Monitoring the emergence and origin of SARS-CoV-2 mutations – Genetic Inter- and Intrahost SARS-CoV-2 diversity in immunocompetent and immunocompromised patients
Final Report Abstract
Within the DFG-funded project, we investigated the extent to which antiviral treatments such as remdesivir have an impact on genomic diversity within the host and the emergence of SARS-CoV2 variants in patients with prolonged infection. This question has arisen at a time in the pandemic when new variants such as Alpha variants, and later Delta variants have altered the pandemic dynamics. In this regard, more case studies have been published reporting evolution of SARS-CoV-2 variants in immunocompromised patients. Increasingly, there has also been discussion as to whether such patients have been and are contributing significantly to the emergence of such variants. Within this application, we performed sequencing and variant analysis of longitudinal samples, totaling 112 respiratory samples from 14 SARS-CoV2-infected patients with severe disease progression. We demonstrated that variants with higher frequency generally do not occur during protracted infection. However, during the implementation of the project we found that remdesivir treatment can increase genomic diversity within the host and lead to the emergence of new major variants that contain fixed mutations. This was particularly evident in a patient with B-cell depletion, who rapidly developed mutations in the gene encoding RNA-dependent RNA polymerase after remdesivir treatment. The emergence of new variants associated with remdesivir treatment is of great interest with respect to treatment guidelines for hospitalized patients with severe SARS-CoV2 disease, as well as remdesivir for preventive treatment of non-hospitalized patients at high risk for severe progression of the disease.
Publications
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Remdesivir-induced emergence of SARS-CoV2 variants in patients with prolonged infection. Cell Reports Medicine, 3(9), 100735.
Heyer, Andreas; Günther, Thomas; Robitaille, Alexis; Lütgehetmann, Marc; Addo, Marylyn M.; Jarczak, Dominik; Kluge, Stefan; Aepfelbacher, Martin; Schulze, zur Wiesch Julian; Fischer, Nicole & Grundhoff, Adam
