Blood Money: Paying for Convalescent Plasma to Treat COVID-19
Convalescent plasma – first used to treat diphtheria in 1890 – has been dusted off the shelf to treat COVID-19. Does it work? Should we rely strictly on the altruism of donors or should people be paid for it?
The biologic theory is that a person who has recovered from a disease has chemicals in their blood, most likely antibodies, that contributed to their recovery, and transferring those to a person who is sick might aid their recovery. Whole blood won't work because there are too few antibodies in a single unit of blood and the body can hold only so much of it.
Plasma comprises about 55 percent of whole blood and is what's left once you take out the red blood cells that carry oxygen and the white blood cells of the immune system. Most of it is water but the rest is a complex mix of fats, salts, signaling molecules and proteins produced by the immune system, including antibodies.
A process called apheresis circulates the donors' blood through a machine that separates out the desired parts of blood and returns the rest to the donor. It takes several times the length of a regular whole blood donation to cycle through enough blood for the process. The end product is a yellowish concentration called convalescent plasma.
Recent History
It was used extensively during the great influenza epidemic off 1918 but fell out of favor with the development of antibiotics. Still, whenever a new disease emerges – SARS, MERS, Ebola, even antibiotic-resistant bacteria – doctors turn to convalescent plasma, often as a stopgap until more effective antibiotic and antiviral drugs are developed. The process is certainly safe when standard procedures for handling blood products are followed, and historically it does seem to be beneficial in at least some patients if administered early enough in the disease.
With few good treatment options for COVID-19, doctors have given convalescent plasma to more than a hundred thousand Americans and tens of thousand of people elsewhere, to mixed results. Placebo-controlled trials could give a clearer picture of plasma's value but it is difficult to enroll patients facing possible death when the flip of a coin will determine who will receive a saline solution or plasma.
And the plasma itself isn't some uniform pill stamped out in a factory, it's a natural product that is shaped by the immune history of the donor's body and its encounter not just with SARS-CoV-2 but a lifetime of exposure to different pathogens.
Researchers believe antibodies in plasma are a key factor in directly fighting the virus. But the variety and quantity of antibodies vary from donor to donor, and even over time from the same donor because once the immune system has cleared the virus from the body, it stops putting out antibodies to fight the virus. Often the quality and quantity of antibodies being given to a patient are not measured, making it somewhat hit or miss, which is why several companies have recently developed monoclonal antibodies, a single type of antibody found in blood that is effective against SARS-CoV-2 and that is multiplied in the lab for use as therapy.
Plasma may also contain other unknown factors that contribute to fighting disease, say perhaps signaling molecules that affect gene expression, which might affect the movement of immune cells, their production of antiviral molecules, or the regulation of inflammation. The complexity and lack of standardization makes it difficult to evaluate what might be working or not with a convalescent plasma treatment. Thus researchers are left with few clues about how to make it more effective.
Industrializing Plasma
Many Americans living along the border with Mexico regularly head south to purchase prescription drugs at a significant discount. Less known is the medical traffic the other way, Mexicans who regularly head north to be paid for plasma donations, which are prohibited in their country; the U.S. allows payment for plasma donations but not whole blood. A typical payment is about $35 for a donation but the sudden demand for convalescent plasma from people who have recovered from COVID-19 commands a premium price, sometimes as high as $200. These donors are part of a fast-growing plasma industry that surpassed $25 billion in 2018. The U.S. supplies about three-quarters of the world's needs for plasma.
Payment for whole blood donation in the U.S. is prohibited, and while payment for plasma is allowed, there is a stigma attached to payment and much plasma is donated for free.
The pharmaceutical industry has shied away from natural products they cannot patent but they have identified simpler components from plasma, such as clotting factors and immunoglobulins, that have been turned into useful drugs from this raw material of plasma. While some companies have retooled to provide convalescent plasma to treat COVID-19, often paying those donors who have recovered a premium of several times the normal rate, most convalescent plasma has come as donations through traditional blood centers.
In April the Mayo Clinic, in cooperation with the FDA, created an expanded access program for convalescent plasma to treat COVID-19. It was meant to reduce the paperwork associated with gaining access to a treatment not yet approved by the FDA for that disease. Initially it was supposed to be for 5000 units but it quickly grew to more than twenty times that size. Michael Joyner, the head of the program, discussed that experience in an extended interview in September.
The Centers for Medicare and Medicaid Services (CMS) also created associated reimbursement codes, which became permanent in August.
Mayo published an analysis of the first 35,000 patients as a preprint in August. It concluded, "The relationships between mortality and both time to plasma transfusion, and antibody levels provide a signature that is consistent with efficacy for the use of convalescent plasma in the treatment of hospitalized COVID-19 patients."
It seemed to work best when given early in infection and in larger doses; a similar pattern has been seen in studies of monoclonal antibodies. A revised version will soon be published in a major medical journal. Some criticized the findings as not being from a randomized clinical trial.
Convalescent plasma is not the only intervention that seems to work better when used earlier in the course of disease. Recently the pharmaceutical company Eli Lilly stopped a clinical trial of a monoclonal antibody in hospitalized COVID-19 patients when it became apparent it wasn't helping. It is continuing trials for patients who are less sick and begin treatment earlier, as well as in persons who have been exposed to the virus but not yet diagnosed as infected, to see if it might prevent infection. In November the FDA eased access to this drug outside of clinical trials, though it is not yet approved for sale.
Show Me the Money
The antibodies that seem to give plasma its curative powers are fragile proteins that the body produces to fight the virus. Production shuts down once the virus is cleared and the remaining antibodies survive only for a few weeks before the levels fade. [Vaccines are used to train immune cells to produce antibodies and other defenses to respond to exposure to future pathogens.] So they can be usefully harvested from a recovered patient for only a few short weeks or months before they decline precipitously. The question becomes, how does one mobilize this resource in that short window of opportunity?
The program run by the Mayo Clinic explains the process and criteria for donating convalescent plasma for COVID-19, as well as links to local blood centers equipped to handle those free donations. Commercial plasma centers also are advertising and paying for donations.
A majority of countries prohibit paying donors for blood or blood products, including India. But an investigation by India Today touted a black market of people willing to donate convalescent plasma for the equivalent of several hundred dollars. Officials vowed to prosecute, saying donations should be selfless.
But that enforcement threat seemed to be undercut when the health minister of the state of Assam declared "plasma donors will get preference in several government schemes including the government job interview." It appeared to be a form of compensation that far surpassed simple cash.
The small city of Rexburg, Idaho, with a population a bit over 50,000, overwhelmingly Mormon and home to a campus of Brigham Young University, at one point had one of the highest per capita rates of COVID-19 in the current wave of infection. Rumors circulated that some students were intentionally trying to become infected so they could later sell their plasma for top dollar, potentially as much as $200 a visit.
Troubled university officials investigated the allegations but could come up with nothing definitive; how does one prove intentionality with such an omnipresent yet elusive virus? They chalked it up to idle chatter, perhaps an urban legend, which might be associated with alcohol use on some other campus.
Doctors, hospitals, and drug companies are all rightly praised for their altruism in the fight against COVID-19, but they also get paid. Payment for whole blood donation in the U.S. is prohibited, and while payment for plasma is allowed, there is a stigma attached to payment and much plasma is donated for free. "Why do we expect the donors [of convalescent plasma] to be the only uncompensated people in the process? It really makes no sense," argues Mark Yarborough, an ethicist at the UC Davis School of Medicine in Sacramento.
"When I was in grad school, two of my closest friends, at least once a week they went and gave plasma. That was their weekend spending money," Yarborough recalls. He says upper and middle-income people may have the luxury of donating blood products but prohibiting people from selling their plasma is a bit paternalistic and doesn't do anything to improve the economic status of poor people.
"Asking people to dedicate two hours a week for an entire year in exchange for cookies and milk is demonstrably asking too much," says Peter Jaworski, an ethicist who teaches at Georgetown University.
He notes that companies that pay plasma donors have much lower total costs than do operations that rely solely on uncompensated donations. The companies have to spend less to recruit and retain donors because they increase payments to encourage regular repeat donations. They are able to more rationally schedule visits to maximize use of expensive apheresis equipment and medical personnel used for the collection.
It seems that COVID-19 has been with us forever, but in reality it is less than a year. We have learned much over that short time, can now better manage the disease, and have lower mortality rates to prove it. Just how much convalescent plasma may have contributed to that remains an open question. Access to vaccines is months away for many people, and even then some people will continue to get sick. Given the lack of proven treatments, it makes sense to keep plasma as part of the mix, and not close the door to any legitimate means to obtain it.
Some hospitals are pioneers in ditching plastic, turning green
This is part 2 of a three part series on a new generation of doctors leading the charge to make the health care industry more sustainable - for the benefit of their patients and the planet. Read part 1 here and part 3 here.
After graduating from her studies as an engineer, Nora Stroetzel ticked off the top item on her bucket list and traveled the world for a year. She loved remote places like the Indonesian rain forest she reached only by hiking for several days on foot, mountain villages in the Himalayas, and diving at reefs that were only accessible by local fishing boats.
“But no matter how far from civilization I ventured, one thing was already there: plastic,” Stroetzel says. “Plastic that would stay there for centuries, on 12,000 foot peaks and on beaches several hundred miles from the nearest city.” She saw “wild orangutans that could be lured by rustling plastic and hermit crabs that used plastic lids as dwellings instead of shells.”
While traveling she started volunteering for beach cleanups and helped build a recycling station in Indonesia. But the pivotal moment for her came after she returned to her hometown Kiel in Germany. “At the dentist, they gave me a plastic cup to rinse my mouth. I used it for maybe ten seconds before it was tossed out,” Stroetzel says. “That made me really angry.”
She decided to research alternatives for plastic in the medical sector and learned that cups could be reused and easily disinfected. All dentists routinely disinfect their tools anyway and, Stroetzel reasoned, it wouldn’t be too hard to extend that practice to cups.
It's a good example for how often plastic is used unnecessarily in medical practice, she says. The health care sector is the fifth biggest source of pollution and trash in industrialized countries. In the U.S., hospitals generate an estimated 6,000 tons of waste per day, including an average of 400 grams of plastic per patient per day, and this sector produces 8.5 percent of greenhouse gas emissions nationwide.
“Sustainable alternatives exist,” Stroetzel says, “but you have to painstakingly look for them; they are often not offered by the big manufacturers, and all of this takes way too much time [that] medical staff simply does not have during their hectic days.”
When Stroetzel spoke with medical staff in Germany, she found they were often frustrated by all of this waste, especially as they took care to avoid single-use plastic at home. Doctors in other countries share this frustration. In a recent poll, nine out of ten doctors in Germany said they’re aware of the urgency to find sustainable solutions in the health industry but don’t know how to achieve this goal.
After a year of researching more sustainable alternatives, Stroetzel founded a social enterprise startup called POP, short for Practice Without Plastic, together with IT expert Nicolai Niethe, to offer well-researched solutions. “Sustainable alternatives exist,” she says, “but you have to painstakingly look for them; they are often not offered by the big manufacturers, and all of this takes way too much time [that] medical staff simply does not have during their hectic days.”
In addition to reusable dentist cups, other good options for the heath care sector include washable N95 face masks and gloves made from nitrile, which waste less water and energy in their production. But Stroetzel admits that truly making a medical facility more sustainable is a complex task. “This includes negotiating with manufacturers who often package medical materials in double and triple layers of extra plastic.”
While initiatives such as Stroetzel’s provide much needed information, other experts reason that a wholesale rethinking of healthcare is needed. Voluntary action won’t be enough, and government should set the right example. Kari Nadeau, a Stanford physician who has spent 30 years researching the effects of environmental pollution on the immune system, and Kenneth Kizer, the former undersecretary for health in the U.S. Department of Veterans Affairs, wrote in JAMA last year that the medical industry and federal agencies that provide health care should be required to measure and make public their carbon footprints. “Government health systems do not disclose these data (and very rarely do private health care organizations), unlike more than 90% of the Standard & Poor’s top 500 companies and many nongovernment entities," they explained. "This could constitute a substantial step toward better equipping health professionals to confront climate change and other planetary health problems.”
Compared to the U.K., the U.S. healthcare industry lags behind in terms of measuring and managing its carbon footprint, and hospitals are the second highest energy user of any sector in the U.S.
Kizer and Nadeau look to the U.K. National Health Service (NHS), which created a Sustainable Development Unit in 2008 and began that year to conduct assessments of the NHS’s carbon footprint. The NHS also identified its biggest culprits: Of the 2019 footprint, with emissions totaling 25 megatons of carbon dioxide equivalent, 62 percent came from the supply chain, 24 percent from the direct delivery of care, 10 percent from staff commute and patient and visitor travel, and 4 percent from private health and care services commissioned by the NHS. From 1990 to 2019, the NHS has reduced its emission of carbon dioxide equivalents by 26 percent, mostly due to the switch to renewable energy for heat and power. Meanwhile, the NHS has encouraged health clinics in the U.K. to install wind generators or photovoltaics that convert light to electricity -- relatively quick ways to decarbonize buildings in the health sector.
Compared to the U.K., the U.S. healthcare industry lags behind in terms of measuring and managing its carbon footprint, and hospitals are the second highest energy user of any sector in the U.S. “We are already seeing patients with symptoms from climate change, such as worsened respiratory symptoms from increased wildfires and poor air quality in California,” write Thomas B. Newman, a pediatrist at the University of California, San Francisco, and UCSF clinical research coordinator Daisy Valdivieso. “Because of the enormous health threat posed by climate change, health professionals should mobilize support for climate mitigation and adaptation efforts.” They believe “the most direct place to start is to approach the low-lying fruit: reducing healthcare waste and overuse.”
In addition to resulting in waste, the plastic in hospitals ultimately harms patients, who may be even more vulnerable to the effects due to their health conditions. Microplastics have been detected in most humans, and on average, a human ingests five grams of microplastic per week. Newman and Valdivieso refer to the American Board of Internal Medicine's Choosing Wisely program as one of many initiatives that identify and publicize options for “safely doing less” as a strategy to reduce unnecessary healthcare practices, and in turn, reduce cost, resource use, and ultimately reduce medical harm.
A few U.S. clinics are pioneers in transitioning to clean energy sources. In Wisconsin, the nonprofit Gundersen Health network became the first hospital to cut its reliance on petroleum by switching to locally produced green energy in 2015, and it saved $1.2 million per year in the process. Kaiser Permanente eliminated its 800,000 ton carbon footprint through energy efficiency and purchasing carbon offsets, reaching a balance between carbon emissions and removing carbon from the atmosphere in 2020, the first U.S. health system to do so.
Cleveland Clinic has pledged to join Kaiser in becoming carbon neutral by 2027. Realizing that 80 percent of its 2008 carbon emissions came from electricity consumption, the Clinic started switching to renewable energy and installing solar panels, and it has invested in researching recyclable products and packaging. The Clinic’s sustainability report outlines several strategies for producing less waste, such as reusing cases for sterilizing instruments, cutting back on materials that can’t be recycled, and putting pressure on vendors to reduce product packaging.
The Charité Berlin, Europe’s biggest university hospital, has also announced its goal to become carbon neutral. Its sustainability managers have begun to identify the biggest carbon culprits in its operations. “We’ve already reduced CO2 emissions by 21 percent since 2016,” says Simon Batt-Nauerz, the director of infrastructure and sustainability.
The hospital still emits 100,000 tons of CO2 every year, as much as a city with 10,000 residents, but it’s making progress through ride share and bicycle programs for its staff of 20,000 employees, who can get their bikes repaired for free in one of the Charité-operated bike workshops. Another program targets doctors’ and nurses’ scrubs, which cause more than 200 tons of CO2 during manufacturing and cleaning. The staff is currently testing lighter, more sustainable scrubs made from recycled cellulose that is grown regionally and requires 80 percent less land use and 30 percent less water.
The Charité hospital in Berlin still emits 100,000 tons of CO2 every year, but it’s making progress through ride share and bicycle programs for its staff of 20,000 employees.
Wiebke Peitz | Specific to Charité
Anesthesiologist Susanne Koch spearheads sustainability efforts in anesthesiology at the Charité. She says that up to a third of hospital waste comes from surgery rooms. To reduce medical waste, she recommends what she calls the 5 Rs: Reduce, Reuse, Recycle, Rethink, Research. “In medicine, people don’t question the use of plastic because of safety concerns,” she says. “Nobody wants to be sued because something is reused. However, it is possible to reduce plastic and other materials safely.”
For instance, she says, typical surgery kits are single-use and contain more supplies than are actually needed, and the entire kit is routinely thrown out after the surgery. “Up to 20 percent of materials in a surgery room aren’t used but will be discarded,” Koch says. One solution could be smaller kits, she explains, and another would be to recycle the plastic. Another example is breathing tubes. “When they became scarce during the pandemic, studies showed that they can be used seven days instead of 24 hours without increased bacteria load when we change the filters regularly,” Koch says, and wonders, “What else can we reuse?”
In the Netherlands, TU Delft researchers Tim Horeman and Bart van Straten designed a method to melt down the blue polypropylene wrapping paper that keeps medical instruments sterile, so that the material can be turned it into new medical devices. Currently, more than a million kilos of the blue paper are used in Dutch hospitals every year. A growing number of Dutch hospitals are adopting this approach.
Another common practice that’s ripe for improvement is the use of a certain plastic, called PVC, in hospital equipment such as blood bags, tubes and masks. Because of its toxic components, PVC is almost never recycled in the U.S., but University of Michigan researchers Danielle Fagnani and Anne McNeil have discovered a chemical process that can break it down into material that could be incorporated back into production. This could be a step toward a circular economy “that accounts for resource inputs and emissions throughout a product’s life cycle, including extraction of raw materials, manufacturing, transport, use and reuse, and disposal,” as medical experts have proposed. “It’s a failure of humanity to have created these amazing materials which have improved our lives in many ways, but at the same time to be so shortsighted that we didn’t think about what to do with the waste,” McNeil said in a press release.
Susanne Koch puts it more succinctly: “What’s the point if we save patients while killing the planet?”
The Friday Five: A surprising health benefit for people who have kids
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.
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Here are the promising studies covered in this week's Friday Five:
- Kids stressing you out? They could be protecting your health.
- A new device unlocks the heart's secrets
- Super-ager gene transplants
- Surgeons could 3D print your organs before operations
- A skull cap looks into the brain like an fMRI