COVID-19 antibody testing. What is it good for?
While it’s too soon to use COVID-19 antibody testing to issue “immunity passports,” the antibody tests available today are good enough to inform decisions about public health, such as how and when to relax social distancing interventions, according to an international group of infectious disease and public health experts. The team’s editorial appeared on May 19 in Science Immunology.
“Antibody tests to detect exposure to SARS-CoV-2, the virus responsible for COVID-19, are rapidly becoming available, and everyone — from governments to medical professionals to employers to individuals — is eager to use them to understand their own health status and to get back to normal life,” said Matthew Ferrari, associate professor of biology at Penn State. “These tests can and should be used right now to monitor large populations of people; however, they are not yet reliable enough to evaluate immunity among individuals.”
For example, he said, some have suggested that detecting antibodies to SARS-CoV-2 become the basis of “immunity passports” that enable people to return to work or school, or to travel. Yet, facts indicate that it is premature to take that step. For one, scientists have yet to determine whether the antibodies, or perhaps a threshold level of antibodies, protect a person from being re-infected. For another, there are multiple antibody tests, none with the levels of specificity needed to declare someone immune.
“In short, we are far from being at a place where a positive antibody test guarantees that a person cannot get COVID-19, nor spread it to someone else,” said Ferrari. “And the stakes are too high to risk getting it wrong.”
Regardless, current antibody tests — also called serological tests — are good enough to monitor the spread of COVID-19 in populations. “There is no need to throw out the baby with the bathwater,” said corresponding author, Daniel Leung, associate professor of internal medicine at University of Utah Health. “We can use serological testing at the population level to get valuable information about transmission and the impact of interventions, and we don’t need a perfect serology test to do it.”
For instance, the tests can help decision makers determine where outbreaks are occurring, who is getting ill and who is protected, if certain populations need extra protection, whether or not specific counties are ready to ease restrictions, and if students are safe to go back to school.
One reason many of today’s tests can work for such public-level decisions is that they do not just give black-and-white answers. Instead, their parameters can be adjusted to fit different needs. One of these characteristics is specificity — how well a test detects antibodies to SARS-CoV-2 and not to antibodies against other coronaviruses. The other is sensitivity — the minimum level of antibodies someone must have in their blood in order to test positive.
“In general, there is a tradeoff between the two,” said Maciej Boni, associate professor of biology at Penn State. “Adjusting a test to prioritize sensitivity makes it not as specific and making a test more specific makes it less sensitive. But it’s okay to sacrifice one for the other in order to answer certain questions.”
Take the situation in a rural countryside where relatively few people have had COVID-19 per capita, Boni explained. In that setting, a test with high sensitivity and low specificity would not be optimal. These characteristics could easily result in the same number of people testing positive who never had COVID-19 as the number of people who really are positive. In this situation, the results would be practically meaningless.
However, the same test can be used if it is tuned for that situation. This can be done by designating a higher cutoff and saying that a test does not count as positive unless it has a stronger signal. Doing so lowers the false positive rate by increasing specificity. In this scenario, positive tests are more likely to be truly positive and that data can be safely used to monitor that population.
On the other hand, an urban setting where higher proportions of the population have been infected would do better with a test prioritized for higher sensitivity. That would give a better snapshot of the spread of COVID-19 by capturing a greater segment of the population.
“Additional studies will only make the results of antibody testing more informative,” said Boni. “For example, we still need to understand whether antibodies remain in the body for months or years, what levels of antibodies provide immunity, and how responses might differ in people who had various severity of infection, or who have other medical conditions.”
The authors noted that equally as important as leveraging the technologies at hand is building an infrastructure that allows states and countries to share protocols, standardize methods, share results and coordinate activities. This would not only improve the response to the current pandemic but could build a foundation for monitoring other infectious diseases, including influenza, cholera, malaria and future pandemics.
“The current crisis presents an opportunity to rethink how health systems generate and use surveillance data,” said Ferrari. “The lessons we are learning from the rapid deployment of these for COVID-19 are opportunities to develop serology as a powerful public health tool around the world.”
Other authors on the paper include Juliet Bryant, Laboratory of Emerging Pathogens, Fondation Mérieux, Lyon, France; Andrew Azman and Kyla Hayford, Johns Hopkins Bloomberg School of Public Health; Benjamin Arnold and Isabel Rodriguez-Barraquer, University of California San Francisco; Yap Boum and Francisco Luquero, Epicentre; Michael Mina, Harvard School of Public Health; Joseph Wu, the University of Hong Kong; Djibril Wade, Institut de Recherche en Santé, Dakar, Senegal; and Guy Vernet, Institut Pasteur de Bangui, Central African Republic.