A Peek Inside the SARS-CoV-2 Diagnostic Pipeline

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A spate of Food and Drug Administration (FDA) emergency use authorizations (EUAs) for SARS-CoV-2 diagnostics reflects a diversity in testing methods and sample types as developers have advanced their innovations during the ongoing COVID-19 pandemic. As of late October, FDA had issued EUAs for 284 tests: 221 molecular tests, 56 antibody tests, and seven antigen tests. Some provide innovative sample collection technologies while others have received updates to allow for screening or home collection.

“We prioritize review of EUA requests for tests taking into account a variety of factors . . . such as the public health need for the product and the availability of the product,” FDA recently stated in its Q&A on testing for SARS-CoV-2. Right now, the agency is prioritizing tests that increase accessibility, such as point-of-care and home collection, or those that increase testing capacity. For this reason and others, FDA said it would not be issuing any EUAs for laboratory-developed tests (LDTs). An AACC panel of laboratory medicine experts recently expounded on the importance of LDTs in diagnosing and managing SARS-CoV-2 and why these tests should not be regulated further by FDA.

Since September 1, FDA has issued 18 new or updated existing EUAs for home collection molecular-based tests/kits. These are:

• the Quest SARS-CoV-2 rRT-PCR test
• the Genetrack SARS-CoV-2 Molecular Assay by Genetrack Biolabs
• Color Genomics’ Color Genomics SARS-CoV-2 RT-LAMP Diagnostic Assay and Color COVID-19 Self-Swab Collection Kit
• Assurance Scientific Laboratories’ Assurance SARS-CoV-2 Panel
• Gravity Diagnostics’ Gravity Diagnostics COVID-19 Assay
• the Ethos Laboratories SARS-CoV-2 MALDI-TOF Assay
• Exact Sciences Laboratories’ SARS-CoV-2 (N gene detection) Test
• LabCorp’s COVID-19 RT-PCR Test
• the Infinity BiologiX TaqPath SARS-CoV-2 Assay
• Kaiser Permanente Mid-Atlantic States’ KPMAS COVID-19 Test
• the Everlywell COVID-19 Test Home Collection Kit
• Viracor Eurofins Clinical Diagnostics’ Viracor SARS-CoV-2 assay
• Clinical Enterprise’s EmpowerDX At-Home COVID-19 PCR Test Kit
• Thermo Fisher Scientific’s TaqPath COVID-19 Combo Kit
• binx health’s binx health At-Home Nasal Swab COVID-19 Sample Collection Kit
• the Wren Laboratories COVID-19 PCR Test
• and the P23 Labs TaqPath SARS-CoV-2 Assay.

Interest in pooling samples has grown as labs continue to face challenges accessing testing supplies. Since September 1, FDA has issued 10 new or updated existing EUAs to permit pooled samples. These are:

• Color Genomics’ Color COVID-19 Self-Swab Collection Kit
• the Everlywell COVID-19 Test Home Collection Kit
• Cepheid’s Xpert Xpress SARS-CoV-2/Flu/RSV test
• the Assurance SARS-CoV-2 Panel
• the Gravity Diagnostics COVID-19 Assay
• Exact Sciences Laboratories’ SARS-CoV-2 (N gene detection) Test
• the Quest SARS-CoV-2 rRT-PCR test
• LabCorp’s COVID-19 RT-PCR Test
• the Infinity BiologiX TaqPath SARS-CoV-2 Assay
• and Kaiser Permanente Mid-Atlantic States’ KPMAS COVID-19 Test.

Providers this fall and winter are facing the daunting task of distinguishing flu from COVID-19. FDA has authorized six multianalyte tests to support those efforts. These are:

• QUIAGEN’s QIAstat-Dx Respiratory SARS-CoV-2 Panel
• Cepheid’s Xpert Xpress SARS-CoV-2/Flu/RSV test
• BioFire Diagnostics’ BioFire Respiratory Panel 2.1-EZ (RP2.1-EZ)
• Roche Molecular Systems’ cobas SARS-CoV-2 & Influenza A/B and cobas SARS-CoV-2 & Influenza A/B test
• and the Centers for Disease Control and Prevention’s Influenza SARS-CoV-2 (Flu SC2) Multiplex Assay.

FDA has also issued updates and new issuances for reverse transcription polymerase chain reaction (RT-PCR) technologies. These include:

• Verily Life Sciences’ Verily COVID-19 RT-PCR Test
• Hologic’s Panther Fusion SARS-CoV-2 Assay
• Fluidigm’s Advanta Dx SARS-CoV-2 RT-PCR Assay
• Quadrant Biosciences’ Clarifi COVID-19 Test Kit
• CENTOGENE US’s CentoSure SARS-CoV-2 RT-PCR Assay
• and Visby Medical’s Visby Medical COVID-19 test.

While most SARS-CoV-2 tests rely on RT-PCR, FDA since September 1 has granted EUAs to 12 tests that use other methods.

• These include four assays based on RT-LAMP:
  • the Color Genomics SARS-CoV-2 RT-LAMP Diagnostic Assay
  • DetectaChem’s MobileDetect Bio BCC19 (MD-Bio BCC19) Test Kit
  • SEASUN BIOMATERIALS’ AQ-TOP COVID-19 Rapid Detection Kit PLUS
  • and Sherlock BioSciences’ Sherlock CRISPR SARS-CoV-2 Kit.
• Two use RT-PCR and MALDI-TOF mass spectrometry:
  • the Ethos Laboratories SARS-CoV-2 MALDI-TOF Assay
  • National Jewish Health’s SARS-CoV-2 MassArray Test
• Two others use RT-PCR and sequencing:
  • Clear Labs’ Clear Dx SARS-CoV-2 Test
  • the University of California, Los Angeles’ UCLA SwabSeq COVID-19 Diagnostic Platform.
• The BillionToOne qSanger-COVID-19 Assay uses sequencing alone.

Abbott Diagnostics Scarborough’s ID NOW COVID-19 test uses RT and isothermal amplification. Alimetrix’s Alimetrix SARS-CoV-2 RT-PCR Assay combines RT-PCR with microarray hybridization. And, Hologic’s Aptima SARS-CoV-2 assay uses transcription-mediated amplification and Dual Kinetic Assay. 

FDA to date has approved seven antigen tests. Three new antigen tests joined the list in October:

• Celltrion USA, Inc.’s Sampinute COVID-19 Antigen MIA
• Access Bio’s CareStart COVID-19 Antigen test
• and Quidel’s Sofia 2 Flu + SARS Antigen FIA test

Among 15 serology tests approved since September 1, four detect total antibodies and four detect IgG and IgM. They use technologies including ELISA, indirect chemiluminescence, fluorescence immunoassay, lateral flow, and photometric immunoassay.

The agency has also approved a number of saliva-based tests since September 1. However Spectrum Solutions’ SDNA-1000 Saliva Collection Device is the first EUA granted specifically for use as a saliva collection device. OraSure Technologies’ DNA Genotek subsidiary on October 19 received an EUA for its saliva collection and stabilization device, enabling unsupervised use of the device at home or in a healthcare setting when used as part of an approved or validated at-home test kit.