Molecular Antigen Antibody
COVID-19 Molecular Testing
The molecular COVID-19 test is the gold standard in diagnosing patients with active viral infections. There are molecular test approved for self-collection both swab and saliva testing. The RT-qPCR is considered the gold standard for COVID-19 testing. The majority of the COVID-19 molecular testing is high complexity, but there are some moderately complex and a few waived as well. Below is a listed of FDA EUA waived COVID-19 molecular system
Helpful resources for COVID-19 Molecular Testing
John Hopkins Center for Health Security had a comprehensive list of COVID-19 molecular testing methodology
https://www.centerforhealthsecurity.org/resources/COVID-19/molecular-based-tests/current-molecular-and-antigen-tests.html#commercial
FDA COVID-19 PCR Reference Panel performance
SARS-CoV-2 Reference Panel Comparative Data | FDA
Helpful resources for COVID-19 Molecular Testing
John Hopkins Center for Health Security had a comprehensive list of COVID-19 molecular testing methodology
https://www.centerforhealthsecurity.org/resources/COVID-19/molecular-based-tests/current-molecular-and-antigen-tests.html#commercial
FDA COVID-19 PCR Reference Panel performance
SARS-CoV-2 Reference Panel Comparative Data | FDA
Manufacturer |
Molecular FDA EUA Waived Diagnostics System |
Abbott Diagnostics |
ID NOW COVID-19 |
BioFire |
BioFire Respiratory Panel 2.1-EZ |
Cepheid |
Xpert Xpress SARS-CoV-2 test |
Cepheid |
Xpert Xpress SARS-CoV-2/Flu/RSV |
Cue Health |
Cue COVID-19 Test |
Lucira Health (Home use with self collection) |
Lucira COVID-19 All-In-One Test Kit |
Mesa Biotech |
Accula SARS-Cov-2 Test |
Roche Diagnostics |
cobas SARS-CoV-2 & Influenza A/B Nucleic Acid Test |
COVID-19 Antigen Testing
The rapid antigen has emerged after molecular and antibody testing, the first FDA EUA approved antigen test didn't come out until May. Currently there are seven FDA EUA antigen test, of which 6 of them can be performed with a certificate of waiver. Only the Abbott BinaxNOW and Access Bio CareStart does not require an analyzer to read the test. Ortho and Roche are developing antigen tests that can be run on existing high throughput immunoassay analyzers.
The sensitivity of the rapid antigen test is lower than RT-PCR but specificity is similar to RT-PCR, which mean false positive result is unlikely if the test is being performed correctly. The FDA has issued a letter concerning false positive result with antigen testing back in Nov, the false positive were mainly due to operator's errors, including: cross contamination, patient misidentification, kit not read at specific time on the package insert and improper storage.
https://www.fda.gov/medical-devices/letters-health-care-providers/potential-false-positive-results-antigen-tests-rapid-detection-sars-cov-2-letter-clinical-laboratory
Currently, all antigen tests are FDA approved only as diagnostic testing on symptomatic person within the first five to twelve days of symptom onset. CMS had stated they will not cite laboratories that perform COVID antigen test on asymptomatic individuals.
The sensitivity of the rapid antigen test is lower than RT-PCR but specificity is similar to RT-PCR, which mean false positive result is unlikely if the test is being performed correctly. The FDA has issued a letter concerning false positive result with antigen testing back in Nov, the false positive were mainly due to operator's errors, including: cross contamination, patient misidentification, kit not read at specific time on the package insert and improper storage.
https://www.fda.gov/medical-devices/letters-health-care-providers/potential-false-positive-results-antigen-tests-rapid-detection-sars-cov-2-letter-clinical-laboratory
Currently, all antigen tests are FDA approved only as diagnostic testing on symptomatic person within the first five to twelve days of symptom onset. CMS had stated they will not cite laboratories that perform COVID antigen test on asymptomatic individuals.
COVID-19 Antibody Testing
COVID-19 antibody test had not received as much attention as the molecular PCR test where after months of ramping up production still experiencing a shortage every step in the supply chain from swab to reagent to instrumentation. Before FDA tighten the standard, there were test kits being imported oversea that have significant performance issues. Currently there are more than 70 test kits on the FDA removal list.
https://www.fda.gov/medical-devices/emergency-situations-medical-devices/faqs-testing-sars-cov-2#nolonger-ivd
Antibody testing is a blood test and can be run on high-throughput immunoassay analyzers already in the lab. Since most high volume lab already has lab automation line connected to immunoassay analyzers it is easier for lab to scale up than molecular testing.
- FDA had approved total antibody, IgG and IgM antibody test.
- Antibody is not recommended nor approved for diagnosis of acute infection or to confirm immunity
- There is waived antibody test, therefore certificate of waiver lab can perform COVID-19 antibody if they use the a waived test kit
- PPV (Positive Predictive Value) and NPV (Negative Predictive Value) are dependent on prevalence, FDA assumes a 5% prevalence rate in calculating PPV and NPV. FDA evaluation of PPV and NPV can be found here. https://www.fda.gov/medical-devices/emergency-situations-medical-devices/eua-authorized-serology-test-performance
- Antibody is useful for identifying blood donor for convalescent plasma, population level sero-prevalence study and children with multisystem inflammatory syndrome (MIS-C)