| Title: |
Extensive evolution and T cell escape by SARS-CoV-2 in a 2.5-year persistent infection of an immunocompromised host |
| Authors: |
Guerra-Assunção, José Afonso; McErlean, Ruairi; Townsend, Katie; Cankat, Selin; Flaxl, Leonhard M.; Tian, Shengwei Jamie; Turner, Thomas R.; Mayor, Neema P.; Breuer, Judith; Swadling, Leo; Lowe, David M. |
| Source: |
Guerra-Assunção, J A, McErlean, R, Townsend, K, Cankat, S, Flaxl, L M, Tian, S J, Turner, T R, Mayor, N P, Breuer, J, Swadling, L & Lowe, D M 2026, 'Extensive evolution and T cell escape by SARS-CoV-2 in a 2.5-year persistent infection of an immunocompromised host', iScience, vol. 29, no. 3, 114917. https://doi.org/10.1016/j.isci.2026.114917 |
| Publication Year: |
2026 |
| Description: |
Prolonged virus-host interaction and suboptimal immunity during persistent SARS-CoV-2 infection of immunocompromised patients enables viral adaptation. We investigated viral evolution and immune escape during a 2.5-year persistent infection in a patient with multiple myeloma and rheumatoid arthritis receiving anti-CD20 therapy. Virus isolated 899-days post-infection revealed an ancestral B.31 lineage with extensive evolution (56 non-synonymous mutations across 20 viral proteins). Many mutations were private or convergent with those seen in other persistent infections and later variants. SARS-CoV-2-specific antibodies were undetectable. Despite prolonged antigen exposure, T cell memory was functional high-in-magnitude and breadth, but with inhibitory receptor expression and dominant spike-specific CD8 response. 38/56 mutations occurred in T cell epitopes, reducing MHC binding or immunogenicity for 69% of CD8 epitopes affected. Importantly, functional assays confirmed T cell escape at 50% (1/2) and 86% (6/7) of CD8 and CD4 epitopes tested in vitro. These findings reveal extensive viral adaptation and T cell immune evasion during persistent infection. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
2589-0042 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41767267; info:eu-repo/semantics/altIdentifier/pissn/2589-0042; info:eu-repo/semantics/altIdentifier/eissn/2589-0042 |
| DOI: |
10.1016/j.isci.2026.114917 |
| Availability: |
https://pure.eur.nl/en/publications/87ac3e94-d0f9-41bc-8b24-eb78ea9c6944; https://doi.org/10.1016/j.isci.2026.114917; https://pure.eur.nl/ws/files/226853288/Extensive_evolution_and_T_cell_escape_by_SARS-CoV-2_in_a_2.5-year_persistent_infection_of_an_immunocompromised_host.pdf; https://www.scopus.com/pages/publications/105030441109 |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.7D3067C9 |
| Database: |
BASE |