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Comparison of Home Antigen Testing With RT-PCR and Viral Culture During the Course of SARS-CoV-2 Infection

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Key Points

Question  How does the diagnostic performance of home antigen tests change during the course of SARS-CoV-2 infection?

Findings  In this prospective cohort study of 225 adults and children with reverse transcription–polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2 infection, antigen test sensitivity was 64% and 84% when compared with same-day RT-PCR and viral culture, respectively. Antigen test sensitivity peaked 4 days after illness onset (77%); a second test 1 to 2 days later showed improved sensitivity (81%-85%).

Meaning  The study results suggest that symptomatic individuals with an initial negative home antigen test result for SARS-CoV-2 infection should test again 1 to 2 days later because test sensitivity seems to peak several days after illness onset.

Abstract

Importance  As self-collected home antigen tests become widely available, a better understanding of their performance during the course of SARS-CoV-2 infection is needed.

Objective  To evaluate the diagnostic performance of home antigen tests compared with reverse transcription–polymerase chain reaction (RT-PCR) and viral culture by days from illness onset, as well as user acceptability.

Design, Setting, and Participants  This prospective cohort study was conducted from January to May 2021 in San Diego County, California, and metropolitan Denver, Colorado. The convenience sample included adults and children with RT-PCR–confirmed infection who used self-collected home antigen tests for 15 days and underwent at least 1 nasopharyngeal swab for RT-PCR, viral culture, and sequencing.

Exposures  SARS-CoV-2 infection.

Main Outcomes and Measures  The primary outcome was the daily sensitivity of home antigen tests to detect RT-PCR–confirmed cases. Secondary outcomes included the daily percentage of antigen test, RT-PCR, and viral culture results that were positive, and antigen test sensitivity compared with same-day RT-PCR and cultures. Antigen test use errors and acceptability were assessed for a subset of participants.

Results  This study enrolled 225 persons with RT-PCR–confirmed infection (median [range] age, 29 [1-83] years; 117 female participants [52%]; 10 [4%] Asian, 6 [3%] Black or African American, 50 [22%] Hispanic or Latino, 3 [1%] Native Hawaiian or Other Pacific Islander, 145 [64%] White, and 11 [5%] multiracial individuals) who completed 3044 antigen tests and 642 nasopharyngeal swabs. Antigen test sensitivity was 50% (95% CI, 45%-55%) during the infectious period, 64% (95% CI, 56%-70%) compared with same-day RT-PCR, and 84% (95% CI, 75%-90%) compared with same-day cultures. Antigen test sensitivity peaked 4 days after illness onset at 77% (95% CI, 69%-83%). Antigen test sensitivity improved with a second antigen test 1 to 2 days later, particularly early in the infection. Six days after illness onset, antigen test result positivity was 61% (95% CI, 53%-68%). Almost all (216 [96%]) surveyed individuals reported that they would be more likely to get tested for SARS-CoV-2 infection if home antigen tests were available over the counter.

Conclusions and Relevance  The results of this cohort study of home antigen tests suggest that sensitivity for SARS-CoV-2 was moderate compared with RT-PCR and high compared with viral culture. The results also suggest that symptomatic individuals with an initial negative home antigen test result for SARS-CoV-2 infection should test again 1 to 2 days later because test sensitivity peaked several days after illness onset and improved with repeated testing.

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Article Information

Accepted for Publication: April 5, 2022.

Published Online: April 29, 2022. doi:10.1001/jamainternmed.2022.1827

Corresponding Author: Noah G. Schwartz, MD, US Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop US12-4, Atlanta, GA 30329 (nschwartz@cdc.gov).

Author Contributions: Drs Chu and Schwartz had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Chu, Schwartz, and Matanock contributed equally to this work as lead authors.

Concept and design: Chu, Schwartz, Donnelly, Chuey, Yousaf, Ruffin, Thornburg, Hughes, Stringer, Albanese, Sheldon, Beatty, Killerby, Hsu, Tate, Kirking, Matanock.

Acquisition, analysis, or interpretation of data: Chu, Schwartz, Donnelly, Chuey, Soto, Yousaf, Schmitt-Matzen, Sleweon, Thornburg, Harcourt, Tamin, Kim, Folster, Hughes, Tong, Stringer, Totten, Hudziec, Matzinger, Dietrich, Sheldon, Stous, McDonald, Austin, Beatty, Staples, Killerby, Hsu, Tate, Kirking, Matanock, Tamin, Totten.

Drafting of the manuscript: Chu, Schwartz, Schmitt-Matzen, Matzinger, Sheldon, McDonald, Austin, Beatty, Matanock.

Critical revision of the manuscript for important intellectual content: Chu, Schwartz, Donnelly, Chuey, Soto, Yousaf, Sleweon, Ruffin, Thornburg, Harcourt, Tamin, Kim, Folster, Hughes, Tong, Stringer, Albanese, Totten, Hudziec, Dietrich, Sheldon, Stous, McDonald, Austin, Beatty, Staples, Killerby, Hsu, Tate, Kirking, Matanock.

Statistical analysis: Chu, Schwartz, Sleweon.

Obtained funding: Kirking.

Administrative, technical, or material support: Chu, Donnelly, Chuey, Schmitt-Matzen, Thornburg, Harcourt, Kim, Folster, Hughes, Stringer, Matzinger, Sheldon, Stous, McDonald, Austin, Beatty, Staples, Killerby, Kirking, Matanock.

Supervision: Thornburg, Hughes, Tong, Stringer, Sheldon, Beatty, Hsu, Tate, Kirking, Matanock, Sleweon.

Other: Ruffin.

Conflict of Interest Disclosures: Dr Stringer reported grants from the US Centers for Disease Control and Prevention (CDC) Epidemiology and Laboratory Capacity for Prevention and Control of Emerging Infectious Diseases during the conduct of the study. No other disclosures were reported.

Funding/Support: This investigation was funded by the CDC. The investigation was supported by the County of San Diego Health and Human Services Agency, California Department of Public Health, Colorado Department of Public Health and Environment, and Tri-County Health Department.

Role of the Funder/Sponsor: Investigators from the CDC, County of San Diego Health and Human Services Agency, California Department of Public Health, Colorado Department of Public Health and Environment, and Tri-County Health Department were involved in all aspects of the study, including the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: A full list of COVID-19 Household Transmission Team contributors is available in Supplement 2.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC, County of San Diego Health and Human Services Agency, California Department of Public Health, Colorado Department of Public Health and Environment, or Tri-County Health Department.

Additional Contributions: We thank the investigation participants and state and local health department and laboratory staff.

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