Epidemiologic Characteristics Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antigen-Based Test Results, Real-Time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) Cycle Threshold Values, Subgenomic RNA, and Viral Culture Results From University Testing
Authors: Ford Laura , Lee Christine , Pray Ian W , Cole Devlin , Bigouette John Paul , Abedi Glen R , Bushman Dena , Delahoy Miranda J , Currie Dustin W , Cherney Blake , Kirby Marie K , Fajardo Geroncio C , Caudill Motria , Langolf Kimberly , Kahrs Juliana , Zochert Tara , Kelly Patrick , Pitts Collin , Lim Ailam , Aulik Nicole , Tamin Azaibi , Harcourt Jennifer L , Queen Krista , Zhang Jing , Whitaker Brett , Browne Hannah , Medrzycki Magdalena , Shewmaker Patricia L , Bonenfant Gaston , Zhou Bin , Folster Jennifer M , Bankamp Bettina , Bowen Michael D , Thornburg Natalie J , Goffard Kimberly , Limbago Brandi , Bateman Allen , Tate Jacqueline E , Gieryn Douglas , Kirking Hannah L , Westergaard Ryan P , Killerby Marie E ,   CDC COVID-19 Surge Laboratory Group, Jiang Baoming , Vinjé Jan , Hopkins Amy L , Katz Eric , Nguyen Kenny , Barclay Leslie , Esona Mathew , Gautam Rashi , Mijatovic-Rustempasic Slavica , Moon Sung-Sil , Bessey Theresa , Chhabra Preeti , Smart Sarah L , Anderson Raydel , Radford Kay W , Kim Gimin , Thompson Dexter , Miao Congrong , Chen Min-hsin , Gade Lalitha , Galloway Renee , Hartloge Claire , Jenkins Brent , Sahibzada Kashif , Wynn Nhien T , Velusamy Srinivasan , Wong Phili , Zheng HaoQiang 
Published: April 2021

Abstract

Background
Real-time reverse transcription polymerase chain reaction (rRT-PCR) and antigen tests are important diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sensitivity of antigen tests has been shown to be lower than that of rRT-PCR; however, data to evaluate epidemiologic characteristics that affect test performance are limited.

Methods
Paired mid-turbinate nasal swabs were collected from university students and staff and tested for SARS-CoV-2 using both Quidel Sofia SARS Antigen Fluorescent Immunoassay (FIA) and rRT-PCR assay. Specimens positive by either rRT-PCR or antigen FIA were placed in viral culture and tested for subgenomic RNA (sgRNA). Logistic regression models were used to evaluate characteristics associated with antigen results, rRT-PCR cycle threshold (Ct) values, sgRNA, and viral culture.

Results
Antigen FIA sensitivity was 78.9% and 43.8% among symptomatic and asymptomatic participants, respectively. Among rRT-PCR positive participants, negative antigen results were more likely among asymptomatic participants (odds ratio [OR] 4.6, 95% confidence interval [CI]: 1.3–15.4) and less likely among participants reporting nasal congestion (OR 0.1, 95% CI: .03–.8). rRT-PCR-positive specimens with higher Ct values (OR 0.5, 95% CI: .4–.8) were less likely, and specimens positive for sgRNA (OR 10.2, 95% CI: 1.6–65.0) more likely, to yield positive virus isolation. Antigen testing was &gt;90% positive in specimens with Ct values &lt; 29. Positive predictive value of antigen test for positive viral culture (57.7%) was similar to that of rRT-PCR (59.3%).

Conclusions
SARS-CoV-2 antigen test advantages include low cost, wide availability and rapid turnaround time, making them important screening tests. The performance of antigen tests may vary with patient characteristics, so performance characteristics should be accounted for when designing testing strategies and interpreting results.