- 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
Background
SARS-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.Methods
We 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.Results
Of 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.Conclusions
We 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.