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Targeting the SARS-CoV-2 reservoir in long COVID
Amy D Proal1, Soo Aleman2, Morgane Bomsel3
1PolyBio Research Foundation, Medford, MA, USA.
The Lancet. Infectious Diseases
|February 13, 2025
Summary
Clinical trials are needed for long COVID, targeting persistent SARS-CoV-2. Key considerations include therapeutic mechanisms, participant selection, and outcome assessments for effective treatment development.
Area of Science:
- Virology
- Immunology
- Clinical Trial Design
Background:
- Post-COVID-19 condition (long COVID) affects millions, with no approved treatments.
- Persistent SARS-CoV-2 infection is a potential driver of long COVID symptoms.
- Urgent need exists for clinical trials targeting persistent SARS-CoV-2.
Purpose of the Study:
- To outline key considerations for designing, implementing, and interpreting clinical trials for long COVID.
- To inform strategies for targeting persistent SARS-CoV-2 in clinical research.
Main Methods:
- Review and synthesis of knowledge from HIV reservoir, hepatitis C, and RNA virus trials.
- Drawing parallels with precision oncology trial methodologies.
- Identifying critical factors for long COVID trial design.
Main Results:
- Lack of understanding of SARS-CoV-2 persistence mechanisms complicates trial design.
- Essential considerations include therapeutic mechanisms, participant selection, treatment duration, biomarkers, and outcome assessments.
- Potential for subgroup responses necessitates post-hoc analyses and combination approaches.
Conclusions:
- Careful consideration of multiple factors is crucial for successful long COVID clinical trials.
- Recommendations provided aim to guide research in this rapidly evolving field.
- Lessons from other viral and cancer research inform strategies for long COVID therapeutic development.
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