SARS-CoV-2 Co-Infection in Immunocompromised Host Leads to Generation of Recombinant Strain.

Recombination related to co-infection is a huge driving force in determining the virus genetic variability, particularly in conditions of partial immune control leading to prolonged infection. Here we characterized a distinctive mutational pattern, highly suggestive of Delta-Omicron double infection, in a lymphoma patient. The specimen was characterized through a combined approach, analyzing the results of deep sequencing in primary sample, viral culture and plaque assay. Bioinformatic analysis on the sequences deriving from the primary sample supports the hypothesis of a double viral population within the host. Plaque assay on viral culture led to the isolation of a recombinant strain deriving from Delta and Omicron lineages, named XS, which virtually replaced its parent lineages within a single viral propagation. It is impossible to establish whether the recombination event happened within the host or in vitro, however it is important to monitor co-infections, especially in the exceptional intra-host environment of immunocompromised patients, as strong driving forces of viral evolution.