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 ≥ 10 4 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.