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
Shirley Sze,
Erol Gaillard,
Manish Pareek,
Iain Stephenson,
Daniel Pan,
Benjamin J Cowling,
Laura Gray,
Christopher A Martin,
Caroline Williams,
Mayuri Gogoi,
Amani Al-Oraibi,
Laura B Nellums,
Joshua Nazareth,
T. Déirdre Hollingsworth,
Pip Divall,
Michael Barer,
Eve Fletcher,
Natalia Grolmusova,
Jonathan Decker,
James Hay,
Rebecca F. Baggaley,
Anne L Wyllie,
Tristan William Clark,
Jonathan Nguyen Van-Tam
Affiliations
Shirley Sze
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
Erol Gaillard
Department of Respiratory Sciences, University of Leicester, Leicester, UK
Manish Pareek
Development Centre for Population Health, University of Leicester, Leicester, UK
Iain Stephenson
Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK
Daniel Pan
WHO Collaborating Centre for Infectious Disease Epidemiology and Control, Hong Kong School of Public Health, Hong Kong, Hong Kong
Benjamin J Cowling
WHO Collaborating Centre for Infectious Disease Epidemiology and Control, Hong Kong School of Public Health, Hong Kong, Hong Kong
Laura Gray
Leicester NIHR Biomedical Research Centre, Leicester, UK
Christopher A Martin
Development Centre for Population Health, University of Leicester, Leicester, UK
Caroline Williams
Department of Respiratory Sciences, University of Leicester, Leicester, UK
Mayuri Gogoi
Development Centre for Population Health, University of Leicester, Leicester, UK
Amani Al-Oraibi
Development Centre for Population Health, University of Leicester, Leicester, UK
Laura B Nellums
College of Population Health, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
Joshua Nazareth
Development Centre for Population Health, University of Leicester, Leicester, UK
T. Déirdre Hollingsworth
Oxford Big Data Institute, University of Oxford, Oxford, UK
Pip Divall
Education Centre Library, University Hospitals of Leicester NHS Trust, Leicester, UK
Michael Barer
Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester, UK
Eve Fletcher
Department of Respiratory Sciences, University of Leicester, Leicester, UK
Natalia Grolmusova
Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK
Jonathan Decker
Department of Respiratory Sciences, University of Leicester, Leicester, UK
James Hay
Oxford Big Data Institute, University of Oxford, Oxford, UK
Rebecca F. Baggaley
Development Centre for Population Health, University of Leicester, Leicester, UK
Anne L Wyllie
Department of Epidemiology of Microbial Diseases, Yale University, New Haven, Connecticut, USA
Tristan William Clark
Clinical and Experimental Sciences, University of Southampton, Southampton, UK
Jonathan Nguyen Van-Tam
Lifespan and Population Health, University of Nottingham, Nottingham, UK
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
