tetano
Editor, Senior Moderator
Open Forum Infect Dis
. 2022 Oct 22;9(11)
fac563.
doi: 10.1093/ofid/ofac563. eCollection 2022 Nov.
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[SUP] 1 2 3 [/SUP], Michelle C Davidson[SUP] 3 4 [/SUP], Khamal Anglin[SUP] 2 3 [/SUP], Scott Lu[SUP] 1 2 3 [/SUP], Sarah A Goldberg[SUP] 1 2 3 [/SUP], Miguel Garcia-Knight[SUP] 5 [/SUP], Michel Tassetto[SUP] 5 [/SUP], Amethyst Zhang[SUP] 5 [/SUP], Mariela Romero[SUP] 2 3 [/SUP], Jesus Pineda-Ramirez[SUP] 2 3 [/SUP], Ruth Diaz-Sanchez[SUP] 2 3 [/SUP], Paulina Rugart[SUP] 2 3 [/SUP], Jessica Y Chen[SUP] 2 3 [/SUP], Kevin Donohue[SUP] 4 [/SUP], Joshua R Shak[SUP] 6 [/SUP], Ahmed Chenna[SUP] 7 [/SUP], John W Winslow[SUP] 7 [/SUP], Christos J Petropoulos[SUP] 7 [/SUP], Brandon C Yee[SUP] 7 [/SUP], Jeremy Lambert[SUP] 8 [/SUP], David V Glidden[SUP] 1 [/SUP], George W Rutherford[SUP] 1 2 [/SUP], Steven G Deeks[SUP] 9 [/SUP], Michael J Peluso[SUP] 9 [/SUP], Raul Andino[SUP] 5 [/SUP], Jeffrey N Martin[SUP] 1 [/SUP], J Daniel Kelly[SUP] 1 2 3 6 [/SUP]
Affiliations
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.
. 2022 Oct 22;9(11)
fac563.doi: 10.1093/ofid/ofac563. eCollection 2022 Nov.
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[SUP] 1 2 3 [/SUP], Michelle C Davidson[SUP] 3 4 [/SUP], Khamal Anglin[SUP] 2 3 [/SUP], Scott Lu[SUP] 1 2 3 [/SUP], Sarah A Goldberg[SUP] 1 2 3 [/SUP], Miguel Garcia-Knight[SUP] 5 [/SUP], Michel Tassetto[SUP] 5 [/SUP], Amethyst Zhang[SUP] 5 [/SUP], Mariela Romero[SUP] 2 3 [/SUP], Jesus Pineda-Ramirez[SUP] 2 3 [/SUP], Ruth Diaz-Sanchez[SUP] 2 3 [/SUP], Paulina Rugart[SUP] 2 3 [/SUP], Jessica Y Chen[SUP] 2 3 [/SUP], Kevin Donohue[SUP] 4 [/SUP], Joshua R Shak[SUP] 6 [/SUP], Ahmed Chenna[SUP] 7 [/SUP], John W Winslow[SUP] 7 [/SUP], Christos J Petropoulos[SUP] 7 [/SUP], Brandon C Yee[SUP] 7 [/SUP], Jeremy Lambert[SUP] 8 [/SUP], David V Glidden[SUP] 1 [/SUP], George W Rutherford[SUP] 1 2 [/SUP], Steven G Deeks[SUP] 9 [/SUP], Michael J Peluso[SUP] 9 [/SUP], Raul Andino[SUP] 5 [/SUP], Jeffrey N Martin[SUP] 1 [/SUP], J Daniel Kelly[SUP] 1 2 3 6 [/SUP]
Affiliations
- PMID: 36381627
- PMCID: PMC9620332
- DOI: 10.1093/ofid/ofac563
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.