Targeting the SARS-CoV-2 reservoir in long COVID

Proal, Amy D., Aleman, Soo, Bomsel, Morgane, Brodin, Petter, Buggert, Marcus, Cherry, Sara, Chertow, Daniel S., Davies, Helen E., Dupont, Christopher L., Deeks, Steven G., Ely, E. Wes, Fasano, Alessio, Freire, Marcelo, Geng, Linda N., Griffin, Diane E., Henrich, Timothy J., Hewitt, Stephen M., Iwasaki, Akiko, Krumholz, Harlan M., Locci, Michela, Marconi, Vincent C., Mehandru, Saurabh, Muller-Trutwin, Michaela, Painter, Mark M., Pretorius, Etheresia, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, Putrino, David, Qian, Yu, Roan, Nadia R., Salmon, Dominique, Tan, Gene S., VanElzakker, Michael B., Wherry, E. John, Van Weyenbergh, Johan, Yonker, Lael M. and Peluso, Michael J. 2025. Targeting the SARS-CoV-2 reservoir in long COVID. The Lancet Infectious Diseases 10.1016/S1473-3099(24)00769-2

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Abstract

There are no approved treatments for post-COVID-19 condition (also known as long COVID), a debilitating disease state following SARS-CoV-2 infection that is estimated to affect tens of millions of people. A growing body of evidence shows that SARS-CoV-2 can persist for months or years following COVID-19 in a subset of individuals, with this reservoir potentially driving long-COVID symptoms or sequelae. There is, therefore, an urgent need for clinical trials targeting persistent SARS-CoV-2, and several trials of antivirals or monoclonal antibodies for long COVID are underway. However, because mechanisms of SARS-CoV-2 persistence are not yet fully understood, such studies require important considerations related to the mechanism of action of candidate therapeutics, participant selection, duration of treatment, standardisation of reservoir-associated biomarkers and measurables, optimal outcome assessments, and potential combination approaches. In addition, patient subgroups might respond to some interventions or combinations of interventions, making post-hoc analyses crucial. Here, we outline these and other key considerations, with the goal of informing the design, implementation, and interpretation of trials in this rapidly growing field. Our recommendations are informed by knowledge gained from trials targeting the HIV reservoir, hepatitis C, and other RNA viruses, as well as precision oncology, which share many of the same hurdles facing long-COVID trials. [Abstract copyright: Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.]

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Publisher:	Elsevier
ISSN:	1473-3099
Date of Acceptance:	12 November 2024
Last Modified:	27 Feb 2025 12:30
URI:	https://orca.cardiff.ac.uk/id/eprint/176510

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