Unusual SARS- CoV-2 intrahost diversity reveals lineage superinfection

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV- 2) has infected almost 200 million people worldwide by July 2021 and the pandemic has been characterized by infection waves of viral lineages showing distinct fitness profiles. The simultaneous infection of a single individual by two distinct SARS- CoV- 2 lineages may impact COVID- 19 disease progression and provides a window of opportunity for viral recombination and the emergence of new lineages with differential phenotype. Several hundred SARS- CoV- 2 lineages are currently well phylogenetically defined, but two main factors have precluded major coinfection/codetection and recombination analysis thus far: (i) the low diversity of SARS- CoV- 2 lineages during the first year of the pandemic, which limited the identification of lineage defining mutations necessary to distinguish coinfecting/recombining viral lineages; and the (ii) limited availability of raw sequencing data where abundance and distribution of intrasample/ intrahost variability can be accessed. Here, we assembled a large sequencing dataset from Brazilian samples covering a period of 18 May 2020 to 30 April 2021 and probed it for unexpected patterns of high intrasample/intrahost variability. This approach enabled us to detect nine cases of SARS- CoV- 2 coinfection with well characterized lineage-defining mutations, representing 0.61 % of all samples investigated. In addition, we matched these SARS- CoV- 2 coinfections with spatio-temporal epidemiological data confirming its plausibility with the cocirculating lineages at the timeframe investigated. Our data suggests that coinfection with distinct SARS- CoV- 2 lineages is a rare phenomenon, although it is certainly a lower bound estimate considering the difficulty to detect coinfections with very similar SARS- CoV- 2 lineages and the low number of samples sequenced from the total number of infections.

Automated summary

This study analyzed sequencing data from Brazilian samples and revealed the occurrence of co-infections with different lineages of SARS-CoV-2, indicating the potential for viral recombination. The results suggest that co-infection with distinct lineages is rare but possible, providing valuable data for further research.