At first, doctors didn’t believe that bacteria could live in the stomach at all. Too acidic, they thought. But in 1984, a young Australian physician named Barry Marshall gulped down an infamous concoction of beef brothlaced with Helicobacter pylori bacteria. On day eight, he started vomiting. On day 10, an endoscopy revealed that H. pylori had colonized his stomach, their characteristic spiral shape unmistakeable under the microscope.
Left untreated, H. pylori usually establishes infections that persist for an entire lifetime, and they’re common: Half of the world’s population harbors H. pylori inside their stomach, as do more than one in three Americans. In most cases, the microbe settles into an asymptomatic chronic infection, but in some, it becomes far more troublesome. It can, for example, cause enough damage to the stomach lining to create ulcers. Worse still, H. pylori can lead to cancer. This single bacterium is by far the No. 1 risk factor in stomach cancers worldwide. By one estimate, some 70 percent can be attributed to H. pylori.
But what still puzzles doctors years later is why H. pylori has such different consequences for different people. Why is it asymptomatic in most but carcinogenic in others? Although the full answer is complex, one key factor seems to be mutations in H. pylori itself. Not every strain is created equal. The presence of select genes intensifies H. pylori’s pathogenicity, and even a single mutation in a single gene, scientists recently found, enhances the link to cancer. A small genetic tweak in a common stomach bug could have profound consequences for us, its unwitting hosts.
H. pylori has lived inside of us for a long time. Our ancestors who left Africa likely carried it inside them as they crossed continents and oceans, built and felled civilizations. And over the course of what some scientists hypothesize to be more than 100,000 years of co-evolution, H. pylori has exquisitely adapted to the harsh, acidic conditions of the human stomach.
It survives, for example, by producing “copious amounts” of an enzyme that neutralizes stomach acid, Richard Peek, a gastroenterologist at Vanderbilt, told me. H. pylori can also burrow into the mucus-gel lining of the stomach using powerful, whiplike flagella. The mucus lining offers a relative haven from stomach acid, but another prize lies underneath too: stomach cells, rich in nutrients that the bacteria needs to survive.
The way that H. pylori steals nutrients could be the key to how it ends up causing cancer. The bacterium isn’t necessarily out to hurt its human host. “H. pylori doesn’t want you to get an ulcer or to get cancer, but it needs to replicate to high enough levels in the stomach that it can be transmitted to another person,” Nina Salama, a biologist at Fred Hutchinson Cancer Center, told me. (The bacteria seem to spread through an infected person’s saliva, vomit, or feces.) But to replicate, it needs nutrients, in particular iron, which our cells probably hoard to starve pathogens.
In response, certain strains of H. pylori have evolved genetic changes that might make its iron-mining more efficient. But this also causes more collateral damage to the host’s stomach, enough damage, perhaps, to eventually trigger cancer. First, the bacteria uses a protein called HtrA—essentially “a pair of molecular scissors,” Peek said—to cut the bonds that hold stomach cells together, so the microbes can slip between. A single mutation in this scissor protein makes it better at cutting, a group based in Germany found in a recent study, and this mutation is disproportionately found in H. pylori strains isolated from people who developed stomach cancer.
Once H. pylori has wedged itself in between cells, it also has clever ways of accessing the nutrients inside. Certain strains carry a set of about 18 genes that collectively encode a molecular needle through which H. pylori injects bacterial proteins, triggering a cascade of changes to the cell. These hijacked cells end up giving up their iron more easily, but they also become worse at essential functions such as fixing damaged DNA. This set of approximately 18 genes, collectively called the “cag pathogenicity island,” are in fact disproportionately found in strains from cancer patients. Stomach cancer thus might be a secondary consequence of the microbe’s aggressive search for nutrients. For the H. pylori, “there’s no selective pressure to cause cancer in 80 years. The selective pressure is to acquire iron now,” Karen Guillemin, a microbiologist at the University of Oregon, said.
But not everyone infected with one of these cancer-linked strains will develop cancer. Other factors likely play a role too: diet, environment, and genetics of the individual patient Stomach-cancer rates vary quite widely around the world, with the highest prevalence in East Asia. In Japan, doctors routinely test for H. pylori in people with no symptoms, and prescribe antibiotics if the tests come back positive. But some scientists have argued against aggressive treatment, pointing at hints that humans derive some benefits from living with H. pylori too. Those infected, for example, tend to have lower rates of asthma and allergy. Genetic signatures associated with more pathogenic H. pylori strains, Peek told me, would help identify those at highest risk, who could most benefit from antibiotics.
Marshall, the Australian doctor who infected himself with H. pylori, ultimately recovered just fine. His self-experiment, in addition to other studies with his collaborator Robin Warren, proved that the bacterium does indeed infect the stomach and does indeed cause stomach ulcers, which later spurred the work linking H. pylori to cancer. Understanding exactly how and why H. pylori becomes pathogenic is still key to finding the way to treat it, but in the past 40 years the significance of H. pylori to human health has become indisputable—so much so that in 2005, Marshall and Warren won the Nobel Prize in Medicine.
Colleen Kennedy, a retired medical assistant, was prepared for the annihilation of chemotherapy and radiation treatment for stage-three lung cancer. She hadn’t expected the hiccup fits that started about halfway through her first treatment round. They left her gasping for air and sent pain ricocheting through her already tender body. At times, they triggered her gag reflex and made her throw up. After they subsided, she felt tired, sore, breathless—as if she’d just finished a tough workout. They were, Kennedy, now 54, told me, “nothing compared to what we would consider normal hiccups at all.” They lasted for nearly a year.
Hiccups are one of the most common bodily experiences that humans (and, rats, squirrels, rabbits, cats, dogs, and horses) have; even fetuses get them. When we hiccup, the diaphragm involuntarily contracts and the vocal cords snap closed, producing the eponymous “hic” sound. These spasms usually disappear within a few minutes. Compared with cancer’s existential threat and the brutal reality of treating it, hiccups are innocuous, banal, and unserious. But these two experiences are, peculiarly, connected. As many as 40 percent of cancer patients deal with bouts of hiccups during their illness. For a smaller subset—about one in 10—those spells last for more than 48 hours.
Chronic hiccups interrupt almost every aspect of life. They disrupt concentration and conversations. They shake a person awake. Eating, drinking, and swallowing can feel like choking. Often, chest aches linger long after a hiccupping fit subsides.
And they are difficult to treat. Doctors have some off-label prescriptions at their disposal, but none has been rigorously tested—none has been proved to work any better than home remedies. Kennedy tried to eradicate her hiccups with deep, forceful inhales and by drinking water from the far rim of a glass; she also trained herself to exhale before drinking or eating to limit the amount of air she swallowed. “Sometimes it worked, but most times it didn’t,” she said. Many try chiropractice or acupuncture. Others recruit household items: sugar, lemons, vinegar, a pencil, a cold spoon. Only one hiccup drug has ever been approved by the Food and Drug Administration.
Hiccups, one of the most basic physiological features of human life, remain deeply mysterious and surprisingly understudied—partly because their fleeting nature makes them hard to examine, partly because they just seem so harmless. But when they’re not, hiccups confront us with how helpless we can be against our own body’s whims.
In popular culture, hiccups are a joke: In a Looney Tunes bit from 1942, Daffy Duck’s hiccups send his hat bouncing. In a 2005 episode of Foster’s Home For Imaginary Friends, Bloo tries everything to cure his hiccups—he pours a box of sugar into his mouth, breathes into a brown paper bag, drinks hot sauce, eats peanut butter, gets scared, takes small sips and big gulps, stands on his head, brushes his teeth while singing, swallows a lemon. Nothing works. In 1937’sSnow White and the Seven Dwarfs, Dopey accidentally swallows a bar of soap and starts hiccuping bubbles. In 1970’s Aristocats, Uncle Waldo gets hiccups from drinking too much. In 1975’s Monty Python and the Holy Grail, a hiccuping guard is commanded by the king to get a drink to rid him of his ailment. In a 1992 episode of The Simpsons, a man who’s been hiccupping for 45 years gives this four-second interview to the local Springfield TV news: “Hic—kill me—hic—kill me—hic—kill me.”
In medicine, hiccups are a conundrum. “There’s really no benefit to a hiccup, as far as anyone knows,” Aminah Jatoi, a Mayo Clinic oncologist who studies hiccups, told me. A transient symptom that appears and disappears randomly, hiccups are nearly impossible to study with rigor. Experiments on treatments are, accordingly, a nightmare to orchestrate. To date, only a handful of randomized, controlled trials have studied pharmacological treatments for hiccups; none recruited more than 40 patients. Most studies rely on storytelling: single-patient case reports, limited case series, and analyses of databases of doctor’s notes.
What we do know: A sudden temperature shift can bring hiccups on, as can drinking alcohol, eating spicy food, and getting excited or stressed. High blood sugar can be to blame. So can low sodium or electrolytes. Many drugs—including steroids, chemotherapy agents, benzodiazepines, opioids, nicotine, antibiotics, anesthesia, and anti-nausea and blood-pressure medicines—are linked with hiccups. Some drugs used to treat intractable hiccups can cause hiccups. In one case study, a patient’s hiccups were incited by a hair brushing against the eardrum; in another, from 1988, the culprit was an ant crawling around the eardrum.
The medical conditions associated with hiccups range the body’s entire upper half: stroke, brain injury, meningitis, multiple sclerosis, ear infection, rhinitis, goiters, sore throat, pneumonia, bronchitis, asthma, tuberculosis, fluid in the lungs or heart, bloating, gas, pregnancy, hernias, ulcers, liver disease, kidney disease. And cancer.
Experts offer two main explanations for the cancer-hiccup connection. In one, cancers that invade the chest, throat, or head (that is, anything along the route of a hiccup) provoke them. In the other, medications prescribed to cancer patients— including chemotherapy drugs, steroids, and opioids—set them off. Regardless of whether cancer itself is to blame or whether they’re a side effect of treatment, hiccups add another layer of misery to the experience.
One study published in 2022 showed that hiccups were a major detriment to the quality of life of about one in 20 of the cancer patients surveyed. Among those with hiccups, almost one in three said they struggled to relax or recreate; a smaller portion said they couldn’t enjoy meals. In another study of 320 cancer patients, hiccups sent one in 10 to the hospital for help. Other research suggests that upwards of three-quarters of hiccup-struck patients deal with the spasms without medical intervention. In a survey of 90 cancer-health-care providers with experience with hiccups, 40 percent rated their patients’ hiccup severity as worse than their nausea and vomiting.
Even so, experts say, hiccups remain an aside for both patients and practitioners.
Given the rapidity of physician visits—on average about 23 minutes, by one measure, for patients with cancer—hiccups may simply fall too low on a list of preoccupations to warrant mention, but “I think part of what happens is patients feel a little embarrassed bringing it up,” Jatoi said. Or “the patient may want to be a ‘good’ patient and not complain,” says Thomas Smith, an oncologist and palliative-medicine specialist at Johns Hopkins—perhaps because they fear their doctors will modify their treatment course if they speak up about any negative side effects.
Oncologists, for their part, don’t consistently or directly ask about hiccups in the way that they screen for pain, nausea, and trouble breathing. “I don’t know of a single symptom-assessment scale in use that has a line for hiccups,” Smith told me. Some brush off patients who do complain of the spasms. “My doctors just shook their heads like I was joking when I told them I got the hiccups all the time,” one patient wrote to Mayo Clinic hiccup researchers.
And so hiccups are relegated to the category of “orphan” symptoms—prevalent, distressing, characteristically unaddressed. Other such symptoms include muscle cramps, itchiness, muscle twitching, restless legs syndrome, loss or distortion of taste, dry mouth, and sweating. The success of palliative care depends on alleviating orphan symptoms: Every hiccup or itch or tingling foot, every flush of sweat or bout of constipation tethers patients to a raw state of awareness. “It’s a common reminder that you have chemotherapy, which is a constant reminder you have cancer, which is a constant reminder you’re facing your mortality,” Smith said. Treating hiccups offers medical relief in the form of escape. “It may make it possible for patients to have a few hours where they don’t think about cancer.”
Jatoi said she often warns patients who are about to start a potentially hiccup-inducing regimen. “That helps patients speak up,” she said, which is a step toward finding relief. Oncologists can try prescribing a muscle-spasm treatment, for example, an off-label use that seems to help some patients. They might tweak the chemotherapy regimen to swap in drugs less likely to cause hiccups. The one treatment for hiccups that the FDA has approved—chlorpromazine, an antipsychotic first synthesized 72 years ago—can come with serious side effects, which research has shown to include low blood pressure and delirium.
In the absence of clinically proven solutions, most hiccup sufferers are shepherded toward home remedies—breath-holding; drinking through hard-to-suck straws; swallowing spoonfuls of sugar, peanut butter, or vinegar. “None of them have been tested to see how effective they are,” Smith said. But without solid alternatives, he added, they’re worth trying. After all, unlike the hiccups themselves, “they’re completely harmless.”
Oct. 11, 2022 – During the early days of the pandemic, Alivia Gustman, then just 8 years old, was in a class tasked with the goal of starting a business.
For Gustman, this wasn’t the time to pitch a bake sale. Instead, having recently watched her mom go through breast cancer treatment, an idea immediately popped into her mind: Why not sell teddy bears to raise money to help kids with cancer — or to anyone whose loved ones are in treatment?
After doing a virtual pitch to her Boca Raton, FL, teacher and classmates, the idea broadened when her dad jumped on board and helped build a website and secure a trademark.
The result: A family-run project and the launch of Cancer Bears, a nonprofit that has already sold more than 1,000 bears in over 30 states and abroad.
Best of all: Thanks to all of these bears being sent across the country (and globe), Cancer Bears has raised $30,000 to date and donated those funds to cancer centers across the country. In fact, since they started the organization, they’ve set up donation partnerships with Boca Raton Regional Hospital, Joe DiMaggio Children’s Hospital, and NYU Langone Perlmutter Cancer Center – all locations that played a role in helping Alivia’s mom – and formed an alliance with Keaton’s Child Care Alliance, a nonprofit that provides support services to families facing a pediatric cancer diagnosis.
So how did a then-third grader make all of this happen?
“Knowing that my mom would be OK motivated me,” says Gustman, now a very busy fifth grader who turns 10 on Oct. 16. “I wanted anybody going through treatment to be able to hold onto something. I thought a bear would be the perfect thing to cuddle with.”
For Tara Gustman, Alivia’s mom, helping others is in the family DNA.
“This was such a simple act of kindness that happened during virtual school and right when I was getting back on my feet again,” says Tara, who was diagnosed with stage II breast cancer in December 2018 and went through a double mastectomy, the removal of 12 lymph nodes, 16 rounds of chemo, and 7 weeks of radiation. She’s now been in remission for 4 years.
“The feedback that we get from everybody is remarkable. We can’t wait to continue to make a difference to those in need.”
And, while Alivia admits that she’s busy with schoolwork– it’s all about time management, she says – there’s nothing better than seeing all of the bears lined up and ready to be shipped out of her (and her grandparents’) garage.
Recently, Alivia and her sister, Savannah, 8, have gotten very busy attaching ribbons to each bear before it’s shipped.
“You can request the ribbon for the person’s cancer – so teal for ovarian, yellow for childhood cancer, and pink for breast cancer,” she says. “My sister is really good at organizing the ribbons.”
Ultimately, this is one family that’s laser-focused on helping others.
“Every 2 minutes, someone is diagnosed with breast cancer in the U.S. and, while that is unfortunate, what we’re doing keeps our entire family motivated,” says Tara. “We’ve become a resource of encouragement in the form of bears and conversation with people in our community. Happily, Alivia’s story keeps getting shared, and the more people know about us, the more we can help others.”
Ask Alivia and she’ll tell you that being a kid should never be a barrier to rolling up your sleeves.
“Personally, I’d tell other kids to follow their dreams,” she says. “If something motivates you to help others – do it.”
On March 25, 2020, Hannah Davis was texting with two friends when she realized that she couldn’t understand one of their messages. In hindsight, that was the first sign that she had COVID-19. It was also her first experience with the phenomenon known as “brain fog,” and the moment when her old life contracted into her current one. She once worked in artificial intelligence and analyzed complex systems without hesitation, but now “runs into a mental wall” when faced with tasks as simple as filling out forms. Her memory, once vivid, feels frayed and fleeting. Former mundanities—buying food, making meals, cleaning up—can be agonizingly difficult. Her inner world—what she calls “the extras of thinking, like daydreaming, making plans, imagining”—is gone. The fog “is so encompassing,” she told me, “it affects every area of my life.” For more than 900 days, while other long-COVID symptoms have waxed and waned, her brain fog has never really lifted.
Of long COVID’s many possible symptoms, brain fog “is by far one of the most disabling and destructive,” Emma Ladds, a primary-care specialist from the University of Oxford, told me. It’s also among the most misunderstood. It wasn’t even included in the list of possible COVID symptoms when the coronavirus pandemic first began. But 20 to 30 percent of patients report brain fog three months after their initial infection, as do 65to85 percent of the long-haulers who stay sick for much longer. It can afflict people who were never ill enoughto need a ventilator—or any hospital care. And it can affect young people in the prime of their mental lives.
Long-haulers with brain fog say that it’s like none of the things that people—including many medical professionals—jeeringly compare it to. It is more profound than the clouded thinking that accompanies hangovers, stress, or fatigue. For Davis, it has been distinct from and worse than her experience with ADHD. It is not psychosomatic, and involves real changes to the structure and chemistry of the brain. It is not a mood disorder: “If anyone is saying that this is due to depression and anxiety, they have no basis for that, and data suggest it might be the other direction,” Joanna Hellmuth, a neurologist at UC San Francisco, told me.
And despite its nebulous name, brain fog is not an umbrella term for every possible mental problem. At its core, Hellmuth said, it is almost always a disorder of “executive function”—the set of mental abilities that includes focusing attention, holding information in mind, and blocking out distractions. These skills are so foundational that when they crumble, much of a person’s cognitive edifice collapses. Anything involving concentration, multitasking, and planning—that is, almost everything important—becomes absurdly arduous. “It raises what are unconscious processes for healthy people to the level of conscious decision making,” Fiona Robertson, a writer based in Aberdeen, Scotland, told me.
For example, Robertson’s brain often loses focus mid-sentence, leading to what she jokingly calls “so-yeah syndrome”: “I forget what I’m saying, tail off, and go, ‘So, yeah …’” she said. Brain fog stopped Kristen Tjaden from driving, because she’d forget her destination en route. For more than a year, she couldn’t read, either, because making sense of a series of words had become too difficult. Angela Meriquez Vázquez told me it once took her two hours to schedule a meeting over email: She’d check her calendar, but the information would slip in the second it took to bring up her inbox. At her worst, she couldn’t unload a dishwasher, because identifying an object, remembering where it should go, and putting it there was too complicated.
Memory suffers, too, but in a different way from degenerative conditions like Alzheimer’s. The memories are there, but with executive function malfunctioning, the brain neither chooses the important things to store nor retrieves that information efficiently. Davis, who is part of the Patient-Led Research Collaborative, can remember facts from scientific papers, but not events. When she thinks of her loved ones, or her old life, they feel distant. “Moments that affected me don’t feel like they’re part of me anymore,” she said. “It feels like I am a void and I’m living in a void.”
Most people with brain fog are not so severely affected, and gradually improve with time. But even when people recover enough to work, they can struggle with minds that are less nimble than before. “We’re used to driving a sports car, and now we are left with a jalopy,” Vázquez said. In some professions, a jalopy won’t cut it. “I’ve had surgeons who can’t go back to surgery, because they need their executive function,” Monica Verduzco-Gutierrez, a rehabilitation specialist at UT Health San Antonio, told me.
Robertson, meanwhile, was studying theoretical physics in college when she first got sick, and her fog occluded a career path that was once brightly lit. “I used to sparkle, like I could pull these things together and start to see how the universe works,” she told me. “I’ve never been able to access that sensation again, and I miss it, every day, like an ache.” That loss of identity was as disruptive as the physical aspects of the disease, which “I always thought I could deal with … if I could just think properly,” Robertson said. “This is the thing that’s destabilized me most.”
Robertson predicted that the pandemic would trigger a wave of cognitive impairment in March 2020. Her brain fog began two decades earlier, likely with a different viral illness, but she developed the same executive-function impairments that long-haulers experience, which then worsened when she got COVID last year. That specific constellation of problems also befalls many people living with HIV, epileptics after seizures, cancer patients experiencing so-called chemo brain, and people with several complex chronic illnesses such as fibromyalgia. It’s part of the diagnostic criteria for myalgic encephalomyelitis, also known as chronic fatigue syndrome, or ME/CFS—a condition that Davis and many other long-haulers now have. Brain fog existed well before COVID, affecting many people whose conditions were stigmatized, dismissed, or neglected. “For all of those years, people just treated it like it’s not worth researching,” Robertson told me. “So many of us were told, Oh, it’s just a bit of a depression.”
Several clinicians I spoke with argued that the term brain fog makes the condition sound like a temporary inconvenience and deprives patients of the legitimacy that more medicalized language like cognitive impairment would bestow. But Aparna Nair, a historian of disability at the University of Oklahoma, noted that disability communities have used the term for decades, and there are many other reasons behind brain fog’s dismissal beyond terminology. (A surfeit of syllables didn’t stop fibromyalgia and myalgic encephalomyelitis from being trivialized.)
For example, Hellmuth noted that in her field of cognitive neurology, “virtually all the infrastructure and teaching” centers on degenerative diseases like Alzheimer’s, in which rogue proteins afflict elderly brains. Few researchers know that viruses can cause cognitive disorders in younger people, so few study their effects. “As a result, no one learns about it in medical school,” Hellmuth said. And because “there’s not a lot of humility in medicine, people end up blaming patients instead of looking for answers,” she said.
People with brain fog also excel at hiding it: None of the long-haulers I’ve interviewed sounded cognitively impaired. But at times when her speech is obviously sluggish, “nobody except my husband and mother see me,” Robertson said. The stigma that long-haulers experience also motivates them to present as normal in social situations or doctor appointments, which compounds the mistaken sense that they’re less impaired than they claim—and can be debilitatingly draining. “They’ll do what is asked of them when you’re testing them, and your results will say they were normal,” David Putrino, who leads a long-COVID rehabilitation clinic at Mount Sinai, told me. “It’s only if you check in on them two days later that you’ll see you’ve wrecked them for a week.”
“We also don’t have the right tools for measuring brain fog,” Putrino said. Doctors often use the Montreal Cognitive Assessment, which was designed to uncover extreme mental problems in elderly people with dementia, and “isn’t validated for anyone under age 55,” Hellmuth told me. Even a person with severe brain fog can ace it. More sophisticated tests exist, but they still compare people with the population average rather than their previous baseline. “A high-functioning person with a decline in their abilities who falls within the normal range is told they don’t have a problem,” Hellmuth said.
This pattern exists for many long-COVID symptoms: Doctors order inappropriate or overly simplistic tests, whose negative results are used to discredit patients’ genuine symptoms. It doesn’t help that brain fog (and long COVID more generally) disproportionately affects women, who have a long history of being labeled as emotional or hysterical by the medical establishment. But every patient with brain fog “tells me the exact same story of executive-function symptoms,” Hellmuth said. “If people were making this up, the clinical narrative wouldn’t be the same.”
Earlier this year, a team of British researchers rendered the invisible nature of brain fog in the stark black-and-white imagery of MRI scans. Gwenaëlle Douaud at the University of Oxford and her colleagues analyzed data from the UK Biobank study, which had regularly scanned the brains of hundreds of volunteers for years prior to the pandemic. When some of those volunteers caught COVID, the team could compare their after scans to the before ones. They found that even mild infections can slightly shrink the brain and reduce the thickness of its neuron-rich gray matter. At their worst, these changes were comparable to a decade of aging. They were especially pronounced in areas such as the parahippocampal gyrus, which is important for encoding and retrieving memories, and the orbitofrontal cortex, which is important for executive function. They were still apparent in people who hadn’t been hospitalized. And they were accompanied by cognitive problems.
Although SARS-CoV-2, the coronavirus that causes COVID, can enter and infect the central nervous system, it doesn’t do so efficiently, persistently, or frequently, Michelle Monje, a neuro-oncologist at Stanford, told me. Instead, she thinks that in most cases the virus harms the brain without directly infecting it. She and her colleagues recently showed that when mice experience mild bouts of COVID, inflammatory chemicals can travel from the lungs to the brain, where they disrupt cells called microglia. Normally, microglia act as groundskeepers, supporting neurons by pruning unnecessary connections and cleaning unwanted debris. When inflamed, their efforts become overenthusiastic and destructive. In their presence, the hippocampus—a region crucial for memory—produces fewer fresh neurons, while many existing neurons lose their insulating coats, so electric signals now course along these cells more slowly. These are the same changes that Monje sees in cancer patients with “chemo fog.” And although she and her team did their COVID experiments in mice, they found high levels of the same inflammatory chemicals in long-haulers with brain fog.
Monje suspects that neuro-inflammation is “probably the most common way” that COVID results in brain fog, but that there are likely many such routes. COVID could possibly trigger autoimmune problems in which the immune system mistakenly attacks the nervous system, or reactivate dormant viruses such as Epstein-Barr virus, which has been linked to conditions including ME/CFS and multiple sclerosis. By damaging blood vessels and filling them with small clots, COVID also throttles the brain’s blood supply, depriving this most energetically demanding of organs of oxygen and fuel. This oxygen shortfall isn’t stark enough to kill neurons or send people to an ICU, but “the brain isn’t getting what it needs to fire on all cylinders,” Putrino told me. (The severe oxygen deprivation that forces some people with COVID into critical care causes different cognitive problems than what most long-haulers experience.)
None of these explanations is set in stone, but they can collectively make sense of brain fog’s features. A lack of oxygen would affect sophisticated and energy-dependent cognitive tasks first, which explains why executive function and language “are the first ones to go,” Putrino said. Without insulating coats, neurons work more slowly, which explains why many long-haulers feel that their processing speed is shot: “You’re losing the thing that facilitates fast neural connection between brain regions,” Monje said. These problems can be exacerbated or mitigated by factors such as sleep and rest, which explains why many people with brain fog have good days and bad days. And although other respiratory viruses can wreak inflammatory havoc on the brain, SARS-CoV-2 does so more potentlythan, say, influenza, which explains both why people such as Robertson developed brain fog long before the current pandemic and why the symptom is especially prominent among COVID long-haulers.
Perhaps the most important implication of this emerging science is that brain fog is “potentially reversible,” Monje said. If the symptom was the work of a persistent brain infection, or the mass death of neurons following severe oxygen starvation, it would be hard to undo. But neuroinflammation isn’t destiny. Cancer researchers, for example, have developed drugs that can calm berserk microglia in mice and restore their cognitive abilities; some are being tested in early clinical trials. “I’m hopeful that we’ll find the same to be true in COVID,” she said.
Biomedical advances might take years to arrive, but long-haulers need help with brain fog now. Absent cures, most approaches to treatment are about helping people manage their symptoms. Sounder sleep, healthy eating, and other generic lifestyle changes can make the condition more tolerable. Breathing and relaxation techniques can help people through bad flare-ups; speech therapy can help those with problems finding words. Some over-the-counter medications such as antihistamines can ease inflammatory symptoms, while stimulants can boost lagging concentration.
“Some people spontaneously recover back to baseline,” Hellmuth told me, “but two and a half years on, a lot of patients I see are no better.” And between these extremes lies perhaps the largest group of long-haulers—those whose brain fog has improved but not vanished, and who can “maintain a relatively normal life, but only after making serious accommodations,” Putrino said. Long recovery periods and a slew of lifehacks make regular living possible, but more slowly and at higher cost.
Kristen Tjaden can read again, albeit for short bursts followed by long rests, but hasn’t returned to work. Angela Meriquez Vázquez can work but can’t multitask or process meetings in real time. Julia Moore Vogel, who helps lead a large biomedical research program, can muster enough executive function for her job, but “almost everything else in my life I’ve cut out to make room for that,” she told me. “I only leave the house or socialize once a week.” And she rarely talks about these problems openly because “in my field, your brain is your currency,” she said. “I know my value in many people’s eyes will be diminished by knowing that I have these cognitive challenges.”
Patients struggle to make peace with how much they’ve changed and the stigma associated with it, regardless of where they end up. Their desperation to return to normal can be dangerous, especially when combined with cultural norms around pressing on through challenges and post-exertional malaise—severe crashes in which all symptoms worsen after even minor physical or mental exertion. Many long-haulers try to push themselves back to work and instead “push themselves into a crash,” Robertson told me. When she tried to force her way to normalcy, she became mostly housebound for a year, needing full-time care. Even now, if she tries to concentrate in the middle of a bad day, “I end up with a physical reaction of exhaustion and pain, like I’ve run a marathon,” she said.
Post-exertional malaise is so common among long-haulers that “exercise as a treatment is inappropriate for people with long COVID,” Putrino said. Even brain-training games—which have questionable value but are often mentioned as potential treatments for brain fog—must be very carefully rationed because mental exertion is physical exertion. People with ME/CFS learned this lesson the hard way, and fought hard to get exercise therapy, once commonly prescribed for the condition, to be removed from official guidance in the U.S. and U.K. They’ve also learned the value of pacing—carefully sensing and managing their energy levels to avoid crashes.
Vogel does this with a wearable that tracks her heart rate, sleep, activity, and stress as a proxy for her energy levels; if they feel low, she forces herself to rest—cognitively as well as physically. Checking social media or responding to emails do not count. In those moments, “you have to accept that you have this medical crisis and the best thing you can do is literally nothing,” she said. When stuck in a fog, sometimes the only option is to stand still.
