Defining within-host SARS-CoV-2 RNA viral load kinetics during acute COVID-19 infection within different respiratory compartments and their respective associations with host infectiousness: a protocol for a systematic review and meta-analysis

Pan, Daniel; Martin, Christopher A.; Nazareth, Joshua; Sze, Shirley; Al-Oraibi, Amani; Gogoi, Mayuri; Grolmusova, Natalia; Divall, Pip; Decker, Jonathan; Fletcher, Eve; Williams, Caroline; Hay, James; Baggaley, Rebecca F.; Wyllie, Anne L.; Stephenson, Iain; Gaillard, Erol; Nellums, Laura B.; Clark, Tristan William; Van-Tam, Jonathan Nguyen; Cowling, Benjamin J.; Hollingsworth, T. Déirdre; Gray, Laura; Barer, Michael; Pareek, Manish

Abstract

Introduction: Understanding how RNA viral load changes (viral load kinetics) during acute infection in SARS-CoV-2 can help to identify when and which patients are most infectious. We seek to summarise existing data on the longitudinal RNA viral load kinetics of SARS-CoV-2 sampled from different parts of the respiratory tract (nose, nasopharynx, oropharynx, saliva and exhaled breath) and how this may vary with age, sex, ethnicity, immune status, disease severity, vaccination, treatment and virus variant.

Methods and analysis: We will conduct a systematic review and meta-analysis, using studies identified through MEDLINE and EMBASE (via Ovid). All research studies reporting primary data on longitudinal RNA viral load kinetics of infected patients with SARS-CoV-2 will be included. Methodological quality will be assessed using a validated checklist for longitudinal studies as well as predefined quality criteria for assessment of individual-level RNA viral load. Should the data allow, we will aim to perform individual patient-level meta-analysis. Our primary outcomes are duration to, and quantity of peak RNA viral load, and total duration of viral load shedding within different respiratory compartments. Secondary outcomes include duration of lateral flow antigen and virus culture positivity and variation of RNA viral load by age, immune status, disease severity, vaccination, treatment, lateral flow tests, viral culture positivity and SARS-CoV-2 variant. Study-level effects affecting observations, but not related to properties of the patient, such as the PCR platform and gene target will also be recorded. Random-effects models will estimate the population mean and individual-level variation in viral shedding conditional on the aforementioned variables. Finally, we will summarise the key mechanistic models used in the literature to reconstruct individual-level viral kinetics and estimate how different factors shape viral dynamics over time.

Ethics and dissemination: Ethical approval is not needed as data will be obtained from published articles or studies with data that have already received and ethical review for analysis. Manuscript(s) will be prepared for publication.

Systematic review protocol registration: PROSPERO ID: CRD42023385315

Citation

Pan, D., Martin, C. A., Nazareth, J., Sze, S., Al-Oraibi, A., Gogoi, M., Grolmusova, N., Divall, P., Decker, J., Fletcher, E., Williams, C., Hay, J., Baggaley, R. F., Wyllie, A. L., Stephenson, I., Gaillard, E., Nellums, L. B., Clark, T. W., Van-Tam, J. N., Cowling, B. J., …Pareek, M. (2024). Defining within-host SARS-CoV-2 RNA viral load kinetics during acute COVID-19 infection within different respiratory compartments and their respective associations with host infectiousness: a protocol for a systematic review and meta-analysis. BMJ Open, 14(12), Article e085127. https://doi.org/10.1136/bmjopen-2024-085127

• Journal Article Type: Article
• Acceptance Date: Nov 1, 2024
• Online Publication Date: Dec 2, 2024
• Publication Date: 2024-12
• Deposit Date: Dec 5, 2024
• Publicly Available Date: Dec 5, 2024
• Journal: BMJ Open
• Electronic ISSN: 2044-6055
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 12
• Article Number: e085127
• DOI: https://doi.org/10.1136/bmjopen-2024-085127
• Public URL: https://nottingham-repository.worktribe.com/output/42818226
• Publisher URL: https://bmjopen.bmj.com/content/14/12/e085127