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Modelling upper respiratory viral load dynamics of SARS-CoV-2

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Title: Modelling upper respiratory viral load dynamics of SARS-CoV-2
Authors: Challenger, J
Foo, C
Wu, Y
Yan, A
Marjaneh, MM
Liew, F
Thwaites, R
Okell, L
Cunnington, A
Item Type: Journal Article
Abstract: Relationships between viral load, severity of illness, and transmissibility of virus, are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response, and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with control of viral load. Neutralizing antibody correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralizing antibody. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions.
Issue Date: 13-Jan-2022
Date of Acceptance: 15-Dec-2021
URI: http://hdl.handle.net/10044/1/93933
DOI: 10.1186/s12916-021-02220-0
ISSN: 1741-7015
Publisher: BioMed Central
Journal / Book Title: BMC Medicine
Volume: 20
Copyright Statement: © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the ata made available in this article, unless otherwise stated in a credit line to the data.
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: MR/R015600/1
Keywords: Antibodies, Viral
Viral Load
Antibodies, Viral
Viral Load
11 Medical and Health Sciences
General & Internal Medicine
Publication Status: Published
Article Number: ARTN 25
Appears in Collections:Department of Infectious Diseases
National Heart and Lung Institute
Imperial College London COVID-19
School of Public Health

This item is licensed under a Creative Commons License Creative Commons