What antibody tests are currently available for COVID-19? Any concerns with results/efficacy?

Comment by InpharmD Researcher

There are currently 13 approved antibody tests available for COVID-19. The sensitivity and specificity of these tests are based upon the prevalence of SARS-COV-2 antibody-positive individuals in the US population, which is currently unknown. The significance of antibody test results are not yet known, as there is not enough evidence to suggest that antibody-positive individuals are protected from re-infection. Point-of-care antibody testing is likely to have high false-negative rates, especially compared to ELISA or CIA testing. A list of the 13 approved antibody tests, along with their predicted sensitivities and specificities, can be seen in Table 1.
Background

Serology/antibody tests are designed to detect IgM, IgA, and/or IgG antibodies in order to assess exposure to SARS-CoV-2. This test may differentiate individuals who have not been exposed to COVID-19 and those previously infected; however, there is not enough evidence to suggest that having antibodies to the virus will protect you from getting the virus again. Antibodies are expected to develop 9-14 days after illness onset (IgM seroconversion happens in about 12 days, while IgG seroconversion happens in about 14 days). This test is not useful in the setting of acute infections and cannot be used to diagnose acute illness. [1], [2], [3], [4], [5], [6], [7]

There are two methods for serology tests: laboratory tests and point-of-care testing. Laboratory tests are conducted via ELISA (enzyme-linked immunosorbent assay) or CIA (chemiluminescent immunoassay), which requires trained personnel and specialized instruments. Point-of-care serology testing is generally lateral flow immunoassays (LFIA), which have been shown to not perform sufficiently well for individual patient applications. Point estimates for the sensitivity of LFIA devices ranged from 55-70% versus PCR and 65-85% versus ELISA, with specificity 95-100% and 93-100% respectively. The results of the point-of-care lateral flow assays have not been adequately validated. Using antibody tests for point of care testing can lead to false negatives which can lead to serious public health consequences. [1], [2], [3], [4], [5], [6], [7]

It should be noted that the sensitivity and specificity of the antibody tests are determined by the estimated population prevalence. We do not currently know the prevalence of SARS-CoV-2 antibody-positive individuals in the U.S. population, and prevalence may change based on the duration the virus is in the country and the effectiveness of mitigations. Per the FDA, authorized serology tests have a range of sensitivities and specificities; however, most of these results are based on a predicted prevalence of 5% [Table1]. The positive predictive values become significantly more accurate with two orthogonal tests instead of just one test result. [3], [4], [5], [6], [7]

The CDC recommends against using antibody tests until evidence confirms that antibodies provide protection; how much antibody is protective; and how long protection lasts. Per the IDSA, there is a multitude of different antibody tests for COVID-19 with variable performance. Tests vary in the viral antigen(s) they target, e.g., nucleoprotein (N protein) or spike protein (S protein). It is not yet clear which antibody responses, if any, are protective or sustained. [3], [4], [5]

The CDC also states that antibody test results should not be used to make decisions about grouping people residing in congregate settings such as schools, dormitories, or correctional facilities. The test results also should not be used to make decisions about returning to the workplace. [3]

References:

[1] Patel R, Babady E, Theel ES, et al. Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS–CoV-2/COVID-19. mBio. 2020;11(2).
[2] Food and Drug Administration. EUA Authorized Serology Test Performance. https://www.fda.gov/medical-devices/emergency-situations-medical-devices/eua-authorized-serology-test-performance. Updated May 22, 2020. Accessed May 30, 2020.
[3] Centers for Disease Control and Prevention. Interim Guidelines for COVID-19 Antibody Testing. https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.html. Updated May 23, 2020. Accessed May 29, 2020.
[4] Infectious Diseases Society of America. IDSA COVID-19 Antibody Testing Primer. https://www.idsociety.org/globalassets/idsa/public-health/covid-19/idsa-covid-19-antibody-testing-primer.pdf. Updated May 4, 2020. Accessed May 30, 2020.
[5] Adams ER, Ainsworth M, Anand R, et al. Antibody testing for COVID-19: A report from the National COVID Scientific Advisory Panel. medRxiv 2020.04.15.20066407.
[6] Zhao J, Yuan Q, Wang H, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019 [published online ahead of print, 2020 Mar 28]. Clin Infect Dis. 2020;ciaa344. doi:10.1093/cid/ciaa344
[7] Abbasi J. The Promise and Peril of Antibody Testing for COVID-19. JAMA. 2020;[E-pub].
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What antibody tests are currently available for COVID-19? Any concerns with results/efficacy?

Please see Table 1 for your response.

 

Test

Technology

Antibody

 Sensitivity (95% CI) Specificity (95% CI) PPV (95% CI)* NPV (95% CI)*
Abbott Alinity i SARS-CoV-2 IgG CMIA IgG 100% (89.9%; 100%) 99.0% (94.6%; 99.8%)

84.0% (46.7%; 96.3%)

 100% (99.4%; 100%)
Abbot Architect SARS-CoV-2 IgG CMIA IgG 100% (95.8%; 100%)

99.6% (99.0%; 99.9%)

 92.9% (83.4%; 98.1%) 100% (99.8%; 100%)
Autobio Anti-SARS-COV-2 Rapid Test LFIA Combined 99.0% (97.1%; 99.7%) 99.0% (97.2%; 99.7%) 84.4% (64.6%; 94.6%) 99.9% (99.8%; 100%)
Bio-Rad Platelia SARS-CoV-2 Total Ab ELISA Pan-Ig 92.2% (81.5%; 96.9%)

99.6% (98.7%; 99.9%)

 91.7% (76.7%; 98.1%) 99.6% (99.0%; 99.8%)

Cellex qSARS-CoV-2 IgG/IgM Rapid Test

 LFIA Combined 93.8% (88.2%; 96.8%) 96.0% (92.8%; 97.8%) 55.2% (39.2%; 69.8%) 99.7% (99.3%; 99.8%)

Chembio Diagnostic Systems DPP Covid-19 IgM/IgG System

 LFIA Combined 93.5% (79.3%; 98.2%) 99.4% (88.9%; 97.3%) 46.8% (27.3%; 65.7%) 99.6% (98.8%; 99.9%)

DiaSorin LIAISON SARS-CoV-2 S1/S2 IgG

 CMIA IgG 97.6% (87.4%; 99.6%) 99.3% (98.6%; 99.6%) 88.0% (76.7%; 92.9%) 99.9% (99.3%; 100%)

EUROIMMUN SARS-COV-2 ELISA (IgG)

 ELISA IgG 90.0% (74.4%; 96.5%) 100% (95.4%; 100%) 100% (46.0%; 100%) 99.5% (98.6%; 99.8%)

Mount Sinai Hospital Clinical Laboratory COVID-19 ELISA Antibody Test

 ELISA Combined 92.5% (80.1%; 97.4%) 100% (95.1%; 100%) 100% (46.2%; 100%) 99.6% (98.9%; 99.9%)

Ortho-Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG test

 CIA IgG 90.0% (76.9%; 96.0%) 100% (99.1%; 100%) 100% (81.8%; 100%) 99.5% (98.8%; 99.7%)

Ortho-Clinical Diagnostics VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Calibrator

 CIA Pan-Ig 100% (92.7%; 100%) 100% (99.0%; 100%) 100% (83.0.%; 100%) 100% (99.6%; 100%)

Roche Elecsys Anti-SARS-CoV-2

 ECLIA Pan-Ig 100% (88.3%; 100%) 99.8% (99.7%; 99.9%) 96.5% (93.9%; 98.1%) 100% (99.4%; 100%)

Wadsworth New York SARS-CoV Microsphere Immunoassay for Antibody Detection

 MIA Pan-Ig 88.0% (80.5%; 92.8%) 98.8% (97.3%; 99.5%) 79.4% (61.1%; 90.7%) 99.4% (99.0%; 99.6%)

CI=confidence interval; PPV=positive predictive value; NPV=negative predictive value; LFIA=lateral flow immunoassay; CMIA=chemiluminescent magnetic microparticle immunoassay; ELSA=enzyme linked immunosorbent assay; CIA= chemiluminescent immunoassay; ECLIA=electrochemiluminescence immunoassay analyzer; MIA=microspehere immunoassay

*All PPVs and NPVs are based on a predicted population antibody-positive prevalence of 5%.

 **This is an incomplete representation of the performance of these tests. The performance of these tests have not been adequately validated and the values may change based on estimated antibody-positive prevalence. 

References:

Food and Drug Administration. EUA Authorized Serology Test Performance. https://www.fda.gov/medical-devices/emergency-situations-medical-devices/eua-authorized-serology-test-performance. Updated May 22, 2020. Accessed May 30, 2020.