RT Journal Article T1 Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2 A1 Pérez Lago, Laura A1 Aldámiz Echevarría, Teresa A1 García Martínez, Rita A1 Pérez Latorre, Leire A1 Herranz, Marta A1 Sola Campoy, Pedro A1 Suárez González, Julia A1 Martínez Laperche, Carolina A1 Comas, Iñaki A1 González Candelas, Fernando A1 Catalán Alonso, Pilar A1 Muñoz García, Patricia Carmen A1 García de Viedma, Darío AB A successful Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant, B.1.1.7, has recently been reported in the UK, causing global alarm. Most likely, the new variant emerged in a persistently infected patient, justifying a special focus on these cases. Our aim in this study was to explore certain clinical profiles involving severe immunosuppression that may help explain the prolonged persistence of viable viruses. We present three severely immunosuppressed cases (A, B, and C) with a history of lymphoma and prolonged SARS-CoV-2 shedding (2, 4, and 6 months), two of whom finally died. Whole-genome sequencing of 9 and 10 specimens from Cases A and B revealed extensive within-patient acquisition of diversity, 12 and 28 new single nucleotide polymorphisms, respectively, which suggests ongoing SARS-CoV-2 replication. This diversity was not observed for Case C after analysing 5 sequential nasopharyngeal specimens and one plasma specimen, and was only observed in one bronchoaspirate specimen, although viral viability was still considered based on constant low Ct values throughout the disease and recovery of the virus in cell cultures. The acquired viral diversity in Cases A and B followed different dynamics. For Case A, new single nucleotide polymorphisms were quickly fixed (13–15 days) after emerging as minority variants, while for Case B, higher diversity was observed at a slower emergence: fixation pace (1–2 months). Slower SARS-CoV-2 evolutionary pace was observed for Case A following the administration of hyperimmune plasma. This work adds knowledge on SARS-CoV-2 prolonged shedding in severely immunocompromised patients and demonstrates viral viability, noteworthy acquired intra-patient diversity, and different SARS-CoV-2 evolutionary dynamics in persistent cases. PB MPDI SN 2227-9059 YR 2021 FD 2021-07-13 LK https://hdl.handle.net/20.500.14352/4648 UL https://hdl.handle.net/20.500.14352/4648 LA eng NO Pérez Lago, L., Aldámimz Echevarría, T., García Martínez, R. et al. «Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2». Biomedicines, vol. 9, n.o 7, julio de 2021, p. 808. DOI.org (Crossref), https://doi.org/10.3390/biomedicines9070808. NO Instituto de Salud Carlos III NO Consejo Superior de Investigaciones Científicas (España) DS Docta Complutense RD 9 abr 2025