Sars-Cov-2 antigen tests predict infectivity based on viral culture: comparison of antigen, PCR viral load, and viral culture testing on a large sample cohort

OBJECTIVE: To define the relationship of SARS-CoV-2 antigen, viral load determined by RT-qPCR, and viral culture detection. Presumptively, viral culture can provide a surrogate measure for infectivity of sampled individuals and thereby inform how and where to most appropriately deploy antigen and nucleic acid amplification-based diagnostic testing modalities. METHODS: We compared the antigen testing results from three lateral flow and one microfluidics assay to viral culture detection and viral load determination performed in parallel in up to 189 nasopharyngeal swab samples positive for SARS-CoV-2. Sample viral loads, determined by RT-qPCR, were distributed across the range of viral load values observed in our testing population. RESULTS: Antigen tests were predictive of viral culture positivity, with the LumiraDx microfluidics method showing enhanced sensitivity (90%; 95% CI 83–94%) compared with the BD Veritor (74%, 95% CI 65–81%), CareStart (74%, 95% CI 65–81%) and Oscar Corona (74%, 95% CI 65–82%) lateral flow antigen tests. Antigen and viral culture positivity were also highly correlated with sample viral load, with areas under the receiver operator characteristic curves of 0.94 to 0.97 and 0.92, respectively. A viral load threshold of 100 000 copies/mL was 95% sensitive (95% CI, 90–98%) and 72% specific (95% CI, 60–81%) for predicting viral culture positivity. Adjusting for sample dilution inherent in our study design, sensitivities of antigen tests were ≥95% for detection of viral culture positive samples with viral loads >10(6) genome copies/mL, although specificity of antigen testing was imperfect. DISCUSSION: Antigen testing results and viral culture were correlated. For culture positive samples, the sensitivity of antigen tests was high at high viral loads that are likely associated with significant infectivity. Therefore, our data provides support for use of antigen testing in ruling out infectivity at the time of sampling.