Project Details
Projekt
Analysis of SARS-CoV-2 intra host evolution in immunocompromised individuals: A potential source of immune escape variants
Subject Area
Virology
Term
from 2021 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 466171387
In late 2020, a novel SARS-CoV-2 variant, VOC 202012/01, with increased transmissibility emerged in the UK. Its origin remains unclear but is possibly associated with intra-host virus evolution in persistently infected, immunocompromised hosts. A recent study showed that these events can result in virus variants that partially escape the antibody response. Therefore, intra-host evolution could result in SARS-CoV-2 variants which are better equipped to cope with the hosts’ immune system and give rise to new strains with increased pandemic potential.Since early 2020, the University Medical Centre, in Freiburg recruited a cohort of immunocompromised patients with a prolonged SARS-CoV-2 infection. In the scope of this project, we plan to perform next-generation sequencing on the already available patient material of this cohort. Our in-house sequencing and bioinformatic pipelines will allow us to evaluate the intra-host evolution of SARS-CoV-2. As our institute is fully equipped with the necessary BSL3 laboratories, we will further attempt to isolate infectious viruses from patient material and generate S-pseudotyped virus-like particles. This will allow us to analyse the viral fitness in cell culture as well as in mice transgenic for the human ACE2 receptor. To assess the immune escape properties of the observed variants, we will test for neutralization by reconvalescent patient sera and perform deep profiling of CD8+ T-cell responses. All proposed methods and infrastructural constraints to perform this study are already established. Monitoring viral evolution during long-term persistence in such extremely vulnerable cohorts is vital for optimized medical care as well as the early detection of emerging variants of concern. This study will give vital insights into SARS-CoV-2 evolution and provide further knowledge about the ability of this pandemic virus to escape the hosts’ immune system.
DFG Programme
Research Grants
Co-Investigator
Dr. Jonas Fuchs
