Antibody Testing Alone is Not the Key to Re-Opening Society

Antibody Testing Alone is Not the Key to Re-Opening Society

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.

Angela Rasmussen
Dr. Angela Rasmussen uses systems biology techniques to interrogate the host response to viral infection. She has studied a huge range of viral pathogens, from the “common cold” (rhinovirus) to Ebola virus to highly pathogenic avian influenza virus to SARS-CoV-2/COVID-19. By combining current classical approaches to modeling infection and pathogenesis with sequencing technology and machine learning, Dr. Rasmussen and her colleagues and collaborators have identified new host mechanisms by which viruses cause disease.
Scientists turn pee into power in Uganda

With conventional fuel cells as their model, researchers learned to use similar chemical reactions to make a fuel from microbes in pee.

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At the edge of a dirt road flanked by trees and green mountains outside the town of Kisoro, Uganda, sits the concrete building that houses Sesame Girls School, where girls aged 11 to 19 can live, learn and, at least for a while, safely use a toilet. In many developing regions, toileting at night is especially dangerous for children. Without electrical power for lighting, kids may fall into the deep pits of the latrines through broken or unsteady floorboards. Girls are sometimes assaulted by men who hide in the dark.

For the Sesame School girls, though, bright LED lights, connected to tiny gadgets, chased the fears away. They got to use new, clean toilets lit by the power of their own pee. Some girls even used the light provided by the latrines to study.

Urine, whether animal or human, is more than waste. It’s a cheap and abundant resource. Each day across the globe, 8.1 billion humans make 4 billion gallons of pee. Cows, pigs, deer, elephants and other animals add more. By spending money to get rid of it, we waste a renewable resource that can serve more than one purpose. Microorganisms that feed on nutrients in urine can be used in a microbial fuel cell that generates electricity – or "pee power," as the Sesame girls called it.

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Jenny Morber
Jenny Morber was trained as a scientist and engineer at Georgia Tech, then lost all chance at a Nobel Prize by pivoting to journalism. She writes from the mossy Pacific Northwest about science, people and the world. She misses seeing atoms but is grateful that her days are filled with fresh air, new ideas and interesting people.
Friday Five: "Cyclic breathing" can increase well-being, Stanford scientists find

In this week's Friday Five, breathing this way may cut down on anxiety, a fasting regimen that could make you sick, this type of job makes men more virile, 3D printed hearts could save your life, and the role of metformin in preventing dementia.

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The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.

Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.

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Matt Fuchs
Matt Fuchs is the host of the Making Sense of Science podcast and served previously as the editor-in-chief of Leaps.org. He writes as a contributor to the Washington Post, and his articles have also appeared in the New York Times, WIRED, Nautilus Magazine, Fortune Magazine and TIME Magazine. Follow him @fuchswriter.