Immunity tests have too many unknowns right now to make them very useful in determining protective antibody status.

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[Editor's Note: We asked experts from different specialties to weigh in on a timely Big Question: "How should immunity testing play a role in re-opening society?" Below, a virologist offers her perspective.]

With the advent of serology testing and increased emphasis on "re-opening" America, public health officials have begun considering whether or not people who have recovered from COVID-19 can safely re-enter the workplace.
"Immunity certificates cannot certify what is not known."

Conventional wisdom holds that people who have developed antibodies in response to infection with SARS-CoV-2, the coronavirus that causes COVID-19, are likely to be immune to reinfection.

For most acute viral infections, this is generally true. However, SARS-CoV-2 is a new pathogen, and there are currently many unanswered questions about immunity. Can recovered patients be reinfected or transmit the virus? Does symptom severity determine how protective responses will be after recovery? How long will protection last? Understanding these basic features is essential to phased re-opening of the government and economy for people who have recovered from COVID-19.

One mechanism that has been considered is issuing "immunity certificates" to individuals with antibodies against SARS-CoV-2. These certificates would verify that individuals have already recovered from COVID-19, and thus have antibodies in their blood that will protect them against reinfection, enabling them to safely return to work and participate in society. Although this sounds reasonable in theory, there are many practical reasons why this is not a wise policy decision to ease off restrictive stay-home orders and distancing practices.

Too Many Scientific Unknowns

Serology tests measure antibodies in the serum—the liquid component of blood, which is where the antibodies are located. In this case, serology tests measure antibodies that specifically bind to SARS-CoV-2 virus particles. Usually when a person is infected with a virus, they develop antibodies that can "recognize" that virus, so the presence of SARS-CoV-2 antibodies indicates that a person has been previously exposed to the virus. Broad serology testing is critical to knowing how many people have been infected with SARS-CoV-2, since testing capacity for the virus itself has been so low.

Tests for the virus measure amounts of SARS-CoV-2 RNA—the virus's genetic material—directly, and thus will not detect the virus once a person has recovered. Thus, the majority of people who were not severely ill and did not require hospitalization, or did not have direct contact with a confirmed case, will not test positive for the virus weeks after they have recovered and can only determine if they had COVID-19 by testing for antibodies.

In most cases, for most pathogens, antibodies are also neutralizing, meaning they bind to the virus and render it incapable of infecting cells, and this protects against future infections. Immunity certificates are based on the assumption that people with antibodies specific for SARS-CoV-2 will be protected against reinfection. The problem is that we've only known that SARS-CoV-2 existed for a little over four months. Although studies so far indicate that most (but not all) patients with confirmed COVID-19 cases develop antibodies, we don't know the extent to which antibodies are protective against reinfection, or how long that protection will last. Immunity certificates cannot certify what is not known.

The limited data so far is encouraging with regard to protective immunity. Most of the patient sera tested for antibodies show reasonable titers of IgG, the type of antibodies most likely to be neutralizing. Furthermore, studies have shown that these IgG antibodies are capable of neutralizing surrogate viruses as well as infectious SARS-CoV-2 in laboratory tests. In addition, rhesus monkeys that were experimentally infected with SARS-CoV-2 and allowed to recover were protected from reinfection after a subsequent experimental challenge. These data tentatively suggest that most people are likely to develop neutralizing IgG, and protective immunity, after being infected by SARS-CoV-2.

However, not all COVID-19 patients do produce high levels of antibodies specific for SARS-CoV-2. A small number of patients in one study had no detectable neutralizing IgG. There have also been reports of patients in South Korea testing PCR positive after a prior negative test, indicating reinfection or reactivation. These cases may be explained by the sensitivity of the PCR test, and no data have been produced to indicate that these cases are genuine reinfection or recurrence of viral infection.

Complicating matters further, not all serology tests measure antibody titers. Some rapid serology tests are designed to be binary—the test can either detect antibodies or not, but does not give information about the amount of antibodies circulating. Based on our current knowledge, we cannot be certain that merely having any level of detectable antibodies alone guarantees protection from reinfection, or from a subclinical reinfection that might not cause a second case of COVID-19, but could still result in transmission to others. These unknowns remain problematic even with tests that accurately detect the presence of antibodies—which is not a given today, as many of the newly available tests are reportedly unreliable.

A Logistical and Ethical Quagmire

While most people are eager to cast off the isolation of physical distancing and resume their normal lives, mere desire to return to normality is not an indicator of whether those antibodies actually work, and no certificate can confer immune protection. Furthermore, immunity certificates could lead to some complicated logistical and ethical issues. If antibodies do not guarantee protective immunity, certifying that they do could give antibody-positive people a false sense of security, causing them to relax infection control practices such as distancing and hand hygiene.

"We should not, however, place our faith in assumptions and make return to normality contingent on an arbitrary and uninformative piece of paper."

Certificates could be forged, putting susceptible people at higher exposure risk. It's not clear who would issue them, what they would entitle the bearer to do or not do, or how certification would be verified or enforced. There are many ways in which such certificates could be used as a pretext to discriminate against people based on health status, in addition to disability, race, and socioeconomic status. Tracking people based on immune status raises further concerns about privacy and civil rights.

Rather than issuing documents confirming immune status, we should instead "re-open" society cautiously, with widespread virus and serology testing to accurately identify and isolate infected cases rapidly, with immediate contact tracing to safely quarantine and monitor those at exposure risk. Broad serosurveillance must be coupled with functional assays for neutralization activity to begin assessing how protective antibodies might actually be against SARS-CoV-2 infection. To understand how long immunity lasts, we should study antibodies, as well as the functional capabilities of other components of the larger immune system, such as T cells, in recovered COVID-19 patients over time.

We should not, however, place our faith in assumptions and make return to normality contingent on an arbitrary and uninformative piece of paper. Re-opening society, the government, and the economy depends not only on accurately determining how many people have antibodies to SARS-CoV-2, but on a deeper understanding of how those antibodies work to provide protection.

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The event on November 12th will explore what lies ahead for science and policy in the near-future.

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EVENT INFORMATION

________

Date

Thu Nov 12, 2020 12:00pm - 1:10pm EDT

                            


Contact

kira@goodinc.com

Location

Virtual

Hosts

LeapsMag, the Aspen Institute's Science and Society Program, and GOOD

"The Future of Science in America Summit" will dive into the high stakes ahead as we emerge from a hotly contested election, with the pandemic on the upswing.

Through rotating paired conversations with five experts from academia, industry, advocacy, and government, followed by a public Q&A, this event will explore (re)building public trust in science, the latest science and policy developments on the COVID vaccine front, and moonshots in science that deserve prioritization over the next four years.


________

Nancy Messonnier, M.D.
Director of the National Center for Immunization and Respiratory Diseases (NCIRD)

Saad Amer
Founder, Plus1Vote, a nonprofit organization dedicated to getting out the vote on issues such as climate change and equality

France Córdova, Ph.D.
Astrophysicist, past Director of the National Science Foundation, past President of Purdue University

Joseph DeRisi, Ph.D.
Professor of Biochemistry and Biophysics, University of California San Francisco and Co-President, Chan Zuckerberg Biohub

Seema Kumar
Global Head of the Office of Innovation, Global Health, and Policy Communication, Johnson & Johnson

Michelle McMurry-Heath, M.D., Ph.D.
President and CEO of the Biotechnology Innovation Organization (BIO)

This summit is co-hosted by LeapsMag, the Aspen Institute Science & Society Program, and the social impact company GOOD, with support from the Gordon and Betty Moore Foundation and the Rita Allen Foundation.

The event accompanies our recently published digital magazine, The Future of Science in America: The Election Issue.

Kira Peikoff
Kira Peikoff is a journalist whose work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and son.

Understanding the vulnerabilities of our own brains can help us guard against fake news.

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This article is part of the magazine, "The Future of Science In America: The Election Issue," co-published by LeapsMag, the Aspen Institute Science & Society Program, and GOOD.

Whenever you hear something repeated, it feels more true. In other words, repetition makes any statement seem more accurate. So anything you hear again will resonate more each time it's said.

Do you see what I did there? Each of the three sentences above conveyed the same message. Yet each time you read the next sentence, it felt more and more true. Cognitive neuroscientists and behavioral economists like myself call this the "illusory truth effect."

Go back and recall your experience reading the first sentence. It probably felt strange and disconcerting, perhaps with a note of resistance, as in "I don't believe things more if they're repeated!"

Reading the second sentence did not inspire such a strong reaction. Your reaction to the third sentence was tame by comparison.

Why? Because of a phenomenon called "cognitive fluency," meaning how easily we process information. Much of our vulnerability to deception in all areas of life—including to fake news and misinformation—revolves around cognitive fluency in one way or another. And unfortunately, such misinformation can swing major elections.

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Gleb Tsipursky
Dr. Gleb Tsipursky is an internationally recognized thought leader on a mission to protect leaders from dangerous judgment errors known as cognitive biases by developing the most effective decision-making strategies. A best-selling author, he wrote Resilience: Adapt and Plan for the New Abnormal of the COVID-19 Coronavirus Pandemic and Pro Truth: A Practical Plan for Putting Truth Back Into Politics. His expertise comes from over 20 years of consulting, coaching, and speaking and training as the CEO of Disaster Avoidance Experts, and over 15 years in academia as a behavioral economist and cognitive neuroscientist. He co-founded the Pro-Truth Pledge project.