'Sweet Spot' for Antibody Tests is 3 to 4 Weeks Postexposure

Marcia Frellick

August 20, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

The Infectious Diseases Society of America (IDSA) is recommending against testing patients for SARS-CoV-2 antibodies in the first 1 to 2 weeks after exposure to the virus.

The "sweet spot" for such testing is 3 to 4 weeks after exposure, Angela M. Caliendo, MD, PhD, professor and executive vice chair with the Department of Medicine at Brown University in Providence, Rhode Island, told reporters this morning in a media briefing.

The IDSA released its antibody testing guidelines this week.

IDSA's expert panel analyzed 47 published studies and found that in the first 2 weeks after exposure, many patients have not yet developed the antibodies.

Panel chair Kimberly E. Hanson, MD, MHS, associate professor of internal medicine at the University of Utah School of Medicine in Salt Lake City, said if clinicians see that a patient has symptoms in the first 2 weeks, but the antibody test is negative, "you really can't rule out the possibility the patients could still have COVID-19."

The researchers said they were surprised to learn that a test that looks at immunoglobulin M (IgM) "doesn't really have a lot of added value over IgG (immunoglobulin G)." IgM antibodies typically show up earlier, but not for SARS-CoV-2, Caliendo said.

"If you're using IgM, it's going to be less sensitive. You're going to miss some people who are, in fact, infected," Caliendo said.

None of the tests is perfect, the researchers acknowledged.

Caliendo said, "There will be false positive results and false negative results, but you'll minimize the number of incorrect results if [you] use an IgG test or a total antibody test 3 to 4 weeks after the onset of symptoms."

Caliendo said their research also suggests that tests for another antibody (IgA) had very low specificity and were not appropriate for use.

Point-of-care tests that are lateral-flow devices can detect and differentiate between IgM and IgG, but the panel found them not specific enough to recommend use.

"Remember, the trouble with low specificity is it gives you false positive results," Caliendo said.

When to Use for Diagnosis

Caliendo said there are two scenarios when antibody testing may be useful for diagnosis.

The first is when patients come in with clear symptoms — cough, fever, a chest X-ray shows pneumonia in a pattern consistent with COVID-19 — but nucleic acid amplification tests are consistently negative.

The virus may no longer be in the nose but may have migrated to the lung and a serologic test may then be useful, especially if it has been 3 to 4 weeks since exposure, Caliendo said.

The other scenario is when a child presents with signs of multisystem inflammatory syndrome in children (MIS-C).

"Here we suggest using nucleic acid testing and serology to help make this diagnosis," Caliendo said. "In fact, now a positive IgG test is part of the definition of multisystem inflammatory syndrome in children."

She notes that children can present with MIS-C and not previously have had symptoms of COVID-19, so it can be difficult to sort out and diagnose.

Best Use for Antibody Tests is Surveillance

By far, the best use of antibody testing, the researchers said, is for serosurveillance — determining what percent of a population has been infected with the virus.

However, critical in use with surveillance, Caliendo said, is that the test used must have a very high specificity — at least 99.5%.

She gave the example of using an antibody test that appears good, with a sensitivity of 95% and a specificity of 99% in a large number of people where the actual prevalence of infection is low at 1%.

"There's going to be an equal number of true positive and false positive results, and your surveillance is going to be skewed," she said. It will appear that a much higher number of people are infected than are actually infected.

If those patients get results individually, they could also be misled to think they have had SARS-CoV-2 and are safe from reinfection, Caliendo added.

"It is essential that the laboratory and the clinicians using the laboratory understand the specific test the lab is using and what its performance characteristics are," she said.

IDSA's expert panel was made up of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature reviews. Members used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to make recommendations. Hanson and Caliendo have disclosed no relevant financial relationships.

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News and Nurse.com and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick.

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