Evaluation of Severe Acute Respiratory Syndrome Coronavirus 2 Nucleocapsid Antigen in the Blood as a Diagnostic Test for Infection and Infectious Viral Shedding

Sujata Mathur; Michelle C Davidson; Khamal Anglin; Scott Lu; Sarah A Goldberg; Miguel Garcia-Knight; Michel Tassetto; Amethyst Zhang; Mariela Romero; Jesus Pineda-Ramirez; Ruth Diaz-Sanchez; Paulina Rugart; Jessica Y Chen; Kevin Donohue; Joshua R Shak; Ahmed Chenna; John W Winslow; Christos J Petropoulos; Brandon C Yee; Jeremy Lambert; David V Glidden; George W Rutherford; Steven G Deeks; Michael J Peluso; Raul Andino; Jeffrey N Martin; J Daniel Kelly

doi:10.1093/ofid/ofac563

Evaluation of Severe Acute Respiratory Syndrome Coronavirus 2 Nucleocapsid Antigen in the Blood as a Diagnostic Test for Infection and Infectious Viral Shedding

Open Forum Infect Dis. 2022 Oct 22;9(11):ofac563. doi: 10.1093/ofid/ofac563. eCollection 2022 Nov.

Authors

Sujata Mathur^{1

2

3}, Michelle C Davidson^{3

4}, Khamal Anglin^{2

3}, Scott Lu^{1

2

3}, Sarah A Goldberg^{1

2

3}, Miguel Garcia-Knight⁵, Michel Tassetto⁵, Amethyst Zhang⁵, Mariela Romero^{2

3}, Jesus Pineda-Ramirez^{2

3}, Ruth Diaz-Sanchez^{2

3}, Paulina Rugart^{2

3}, Jessica Y Chen^{2

3}, Kevin Donohue⁴, Joshua R Shak⁶, Ahmed Chenna⁷, John W Winslow⁷, Christos J Petropoulos⁷, Brandon C Yee⁷, Jeremy Lambert⁸, David V Glidden¹, George W Rutherford^{1

2}, Steven G Deeks⁹, Michael J Peluso⁹, Raul Andino⁵, Jeffrey N Martin¹, J Daniel Kelly^{1

2

3

6}

Affiliations

¹ Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.
² Institute for Global Health Sciences, University of California, San Francisco, California, USA.
³ Francis I. Proctor Foundation, University of California, San Francisco, California, USA.
⁴ School of Medicine, University of California, San Francisco, California, USA.
⁵ Department of Microbiology and Immunology, University of California, San Francisco, California, USA.
⁶ San Francisco Veterans Affairs Medical Center, San Francisco, California, USA.
⁷ Labcorp-Monogram Biosciences, South San Francisco, California, USA.
⁸ Quanterix Laboratories, Billerica, Massachusetts, USA.
⁹ Division of HIV, Infectious Disease, and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA.

Abstract

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.

Keywords: blood; infectiousness; infectivity; nucleocapsid antigen; performance.

Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.

Abstract

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