Limitations of molecular and antigen test performance for SARS-CoV-2 in symptomatic and asymptomatic COVID-19 contacts [preprint]

UMMS Affiliation

Department of Medicine, Division of Cardiovascular Medicine; Division of Infectious Diseases and Immunology, Department of Medicine

Publication Date


Document Type

Article Preprint


Diagnosis | Health Services Administration | Immunology and Infectious Disease | Infectious Disease | Microbiology | Virus Diseases


Objectives: COVID-19 has brought unprecedented attention to the crucial role of diagnostics in pandemic control. We compared SARS-CoV-2 test performance by sample type and modality in close contacts of SARS-CoV-2 cases.

Methods: Close contacts of SARS-CoV-2 positive individuals were enrolled after informed consent. Clinician-collected nasopharyngeal (NP) swabs in viral transport media (VTM) were tested with a nucleic acid test (NAT). NP VTM and self-collected passive drool were tested using the PerkinElmer real-time reverse transcription PCR (RT-PCR) assay. For the first 4 months of study, mid-turbinate swabs were tested using the BD Veritor rapid antigen test. NAT positive NP samples were tested for infectivity using a VeroE6TMPRSS2 cell culture model.

Results: Between November 17, 2020, and October 1, 2021, 235 close contacts of SARS-CoV-2 cases were recruited, including 95 with symptoms (82% symptomatic for < 5 days) and 140 asymptomatic individuals. NP swab reference tests were positive for 53 (22.6%) participants; 24/50 (48%) were culture positive. PerkinElmer testing of NP and saliva samples identified an additional 28 (11.9%) SARS-CoV-2 cases who tested negative by clinical NAT. Antigen tests performed for 99 close contacts showed 83% positive percent agreement (PPA) with reference NAT among early symptomatic persons, but 18% PPA in others; antigen tests in 8 of 11 (72.7%) culture-positive participants were positive.

Conclusions: Contacts of SARS-CoV-2 cases may be falsely negative early after contact, which more sensitive platforms may identify. Repeat or serial SARS-CoV-2 testing with both antigen and molecular assays may be warranted for individuals with high pretest probability for infection.


COVID-19, SARS-CoV-2, testing, antigen assays, molecular assays

DOI of Published Version



Robinson ML, Mirza A, Gallagher N, Boudreau A, Garcia L, Yu T, Norton J, Luo CH, Conte A, Zhou R, Kafka K, Hardick J, McManus DD, Gibson LL, Pekosz A, Mostafa H, Manabe YC. Limitations of molecular and antigen test performance for SARS-CoV-2 in symptomatic and asymptomatic COVID-19 contacts. medRxiv [Preprint]. 2022 Feb 7:2022.02.05.22270481. doi: 10.1101/2022.02.05.22270481. PMID: 35169814; PMCID: PMC8845435.. Link to preprint on medRxiv.

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medRxiv : the preprint server for health sciences


This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.

Full author list omitted for brevity. For the full list of authors, see preprint.

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