Yang et al. validate two novel biosensors for detecting early antibody response to SARS-CoV-2 infection and better predicting COVID-19 patient outcomes. Researchers developed two fast, automated, and highly sensitive biosensor assays for detecting SARS-CoV-2 antibodies in the first week after symptom onset. The first testing-on-a-probe (TOP) assay quantifies overall binding between the total SARS-CoV-2 antibodies (TAb) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, whereas the second detects the surrogate neutralizing antibodies (SNAb) that inhibit RBD attachment to angiotensin converting enzyme 2 (ACE2). The performance of TOP-TAb and TOP-SNAb was compared to the FDA-approved Roche Elecsys Anti-SARS-CoV-2 assay. In a 116 serum sample study, TOP-TAb was significantly more sensitive than the Roche assay, while TOP-SNAb was more sensitive than the Roche assay but the difference was not statistically significant. In another 120 patient study of day 0 serum samples, a higher percentage of patients that survived SARS-CoV-2 tested positive for TAb (63.6%) and SNAb (61.2%) than patients that died (34.4% for TAb and 24.1% for SNAb).