Last Updated on 03/06/2021 @ 1:34 PM EST
- Clinical Guidance
- NIH Recommendations for Testing for SARS-CoV-2 Infection
- SARS-CoV-2 Testing for Public Health Use: Core Principles and Considerations for Defined Use Settings
- CDC Guidance for SARS-CoV-2 Point-of-Care Testing
- CDC Interim Guidance for Antigen Testing for SARS-CoV-2
Antigen tests (also known as rapid tests) are diagnostic tests and not screening tests for patients with signs or symptoms consistent with COVID-19. Antigen tests are not as sensitive as nucleic acid amplification (including PCR) tests, there is a higher chance of false negatives, thus negative results do not rule out infection and may need to be confirmed with a nucleic acid amplification testing prior to making treatment or isolation decisions (see CDC Testing Basics).
CDC Interim Guidelines for COVID-19 Antibody Testing
Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens for COVID-19
FDA FAQs on Testing for SARS-CoV-2
NEJM Video: How to Obtain a Nasopharyngeal Swab Specimen (Diagram)
Interpreting Diagnostic Tests for SARS-CoV-2
COVID-19 Testing: One Size Does Not Fit All
Nucleic Acid Amplification Testing
- Diagnostics for SARS-CoV-2 Infections (Feb 2021)
Cycle (Ct) Thresholds
- Woloshin S, et al. False Negative Tests for SARS-CoV-2 Infection — Challenges and Implications. N Engl J Med. Aug 2020.
- Wikramaratna PS, et al. Estimating False-negative Detection Rate of SARS-CoV-2 by RT-PCR. Euro Surveill. Dec 2020.
Testing throat and nasal swabs by RT-PCR is not guaranteed to yield a positive result for SARS-CoV-2 infection and this probability decreases with time since the onset of symptoms. In a single test of someone who first developed symptoms ten days ago, there’s a 33% chance of a false negative with a nasopharyngeal swab and 53% chance of a false negative with an oropharyngeal swab.
- Higgins TS, et al. SARS-CoV-2 Nasopharyngeal Swab Testing—False-Negative Results From a Pervasive Anatomical Misconception. JAMA Otolaryngol Head Neck Surg. Sep 2020.
- Sullivan CB, et al. Cerebrospinal Fluid Leak After Nasal Swab Testing for Coronavirus Disease 2019. JAMA Otolaryngol Head Neck Surg. Oct 2020.
- Collier DA, et al. Point of Care Nucleic Acid Testing for SARS-CoV-2 in Hospitalized Patients: A Clinical Validation Trial and Implementation Study. Cell Rep Med. Nov 2020.
- Gibani MM, et al. Assessing a Novel, Lab-Free, Point-of-Care Test for SARS-CoV-2 (CovidNudge): A Diagnostic Accuracy Study. Lancet Microbe. Nov 2020.
- Atherstone C, et al. Time from Start of Quarantine to SARS-CoV-2 Positive Test Among Quarantined College and University Athletes — 17 States, June–October 2020. MMWR Morb Mortal Wkly Rep. Jan 2021.
Specimen Type (NP Swab vs Saliva) and Collection
- Pekosz A, et al. Antigen-Based Testing but Not Real-Time Polymerase Chain Reaction Correlates With Severe Acute Respiratory Syndrome Coronavirus 2 Viral Culture . Clin Infect Dis. Jan 2021.
The correlation between SARS-CoV-2 antigen and SARS-CoV-2 culture positivity represents a significant advancement in determining the risk for potential transmissibility beyond that which can be achieved by detection of SARS-CoV-2 genomic RNA.
- Prince-Guerra JL, et al. Evaluation of Abbott BinaxNOW Rapid Antigen Test for SARS-CoV-2 Infection at Two Community-Based Testing Sites — Pima County, Arizona, November 3–17, 2020. MMWR Morb Mortal Wkly Rep. Jan 2021.
Sensitivity of the BinaxNOW antigen test, compared with polymerase chain reaction testing, was lower when used to test specimens from asymptomatic (35.8%) than from symptomatic (64.2%) persons, but specificity was high. Sensitivity was higher for culture-positive specimens (92.6% and 78.6% for those from symptomatic and asymptomatic persons, respectively); however, some antigen test-negative specimens had culturable virus.
- Pilarowski G, et al. Performance Characteristics of a Rapid SARS-CoV-2 Antigen Detection Assay at a Public Plaza Testing Site in San Francisco. J Infect Dis. Jan 2021.
- Schwob JM, et al. Antigen Rapid Tests, Nasopharyngeal PCR and Saliva PCR to Detect SARS-CoV-2: A Prospective Comparative Clinical Trial. Nov 2020. (Not Peer Reviewed)
The high performance of rapid diagnostic [antigen] tests allows rapid identification of COVID cases with immediate isolation of the vast majority of contagious individuals.
- Bastos ML, et al. The Sensitivity and Costs of Testing for SARS-CoV-2 Infection With Saliva Versus Nasopharyngeal Swabs. Ann Intern Med. Jan 2021.
“Thirty-seven studies with 7,332 paired samples were included. The sensitivity of saliva was 3.4 percentage points lower than that of nasopharyngeal swabs. Among persons with previously confirmed SARS-CoV-2 infection, saliva’s sensitivity was 1.5 percentage points higher than that of nasopharyngeal swabs. Among persons without a previous SARS-CoV-2 diagnosis, saliva was 7.9 percentage points less sensitive. In this subgroup, if testing 100,000 persons with a SARS-CoV-2 prevalence of 1%, nasopharyngeal swabs would detect 79 more persons with SARS-CoV-2 than saliva, but with an incremental cost per additional infection detected of $8,093.”
- Butler-Laporte G, et al. Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2: A Systematic Review and Meta-analysis. JAMA Intern Med. Jan 2021.
Both nasopharyngeal and saliva specimens had high sensitivity and specificity.
- Yokota I, et al. Mass Screening of Asymptomatic Persons for SARS-CoV-2 Using Saliva. Clin Infect Dis. Sep 2020.
- Babady NE, et al. Performance of SARS-CoV-2 Real-Time RT-PCR Tests on Oral Rinses and Saliva Samples. J Mol Diagn. Nov 2020.
- Wyllie AL, et al. Saliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2. N Engl J Med. Sep 2020.
- McCulloch DJ, et al. Comparison of Unsupervised Home Self-collected Midnasal Swabs With Clinician-Collected Nasopharyngeal Swabs for Detection of SARS-CoV-2 Infection. JAMA Netw Open. Jul 2020.
In this small study, researchers compared home-collected versus clinician-collected nasopharyngeal swabs for COVID-19 testing. The two methods were comparable.
- Ning B, et al. A Smartphone-Read Ultrasensitive and Quantitative Saliva Test for COVID-19. Sci Adv. Jan 2021.
The authors describe an ultrasensitive saliva-based COVID-19 assay with a 15-minute sample-to-answer time that does not require RNA isolation or laboratory equipment. This assay uses CRISPR-Cas12a activity to enhance a viral amplicon signal, which is stimulated by the laser diode of a smartphone-based fluorescence microscope device. This device robustly quantified viral load over a broad linear range and exhibited a limit of detection below that of the PCR gold standard assay. CRISPR data of SARS-CoV-2 RNA levels were similar in saliva and nasal swabs, and viral loads measured by RT-PCR and the smartphone-read CRISPR assay demonstrated good correlation.
- Larremore DB, et al. Modeling the Effectiveness of Olfactory Testing to Limit SARS-2-CoV Transmission. Dec 2020. (Not Peer Reviewed)
Evaluation of an alternative strategy based on the monitoring of olfactory dysfunction, a symptom identified in 76-83% of SARS-CoV-2 infections—including those that are otherwise asymptomatic—when a standardized olfaction test is used. The authors model how screening for olfactory dysfunction, with reflexive molecular tests, could be beneficial in reducing community spread of SARS-CoV-2 by varying testing frequency and the prevalence, duration, and onset time of olfactory dysfunction and believe that self-monitoring olfactory dysfunction could reduce spread via regular screening.
- Basile K, et al. Cell-Based Culture of SARS-CoV-2 Informs Infectivity and Safe De-Isolation Assessments during COVID-19.Clin Infect Dis. Oct 2020.
SARS-CoV-2 culture may be used as a surrogate marker for infectivity and inform de-isolation protocols.