Systematic genomic analysis of SARS-CoV-2 co-infections throughout the whole pandemic and segregation of the involved strains. undefined

SARS-CoV-2 recombinants have been recently described, involving the divergent Delta and Omicron lineages. Recombination requires the simultaneous co-existence of two SARS-CoV-2 strains in the same individual, but only a limited number of studies have focused on identifying co-infection in COVID-19. In addition, most of them are restricted to the identification of co-infections involving Delta/Omicron lineages and limited to the narrow time period when they co-circulated. We performed a systematic identification of SARS-CoV-2 co-infections throughout the pandemic, not biased towards the involvement of highly divergent lineages. Among the 7609 different COVID-19 patients sequenced between March 2020 and September 2022 in our population, we identified 14 (0.18%) co-infections with ≥8 heterozygous calls (8-85 HZs). These co-infections were robustly assigned by a series of thorough validations based on the distribution of allelic frequencies, phylogenetic consistency, re-sequencing, host genetic analysis and contextual epidemiological analysis. Co-infections were identified throughout the pandemic, preceding the most recent stages when highly divergent lineages are co-circulating. Co-infections involved in the same proportion strains from different lineages/sublineages (including pre-Alpha variants, Delta or Omicron) or strains from the same lineage (involving pre-Alpha or Omicron strains). Co-infected cases were mainly non-vaccinated, with a mild or asymptomatic clinical presentation. The segregation of the involved strains allowed the integration of their sequences to clarify nosocomial outbreaks, whose analysis had been impaired due to the co-infection.