More than 5,200 of the 6.2 million U.S. children diagnosed with COVID have developed MIS-C.

By Liz Szabo October 20, 2021

Like most other kids with COVID, Dante and Michael DeMaino seemed to have no serious symptoms.

Infected in mid-February, both lost their senses of taste and smell. Dante, 9, had a low-grade fever for a day or so. Michael, 13, had a "tickle in his throat," said their mother, Michele DeMaino, of Danvers, Massachusetts.

At a follow-up appointment, "the pediatrician checked their hearts, their lungs, and everything sounded perfect," DeMaino said.

Then, in late March, Dante developed another fever. After examining him, Dante's doctor said his illness was likely "nothing to worry about" but told DeMaino to take him to the emergency room if his fever climbed above 104.

Two days later, Dante remained feverish, with a headache, and began throwing up. His mother took him to the ER, where his fever spiked to 104.5. In the hospital, Dante's eyes became puffy, his eyelids turned red, his hands began to swell and a bright red rash spread across his body.

Hospital staffers diagnosed Dante with multisystem inflammatory syndrome in children, or MIS-C, a rare but life-threatening complication of COVID-19 in which a hyperactive immune system attacks a child's body. Symptoms — fever, stomach pain, vomiting, diarrhea, bloodshot eyes, rash and dizziness — typically appear two to six weeks after what is usually a mild or even asymptomatic infection.

More than 5,200 of the 6.2 million U.S. children diagnosed with COVID have developed MIS-C. About 80% of MIS-C patients are treated in intensive care units, 20% require mechanical ventilation, and 46 have died.

Throughout the pandemic, MIS-C has followed a predictable pattern, sending waves of children to the hospital about a month after a COVID surge. Pediatric intensive care units — which treated thousands of young patients during the late-summer delta surge — are now struggling to save the latest round of extremely sick children.

The South has been hit especially hard. At the Medical University of South Carolina Shawn Jenkins Children's Hospital, for example, doctors in September treated 37 children with COVID and nine with MIS-C — the highest monthly totals since the pandemic began.

Doctors have no way to prevent MIS-C, because they still don't know exactly what causes it, said Dr. Michael Chang, an assistant professor of pediatrics at Children's Memorial Hermann Hospital in Houston. All doctors can do is urge parents to vaccinate eligible children and surround younger children with vaccinated people.

Given the massive scale of the pandemic, scientists around the world are now searching for answers.

Although most children who develop MIS-C were previously healthy, 80% develop heart complications. Dante's coronary arteries became dilated, making it harder for his heart to pump blood and deliver nutrients to his organs. If not treated quickly, a child could go into shock. Some patients develop heart rhythm abnormalities or aneurysms, in which artery walls balloon out and threaten to burst.

"It was traumatic," DeMaino said. "I stayed with him at the hospital the whole time."

Such stories raise important questions about what causes MIS-C.

"It's the same virus and the same family, so why does one child get MIS-C and the other doesn't?" asked Dr. Natasha Halasa of the Vanderbilt Institute for Infection, Immunology and Inflammation.

Doctors have gotten better at diagnosing and treating MIS-C; the mortality rate has fallen from 2.4% to 0.7% since the beginning of the pandemic. Adults also can develop a post-COVID inflammatory syndrome, called MIS-A; it's even rarer than MIS-C, with a mortality rate seven times as high as that seen in children.

Although MIS-C is new, doctors can treat it with decades-old therapies used for Kawasaki disease, a pediatric syndrome that also causes systemic inflammation. Although scientists have never identified the cause of Kawasaki disease, many suspect it develops after an infection.

Researchers at Boston Children's Hospital and other institutions are looking for clues in children's genes.

In a July study, the researchers identified rare genetic variants in three of 18 children studied. Significantly, the genes are all involved in "removing the brakes" from the immune system, which could contribute to the hyperinflammation seen in MIS-C, said Dr. Janet Chou, chief of clinical immunology at Boston Children's, who led the study.

Chou acknowledges that her study — which found genetic variants in just 17% of patients — doesn't solve the puzzle. And it raises new questions: If these children are genetically susceptible to immune problems, why didn't they become seriously ill from earlier childhood infections?

Some researchers say the increased rates of MIS-C among racial and ethnic minorities around the world — in the United States, France and the United Kingdom — must be driven by genetics.

Others note that rates of MIS-C mirror the higher COVID rates in these communities, which have been driven by socioeconomic factors such as  high-risk working and living conditions.

"I don't know why some kids get this and some don't," said Dr. Dusan Bogunovic, a researcher at the Icahn School of Medicine at Mount Sinai who has studied antibody responses in MIS-C. "Is it due to genetics or environmental exposure? The truth may lie somewhere in between."

A Hidden Enemy and a Leaky Gut

Most children with MIS-C test negative for COVID, suggesting that the body has already cleared the novel coronavirus from the nose and upper airways.

That led doctors to assume MIS-C was a "postinfectious" disease, developing after "the virus has completely gone away," said Dr. Hamid Bassiri, a pediatric infectious diseases specialist and co-director of the immune dysregulation program at Children's Hospital of Philadelphia.

Now, however, "there is emerging evidence that perhaps that is not the case," Bassiri said.

Even if the virus has disappeared from a child's nose, it could be lurking — and shedding — elsewhere in the body, Chou said. That might explain why symptoms occur so long after a child's initial infection.

Dr. Lael Yonker noticed that children with MIS-C are far more likely to develop gastrointestinal symptoms — such as stomach pain, diarrhea and vomiting — than the breathing problems often seen in acute COVID.

In some children with MIS-C, abdominal pain has been so severe that doctors misdiagnosed them with appendicitis; some actually underwent surgery before their doctors realized the true source of their pain.

Yonker, a pediatric pulmonologist at Boston's MassGeneral Hospital for Children, recently found evidence that the source of those symptoms could be the coronavirus, which can survive in the gut for weeks after it disappears from the nasal passages, Yonker said.

In a May study in The Journal of Clinical Investigation, Yonker and her colleagues showed that more than half of patients with MIS-C had genetic material — called RNA — from the coronavirus in their stool.

The body breaks down viral RNA very quickly, Chou said, so it's unlikely that genetic material from a COVID infection would still be found in a child's stool one month later. If it is, it's most likely because the coronavirus has set up shop inside an organ, such as the gut.

While the coronavirus may thrive in our gut, it's a terrible houseguest.

In some children, the virus irritates the intestinal lining, creating microscopic gaps that allow viral particles to escape into the bloodstream, Yonker said.

Blood tests in children with MIS-C found that they had a high level of the coronavirus spike antigen — an important protein that allows the virus to enter human cells. Scientists have devoted more time to studying the spike antigen than any other part of the virus; it's the target of COVID vaccines, as well as antibodies made naturally during infection.

"We don't see live virus replicating in the blood," Yonker said. "But spike proteins are breaking off and leaking into the blood."

Viral particles in the blood could cause problems far beyond upset stomachs, Yonker said. It's possible they stimulate the immune system into overdrive.

In her study, Yonker describes treating a critically ill 17-month-old boy who grew sicker despite standard treatments. She received regulatory permission to treat him with an experimental drug, larazotide, designed to heal leaky guts. It worked.

Yonker prescribed larazotide for four other children, including Dante, who also received a drug used to treat rheumatoid arthritis. He got better.

But most kids with MIS-C get better, even without experimental drugs. Without a comparison group, there's no way to know if larazotide really works. That's why Yonker is enrolling 20 children in a small randomized clinical trial of larazotide, which will provide stronger evidence.

Rogue Soldiers

Dr. Moshe Arditi has also drawn connections between children's symptoms and what might be causing them.

Although the first doctors to treat MIS-C compared it to Kawasaki disease — which also causes red eyes, rashes and high fevers — Arditi notes that MIS-C more closely resembles toxic shock syndrome, a life-threatening condition caused by particular types of strep or staph bacteria releasing toxins into the blood. Both syndromes cause high fever, gastrointestinal distress, heart muscle dysfunction, plummeting blood pressure and neurological symptoms, such as headache and confusion.

Toxic shock can occur after childbirth or a wound infection, although the best-known cases occurred in the 1970s and '80s in women who used a type of tampon no longer in use.

Toxins released by these bacteria can trigger a massive overreaction from key immune system fighters called T cells, which coordinate the immune system's response, said Arditi, director of the pediatric infectious diseases division at Cedars-Sinai Medical Center.

T cells are tremendously powerful, so the body normally activates them in precise and controlled ways, Bassiri said. One of the most important lessons T cells need to learn is to target specific bad guys and leave civilians alone. In fact, a healthy immune system normally destroys many T cells that can't distinguish between germs and healthy tissue in order to prevent autoimmune disease.

In a typical response to a foreign substance — known as an antigen — the immune system activates only about 0.01% of all T cells, Arditi said.

Toxins produced by certain viruses and the bacteria that cause toxic shock, however, contain "superantigens," which bypass the body's normal safeguards and attach directly to T cells. That allows superantigens to activate 20% to 30% of T cells at once, generating a dangerous swarm of white blood cells and inflammatory proteins called cytokines, Arditi said.

This massive inflammatory response causes damage throughout the body, from the heart to the blood vessels to the kidneys.

Although multiple studies have found that children with MIS-C have fewer total T cells than normal, Arditi's team has found an explosive increase in a subtype of T cells capable of interacting with a superantigen.

Several independent research groups — including researchers at Yale School of Medicine, the National Institutes of Health and France's University of Lyon — have confirmed Arditi's findings, suggesting that something, most likely a superantigen, caused a huge increase in this T cell subtype.

Although Arditi has proposed that parts of the coronavirus spike protein could act like a superantigen, other scientists say the superantigen could come from other microbes, such as bacteria.

"People are now urgently looking for the source of the superantigen," said Dr. Carrie Lucas, an assistant professor of immunobiology at Yale, whose team has identified changes in immune cells and proteins in the blood of children with MIS-C.

Uncertain Futures

One month after Dante left the hospital, doctors examined his heart with an echocardiogram to see if he had lingering damage.

To his mother's relief, his heart had returned to normal.

Today, Dante is an energetic 10-year-old who has resumed playing hockey and baseball, swimming and rollerblading.

"He's back to all these activities," said DeMaino, noting that Dante's doctors rechecked his heart six months after his illness and will check again after a year.

Like Dante, most other kids who survive MIS-C appear to recover fully, according to a March study in JAMA.

Such rapid recoveries suggest that MIS-C-related cardiovascular problems result from "severe inflammation and acute stress" rather than underlying heart disease, according to the authors of the study, called Overcoming COVID-19.

Although children who survive Kawasaki disease have a higher risk of long-term heart problems, doctors don't know how MIS-C survivors will fare.

The NIH and Centers for Disease Control and Prevention have launched several long-term trials to study young COVID patients and survivors. Researchers will study children's immune systems to uncover clues to the cause of MIS-C, check their hearts for signs of long-term damage and monitor their health over time.

DeMaino said she remains far more worried about Dante's health than he is.

"He doesn't have a care in the world," she said. "I was worried about the latest cardiology appointment, but he said, 'Mom, I don't have any problems breathing. I feel totally fine.'"

Liz Szabo: lszabo@kff.org, @LizSzabo

Nearly 20% of Americans age 50 and older say they have experienced discrimination in healthcare settings.

This article was published on Wednesday, October 20, 2021 in Kaiser Health News.

By Judith Graham  

Joanne Whitney, 84, a retired associate clinical professor of pharmacy at the University of California-San Francisco, often feels devalued when interacting with healthcare providers.

There was the time several years ago when she told an emergency room doctor that the antibiotic he wanted to prescribe wouldn't counteract the kind of urinary tract infection she had.

He wouldn't listen, even when she mentioned her professional credentials. She asked to see someone else, to no avail. "I was ignored and finally I gave up," said Whitney, who has survived lung cancer and cancer of the urethra and depends on a special catheter to drain urine from her bladder. (An outpatient renal service later changed the prescription.)

Then, earlier this year, Whitney landed in the same emergency room, screaming in pain, with another urinary tract infection and a severe anal fissure. When she asked for Dilaudid, a powerful narcotic that had helped her before, a young physician told her, "We don't give out opioids to people who seek them. Let's just see what Tylenol does."

Whitney said her pain continued unabated for eight hours.

"I think the fact I was a woman of 84, alone, was important," she told me. "When older people come in like that, they don't get the same level of commitment to do something to rectify the situation. It's like 'Oh, here's an old person with pain. Well, that happens a lot to older people.'"

Whitney's experiences speak to ageism in healthcare settings, a long-standing problem that's getting new attention during the COVID pandemic, which has killed more than half a million Americans age 65 and older.

Ageism occurs when people face stereotypes, prejudice or discrimination because of their age. The assumption that all older people are frail and helpless is a common, incorrect stereotype. Prejudice can consist of feelings such as "older people are unpleasant and difficult to deal with." Discrimination is evident when older adults' needs aren't recognized and respected or when they're treated less favorably than younger people.

In healthcare settings, ageism can be explicit. An example: plans for rationing medical care ("crisis standards of care") that specify treating younger adults before older adults. Embedded in these standards, now being implemented by hospitals in Idaho and parts of Alaska and Montana, is a value judgment: Young peoples' lives are worth more because they presumably have more years left to live.

Justice in Aging, a legal advocacy group, filed a civil rights complaint with the U.S. Department of Health and Human Services in September, charging that Idaho's crisis standards of care are ageist and asking for an investigation.

In other instances, ageism is implicit. Dr. Julie Silverstein, president of the Atlantic division of Oak Street Health, gives an example of that: doctors assuming older patients who talk slowly are cognitively compromised and unable to relate their medical concerns. If that happens, a physician may fail to involve a patient in medical decision-making, potentially compromising care, Silverstein said. Oak Street Health operates more than 100 primary care centers for low-income seniors in 18 states.

Emogene Stamper, 91, of the Bronx in New York City, was sent to an under-resourced nursing home after becoming ill with COVID in March. "It was like a dungeon," she remembered, "and they didn't lift a finger to do a thing for me." The assumption that older people aren't resilient and can't recover from illness is implicitly ageist.

Stamper's son fought to have his mother admitted to an inpatient rehabilitation hospital where she could receive intensive therapy. "When I got there, the doctor said to my son, 'Oh, your mother is 90,' like he was kind of surprised, and my son said, "You don't know my mother. You don't know this 90-year-old," Stamper told me. "That lets you know how disposable they feel you are once you become a certain age."

At the end of the summer, when Stamper was hospitalized for an abdominal problem, a nurse and nursing assistant came to her room with papers for her to sign. "Oh, you can write!" Stamper said the nurse exclaimed loudly when she penned her signature. "They were so shocked that I was alert, it was insulting. They don't respect you."

Nearly 20% of Americans age 50 and older say they have experienced discrimination in healthcare settings, which can result in inappropriate or inadequate care, according to a 2015 report. One study estimates that the annual health cost of ageism in America, including over- and undertreatment of common medical conditions, totals $63 billion.

Nubia Escobar, 75, who emigrated from Colombia nearly 50 years ago, wishes doctors would spend more time listening to older patients' concerns. This became an urgent issue two years ago when her longtime cardiologist in New York City retired to Florida and a new physician had trouble controlling her hypertension.

Alarmed that she might faint or fall because her blood pressure was so low, Escobar sought a second opinion. That cardiologist "rushed me — he didn't ask many questions and he didn't listen. He was sitting there talking to and looking at my daughter," she said.

It was Veronica Escobar, an elder law attorney, who accompanied her mother to that appointment. She remembers the doctor being abrupt and constantly interrupting her mother. "I didn't like how he treated her, and I could see the anger on my mother's face," she told me. Nubia Escobar has since seen a geriatrician who concluded she was overmedicated.

The geriatrician "was patient," Nubia Escobar told me. "How can I put it? She gave me the feeling she was thinking all the time what could be better for me."

Pat Bailey, 63, gets little of that kind of consideration in the Los Angeles County, California, nursing home where she's lived for five years since having a massive stroke and several subsequent heart attacks. "When I ask questions, they treat me like I'm old and stupid and they don't answer," she told me in a telephone conversation.

One nursing home resident in every five has persistent pain, studies have found, and a significant number don't get adequate treatment. Bailey, whose left side is paralyzed, said she's among them. "When I tell them what hurts, they just ignore it or tell me it's not time for a pain pill," she complained.

Most of the time, Bailey feels like "I'm invisible" and like she's seen as "a slug in a bed, not a real person." Only one nurse regularly talks to her and makes her feel she cares about Bailey's well-being.

"Just because I'm not walking and doing anything for myself doesn't mean I'm not alive. I'm dying inside, but I'm still alive," she told me.

Ed Palent, 88, and his wife, Sandy, 89, of Denver, similarly felt discouraged when they saw a new doctor after their long-standing physician retired. "They went for an annual checkup and all this doctor wanted them to do was ask about how they wanted to die and get them to sign all kinds of forms," said their daughter Shelli Bischoff, who discussed her parents' experiences with their permission.

"They were very upset and told him, 'We don't want to talk about this,' but he wouldn't let up. They wanted a doctor who would help them live, not figure out how they're going to die."

The Palents didn't return and instead joined another medical practice, where a young doctor barely looked at them after conducting cursory examinations, they said. That physician failed to identify a dangerous staphylococcus bacterial infection on Ed's arm, which was later diagnosed by a dermatologist. Again, the couple felt overlooked, and they left.

Now they're with a concierge physician's practice that has made a sustained effort to get to know them. "It's the opposite of ageism: It's 'We care about you and our job is to help you be as healthy as possible for as long as possible,'" Bischoff said. "It's a shame this is so hard to find."

We're eager to hear from readers about questions you'd like answered, problems you've been having with your care and advice you need in dealing with the healthcare system. Visit khn.org/columnists to submit your requests or tips.

KFF's Kaiser Health News and The John A. Hartford Foundation will hold a 90-minute interactive web event on ageism in healthcare beginning at noon Eastern Time on Thursday, Oct. 21. Join us for a frank, practical and empowering conversation about this pervasive, systemic problem of bias, discrimination or stereotyping based on age.

Judith Graham: khn.navigatingaging@gmail.com, @judith_graham

The return to school raises particular health issues for children with disabilities who are at increased risk for serious bouts of COVID-19.

This article was published on Tuesday, October 19, 2021 in Kaiser Health News.

By Heidi de Marco   

LOS ANGELES — Christopher Manzo, a boy with curly brown hair and bright-blue-and-yellow glasses, has lived a third of his five years at home because of the pandemic.

And he is more than ready for kindergarten.

Hand in hand with his mother, Martha Manzo, he walks into the Blind Children's Center, a low-rise building nestled among apartment complexes in East Hollywood. In the brightly colored hallway, filled with paintings of animals, Manzo kneels to hug Christopher before he scurries unsteadily to his cubby.

"God take care of you and be with you," she says. "And have fun."

Born with congenital hydrocephalus that damaged his brain and left him with severely impaired vision, cognitive difficulties and a lack of coordination, Christopher hasn't missed only school the past 18 months — he's missed out on a host of vital occupational, physical and language therapies, as well as socialization with other kids.

At home, Christopher couldn't look at a computer screen long enough to attend therapies or classes on Zoom, said Manzano, in an interview conducted in Spanish. "He would strain his eyes, look away, and his attention would falter," she said. "He couldn't devote the same attention as a kid without disabilities.''

Christopher "could have advanced much more" since the pandemic hit if he hadn't missed so much school, said Manzano, who is 36 and has three other children, ages 12, 10 and 8, whom she also has had to guide through months of home-schooling.

Yet the return to school raises particular health issues for Christopher and other children with disabilities who are at increased risk for serious bouts of COVID-19, said his pediatrician at Children's Hospital Los Angeles, Dr. Liza Mackintosh. Though he isn't immunosuppressed, Christopher has trouble coughing up secretions, which leaves him vulnerable to lung and respiratory infections, she said.

Compared with other adults in contact with children, his parents, teachers and therapists "have to be more vigilant about mask-wearing, hand hygiene and social distancing," she said.

In short, Manzo was deeply worried about the threat of COVID exposure Christopher faced at school. But it was a risk she felt he could no longer avoid, to get on with his life.

Trying to learn from home was "really hard on him," Manzo said. "He couldn't understand why he couldn't go to school or the park or to his therapies."

"I know COVID is still among us, but I also can't keep him at home like he's a crystal bubble and protect him," she said. "He needs contact with other kids and his teachers."

The challenges faced by Christopher during the pandemic have been shared by many of the roughly 7 million U.S. children and young adults, ages 3 to 21, with special needs. Online platforms usually don't work for them. For example, Christopher needs to feel Braille letters to read — he can't do that on a computer screen.

Students with disabilities had "sort of this double hit where it was very hard to access school services and very challenging to continue to work on developing new skills," said Dr. Irene Koolwijk, a specialist in developmental-behavioral pediatrics at UCLA Health.

It took a lot of preparation to get Christopher and the 40 or so other children attending the Blind Children's Center back into the building of the private, infant-to-kindergarten school. All the children are blind or visually impaired, and most also have disorders ranging from autism and albinism to cerebral palsy and epilepsy. The school practices reverse mainstreaming, in which a few children with typical development share the classroom with children with disabilities.

Months before the school doors reopened, the center started teaching the students about wearing masks.

"Little by little, we started training the kids to wear masks on Zoom. It started off with the duration of a song, then two songs," said Rosalinda Mendiola, adaptive services specialist at the Blind Children's Center. "Our goal was that by the time we opened back up, they would be used to them."

But it was difficult. Many children with special needs have a hard time wearing their masks and understanding the concept of distancing, said Mackintosh. Children with some forms of autism, in particular, have sensory issues that make it bothersome to have something on their faces.

"Children learn the most from modeling. They watch their parents, their teachers, their friends," said Bianca Ciebrant, the center's director of early childhood education. "But children who are visually impaired and blind can't see the mask-wearing. That's probably one of the harder barriers."

It took Christopher seven months to start wearing a mask. "At first, he didn't even want it in front of his face," said Manzo. "He started to slowly accept it when he saw his siblings wear it."

To reopen in September, the school also adopted new COVID safety protocols. All 30 staff members are vaccinated, temperature checks are performed at drop-off, and parents aren't allowed inside classrooms.

All students wear masks except for three of them who have limited motor ability and couldn't safely remove a mask or don't understand the mask-wearing process "and therefore it becomes sensory overload and behavior breakdown," Ciebrant said.

There are six kids in each class, overseen by a teacher and two assistants. Christopher needs someone near him to remind him where to walk and to hold on to the banister for balance.

With so many staffers around, "creating a shield of vaccinated individuals around the child is important to making the transition back to school as safe as possible," said Dr. Christine Bottrell Mirzaian, a pediatrician at Children's Hospital Los Angeles.

Martha and her husband, Fausto Manzo, were vaccinated last March, and their 12-year-old daughter, Samantha, also has been immunized against COVID.

"Our health is important to be able to continue taking care of him," Martha Manzo said.

On a recent Wednesday, Christopher wore a teddy bear mask and a Ryan's World backpack to school. This is his last year at the center. When he started, he was only 2 and hadn't learned to walk.

"He has received a lot of help," Manzo said. "His movements have improved, and his communication skills."

Christopher toddles around the playground during recess and greets his friends with a wave. "His balance is off, but he's walking now," his mother said. "I always wanted to see him run and explore."

School staff members were happy to have their students back.

"We all felt this little warmth in our heart to hear their voices back in the hallway, whether it was crying or laughing or talking to their friends," said Ciebrant. "This is what we've been waiting for, to hear those moments."

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Healthcare Foundation.

Heidi de Marco: heidid@kff.org, @Heidi_deMarco

The Hulu series dovetails with the broader reality KFF's journalists and analysts have been documenting in their work for the past few years.

This article was published on Monday, October 18, 2021 in Kaiser Health News.

KHN and policy colleagues at our parent organization KFF teamed up with Hulu for a discussion of America's opioid crisis, following the Oct. 13 premiere of the online streaming service's new series "Dopesick."

The discussion explored how the series' writers worked with journalist Beth Macy, author of the book "Dopesick: Dealers, Doctors, and the Drug Company That Addicted America," and showrunner Danny Strong to create and fact-check scripts and develop characters. It quickly moved on to a deeper discussion of how the fictionalized version of the opioid epidemic portrayed in the Hulu series dovetailed with the broader reality KFF's journalists and analysts have been documenting in their work for the past few years.

Providing perspective on the role of public health and treatment were KHN correspondent Aneri Pattani, who has reported extensively on opioid policy, substance use and mental health, and KFF senior policy analyst Nirmita Panchal, whose analytical work focuses on mental health and substance use.

The forum was moderated by Chaseedaw Giles, audience engagement editor and digital strategist at KHN who has written about hip-hop music's relationship with opioid abuse. It was filmed in KFF's Washington, D.C., conference center to an audience of no one (courtesy of COVID-19).

You can read a transcript of the forum by clicking here.