‘Sweet Spot’ for antibody testing is 3 to 4 weeks postexposure


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The Infectious Diseases Society of America (IDSA) is advised 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 tests is 3 to 4 weeks after exposure, Angela M. Caliendo, MD, PhD, professor and executive vice president with the Department of Medicine at Brown University in Providence, Rhode Island, told reporters. tomorrow in a media briefing.

The IDSA released its guidelines for antibody testing this week.

The IDSA expert panel analyzed 47 published studies and found that in the first 2 weeks after exposure, many patients had 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 as clinicians see that a patient has symptoms within the first 2 weeks, but the test of antibody is negative, “you really can not rule out the possibility that patients may still have COVID-19.”

The researchers said they were surprised to learn that an immunoglobulin M (IgM) test “does not really have much added value about IgG (immunoglobulin G).” IgM antibodies typically appear earlier, but not for SARS-CoV-2, Caliendo said.

“If you use IgM, it will be less sensitive. You will miss some people who are actually 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 will minimize the number of wrong results if [you] use an IgG test as a total antibody test 3 to 4 weeks after the onset of symptoms. “

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

Point-of-care tests that are lateral flow devices may detect and distinguish between IgM and IgG, but the panel did not find them specific enough to recommend use.

“Remember, the problem with low specificity is that you give false positive results,” Caliendo said.

When to use for diagnosis

Caliendo said there are two scenarios where antibody testing could be useful for diagnosis.

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

The virus may no longer be in the nose, but may have migrated to the lung and a serological test may then be helpful, especially if it is 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 propose to use nucleic acid testing and serology to make this diagnosis,” Caliendo said. “In fact, a positive IgG test is now part of the definition of multisystem inflammatory syndrome in children.”

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

The best use for antibody testing is supervision

Remote is the best use of anticrochet testing, the researchers said, for serosurveillance – determining what percentage of a population is infected with the virus.

However, critical in use in supervision, 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 will be an equal number of true positive and false positive results, and your oversight will be skewed,” she said. It will turn out that a much higher number of people are infected than are actually infected.

If those patients get individual results, they may also be misled into thinking they have SARS-CoV-2 and are safe from reinfection, Caliendo added.

“It is essential that the laboratory and the physicians who use the laboratory understand the specific test that the lab uses and what the performance characteristics are,” she said.

IDSA’s expert panel consisted of infectious disease clinicians, clinical microbiologists, and experts in systematic literature reviews. Members used the Grading or Recommendations Assessment, Development and Evaluation (GRADE) method to make recommendations. Hanson and Caliendo have not disclosed any relevant financial relationships.

Marcia Frellick is a Chicago-based freelance journalist. 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 @mfrellick.

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