Commercial Serology Assays Predict Neutralization Activity Against SARS-CoV-2

Suhandynata, Raymond T; Hoffman, Melissa A; Huang, Deli; Tran, Jenny T; Kelner, Michael J; Reed, Sharon L; McLawhon, Ronald W; Voss, James E; Nemazee, David; Fitzgerald, Robert L

BACKGROUND: It is unknown whether a positive serology result correlates with protective immunity against SARS-CoV-2. There are also concerns regarding the low positive predictive value of SARS-CoV-2 serology tests, especially when testing populations with low disease prevalence. METHODS: A neutralization assay was validated in a set of PCR confirmed positive specimens and in a negative cohort. In addition, 9,530 specimens were screened using the Diazyme SARS-CoV-2 IgG serology assay and all positive results (N = 164 individuals) were reanalyzed using the neutralization assay, the Roche total immunoglobin assay, and the Abbott IgG assay. The relationship between the magnitude of a positive SARS-CoV-2 serology result and neutralizing activity was determined. Neutralizing antibody titers (ID50) were also longitudinally monitored in SARS-CoV-2 PCR confirmed patients. RESULTS: The SARS-CoV-2 neutralization assay had a positive percent agreement (PPA) of 96.6% with a SARS-CoV-2 PCR test and a negative percent agreement (NPA) of 98.0% across 100 negative control individuals. ID50 neutralization titers positively correlated with all three clinical serology platforms. Longitudinal monitoring of hospitalized PCR confirmed COVID-19 patients demonstrated they made high neutralization titers against SARS-CoV-2. PPA between the Diazyme IgG assay alone and the neutralization assay was 50.6%, while combining the Diazyme IgG assay with either the Roche or Abbott platforms increased the PPA to 79.2% and 78.4%, respectively. CONCLUSIONS: These three clinical serology assays positively correlate with SARS-CoV-2 neutralization activity observed in COVID-19 patients. All SARS-CoV-2 PCR positive patients develop neutralizing antibodies.