SARS-CoV-2 variants under investigation (VUIs) and variants of concern (VOCs); phenotyping gaps in transmission, reinfection and response to medical countermeasures

Mubareka, Samira | $499,276

Ontario Sunnybrook Research Institute 2021 CIHR Operating Grant

Over the course of this pandemic, we have been monitoring how the SARS-CoV-2 virus has been changing using whole genome sequencing. We now know that many Canadians are infected with variants of concern (VOCs). These are viruses bearing mutations which change how the virus causes disease, transmits or responds to antivirals and vaccines. We have also identified several viruses that harbour suspicious mutations that require further investigation (variants under investigation or VUIs) to determine whether they are VOCs or not. Our group has sequenced over two thousand SARS-CoV-2 viruses from patients, and made these data publicly available to enable others to address a broad range of research gaps. Many of these data are used for general surveillance, but segments of the population do not benefit equally from these technological advances. In March of 2020 we isolated the SARS-CoV-2 virus in a high containment laboratory, and since then we have cultured hundreds of viruses including VOCs and VUIs. We have also established experimental models for SARS-CoV infection and transmission to answer critical questions as they relate to viral disease and spread. We have already done this with a variant called D614G which established itself in Canada early in the pandemic. We propose to use both our virobank and the models we have established to characterize emerging VOCs and VUIs to identify viral determinants of transmission, reinfection and disease, including at risk populations with a focus on the corrections system. Our group moves seamlessly from bedside to bench and back, translating research starting with patient material to generate viral genomes and isolates which we then study in cell and animal models in high containment. This work stands to impact patient care and public health; the pandemic is sustained through person-to-person transmission, and as vaccines and therapeutics are put into broad use, we need to ensure that these interventions remain effective.

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