The RADxSM Tech Process: Accelerating Innovation for COVID-19 Testing.

In the wake of the COVID-19 pandemic, the need for rapid and accurate diagnostic testing across populations quickly became evident. In response, the National Institutes of Health (NIH) was determined not only to invest heavily in this area but to change the process by which grant proposals were reviewed and funded in order to spur faster development of viable technologies. The Rapid Acceleration of Diagnostics (RADx) initiative was designed to speed innovation, commercialization, and implementation of potential COVID-19 diagnostic technology. As part of this effort, the RADx Tech initiative focuses on the development, validation, and commercialization of innovative point-of-care, home-based, and clinical lab-based tests that can detect SARS-CoV-2. This effort was enabled through the NIH's National Institute of Biomedical Imaging and Bioengineering (NIBIB) Point-of-Care Technology Research Network (POCTRN).

A rapid, point-of-care red blood cell agglutination assay detecting antibodies against SARS-CoV-2.

The COVID-19 pandemic has caused significant morbidity and mortality. There is an urgent need for serological tests to detect antibodies against SARS-CoV-2, which could be used to assess past infection, evaluate responses to vaccines in development, and determine individuals who may be protected from future infection. Current serological tests developed for SARS-CoV-2 rely on traditional technologies such as enzyme-linked immunosorbent assays (ELISA) and lateral flow assays, which have not scaled to meet the demand of hundreds of millions of antibody tests so far. Herein, we present an alternative method of antibody testing that depends on one protein reagent being added to patient serum/plasma or whole blood with direct, visual readout. Two novel fusion proteins, RBD-2E8 and B6-CH1-RBD, were designed to bind red blood cells (RBCs) via a single-chain variable fragment (scFv), thereby displaying the receptor-binding domain (RBD) of SARS-CoV-2 spike protein on the surface of RBCs. Mixing mammalian-derived RBD-2E8 and B6-CH1-RBD with convalescent COVID-19 patient serum and RBCs led to visible hemagglutination, indicating the presence of antibodies against SARS-CoV-2 RBD. B6-CH1-RBD made in bacteria was not as effective in inducing agglutination, indicating better recognition of RBD epitopes from mammalian cells. Given that our hemagglutination test uses methods routinely used in hospital clinical labs across the world for blood typing, we anticipate the test can be rapidly deployed at minimal cost. We anticipate our hemagglutination assay may find extensive use in low-resource settings for detecting SARS-CoV-2 antibodies.