New study evaluates effectiveness and use of COVID-19 antibody testing

A research team from the Weizmann Institute of Science in Israel reviews the different types of antibody tests for COVID-19, and their importance, in a January 2021 preprint of Cell Reports Medicine. 

COVID-19 antibody testing can provide information about people who may have had the disease without symptoms as well as those who may have died from undiagnosed COVID-19. Thus, antibody testing is valuable in estimating the actual scope of the pandemic and in assessing the development of herd immunity. 

Antibody testing will also be helpful after vaccines have been widely used to assess how long the vaccines protect against reinfection.

After virus infection, the body's immune system responds by producing specific antibodies: IgM, IgG and IgA which can be detected by analysis of blood. Current antibody testing for SARS-CoV-2, the virus that causes COVID-19, usually looks for both IgM and IgG.

The researchers report that "detectable amounts of IgM appear after ca. 5 days after infection and level off at ca. 10 days, whereas IgG production is at first delayed but surpasses IgM concentrations after ca. 10 days." 

The researchers note that IgA is also a potential target for antibody testing.

The magnitude of antibody response varies, according to the severity of the disease. At present, antibody tests cannot distinguish between SARS-CoV-2 strains with different mutations. Also, it's not known if antibodies from other CoV viruses, some of them common, might be cross-reactive and interfere with the SARS-CoV-2 antibody testing.

The researchers discuss four types of antibody tests: the lateral flow assay (LFA), the enzyme linked immunosorbent assay (ELISA), the chemiluminescent immunoassay (CLIA) and the neutralization assay.

The LFA, also known as RDT for rapid diagnostic test, uses a small device with no additional equipment. It provides results within minutes, but at the expense of accuracy.

ELISA testing requires trained personnel and lab equipment and takes longer, but its results are more accurate because "they allow for enzymatic signal amplification." The same is true for CLIA testing.

The neutralization assay is more complex: it detects how antibodies inhibit viral infection of cultured target cells.

The authors suggest that deployment of antibody testing on a wide scale would require "in-depth analysis of repeated measurements of many individuals." This would provide information about systematic errors caused by cross-reaction of antibodies produced against common coronaviruses. It would also identify the sensitivity and specificity of the different antibody tests.

The researchers conclude that ELISA and CLIA tests "appear currently as the method of choice for monitoring the population-wide spread in a post-lockdown world." They note that this strategy can work in high-income countries, but for other parts of the world "improving low-cost, rapid diagnostic kits will be critical." 

The authors suggest that LFAs should test for "multiple antigens and isotypes (including IgA) in a single assay, or combining different low-cost tests with independent systematic biases to reduce the overall error rates of LFAs."

Antibody testing will be critical, they conclude, to "assess long-term antibody responses of recovered patients," the duration of vaccines' protection against reinfection, and to understand the "true prevalence of COVID-19." It may be that large-scale antibody testing will reveal that more people have had COVID-19 without being diagnosed, and thus the infection fatality rate may be less than estimated from COVID-19 testing to date.