Screening

COVID-19 Testing Brief

4/6/2021 - The section At-Home COVID-19 Test Kits section was updated to reflect the approval two new OTC COVID-19 tests (see At-Home COVID-19 Test Kits)

Since the identification of the COVID-19 virus, the US Food and Drug Administration (FDA) has issued hundreds of Emergency Use Authorizations (EUAs) to various testing kits and assays to aid in the detection of the coronavirus. There are 3 main types of diagnostic tests currently used to diagnose persons with COVID-19. In December 2020, we have had the approval of the first fully at home COVID-19 test kits. As researchers continue to develop testing capabilities, the availability of at-home COVID-19 tests will expand. As of January 20, 2021, there are 319 tests and sample collection devices authorized by the FDA via and EUA.1 This includes 237 molecular tests and collection devices, 69 antibody tests, and 13 antigen tests.1 Of the total 319 tests and collection devices, there are 32 molecular authorizations for home collection of samples.1 One molecular test and one antigen test, both prescription only, are authorized for at-home use and one antigen test is available over the counter for at-home use.1

Navigate this resource by topic:

I. TYPES OF COVID-19 TESTS
     a. Table 1. Types of Diagnostic Tests
     b. Nucleic Acid Amplification Test
     c. Antigen Testing
     d. Serologic or Antibody Testing

II. NIH RECOMMENDATIONS

III. SPECIMEN COLLECTION
      a. Table 2. Specimen Collection 

IV. POINT OF CARE TESTING

V. AT-HOME COVID-19 TEST KITS
     a. Table 3. Available Home Collection Kits
     b. Color Test Kit
     c. Ellume
     d. Lucira Test Kit

VI. GENETIC VARIANTS AND FALSE NEGATIVES

VII. TESTING STRATEGIES

VIII. REFERENCES

 

TYPES OF COVID-19 TESTS

Table 1. Types of COVID-19 Tests2,3,4

Diagnostic TestBenefitsDrawbacks
Nucleic Acid Amplification Test (NAAT)

  • The gold standard for COVID-19 detection

  • Most require a nasopharyngeal swab

  • Results are not rapid

  • Can have positive results several weeks after the infection is no longer contagious

  • Usually more costly

Antigen Test

  • Can diagnose acute COVID-19 infection

  • A shorter period until results

  • Some are CLIA-waived and can be used for point of care testing

  • Can use a nasal or oral swab

  • Lower sensitivity compared to PCR tests

  • False negatives possible
Antibody Test

  • Can provide evidence of past COVID-19 infection

  • Can only be used a minimum of 2 weeks after symptom onset

  • Cannot diagnose an active infection

  • Antibody presence does not indicate protection against COVID-19

 

Nucleic Acid Amplification Testing (NAAT)
The gold standard of NAAT testing for detecting SARS-CoV-2 is reverse transcriptase-polymerase chain reaction (RT-PCR)-based tests.2 NAATs can also include other platforms such as real-time loop-mediated isothermal amplification (RT-LAMP). The main concern with NAAT testing is false negatives. Clinically, viral nucleic acids may take up to 5 days before they can be detected. Therefore, if a person is tested early, he or she may receive a negative result despite having COVID-19. Because of this, a single negative test does not exclude the diagnosis of COVID-19 if the person has a high likelihood of infection based on symptoms or exposure history.2

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Antigen Testing

Antigen tests are less sensitive the PR tests, but their specificity is similar. The first antigen tests issued EUAs by the FDA had a sensitivity ranging from 84.0% to 97.6% compared to RT-PCR.2 Antigen tests work best early in the disease course when viral load is high. If a person suspected of having COVID tests negative with an antigen test, use of a retest with NAAT should be considered. Antigen tests are cheaper and have a quicker time to results, making them ideal for point-of-care testing.2 Current antigen tests can provide results within as few as 15 minutes.3 As PCR tests are the gold standard for diagnosing SARS-CoV-2, patients who receive a positive result from an antigen test should receive a NAAT.3

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Serologic or Antibody Tests

Serologic or antibody tests are utilized to identify patients who have had recent or prior COVID-19 infection but are asymptomatic. The National Institutes of Health (NIH) COVID-19 Treatment Guideline Panel does not recommend the use of serologic testing for the diagnosis of COVID-19, as it can take 21 days or longer after symptom onset for a serologic or antibody test to detect the presence of COVID-19.2 Serologic or antibody tests can be used on top of NAATs and antigen tests for patients who were suspected to have COVID-19 but received negative test results. At this time, there are no FDA-approved SARS-CoV-2 tests. However, some have received EUA issuance by the FDA.2

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NIH RECOMMENDATIONS

The NIH COVID-19 Treatment Guideline Panel recommends the use of a nucleic acid amplification test (NAAT) or antigen test to detect SARS-COV-2 in all people with COVID-19 symptoms or who have been exposed to COVID-19.2 To date, no diagnostic test is FDA approved, but several have been issued EUAs.2 In patients who have been intubated or mechanically ventilated, the NIH panel recommends using a lower respiratory tract sample if the initial upper respiratory tract sample is negative.2 When collecting these lower respiratory tract samples, the panel recommends endotracheal aspirates over bronchial was or bronchoalveolar lavage samples.2 

In patients who are asymptomatic, NAAT testing should not be repeated with 90 days of a previous coronavirus infection, even if that patient is directly exposed to COVID-19.2 However, as COVID-19 reinfection can occur, a person who previously had COVID-10 should be retested with a NAAT if they present with COVID-19 symptoms.2  

The NIH COVID-19 Treatment Guideline Panel additionally recommends against the use of serologic or antibody testing to determine immunity.2 Currently, it is not fully understood how long antibodies last following COVID-19 infection and whether the presence of antibodies provides immunity against future COVID-19 infection.2

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SPECIMEN COLLECTION

The current standard for testing is nasopharyngeal swabs, but nasal or oropharyngeal swabs are also acceptable.2 There are various acceptable specimens that can be collected depending on the test being used (Table 3).3 Lower respiratory tract samples provide a higher yield but result in aerosolization during sample collection, raising concern for exposure to the healthcare worker collecting the sample. In certain clinical situations (eg, invasive mechanical ventilation), a lower respiratory tract aspirate or bronchoalveolar lavage sample can be collected and tested.3

 

 Table 2. Specimen Collection

SpecimenCollected By
Nasopharyngeal (NP)Trained Health Care Professional
Oropharyngeal (OP)Trained Health Care Professional
Nasal Mid-Turbinate Swab

Trained Healthcare Professional

Supervised Self-Collection

Anterior Nares (Nasal) Swab

Trained Health Care Professional

Supervised Self-Collection

Nasopharyngeal Wash/Aspirate

Nasal Wash/Aspirate

Trained Health Care Professional
Saliva

Supervised Self-Collection

Unsupervised Self-Collection

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POINT OF CARE (POC) TESTING

POC testing can be performed by any site that has a Clinical Laboratory Improvement Amendments (CLIA) certificate. The site can utilize any SARS-CoV-2 POC test that has received a EUA. A list of approved tests can be found online on the FDA’s website. Tests that are designated for POC use will have a “W” associated with their test name.5

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AT-HOME COVID-19 TEST KITS
 

 Table 3. Available At-Home COVID-19 Tests5

ProductTest TypeTesting TechnologyAvailability
Ellume COVID-19 Home Test

OTC

Fully At-Home

Rapid, Lateral Flow Antigen Test

About $30 per test

Expected by January 20216

Lucira COVID-19 All-In-One Test KitFully At-HomeRT-LAMP

About $50 per test

Expected by spring 2021, requires prescription7

Color Genomics COVID-19 Self Swab Collection Kit and RT-LAMP Diagnostic AssayHome CollectionRT-LAMPFocused on large population testing8
Kroger Health COVID-19 Test Home Collection KitHome CollectionRT-PCR

Available online

Requires a Benefit Code9

LabCorp Pixel COVID-19 Home Collection Kit

Direct to Consumer

Home Collection

RT-PCR

$119

Available Online10

Infinity BiologiX TaqPath SARS-CoV-2 Assay

Saliva

Home Collection

RT-PCR

$119

Available Online11

Quest Diagnostics SARS-CoV2Home Collection RT-PCR

$119

Available Online12

PrivaPath LetsGetChecked Coronavirus (COVID-19) TestHome CollectionRT-PCR/TMA

$119

Available Online13

Helix COVID-19 TestHome CollectionRT-PCRNot Listed
P23 Labs TaqPath SARS-CoV-2 Assay

Saliva

Home Collection

RT-PCR

$99

Available Online14

Wren Laboratories COVID-19 PCR Test

Saliva

Home Collection

RT-PCR

$150

Must get in touch with a company representative15 

Assurance SARS-CoV-2 PanelHome CollectionRT-PCR$15016
Exact Sciences Laboratories SARS-CoV-2 TestHome CollectionRT-PCR

$149

Provider Ordered17

DxTerity SARS-CoV-2 RT PCR CE Test

Saliva

Home Collection

RT-PCR

$125

Available Online18

QDx SARS-CoV-2 AssayHome CollectionRT-PCRPhysician Ordered19
Clinical Reference Laboratory Rapid Response

Saliva

Home Collection

RT-PCR

$100

Available Online20

Compass Laboratory Services SARS-CoV-2 AssayHome CollectionRT-PCR

$100

Physician Ordered21

Phosphorus COVID-19 RT-PCR Test

Saliva

Home Collection

RT-PCR

$140

Available Online22

Fulgent COVID-19 by RT-PCR TestHome CollectionRT-PCR

Physician Ordered23

Binx Health At-Home Nasal Swab COVID-19 Sample Collection KitHome CollectionRT-PCR

$99

Available Online24

RapidRona Self-Collection KitHome CollectionRT-PCR

$198.50

Reserve Kit Online, Not Yet Available25

Clinical Enterprise EmpowerDX At-Home COVID-19 PCR Test KitHome CollectionRT-PCR

$99

Available Online26

Everlywell COVID-19 Test Home Collection KitHome CollectionRT-PCR

$109

Available Online27

QuickVue At-Home OTC COVID-19 Test Kit

OTC

Fully At-Home

Rapid Lateral FlowAvailable Soon36
Abbott BinaxNow

OTC

Fully At-Home

Rapid Lateral FlowAvailable Soon37


RT-PCR: Reverse transcriptase-polymerase chain reaction, TMA: transcription-mediated amplification, LAMP: loop-mediated isothermal amplification

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Color Test Kit

Color received a EUA from the FDA in May 2020 to utilize Loop-mediated isothermal amplification (LAMP) testing technology for their COVID-19 test.28 LAMP technology delivers COVID-19 test results with similar accuracy to RT-PCR, the current gold standard for COVID-19 testing.28 Unlike the multiple heating and cooling cycles required by RT-PCR, LAMP amplification of viral genome segments occurs at a consistent temperature. This consistent temperature allows for increased automation in the process, which decreases the processing time. Color has reported that LAMP processing occurs 50% faster than RT-PCR when testing for COVID-19.28 Additionally, LAMP testing requires different reagents, so it is not dependent upon the same supply chains as other COVID-19 testing methods.28 LAMP testing has previously been used as point-of-care testing for Zika and dengue fever.

On September 16, 2020, Color’s self-swab home collection kit was granted a EUA.29 This allows individuals to collect their specimen samples at home without healthcare provider supervision.29 A week later on September 24, 2020, United Airlines partnered with color to develop a COVID-19 testing program for persons traveling via airplane.29 The pilot program, which started on October 15, 2020, will give persons traveling with United Airlines from San Francisco International Airport to Hawaii the option to take a rapid rest for COVID-19 while at the airport or self-collect and mail the test in ahead of time. Color will be providing the mail-test option and Abbott will be providing the rapid test option.30

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Ellume Test Kit

Ellume’s COVID-19 home test was issued a EUA on December 15, 2020, making it the first over-the-counter, at-home diagnostic for COVID-19.31 The test works by detecting fragments of proteins when a liquid sample is run along a surface with reactive molecules. The test has been approved for use in persons 2 years of age or older.31

Ellume’s at home COVID-19 test requires mid-turbinate nasal swab collection.31 To date, this style of collection has only been recommended to be collected by or in the presence of a healthcare professional. The Ellume COVID-19 home test has an associate application for smartphones that helps the person perform the sample collection and interpret the results. Results can take as little as 20 minutes and are delivered directly to the user’s smartphone.31

During studies of the test, Ellume reported that the test correctly identified 96% of the positive samples and 100% of the negative sample in patients who were experiencing symptoms.31 In patients who were not experiencing symptoms, the test correctly identified 91% of the positive samples and 96% of the negative samples.31

As discussed in the antigen test section, there is a small possibility of false-positive and negatives. The FDA recommends treating individuals without symptoms but a positive test results as a positive COVID-19 case until another test can confirm.31 The FDA additionally recommends that persons who have COVID-like symptoms but test negative should follow-up with a healthcare provider.31

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Lucira

The Lucira COVID-19 All-In-One Test Kit is the first FDA EUA authorized prescription at-home test kit for persons aged 14 and older.32 The kit was authorized on November 17, 2020.32 When compared to the high-sensitivity RT-PCR tests, Lucira had a 94% positive percent agreement and 98% negative percent agreement.33 The test utilizes the same testing technology, RT-LAMP, as the Color test.32

The Lucira test has 3 easy to follow steps; (1) collect sample via nasal swab, (2) swirl nasal swab in specimen vial, and (3) place the vial in the reader. Results are ready within 30 minutes, the device lights up when results are ready. The test is single use.32

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QuickVue

The QuickVue At-Home COVID-19 test was issued an EUA for individuals with or without COVID-19 symptoms when tested twice over 2 or three days, with 24 to 36 hours between tests.36 The test is conducted via nasal swab and is approved for self-collection in individuals 14 years of age or older, or adult-collection in indiviuals aged 2 years or older.36 The QuickVue test was previously approved for physician order but will now be available over the counter.38 

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BinaxNow

The BinaxNow test has been available under an EUA for professional use since August 2020, but is now awailable over-the counter for both symptomatic and asymptomatic individuals.37 The BinaxNow test was approved for 3 different configurations: (1) at-home serial screening, (2) at-home serial screening with telehealth proctor, and (3) point-of-care serial screaining without a prescription.38 

GENETIC VARIANTS AND FALSE NEGATIVES

On January 8, 2021, the FDA released a letter to clinical laboratory staff and health care providers that warned new genetic variants of SARS-CoV-2 virus may cause false negative results on molecular based tests.

False negatives occur when mutations develop in the part of the virus' genome that the molecular test assesses. Molecular tests that analyze multiple targets on the virus are less susceptible to genetic variation. However, all laboratory tests possess the risk for a false positive. The FDA continues to monitor the genetic variants of COVID-10 that arise and how these variants affect the molecular tests that have received EUA. To date, the FDA has identified 3 tests that may be affected by the new genetic variants:34

  • Accula SARS-CoV-2 Test
    • Genetic variant at position 28881 (GGG to AAC) may be impacted.
    • Currently, the change does not appear to be significant.
  • TaqPath COVID-19 Combo Kit
    • One of the 3 targets has significantly reduced sensitivity to the B117 variant as reported by the FDA, the manufacturer (Thermo Fisher Scientific, Inc.), and by multiple clinical laboratories.
    • Overall sensitivity should not be affected, as the kit tests for multiple targets.
  • Linea COVID-19 Assay Kit
    • One of the 2 targets has reduced sensitivity to the B117 variant as reported by the FDA and the manufacturer (Applied DNA Sciences, Inc.).
    • Overall sensitivity should not be affected, as the kit tests for multiple targets.

The FDA recommends clinical laboratory staff and other health care providers stay up to date on the genetic variants of COVID-19. Laboratories should use tests that target multiple genomic locations when possible to decrease the risk of false negatives. Additionally, if a patient's tests result is negative, but has symptoms of or has been exposed to COVID-19, repeat testing should be considered.34

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TESTING STRATEGIES

A modeling study, published February 4, 2021, compared the cost-effectiveness of different COVID-19 testing strategies in the U.S. to assess how increasing testing (both availability and speed) would affect the economy and public health.35 Researcher working on the study, utilizing a multiscale model, found that in times of high transmission, testing should occur weekly and those who test positive should observe a 2 week isolation period.35 When transmission rates are lower, monthly testing and a 1 week isolation period would be ideal.35 Overall, researchers propose that increasing the frequency and speed of tests, as well as enforcing a 2-week isolation period, is necessary to manage the coronavirus pandemic. The researchers recognize, however, that the recommended results of their model are not yet logistically feasible. Low-cost antigen tests available in large quantities, with an established distribution plan, would need to be established first.35 Ultimately, while the ramped-up testing would be substantially more costly upfront, implementation of asymptomatic testing nationwide is most cost-effective long term to manage the current coronavirus pandemic.35 

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REFERENCES

  1. Coronavirus (COVID-19) update: January 19, 2021. U.S. Food and Drug Administration. January 19, 2021. News Release. Accessed Janaury 20, 2021. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-january-19-2021 
  2. Testing for SARS-CoV-2 infection. National Institute of Health COVID-19 Treatment Guidelines. Updated November 3, 2020. Accessed December 3, 2020. https://www.covid19treatmentguidelines.nih.gov/overview/sars-cov-2-testing/
  3. Interim guidelines for collecting, handling, and testing clinical specimens for COVID-19. Centers for Disease Control and Prevention. Updated November 30, 2020. Accessed December 3, 2020. https://www.cdc.gov/coronavirus/2019-nCoV/lab/guidelines-clinical-specimens.html
  4. COVID-19 testing guidance. American Academy of Pediatrics. Updated September 30, 2020. Accessed December 3, 2020. https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/covid-19-testing-guidance/
  5. In vitro diagnostics EUAs. U.S Food and Drug Administration. Updated December 17, 2020. Accessed December 17, 2020. https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#imft1
  6. Stein, R. FDA authorizes 1st home coronavirus test that doesn’t require a prescription. NPR. December 15, 2020. Accessed December 17, 2020. https://www.npr.org/sections/health-shots/2020/12/15/946692950/fda-authorizes-first-home-coronavirus-test-that-doesnt-require-a-prescription
  7. Bryant, M. Lucira health wins FDA nod for first completely in-home COVID-19 test. BioWorld. November 18, 2020. Accessed December 17, 2020. https://www.bioworld.com/articles/500364-lucira-health-wins-fda-nod-for-first-completely-in-home-covid-19-test
  8. COVID-19 overview. Color. 2020. Accessed December 17, 2020. https://www.color.com/covid
  9. Home Testing FAQs. Kroger Health. 2020. Accessed December 17, 2020. https://www.thelittleclinic.com/home-testing/faqs
  10. COVID-19 test (at-home collection kit). Pixel by LabCorp. 2020. Accessed December 17, 2020. https://www.pixel.labcorp.com/at-home-test-kits/covid-19-test-home-collection-kit
  11. COVID-19 test kit. Vault. 2020. Accessed December 17, 2020. https://www.vaulthealth.com/covid
  12. COVID-19 active infection. QuestDirect Quest Diagnostics. 2020. Accessed December 17, 2020. https://questdirect.questdiagnostics.com/products/covid-19-active-infection/2713afd8-3d0c-4819-b877-6880a776cc46
  13. Coronavirus test (COVID-19). LetsGetChecked. 2020. Accessed December 17, 2020. https://www.letsgetchecked.com/us/en/home-coronavirus-test/
  14. Frequently asked questions. P23 Labs. 2020. Accessed December 17, 2020. https://p23labs.com/faqs
  15. COVID-19 testing solution. Wren Laboratories. 2020. Accessed December 17, 2020. https://wrencovidtesting.com/
  16. COVID-19 (coronavirus). Asurance Scientific Laboratories. 2020. Accessed December 17, 2020. https://assurancescientificlabs.com/coronavirus/
  17. COVID-19 testing. Exact Science Laboratories. 2020. Accessed December 17, 2020. https://www.exactlabs.com/covid-19-testing-information
  18. COVID-19. DxTerity. 2020. Accessed December 17, 2020. https://dxterity.com/covid-19/
  19. Tests for coronavirus (COVID-19). QDxPathology Services. 2020. Accessed December 17, 2020. https://qdxpath.com/sars-cov-2-covid-19/
  20. FDA authorized COVID-10 test. Clinical Reference Laboratory. 2020. Accessed December 17, 2020. https://order.crlcorp.com/
  21. Molecular Diagnostics. Compass Lab Services. 2020. Accessed December 17, 2020. http://www.compasslabservices.com/molecular-diagnostics
  22. COVID-19 at-home RT-qPCR test. Phosphorus. 2020. Accessed December 17, 2020. https://www.phosphorus-c19-pcr.com/order-now/p/covid-19-rt-qpcr-test
  23. COVID-19 molecular testing. Fulgent. 2020. Accessed December 17, 2020. https://www.fulgentgenetics.com/covid19/molecular
  24. COVID-19 at-home testing. Binx. 2020. Accessed December 17, 2020. https://app.mybinxhealth.com/covid
  25. RapidRona. December 17, 2020. https://www.rapidrona.com/
  26. At-home COVID-19 nasal PCR test (home-collected). EmpowerDX. 2020. Accessed December 17, 2020. https://empowerdxlab.com/nasal-test/
  27. COVID-19 test. Everlywell. 2020. Accessed December 17, 2020. https://www.everlywell.com/products/covid-19-test/
  28. Color receives emergency use authorization for COVID-19 testing technology; releases return to work protocol. Color News Release. May 20, 2020. Accessed December 17, 2020. https://www.color.com/lamp-eua-press-release
  29. Latest updates. Color. October 1, 2020. Accessed December 17, 2020. https://www.color.com/covid-latest-updates
  30. United Airlines becomes first U.S. carrier to make COVID-19 tests available to customers. United Airlines. September 24, 2020. Accessed December 17, 2020. https://hub.united.com/2020-09-24-united-airlines-becomes-first-u-s-carrier-to-make-covid-19-tests-available-to-customers-2647787602.html
  31. Coronavirus (COVID-19) update: FDA authorizes antigen test as first over-the-counter fully at-home diagnostic test for COVID-19. U.S. Food and Drug Administration. News Release. December 15, 2020. Accessed December 17, 2020. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-antigen-test-first-over-counter-fully-home-diagnostic
  32. Coronavirus (COVID-19) update: FDA authorizes first COVID-19 test for self-testing at home. U.S. Food and Drug Administration. News Release. November 17, 2020. Accessed December 17, 2020. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-covid-19-test-self-testing-home
  33. Lucira Health. Lucira Health. 2020. Accessed December 17, 2020. https://www.lucirahealth.com/
  34. Genetic variants of SARS-CoV-2 may lead to false negative results with molecular tests for detection of SARS-CoV-2 - letter to clinical laboratory staff and healthcare providers. News release. US Food and Drug Administration; January 8, 2021. Accessed January 20, 2021. https://www.fda.gov/medical-devices/letters-health-care-providers/genetic-variants-sars-cov-2-may-lead-false-negative-results-molecular-tests-detection-sars-cov-2
  35. Du Z, Pandey A, Bai Y, et al. Comparative cost-effectiveness of SARS-CoV-2 testing strategies in the USA: a modelling study. The Lancet. Published online February 4, 2021. doi: 10.1016/S2468-2667(21)00002-5 
  36. QuickVue At Home. Quidel. Updated 2021. Accessed April 6, 2021. https://quickvueathome.com/ 
  37. Abbott's BinaxNox rapid antigen self rest receives FDA emergency use authorization for asymptomatic, over-the-counter, non-prescription, multi-test use. Abbott. News Release. Updated March 31, 2021. Accessed April 6, 2021. https://abbott.mediaroom.com/2021-03-31-Abbotts-BinaxNOW-TM-Rapid-Antigen-Self-Test-Receives-FDA-Emergency-Use-Authorization-for-Asymptomatic-Over-the-Counter-Non-Prescription-Multi-Test-Use 
  38. Coronavirus (COVID-19) update: FDA continues to advance over-the counter and other screening test development. US Food and Drug Administration. News Release. March 31, 2021. Accessed April 6, 2021. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-continues-advance-over-counter-and-other-screening-test-development