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

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.