Performance of Blood-Based Nucleocapsid Antigen Tests for Diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Infectious Viral Shedding: A Systematic Review

Abstract

Data on the performance of blood-based nucleocapsid antigen tests for diagnosing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and infectious viral shedding are limited. To address this knowledge gap, we conducted a systematic review to assess the performance of blood-based nucleocapsid (N) antigen tests in diagnosing SARS-CoV-2 infection and identifying infectiousness. This review was registered on PROSPERO (registration no. CRD42022339635). We comprehensively searched PubMed, Embase, Web of Science, and the Coronavirus Research Database for relevant studies published through 27 February 2023. Each study's risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Our findings indicate that the performance of the N-antigen test is influenced by factors such as assay type, sampling timing, and illness severity. Sensitive assays provide suitable methods for viable screening and laboratory diagnostic tests in different clinical and research settings during the early phase of illness.

Keywords: SARS-CoV-2; blood; nucleocapsid antigen; sensitivity and specificity; systematic review.

Figure 1.

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram detailing the number of screened and included abstracts and articles, In total, 16 studies met inclusion criteria and were included in the analysis. Abbreviation: NP, nasopharyngeal.

Figure 2.

QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) criteria for the 16 studies included in this systematic review [15–30]. Orange = High, Blue = Unclear, Green = Low.