A new syndrome is striking children and adolescents who have been infected with SARS-CoV-2. It causes the immune system to go haywire and can be life-threatening. Doctors are trying to find patterns in who falls ill.
By now, Christian Dohna-Schwake knows a thing or two about these children – some as young as 5, others up to 17 years old – who are transferred to the intensive care unit where he works at the University Hospital in Essen because of high fevers and unstable circulation. He also knows that starting in around mid-April, their numbers will increase.
Pinpointing who will fall ill is, of course, impossible. But one thing can be said with certainty: The patients will have previously been infected with SARS-CoV-2. Indeed, those who will show up in April are contracting the coronavirus right about now.
Dohna-Schwake is closely monitoring the growing third wave of the coronavirus pandemic in Germany. This time around, the proportion of children contracting the infection is higher than in the first and second waves. The numbers are rising “very rapidly ” among young people under 15, Lothar Wieler, the head of the Robert Koch Institute, Germany’s center for disease control, said last week. And that means more patients suffering from Pediatric Inflammatory Multisystem Syndrome for Dohna-Schwake.
Nineteen cases of PIMS have been treated in Essen so far, a higher number than in any other German hospital. One year ago, this illness was unknown to the medical world. Now, though, it is understood that PIMS is a rare, but particularly insidious, late consequence of a coronavirus infection. “We have learned a lot, ” says Dohna-Schwake, “and we’re still learning. ”
None of his PIMS patients has died. That, he says, is partially the product of luck, since some of the cases have been quite critical. The condition of one six-year-old, for example, was “definitely life-threatening, ” Dohna-Schwake recalls. A smaller hospital nearby had initially provided treatment for the boy in October, just as Germany’s second coronavirus wave was swelling.
The boy was feverish, his eyes were inflamed, his body was covered with a rash. But worst of all, he suffered from severe abdominal pain. He was given antibiotics, but the treatment didn’t work. The fever just wouldn’t go down.
The doctors were puzzled. Ultimately, though, they began wondering: Could this possibly be the novel syndrome they had read about in the medical journals? Doctors in Essen shared their suspicions. There was no evidence that the boy had come into contact with the coronavirus, but that doesn’t necessarily mean anything. “Often, the infection itself goes unnoticed, ” Dohna-Schwake says. Serious symptoms don’t appear until the virus is long gone.
The patient was transferred to the University Hospital in Essen, where his condition worsened. His blood vessels dilated and an increasing amount of fluid leaked through the vessel walls into the surrounding tissue, and his blood pressure fell. “We had to counteract with drugs, ” Dohna-Schwake says, “with amounts of circulatory stabilizing medication that I have rarely seen. ”
Then the boy’s lungs began collecting water as well. The boy suffered from shortness of breath and the oxygen saturation in his blood decreased. “We had to put him in an artificial coma so we could ventilate him, ” Dohna-Schwake says. His condition only began to improve after he was given high doses of cortisone. After four or five days, the doctors were able to bring their patient out of the coma.
By now, every doctor working in pediatric intensive care has heard of cases like this. The doctors now know that the syndrome is the result of a dysregulated immune system response that can lead to inflammatory processes in various organs and in the blood vessels.
PIMS appears to occur in about one out of a thousand children who have been infected with SARS-CoV-2 in Germany. The factors that determine when an outbreak will occur are still unknown.
The German Society for Pediatric Infectious Diseases (DGPI) has asked all hospitals in Germany and Austria to report any PIMS cases that are diagnosed to Dresden’s University Hospital.
Setting Up a Registry
The registry there is being maintained by two pediatricians, Reinhard Berner and Jakob Armann. Recalling its launch, Armann says, “it was about a year ago. Like everyone else, DGPI had also largely switched to Zoom meetings.” The subject of the first meeting was the role pediatricians would play in the pandemic.
At the time, hospitals across Germany were preparing for the expected surge of patients. Any non-critical operations were canceled and entire wards were cleared for COVID-19 patients. But children’s hospitals were largely unaffected. It became apparent that children only rarely fell ill; and when they did, it usually wasn’t severe. But would that mean that pediatricians would just sit idly on the sidelines during the pandemic?
Children, the DGPI quickly agreed, need to be given special attention in any type of epidemic. Even if they didn’t show any symptoms, they could still be transmitters of the disease. It is also important to understand why the virus largely spares children and when there are exceptions to this rule.
They resolved to keep as close an eye on the situation as possible. Because the number of COVID-19 cases among children was so low, it would be necessary to pool all the observations centrally. “The task of creating such a registry fell to us,” Armann says.
When the first reports of PIMS cases arrived from Britain and America in April, it was clear to the Dresden-based doctors that the registry had been set up to deal with exactly this kind of phenomenon. It quickly became clear that children can also fall severely ill from the effects of the coronavirus, although the symptoms look a lot different than COVID-19.
At the time, PIMS didn’t yet have a name. It was described as a new type of inflammatory condition that was strikingly similar to an illness known as Kawasaki syndrome, which was first identified around 50 years ago. It primarily affects infants and preschool children and is more common in Japan.
Severe Abdominal Pain
Over the course of a year of clinical experience with SARS-CoV-2, striking differences have now emerged between PIMS and Kawasaki syndrome. One significant difference is the age group most commonly affected. Although young children can also contract PIMS, the majority of patients are much older, typically between 7 and 10 years old, but 13-, 16- or even 20-year-olds are sometimes admitted to hospitals with PIMS.
The symptoms of PIMS and Kawasaki syndrome also differ. “What is striking is how often the stomach and intestines are involved with PIMS,” says Dohna-Schwake, the intensive care physician in Essen. Around a third of the patients he has treated have complained of severe abdominal pain. In some cases, doctors feared appendicitis and opened the abdomen only to find that there was nothing to operate on.
Doctors opened the abdomen only to find that there was nothing to operate on.
Despite all the differences, what both syndromes have in common is that they are rooted in an overreaction of the immune system. “What makes PIMS so fascinating is that we know what triggers it,” says Armann. This also allows for some conclusions to be drawn for the classic Kawasaki syndrome: The epidemiological data suggests that a viral infection could be responsible for triggering that illness as well.
The clue: In parallel with the uptick in cases of PIMS, the number of cases of Kawasaki has decreased. Doctors believe the reason for that decrease are the measures aimed at containing the coronavirus: Social distancing has ensured that there has been less spread than usual of the pathogens that cause flu and colds. Because such viruses are hardly being spread any longer, the secondary complications they can have aren’t appearing as often either.
A total of 238 cases of PIMS have now been recorded in the Dresden registry. The occurrences follow the course of the COVID-19 curve, though with a delay of a few weeks. Medical records reflect different progressions of the disease depending on which organs are affected. In every fourth case, the inflammation spreads to the nervous system, which can lead to seizures. In every fifth case, the kidneys or liver are affected.
Disturbing News from America
Of the cases documented in Dresden, 59 percent ended up in intensive care, mostly because the patients’ circulation could no longer be stabilized without medical support. None of the children died.
Meanwhile, doctors are reporting disturbing news from the United States. They suggest that PIMS is becoming increasingly aggressive there, without any explanation for why that might be happening. America’s Centers for Disease Control (CDC) has already reported 33 deaths. “I exchange information with a colleague in New York,” Dohna-Schwake says. “He told me that almost all PIMS patients there now require intensive care.” Six months ago, the rate was still only 40 percent.
Fortunately, such a trend hasn’t yet developed in Germany. Nor is there any evidence so far that the new variants of the SARS-CoV-2 virus will worsen the progression of PIMS.
According to reports from German hospitals, PIMS is quite treatable. “That standard treatment for Kawasaki syndrome is working, ” Armann states. Rebellious immune systems can be calmed with the help of cortisone. Immunoglobulins obtained from donor blood plasma are also effective. It’s unclear why a mix of non-specific antibodies is capable of regulating the body’s defenses. But Dohna-Schwake offers confirmation: “It’s very impressive. Immunoglobulins, high doses of cortisone and, after 48 hours, the nightmare is over. ”
The Dresden PIMS register shows that almost half of the patients were discharged in healthy condition. In almost one in 10 cases, however, the children have been left with long-term problems. Fifteen of the children and adolescents suffered lasting damage to their hearts and will have to be monitored by doctors in the long term.
The spectrum of often subtle long-term effects is wide and still far from being fully understood, says Dohna-Schwake. For example, two of the girls he treated in Essen complained of problems with their periods after they were discharged. The six-year-old he discharged last autumn still suffers from muscular weakness today.
After his release from the university hospital in Essen, he first had to be sent to physical rehabilitation, where he had to learn how to walk again. The strength in his arms still hasn’t completely returned – a striking testament to how mistaken it would be to believe that the coronavirus isn’t particularly dangerous for children.