Unusual SARS-CoV-2 intra-host diversity reveals lineages superinfection

Dezordi, F. Z.; Resende, P. C.; Naveca, F. G.; do Nascimento, V. A.; de Souza, V. C.; Paixao, A. C. D.; Appolinario, L.; Lopes, R. S.; Mendonca, A. C. d. F.; da Rocha, A. S. B.; Venas, T. M. M.; Pereira, E. C.; Salvato, R. S.; Gregianini, T. S.; Martins, L. G.; Pereira, F. M.; Rovaris, D. B.; Fernandes, S. B.; Ribeiro-Rodrigues, R.; Costa, T. O.; Sousa, J. C.; Miyajima, F.; Delatorre, E.; Graf, T.; Bello, G.; Siqueira, M. M.; Wallau, G. L.

The 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 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 characterized but two main factors have precluded major coinfection/codetection 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 viral lineages; and the ii) limited availability of raw sequencing data where abundance and distribution of intrasample/intrahost variability can be accessed. Here, we have put together 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. It enabled us to detect nine cases of SARS-CoV-2 coinfection with well characterized lineage-defining mutations. In addition, we matched these SARS-CoV-2 coinfections with spatio-temporal epidemiological data confirming their plausibility with the co-circulating lineages at the timeframe investigated. These coinfections represent around 0.61% of all samples investigated. Although our data suggests that coinfection with distinct SARS-CoV-2 lineages is a rare phenomenon, it is likely an underestimation and coinfection rates warrants further investigation.