Infectious disease society guidelines start clarifying use cases for COVID-19 serology
Guidelines released Thursday by the Infectious Diseases Society of America are beginning to spell out which questions serological tests can answer, and which are still out of reach.
Many hoped serological tests, which indicate past exposure to SARS-CoV-2 by detecting host antibodies against the virus, could identify who is protected from reinfection. IDSA made it clear there is still not enough evidence to infer protection from serology; however, it conditionally recommended three use cases for the tests, and parameters for how best to use them, based on a survey of thousands of papers that focused on 47 high-quality studies.
IDSA said the best use case for the tests is in serosurveillance studies to determine what percentage of the population has been infected by the virus. Given the large target populations for this use case and the likelihood of low prevalence, the society said it is essential to use very specific tests for this application, and recommended a specificity cutoff of 99.5% to minimize false positives (see “Good Test Hunting”).
In clinical settings, IDSA recommended using serological tests in patients who present with symptoms strongly suggestive of COVID-19, but test negative repeatedly for SARS-CoV-2 infection via molecular diagnostics. The hypothesis is that some patients might test negative because the infection has migrated deeper into their upper respiratory tract, out of the reach of swabs.
IDSA also recommended using serological tests in pediatric patients presenting with multisystem inflammatory syndrome, who may never have shown typical COVID-19 symptoms.
The society determined that the best time window for taking serological tests is three to four weeks after the onset of symptoms, and recommended against testing in the first one to two weeks after exposure given the high variability in test performance within that time frame.
In addition, while IgM antibodies are typically generated earlier than IgG in the context of other infections, that does not appear to be the case for SARS-CoV-2. That limits the advantage of testing for both IgM and IgG, the society said.
IDSA’s review also indicated rapid, lateral flow “dipstick” serology tests, which can be used at the point of care, had more variable performance compared with lab-based enzyme-linked immunosorbent assays (ELISAs) or chemiluminescent immunoassays. The society’s guidelines include data on the performance of the individual tests it evaluated.
Guideline co-author Angela Caliendo, a professor of medicine at Brown University, said the takeaway is not that rapid serology tests perform worse as a rule.
“It’s really a test-dependent phenomenon,” she said.