Diagnostic Utility of SARS-CoV-2 Nucleocapsid Antigenemia: A Meta-analysis

Background: Studies of the diagnostic performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid antigen in blood (antigenemia) have reached variable conclusions. The potential utility of antigenemia measurements as a clinical diagnostic test needs clarification.

Methods: We performed a systematic review of Pubmed, Embase, and Scopus through July 15, 2023, and requested source data from corresponding authors.

Results: Summary sensitivity from 16 studies (4543 cases) sampled at ≤14 days of symptoms was 0.83 (0.75-0.89), and specificity was 0.98 (0.87-1.00) from 6 studies (792 reverse transcription polymerase chain reaction-negative controls). Summary sensitivity and specificity for paired respiratory specimens with cycle threshold values ≤33 were 0.91 (0.85-0.95) and 0.56 (0.39-0.73) from 10 studies (612 individuals). Source data from 1779 cases reveal that >70% have antigenemia 2 weeks following symptom onset, which persists in <10% at 28 days. The available studies suffer from heterogeneity, and Omicron-era data are scarce.

Conclusions: Nucleocapsid antigenemia currently has limited utility due to limitations of existing studies and lack of Omicron-era data. Improved study designs targeting potential clinical uses in screening, surveillance, and complex clinical decision-making-especially in immunocompromised patients-are needed.