NEW YORK (Reuters Health) - Given what little we know about the immune response to SARS-CoV-2, it remains unclear what role serologic testing for antibodies to the virus should play, according to a commentary.
“There is too much uncertainty in serologic testing to have it play any role in disease management or policy at this time,” coauthor Dr. Richard Torres from Yale University School of Medicine’s Department of Laboratory Medicine, New Haven, Connecticut, told Reuters Health by email.
Various real and self-proclaimed experts, as well as politicians and other professionals, have advocated for SARS-CoV-2 antibody testing to identify individuals who have developed immunity and could potentially reenter the workplace safely despite the ongoing presence of the virus.
Dr. Torres and Dr. Henry M. Rinder consider whether SARS-CoV-2 serologic tests are safe for those purposes in their online American Journal of Clinical Pathology editorial.
What we know now, they say, is that individuals with symptomatic SARS-CoV-2 infection generally will not have detectable antibodies to SARS-CoV-2 within the first week of the onset of symptoms. Most hospitalized individuals with confirmed SARS-CoV-2 infection will have detectable IgG antibodies 14 to 28 days after symptom onset.
It remains unclear, however, whether the presence of antibodies to SARS-CoV-2 confers protection, especially in seriously ill patients. About one-third of SARS-CoV-2-infected patients who developed antibodies during hospitalization appeared to lack antibodies that neutralize virus in plaque growth assays, the standard test for antibody effectiveness.
Moreover, the presence of antibodies does not guarantee that an individual is noninfectious; there may still be active viral shedding, especially if the antibodies are non-neutralizing.
The quality of serologic tests could also be an issue. Although there has been minimal cross-reactivity with the 4 prevalent non-SARS-CoV-2 coronaviruses, validation studies are still required to eliminate the risk that some assays may just reflect prior exposure to the common cold.
Finally, virtually nothing is known about the patterns of antibody response to SARS-CoV-2 in asymptomatic individuals or the correlation of antibody response with susceptibility to reinfection.
“The best test for susceptibility to infection from SARS-CoV-2 will depend heavily on a better understanding of the pathophysiology of the disease,” Dr. Torres said. “Specifically, we need to know if antibodies are a requirement for preventing symptomatic disease or whether other aspects of the immune system can defend without relying on the antibodies. And if we do need antibodies, how many antibodies do we need and what part of the virus they need to be directed to.”
“The best ‘test’ may remain a simple symptom screen,” he said. “In the interim, monitoring individuals with direct nucleic acid testing for SARS-CoV-2 viral RNA (and symptom screens) and then characterizing the rate of recovery and any reinfection (if it occurs) is likely to help sort out susceptibility risk both in any given individual and the population at large.”
Dr. Torres concluded, “We cannot assess the value of serology until it is properly paired with nucleic acid testing and long-term follow-up in a well-designed study, so it should not be used for policy. We do not need to test everyone to get the answers we need. Smart sampling, good data collection, and strong statistical analysis should get us the information we desperately need.”
Dr. Bobbi S. Pritt, a clinical microbiologist involved in the COVID-19 response at Mayo Clinic, Rochester, Minnesota, told Reuters Health by email, “A neutralizing antibody test is required to determine if the antibodies that a particular individual is producing will actually protect them from reinfection with SARS-CoV-2. A serology test cannot tell if someone is no longer infectious. However, one or more negative PCR tests for SARS-CoV-2 can be used for this purpose, in conjunction with resolution of clinical symptoms.”
“There are many caveats to serologic testing,” she said. “Serology cannot, unfortunately, be used as a reliable immunologic passport to send people back to work.”
Dr. Patrick S. Sullivan, epidemiologist from Emory University Rollins School of Public Health, Atlanta, Georgia, who is currently testing the ability of patients to self-collect sufficient specimens for SARS-CoV-2 viral detection and serology, told Reuters Health by email, “One issue that is going to be important in clinical practice is the understanding that in low prevalence populations, such as population screening irrespective of symptoms, that many of the positive results on antibody tests may well be false positive results. So population-based screening programs will provide some information about immunologic experience with the virus among those populations, but for any individual participant in those studies the meaning of a positive test may be unclear.”
“I’m a public health guy, so I think I would make the case that we should be focusing more on population-based studies that will give us unbiased estimates of the extent of exposure to SARS Co V2 in populations, rather than on convenience samples or studies that are intended to inform putative immunity or back to work policies,” he said. “In many senses, trends over time in the prevalence of antibodies in populations are more likely to provide credible information about the condition of communities and the potential for herd immunity, compared to looking at individual results of tests and trying to decide which individuals might be immune.”
“We need to have an appropriate degree of humility about what we don’t know about the meaning of this current generation of antibody tests, especially when trying to interpret the clinical significance of any particular test for a specific patient,” Dr. Sullivan said.
SOURCE: bit.ly/2xqoyNw American Journal of Clinical Pathology, online April 23, 2020.