학술논문
Evaluation of Severe Acute Respiratory Syndrome Coronavirus 2 Nucleocapsid Antigen in the Blood as a Diagnostic Test for Infection and Infectious Viral Shedding
Document Type
article
Author
Mathur, Sujata; Davidson, Michelle C; Anglin, Khamal; Lu, Scott; Goldberg, Sarah A; Garcia-Knight, Miguel; Tassetto, Michel; Zhang, Amethyst; Romero, Mariela; Pineda-Ramirez, Jesus; Diaz-Sanchez, Ruth; Rugart, Paulina; Chen, Jessica Y; Donohue, Kevin; Shak, Joshua R; Chenna, Ahmed; Winslow, John W; Petropoulos, Christos J; Yee, Brandon C; Lambert, Jeremy; Glidden, David V; Rutherford, George W; Deeks, Steven G; Peluso, Michael J; Andino, Raul; Martin, Jeffrey N; Kelly, J Daniel
Source
Open Forum Infectious Diseases. 9(11)
Subject
Language
Abstract
BackgroundSARS-CoV-2 nucleocapsid antigen can be detected in plasma, but little is known about its performance as a diagnostic test for acute SARS-CoV-2 infection or infectious viral shedding among nonhospitalized individuals.MethodsWe used data generated from anterior nasal and blood samples collected in a longitudinal household cohort of SARS-CoV-2 cases and contacts. Participants were classified as true positives if polymerase chain reaction (PCR) positive for SARS-CoV-2 and as true negatives if PCR negative and seronegative. Infectious viral shedding was determined by the cytopathic effect from viral culture. Stratified by 7 days after symptom onset, we constructed receiver operating characteristic (ROC) curves to describe optimized accuracy (Youden index), optimized sensitivity, and specificity.ResultsOf 80 participants, 58 (73%) were true positives while 22 (27%) were true negatives. Using the manufacturer's cutoff of 1.25 pg/mL for evaluating infection, sensitivity was higher from 0 to 7 days (77.6% [95% confidence interval {CI}, 64%-88.2%]) than from 8 to 14 days (43.2% [95% CI, 31.1%-54.5%]) after symptom onset; specificity was unchanged at 100% (95% CI, 88.1%-100%). This test had higher sensitivity (100% [95% CI, 88.4%-100%]) and lower specificity (65% [95% CI, 40.8%-84.6%]) for infectious viral shedding as compared with infection, particularly within the first week of symptom onset. Although the presence of N-antigen correlated with infectious viral shedding (r = 0.63; P < .01), sensitivity still declined over time. Additional cutoffs from ROC curves were identified to optimize sensitivity and specificity.ConclusionsWe found that this SARS-CoV-2 N-antigen test was highly sensitive for detecting early but not late infectious viral shedding, making it a viable screening test for community-dwelling individuals to inform isolation practices.