We investigated intra-host genetic evolution using two SARS-CoV-2 isolates from a fully vaccinated (primary schedule x2 doses of AstraZeneca plus a booster of Pfizer), >70-year-old woman with a history of lymphoma and hypertension who presented a SARS-CoV-2 infection for 3 weeks prior to death due to COVID-19. Two full genome sequences were determined from samples taken 13 days apart with both belonging to Pango lineage FL.2: the first detection of this Omicron sub-variant in Botswana. FL.2 is a sub-lineage of XBB.1.9.1. The repertoire of mutations and minority variants in the Spike protein differed between the two time points. Notably, we also observed deletions within the ORF1a and Membrane proteins; both regions are associated with high T-cell epitope density. The internal milieu of immune-suppressed individuals may accelerate SARS-CoV-2 evolution; hence, close monitoring is warranted.

Keywords: Botswana; Evolution; FL.2; Immunocompromised; SARS-CoV-2.