Antibody Testing Alone is Not the Key to Re-Opening Society
[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.
Your Future Smartphone May Detect Problems in Your Water
In 2014, the city of Flint, Michigan switched the residents' water supply to the Flint river, citing cheaper costs. However, due to improper filtering, lead contaminated this water, and according to the Associated Press, many of the city's residents soon reported health issues like hair loss and rashes. In 2015, a report found that children there had high levels of lead in their blood. The National Resource Defense Council recently discovered there could still be as many as twelve million lead pipes carrying water to homes across the U.S.
What if Flint residents and others in afflicted areas could simply flick water onto their phone screens and an app would tell them if they were about to drink contaminated water? This is what researchers at the University of Cambridge are working on to prevent catastrophes like what occurred in Flint, and to prepare for an uncertain future of scarcer resources.
Underneath the tough glass of our phone screen lies a transparent layer of electrodes. Because our bodies hold an electric charge, when our finger touches the screen, it disrupts the electric field created among the electrodes. This is how the screen can sense where a touch occurs. Cambridge scientists used this same idea to explore whether the screen could detect charges in water, too. Metals like arsenic and lead can appear in water in the form of ions, which are charged particles. When the ionic solution is placed on the screen's surface, the electrodes sense that charge like how they sense our finger.
Imagine a new generation of smartphones with a designated area of the screen responsible for detecting contamination—this is one of the possible futures the researchers propose.
The experiment measured charges in various electrolyte solutions on a touchscreen. The researchers found that a thin polymer layer between the electrodes and the sample solution helped pick up the charges.
"How can we get really close to the touch electrodes, and be better than a phone screen?" Horstmann, the lead scientist on the study, asked himself while designing the protective coating. "We found that when we put electrolytes directly on the electrodes, they were too close, even short-circuiting," he said. When they placed the polymer layer on top the electrodes, however, this short-circuiting did not occur. Horstmann speaks of the polymer layer as one of the key findings of the paper, as it allowed for optimum conductivity. The coating they designed was much thinner than what you'd see with a typical smartphone touchscreen, but because it's already so similar, he feels optimistic about the technology's practical applications in the real world.
While the Cambridge scientists were using touchscreens to measure water contamination, Dr. Baojun Wang, a synthetic biologist at the University of Edinburgh, along with his team, created a way to measure arsenic contamination in Bangladesh groundwater samples using what is called a cell-based biosensor. These biosensors use cornerstones of cellular activity like transcription and promoter sequences to detect the presence of metal ions in water. A promoter can be thought of as a "flag" that tells certain molecules where to begin copying genetic code. By hijacking this aspect of the cell's machinery and increasing the cell's sensing and signal processing ability, they were able to amplify the signal to detect tiny amounts of arsenic in the groundwater samples. All this was conducted in a 384-well plate, each well smaller than a pencil eraser.
They placed arsenic sensors with different sensitivities across part of the plate so it resembled a volume bar of increasing levels of arsenic, similar to diagnostics on a Fitbit or glucose monitor. The whole device is about the size of an iPhone, and can be scaled down to a much smaller size.
Dr. Wang says cell-based biosensors are bringing sensing technology closer to field applications, because their machinery uses inherent cellular activity. This makes them ideal for low-resource communities, and he expects his device to be affordable, portable, and easily stored for widespread use in households.
"It hasn't worked on actual phones yet, but I don't see any reason why it can't be an app," says Horstmann of their technology. Imagine a new generation of smartphones with a designated area of the screen responsible for detecting contamination—this is one of the possible futures the researchers propose. But industry collaborations will be crucial to making their advancements practical. The scientists anticipate that without collaborative efforts from the business sector, the public might have to wait ten years until this becomes something all our smartphones are capable of—but with the right partners, "it could go really quickly," says Dr. Elizabeth Hall, one of the authors on the touchscreen water contamination study.
"That's where the science ends and the business begins," Dr. Hall says. "There is a lot of interest coming through as a result of this paper. I think the people who make the investments and decisions are seeing that there might be something useful here."
As for Flint, according to The Detroit News, the city has entered the final stages in removing lead pipe infrastructure. It's difficult to imagine how many residents might fare better today if they'd had the technology that scientists are now creating.
Of all its tragedy, COVID-19 has increased demand for at-home testing methods, which has carried over to non-COVID-19-related devices. Various testing efforts are now in the public eye.
"I like that the public is watching these directions," says Horstmann. "I think there's a long way to go still, but it's exciting."
Fungus is the ‘New Black’ in Eco-Friendly Fashion
A natural material that looks and feels like real leather is taking the fashion world by storm. Scientists view mycelium—the vegetative part of a mushroom-producing fungus—as a planet-friendly alternative to animal hides and plastics.
Products crafted from this vegan leather are emerging, with others poised to hit the market soon. Among them are the Hermès Victoria bag, Lululemon's yoga accessories, Adidas' Stan Smith Mylo sneaker, and a Stella McCartney apparel collection.
The Adidas' Stan Smith Mylo concept sneaker, made in partnership with Bolt Threads, uses an alternative leather grown from mycelium; a commercial version is expected in the near future.
Adidas
Hermès has held presales on the new bag, says Philip Ross, co-founder and chief technology officer of MycoWorks, a San Francisco Bay area firm whose materials constituted the design. By year-end, Ross expects several more clients to debut mycelium-based merchandise. With "comparable qualities to luxury leather," mycelium can be molded to engineer "all the different verticals within fashion," he says, particularly footwear and accessories.
More than a half-dozen trailblazers are fine-tuning mycelium to create next-generation leather materials, according to the Material Innovation Initiative, a nonprofit advocating for animal-free materials in the fashion, automotive, and home-goods industries. These high-performance products can supersede items derived from leather, silk, down, fur, wool, and exotic skins, says A. Sydney Gladman, the institute's chief scientific officer.
That's only the beginning of mycelium's untapped prowess. "We expect to see an uptick in commercial leather alternative applications for mycelium-based materials as companies refine their R&D [research and development] and scale up," Gladman says, adding that "technological innovation and untapped natural materials have the potential to transform the materials industry and solve the enormous environmental challenges it faces."
In fewer than 10 days in indoor agricultural farms, "we grow large slabs of mycelium that are many feet wide and long. We are not confined to the shape or geometry of an animal."
Reducing our carbon footprint becomes possible because mycelium can flourish in indoor farms, using agricultural waste as feedstock and emitting inherently low greenhouse gas emissions. Carbon dioxide is the primary greenhouse gas. "We often think that when plant tissues like wood rot, that they go from something to nothing," says Jonathan Schilling, professor of plant and microbial biology at the University of Minnesota and a member of MycoWorks' Scientific Advisory Board.
But that assumption doesn't hold true for all carbon in plant tissues. When the fungi dominating the decomposition of plants fulfill their function, they transform a large portion of carbon into fungal biomass, Schilling says. That, in turn, ends up in the soil, with mycelium forming a network underneath that traps the carbon.
Unlike the large amounts of fossil fuels needed to produce styrofoam, leather and plastic, less fuel-intensive processing is involved in creating similar materials with a fungal organism. While some fungi consist of a single cell, others are multicellular and develop as very fine threadlike structures. A mass of them collectively forms a "mycelium" that can be either loose and low density or tightly packed and high density. "When these fungi grow at extremely high density," Schilling explains, "they can take on the feel of a solid material such as styrofoam, leather or even plastic."
Tunable and supple in the cultivation process, mycelium is also reliably sturdy in composition. "We believe that mycelium has some unique attributes that differentiate it from plastic-based and animal-derived products," says Gavin McIntyre, who co-founded Ecovative Design, an upstate New York-based biomaterials company, in 2007 with the goal of displacing some environmentally burdensome materials and making "a meaningful impact on our planet."
After inventing a type of mushroom-based packaging for all sorts of goods, in 2013 the firm ventured into manufacturing mycelium that can be adapted for textiles, he says, because mushrooms are "nature's recycling system."
The company aims for its material—which is "so tough and tenacious" that it doesn't require any plastic add-on as reinforcement—to be generally accessible from a pricing standpoint and not confined to a luxury space. The cost, McIntyre says, would approach that of bovine leather, not the more upscale varieties of lamb and goat skins.
Already, production has taken off by leaps and bounds. In fewer than 10 days in indoor agricultural farms, "we grow large slabs of mycelium that are many feet wide and long," he says. "We are not confined to the shape or geometry of an animal," so there's a much lower scrap rate.
Decreasing the scrap rate is a major selling point. "Our customers can order the pieces to the way that they want them, and there is almost no waste in the processing," explains Ross of MycoWorks. "We can make ours thinner or thicker," depending on a client's specific needs. Growing materials locally also results in a reduction in transportation, shipping, and other supply chain costs, he says.
Yet another advantage to making things out of mycelium is its biodegradability at the end of an item's lifecycle. When a pair of old sneakers lands in a compost pile or landfill, it decomposes thanks to microbial processes that, once again, involve fungi. "It is cool to think that the same organism used to create a product can also be what recycles it, perhaps building something else useful in the same act," says biologist Schilling. That amounts to "more than a nice business model—it is a window into how sustainability works in nature."
A product can be called "sustainable" if it's biodegradable, leaves a minimal carbon footprint during production, and is also profitable, says Preeti Arya, an assistant professor at the Fashion Institute of Technology in New York City and faculty adviser to a student club of the American Association of Textile Chemists and Colorists.
On the opposite end of the spectrum, products composed of petroleum-based polymers don't biodegrade—they break down into smaller pieces or even particles. These remnants pollute landfills, oceans, and rivers, contaminating edible fish and eventually contributing to the growth of benign and cancerous tumors in humans, Arya says.
Commending the steps a few designers have taken toward bringing more environmentally conscious merchandise to consumers, she says, "I'm glad that they took the initiative because others also will try to be part of this competition toward sustainability." And consumers will take notice. "The more people become aware, the more these brands will start acting on it."
A further shift toward mycelium-based products has the capability to reap tremendous environmental dividends, says Drew Endy, associate chair of bioengineering at Stanford University and president of the BioBricks Foundation, which focuses on biotechnology in the public interest.
The continued development of "leather surrogates on a scaled and sustainable basis will provide the greatest benefit to the greatest number of people, in perpetuity," Endy says. "Transitioning the production of leather goods from a process that involves the industrial-scale slaughter of vertebrate mammals to a process that instead uses renewable fungal-based manufacturing will be more just."