Monitoring the emergence and origin of SARS-CoV-2 mutations – Genetic Inter- and Intrahost SARS-CoV-2 diversity in immunocompetent and immunocompromised patients

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The recent emergence of SARS-CoV-2 variants with potentially increased transmissibility (i.e., the United Kingdom (UK) variant VOC202012/01 and the South African variant 501.V2) clearly emphasize the importance of tracking the emergence of variants and their spread. The fact that VOC202012/01 might have acquired an unusually high number of mutations within a short period of time has led to the speculation that this variant may have rapidly evolved in patients suffering from a prolonged infection, e.g. immunosuppressed patients under antiviral therapy. However, the dynamics with which novel variants evolve or emerge during infection and transmission events are understudied. In this proposal, we will address the emergence and origin of SARS-CoV-2 variants by systematic and comprehensive investigation of variant emergence and transmissibility across a substantial number of samples from local infection clusters, as well as evaluation of intra-host genomic diversity in longitudinal samples from hospitalized patients suffering from long-term (40-140 days) SARS-CoV-2 infection. In addition to patient sample collections that are available via the University Medical Center Hamburg Eppendorf (UKE), this work will take advantage of a SARS-CoV-2 genome surveillance platform that, in close collaboration with local health authorities, has already been established by UKE and the Heinrich Pette Institute (HPI). The platform has so far produced more than 1,400 full-length SARS-CoV-2 sequences from the general population in Hamburg and will produce an additional ~4,500 sequences until June 2021. We expect that our data will strongly contribute to our current understanding of variant emergence and the threats that may be posed by complex variants such as VOC202012/01 and 501.V2. Only after identification of the precise mechanisms and patient populations that promote the evolution of potential variants of concern will we be able to mitigate their emergence and spread, e.g. by means of hygiene management and/or optimized patient treatment regimen.