Blood Test to Assess Immunity to SARS-CoV-2 and Detect Latent Viral Infections

Currently available immunological tests for SARS-CoV-2 assess only antibody responses, and no routine test is available to determine T cell immunity despite the growing evidence that T cells play a crucial role in protection, especially against emerging viral variants. The prognostic value of SARS-CoV-2-specific antibodies for determining whether individuals are immune and protected against disease remains uncertain. This is in part due to: (a) specificity and limitations such as sensitivity of antibody tests and (b) the lack of correlation between antibody titers (quantity) and antiviral function of antibodies (quality). Approximately a quarter of SARS-CoV-2-infected patients with symptoms show up negative in serological assays. The proposed project will result in a cell-based assay to detect previous exposure to, or latent infections with, SARS-CoV-2. The developed assay will be suitable for any clinical laboratory equipped with an ELISA plate reader. There will be the option to conduct the test on the ECLIA-based platform, which would increase the throughput of the assay further as no serial dilutions of the supernatants have to be evaluated and no replicates are required. The envisioned logistic of the assay follows the rationale of the only licensed cell-based diagnostics assay (Quantiferon Gold) for the detection of latent Mycobacterium tuberculosis infection. Together with the assay prototype protocol, a script for Excel and/or Softmax will be provided that will turn the data into actionable results. This will also be one of the first systematic studies assessing the prevalence of cellular responses against SARS-CoV-2 and seasonal CoVs using a high-throughput testing platform that establishes the cellular landscape of pan-CoV immunity. SARS-CoV-2 infection presents an imminent threat to the deployed Warfighter and challenges the ability of Commanders to calibrate Force requirements because of: (1) the direct impact of infection on the Force (i.e., immediate as well as longer-term disability and death among those infected); (2) the disproportionate consumption of medical resources (materiel and personnel) and evacuation capability; and (3) the restriction of movement of high-risk, exposed members of the Force due to quarantine requirements. SARS-CoV-2 infection also has indirect sociopolitical and economic impacts associated with fear, consequent insecurity, and the use of misinformation campaigns by our adversaries. Deploying a simple blood test able to determine SARS-CoV-2-specific immunity and exposure history will provide Commanders with actionable data to ensure Warfighter readiness as well as be an invaluable tool to assess the prevalence of SARS-CoV-2 in civilian populations. Less