Blood cleaning? Long COVID patients turn to unproven treatments
Desperate for relief, some patients are flying across the world for costly apheresis treatments—even though there’s no evidence it works.
Ever since she first experienced such hallmark COVID-19 symptoms as fever, shortness of breath, and muscle pain, in March 2020, 39-year-old Miriam has continued to suffer. In 2021, her health dramatically worsened; her breathing issues returned, she struggled to walk, she experienced post-exertional malaise, sometimes she had gastrointestinal issues, and she started stuttering.
Her family suspected Miriam had long COVID, and the doctor treating her in her hometown of Zürich, Switzerland, labeled the case “too complex” to continue treating her. Miriam, who asked that her last name not be used due to stigma surrounding long COVID, had to find another doctor. But going from expert to expert and waiting months for appointments while her condition deteriorated was unbearable.
“So I started looking for alternatives,” Miriam says. “I was kind of desperate.”
That’s when she learned about a dialysis-like medical procedure called heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) apheresis that essentially “cleans” the blood. Her father had watched a long COVID documentary in which a physician from the United Kingdom who developed long COVID and had travelled to a clinic in Mülheim, Germany, to undergo apheresis.
After several sessions, the U.K. doctor went from being wheelchair-bound to walking again. Beate Jaeger, an internist who runs the clinic, had suggested in the same documentary that H.E.L.P. apheresis might work by removing tiny blood clots in small vessels suspected of causing long COVID symptoms, along with other disease-inducing elements. However, Jaeger and other clinicians haven’t published any data to show whether and to what extent this treatment is effective.
“They have a hypothesis that this process is going to influence the disease,” says Jeffery Winters, an apheresis expert at the Mayo Clinic in Rochester, Minnesota. “They may be right, maybe this is a great treatment, but what’s frustrating to me as a practitioner is that we don’t have any quantifiable proof that it is altering the disease outcome.”
How H.E.L.P. apheresis works
Apheresis is a medical procedure that involves withdrawing blood, removing disease-triggering components such as abnormal cells or cholesterol-rich proteins, and returning this “filtered” blood to the patient. In some cases, the extracted elements are replaced with healthy counterparts from a blood donor.
In 1996, the U.S. Food and Drug Administration approved H.E.L.P. apheresis to treat patients with cardiovascular disorders, who, for genetic reasons, have very high LDL or “bad” cholesterol levels or who don’t tolerate or respond to cholesterol-lowering drugs.
The first step involves separating the straw-colored fluid component of blood—plasma—from the cells. Then artery-clogging proteins are removed from the plasma using an anticoagulant called heparin, and then the clean plasma and blood cells are returned to the patient.
A single apheresis procedure—commonly combined with medications for high cholesterol—can reduce the amount of bad cholesterol by about 50 to 80 percent. But the quantity will typically return to pre-treatment levels, and the process must be repeated weekly or every other week.
A six-year study from Japan noted a 58 percent reduction in bad cholesterol among 43 patients with a high cholesterol disorder who were treated with apheresis and medication compared to a 28 percent decline in 87 patients who only took medications. Some apheresis studies have also documented reduction in C-reactive protein and interleukin-6, which at elevated levels indicate inflammation, and fibrinogen, a key blood-clotting protein linked to higher cardiovascular disease risk when present at high levels.
But such studies typically have been small, and there have not been many randomized clinical trials—the gold standard for evaluating the effectiveness of an intervention. “The problem is that many of the diseases we treat [with apheresis] are extremely rare,” Winters says. “We cannot get enough patients to get into a randomized clinical trial.”
Also, some patients experience side effects such as fatigue, nausea, vomiting, low blood pressure, and chest pain caused by reduced blood flow to the heart. Use of anticoagulants also increases bleeding risks if someone bruises. Another challenge is that each apheresis session can last two to four hours and cost a few thousand dollars, although most health insurers in the United States cover the expense for approved usage.
“Over the last couple of decades, there’s been a real push by a lot of apheresis practitioners to practice evidence-based medicine,” Winters says, “meaning that we really want to hammer out the rationale for why we’re doing the treatment.”
Off-label use of apheresis for long COVID
Jaeger has been using apheresis for nearly three decades to treat certain life-threatening cardiovascular conditions. In an article in Frontiers in Cardiovascular Medicine, Jaeger and her colleagues write that long COVID patients could also benefit from H.E.L.P. apheresis treatments. This suggestion is based on the hypotheses that high levels of inflammatory proteins and lingering SARS-CoV-2 viral particles could cause tissue damage in the body, resulting in inflammation or triggering the immune system to attack the body’s healthy cells or forming tiny clots in small blood vessels, hindering oxygen supply.
Jaeger and her team argue that apheresis has the potential to remove lingering SARS-CoV-2 spike protein particles, as well as substantial amounts of fibrinogen—one of the key components of microclots observed in long COVID patients. They also argue the procedure might remove molecules involved in post-COVID inflammation or those that target the patient’s healthy cells.
Since 2021, Jaeger’s team has worked with more than a thousand long COVID patients (with about 50,000 currently on the waitlist), where each individual, on average, has undergone four to five apheresis sessions, she says. A few other clinics in Germany, Switzerland, and Cyprus are also using apheresis to treat long COVID patients. Depending on each patient’s condition, they also use anticoagulants and antiplatelet medication in combination with apheresis, as well as antihistamines or antivirals, which might ease long COVID symptoms.
In February 2022, Miriam traveled to the Mülheim clinic, and her blood scan revealed microclots accompanied by sticky platelets—a hallmark of COVID-19 that trigger excessive clotting. Over the next few months, she underwent 20 apheresis sessions in Germany and later in Switzerland, and spent more than $35,000. “I was really scared,” Miriam says, “but I didn’t know what else to do.”
Despite the lack of clinical trials or peer-reviewed data to back the use of H.E.L.P. apheresis for long COVID, many patients, desperate for relief, are opting for apheresis. In the Mülheim clinic, Jaeger and her team measure a patient’s blood viscosity, record oxygen and fibrinogen levels, scan for microclots, and assess other factors prior to starting apheresis.
After every few sessions she reexamines these markers and looks for improvements in a patient’s clinical symptoms. But long COVID isn’t one illness, and scientists are still figuring out the biomarkers associated with the multifaceted condition, explains apheresis expert Patrick Moriarty at the University of Kansas Medical Center.
Although Jaeger hasn’t published any case reports or studies from more than a year of using H.E.L.P. apheresis to treat long COVID patients, she’s working with her collaborators to analyze the mounting data. In some cases, she’s seen great success after just one, two, or three, apheresis sessions, and “they’re still healthy today,” Jaeger says. “But this does not apply to all patients.”
Miriam, for instance, believes that apheresis saved her life. She went from being unable to stand up from a chair without help or preparing food for herself, experiencing tremors and stuttering, struggling with simple calculations and keeping in touch with friends and family to running small errands using her electrical wheelchair, writing emails or talking over the phone for 30 minutes or so, and she no longer stutters or has tremors. Miriam is still mostly house and bed-bound and gets exhausted after minimal mental or physical exertion, “but the quality of life is already much better than what it was a year ago,” she says.
Her health status has plateaued and Miriam is now looking for other therapeutics to improve her symptoms or target long COVID’s root cause, which is still unclear. “Obviously I wouldn’t want to keep doing apheresis, but I will do it as maintenance,” she says. “It’s not a cure.”
Kate Stott, a 36-year-old from Scotland, underwent four apheresis sessions in Mülheim in November 2022. She says she felt a little stronger and more alert after the treatment, although a chest infection in January set her back.
For Dublin-based Oonagh Carr, two sessions in November helped her function a little bit more compared to her pre-treatment activity. “I’m still very fatigued, experience dizziness, and have post-exertional malaise,” the 47-year-old says. “It’s not a magic pill.” She will be traveling to Mülheim to complete three more sessions this year.
Pamela Bishop, who lives in Tennessee and underwent six apheresis sessions in a clinic in Cyprus in November, says she has more energy, but still feels nauseated, has cognitive issues, gets headaches and migraines every day, and has postural orthostatic tachycardia syndrome—a condition documented in many long COVID patients known to disrupt breathing and cause heart palpitations and dizziness on standing up. She was mostly bed-bound pre-apheresis. “I can be up and interact with my family more, I can help with my children more, for now,” she says. “But I’m very aware these gains will not sustain.”
Moriarty also used an apheresis technique similar to H.E.L.P. to treat three long COVID patients in the U.S. A single session seemed to help one long COVID patient, but the other two individuals did not benefit from two rounds of apheresis.
“It’s a gamble at this point; no one knows why and how some people get better and others have no gains at all,” Bishop says. While apheresis seems to have somewhat eased suffering in some, “it’s part of the collective experiment that we’re trying on ourselves.”