Communications, 2026
Peluso M., Ryder D., Dalhuisen T., Chu D., Williams M., Rodriguez A., LaFranchi B., Vinden J., Fehrman E., Huang B., Hoh R., Asare K., Bellon Pizarro K., Rahman M., de Narvaez E., Painter M., Wherry E., Swank Z., Hansen L., Walt D., Fukazawa Y., Sekar A., Bellan S., Tieu H., Asiago J., Bhuyan P., Venkayya R., Flavell R., VanBrocklin H., Kelly J., Hsue P., Durstenfeld M., Hunt P., Calabrese L., Somsouk M., Martin J., Glidden D., Deitchman A., Henrich T., Deeks S.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Plasma | R Reveal |
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.