The first COVID-19 test to be widely used across the globe was a polymerase chain reaction (PCR) nasal swab test, which is designed to identify the presence viral RNA in samples from a patient’s respiratory tract.

While these tests have played a key role in identifying SARS-CoV-2 infections, they are most effective when used early on in the disease course.

Researchers at Mass General, the Ragon Institute of MGH, Harvard and MIT and beyond are now looking to blood-based serology tests to get a better sense of how many people have been exposed to the virus and had mild or no symptoms. By doing so, they hope to understand how far the virus has spread into the community.

Serology tests are designed to analyze blood samples to identify the presence and/or quantity of antibodies to specific diseases.

At a recent virtual town hall, David Louis, MD, chief of Pathology at Mass General, spoke about two types of serology tests our researchers are working on, what they show and why they are valuable.

Rapid Test: Lateral Flow Assay

A lateral flow assay is a small, handheld test that can be easily completed and produces rapid results. This can be used either at the point-of-care or in a clinical laboratory at the hospital.

Mass General pathology researchers have evaluated a series of these tests, including some that detect the presence of IgM and IgG antibodies associated with SARS-CoV-2, the virus that causes COVID-19.

To use the lateral flow assay, a drop of blood—either from a person’s fingertip or from a tube of blood—is placed on a small well with a buffer solution. Similar to a pregnancy test, colored bands should appear on the readout panel after 10 or 15 minutes.

One band is for a control to ensure the test is working (regardless of the results), while two others indicate the presence of IgM and/or IgG antibodies.

In many infections, IgM antibodies seem to act as the first line of defense when a patient is infected, while IgGs develop later and may promote long term immunity after exposure. Therefore, the presence of an IgM band may indicate recent exposure, while the presence of an IgG band may signify past exposure.

The relationship between IgM and IgG levels is still being investigated in COVID-19, however.

Lab Test: ELISA

ELISA stands for enzyme-linked immunosorbent assay, and unlike lateral flow assays, ELISAs are typically done on a high-throughput machine in a laboratory setting.

Researchers at Mass General and the Ragon Institute worked together to develop a “homebrew” ELISA that can both detect and quantify the number of IgG, IgM and IgA antibodies.

Quantifying the different types of antibodies is important because it provides information on how strongly the immune system is responding to SARS-CoV-2.

Using Controls and Sensitivity vs. Specificity

Control samples—the randomized testing of samples with a known quantity on them to ensure the accuracy of results—are critical to developing tests. Mass General teams have done many hundreds of control samples for these tests so far, Louis says, but it is difficult to know whether that is enough.

To date, both the point-of-care and ELISA tests were evaluated for crossover with many strains of “common cold” viruses, and only one showed an IgM band on the lateral flow assay. Thus, the number of false positives is very low—meaning the test’s specificity (ability to identify a true positive sample) is high.

The sensitivity of these tests (i.e. the frequency that it produces false negative results) may depend on the test itself and whether the samples are obtained and transported to the lab correctly.

When to Use Each Test

PCR tests are best suited for detecting an active infection during the first week of onset, while serology tests are best to test if someone has been exposed to the virus at least one week ago.

Serology tests can confirm that a person has been exposed to the virus, but cannot yet show whether that individual is still actively infected or is immune to further infection.

To investigate these questions and gather more information on the extent of exposure in the community, Mass General is moving forward with studies that will examine how COVID-19 has affected several populations, including community residents, health care workers and researchers.

COVID-19 Research at Mass General
Researchers and clinicians at Massachusetts General Hospital Research Institute are mobilizing to develop new strategies to diagnose, treat and prevent COVID-19. Learn more.