Titre
Intra-Host Evolution Analyses in an Immunosuppressed Patient Supports SARS-CoV-2 Viral Reservoir Hypothesis.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Fournelle, D.
Auteure/Auteur
Mostefai, F.
Auteure/Auteur
Brunet-Ratnasingham, E.
Auteure/Auteur
Poujol, R.
Auteure/Auteur
Grenier, J.C.
Auteure/Auteur
Gálvez, J.H.
Auteure/Auteur
Pagliuzza, A.
Auteure/Auteur
Levade, I.
Auteure/Auteur
Moreira, S.
Auteure/Auteur
Benlarbi, M.
Auteure/Auteur
Beaudoin-Bussières, G.
Auteure/Auteur
Gendron-Lepage, G.
Auteure/Auteur
Bourassa, C.
Auteure/Auteur
Tauzin, A.
Auteure/Auteur
Grandjean Lapierre, S.
Auteure/Auteur
Chomont, N.
Auteure/Auteur
Finzi, A.
Auteure/Auteur
Kaufmann, D.E.
Auteure/Auteur
Craig, M.
Auteure/Auteur
Hussin, J.G.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1999-4915
Statut éditorial
Publié
Date de publication
2024-02-23
Volume
16
Numéro
3
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Throughout the SARS-CoV-2 pandemic, several variants of concern (VOCs) have been identified, many of which share recurrent mutations in the spike glycoprotein's receptor-binding domain (RBD). This region coincides with known epitopes and can therefore have an impact on immune escape. Protracted infections in immunosuppressed patients have been hypothesized to lead to an enrichment of such mutations and therefore drive evolution towards VOCs. Here, we present the case of an immunosuppressed patient that developed distinct populations with immune escape mutations throughout the course of their infection. Notably, by investigating the co-occurrence of substitutions on individual sequencing reads in the RBD, we found quasispecies harboring mutations that confer resistance to known monoclonal antibodies (mAbs) such as S:E484K and S:E484A. These mutations were acquired without the patient being treated with mAbs nor convalescent sera and without them developing a detectable immune response to the virus. We also provide additional evidence for a viral reservoir based on intra-host phylogenetics, which led to a viral substrain that evolved elsewhere in the patient's body, colonizing their upper respiratory tract (URT). The presence of SARS-CoV-2 viral reservoirs can shed light on protracted infections interspersed with periods where the virus is undetectable, and potential explanations for long-COVID cases.
PID Serval
serval:BIB_F51EF3385B1B
PMID
Open Access
Oui
Date de création
2024-04-02T08:13:00.606Z
Date de création dans IRIS
2025-05-21T06:18:25Z
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Nom
38543708.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
1.17 MB
Format
Adobe PDF
PID Serval
serval:BIB_F51EF3385B1B.P001
URN
urn:nbn:ch:serval-BIB_F51EF3385B1B3
Somme de contrôle
(MD5):55db2a4797e0e55f53d97d444e0f0ef7