A cell-based assay to measure immune competence in SARS-CoV-2 infection and vaccination

De Serres, Sacha | $246,164

Quebec Université Laval 2021 CIHR Operating Grant

One of most challenging aspects of COVID‑19 is the heterogeneity in the disease severity. While most patients will suffer from a relatively mild flu-like episode, a minority will experience a life-threatening or long-term disease. Being able to better understand why and who will have serious versus mild COVID‑19 would improve the prediction of risk associated with COVID, the public health planning and the clinical care of the patients. A clinical tool that measures immune competence could achieve this goal. Over the last years we developed an assay based on live peripheral blood cells (monocytes and B cells) to help predict who, among transplant recipients, are more likely to suffer from severe infections. To measure the ability of the immune system to respond to a foreign aggression, we cultured these cells with peptides of the Epstein-Barr virus and assessed their response by flow cytometry. This sequential, two-step assay was developed based on extensive preliminary studies in cohorts of kidney recipients. We have completed and reported a first round of validation of the assay and we are currently performing a second, multicenter international, validation. Combined, the two steps of the assay seem to predict the risk of infection with a high predictive value in immunosuppressed patients. Here we want to assess the capacity of this assay to predict disease severity of COVID‑19 in the general population. Because severe COVID is an inflammatory condition that occurs in patients who fail to clear the virus early, there is a strong rationale to believe that the ‘immuno-meter’ that we developed will be informative with this regard. We also want to investigate whether the result of the assay can predict how well immunosuppressed patients respond to SARS-CoV-2 vaccination. On the long run, the assay could prove to be useful not only in the transplant setting or in the COVID‑19 setting, but also in the prediction of the response to other infections and other vaccines.

With funding from the Government of Canada

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