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, Pilar
A1 Muñoz García, Patricia
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 Instituto de Salud Carlos III
NO Consejo Superior de Investigaciones Científicas (CSIC)
DS Docta Complutense
RD 3 may 2024