Assessment of Residual-Serum SARS-CoV-2-N-Antigen Testing for Hospital Surveillance in Germany

Abstract

Routine SARS-CoV-2 surveillance in hospitals is crucial for preventing in-hospital transmission, especially among elderly and multimorbid patients. While RT-PCR testing is sensitive, it is resource-intensive, and rapid antigen tests lack sensitivity. This study evaluates the diagnostic performance and utility of serum N-antigen ELISA for detecting active SARS-CoV-2 infection in hospitalized patients during the Omicron period. A prospective, non-interventional diagnostic accuracy study was conducted at a tertiary-care university hospital in Germany from 6 January to 8 February 2023. Residual serum samples were tested for N-antigen using a commercial ELISA and compared with RT-PCR results from respiratory swabs. Diagnostic latency, sensitivity, specificity, and predictive values were calculated at the sample and patient levels. Among 2030 inpatients (12,558 patient-days), 610 were screened by ELISA. Sensitivity and specificity were 60.6% and 99.9%, respectively, increasing to 89.6% and 99.9% for samples with >= 104 genome equivalents/mL. Early infection showed higher sensitivity (78.6%) compared to late infection (25.5%). In a paired same-cohort PCR-only scenario, the combined PCR plus available serum N-antigen workflow reduced unknown-risk time by 243 patient-days, corresponding to 1.94 fewer unknown-risk days per 100 cohort patient-days (95% bootstrap CI, 1.38-2.57). Residual-serum SARS-CoV-2 N-antigen testing offers high specificity and early-phase sensitivity, complementing PCR-based hospital surveillance without additional sampling. This approach may enhance the efficient detection of unsuspected infections in routine inpatient care.