LDTs

Battle of the SARS-CoV-2 Antibody Immunoassays: Only One Test Meets Both UK Sensitivity and Specificity Targets

Several of the world’s biggest testing companies have created and secured emergency regulatory clearance for immunoassays that detect antibodies to the SARS-CoV-2 virus. But how reliable are these tests? And how do they stack up against each other? A July report from Public Health England (PHE) offers just a wee bit of insight into these questions.

The Head-to-Head Study

 The two-month study was commissioned by the UK Department of Health and Social Care to compare four of the commercial immunoassays available in the UK for detection of SARS-CoV-2 antibodies:

  • Abbott Laboratories’ SARS-CoV-2 Immunoassay;
  • DiaSorin’s Liaison SARS-CoV-2 S1/S2 IgG assay;
  • Roche’s Elecsys Anti-SARS-CoV-2 test; and
  • Siemens’ SARS-CoV-2 Total (COV2T) test.

The assays were performed in accordance with the manufacturers’ instructions and at the prespecified thresholds for determining positive vs. negative test results. The investigators calculated sensitivity and specificity for each test for comparison against Target Product Profile (TPP)-sensitivity criteria for “enzyme immunoassays” developed by the UK Medicines and Healthcare Products Regulatory Agency (MHRA).

The sensitivity of a test refers to its capacity to identify known positives, i.e., infected individuals; specificity is the test’s capacity to identify known negatives, i.e., uninfected individuals. The investigators evaluated sensitivity using 536 positive samples from adults with a lab-confirmed SARS-CoV-2 infection, taken at equal to or greater than 20 days post-symptom onset. They evaluated specificity on 994 specimens from healthy adults collected before the pandemic.

The Findings

As the report notes, the TPP for enzyme immunoassays requires a clinical sensitivity of greater than or equal to 98 percent in SARS-CoV-2-positive cases confirmed equal to or greater than 20 days after the appearance of first symptoms. It requires a clinical specificity of equal to or greater than 98 percent on samples collected greater than 6 months before the first identified cases of SARS-CoV-2 infection.

While all four tests met the specificity criteria, only the Siemens test met both the sensitivity and specificity criteria. The table below illustrates the primary results.

Primary Results

Takeaway: Even though the Siemens’ test was the only immunoassay to meet both targets, the other products did not walk away empty-handed. In addition to meeting the specificity criteria, the   Abbott, DiaSorin and Roche assays did meet the sensitivity target after PHE tweaked the parameters. Thus, the Roche test exceeded the TTP sensitivity mark when the assay thresholds were changed to lower test specificity to 98%. The Abbott and DiaSorin tests fell just a tad short of the 98% sensitivity target. In addition, all four tests met the sensitivity and specificity criteria when the revised assay thresholds were applied to samples taken more than 30 days after the onset of symptoms.

Assay Sensitivity
[95% CI]
Specificity
[95% CI]
Appraisal against MHRA Target
Product Profile (TPP)
Abbott 92.7 (90.2, 94.8) 99.9 (99.4, 100) Meets specificity criterion
DiaSorin 95.0 (92.8, 96.7) 98.6 (97.6, 99.2) Meets specificity criterion
Roche 97.2 (95.4, 98.4) 99.8 (99.3, 100) Meets specificity criterion
Siemens 98.1 (96.6, 99.1) 99.9 (99.4, 100) Meets sensitivity and specificity criteria

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