Evaluation of Commerical Antibody Tests for COVID-19

Background

Molecular (RT-PCR) tests are currently the gold standard for diagnosis of COVID-19. They detect viral RNA and are a good marker for current infection and infectivity. However, these tests are expensive and in short supply. In advanced COVID-19 cases, virus concentration in the upper respiratory tract is often low, as the infection has spread to the lungs and viral RNA is sometimes undetectable by RT-PCR using nasal swaps. Antibody tests detect human antibodies to viral proteins in the blood or other body fluids. They could be useful for diagnosing current infections (slightly less sensitive than RT-PCR tests), and they remain positive after persons have recovered from the infection. Thus, antibody tests are expected to be useful for diagnosis of current infections, for verifying recent infections in persons who were not tested by RT-PCR when they were ill, and for documenting possible immunity to the virus. Antibody tests may be especially valuable for use in low and middle income countries that lack resources for widespread molecular testing for SARS-CoV-2 infection.

Anticipated test sensitivity and specificity. Manufacturer data for several antibody tests claim that more than 90% of persons with COVID-19 (clinical symptoms and positive molecular tests) have positive antibody test results for IgM and/or IgG. They also claim specificity in the range of 93-95% for samples from persons who have not been exposed to SARS-CoV-2.

Availability of antibody tests. In recent months, many antibody tests have been developed and marketed. The Foundation for Innovative New Diagnostics (FIND, closely linked to World Health Organization (WHO) and supported by a large grant from the United Kingdom government) in Geneva Switzerland reported that they had identified more than 70 such tests, and they shortlisted 27 tests for further evaluation. Of these, only one test produced in the USA (produced by Cellex) has received an emergency use authorization (EUA) from the US FDA, and no test has formal FDA approval. Antibody tests use different diagnostic platforms, but most tests use the SARS-CoV-2 S1protein, and a few tests also use the SARS-CoV-2 N protein. Few studies that independently evaluated the performance of these rapid antibody tests have been published to date in peer-reviewed journals. Therefore, more data are needed to evaluate the sensitivity, specificity, and value of these tests.

Methods