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What is MIS-A? Doctors discuss COVID-19-associated syndrome in adults

It was a rash that killed Dr. Alisa Femia.

Femia, director of inpatient dermatology at NYU Langone Health in New York City, looked at a patient’s chart that contained several photos of the 45-year-old man who had cared for his wife in recent weeks while ill with COVID-19 . The man had dark red circular spots on the palms and soles of his feet. His eyes were pink and his lips were extremely chapped.

His body erupted with the kind of extreme inflammation that was almost exclusively noted in children at the time.

“Before I even saw the patient,”

; Femia recalled, “I said, ‘This has not been reported yet. This must be MIS-A.'”

MIS-A stands for “multi-system inflammatory syndrome in adults.” When the condition was identified in children in the spring, it was named MIS-C, where C stood for “children”.

Children developed dangerous inflammation around the heart and other organs, often weeks after their first infections with SARS-CoV-2, the virus that causes COVID-19.

The Centers for Disease Control and Prevention warned doctors about MIS-C in May. As of October 1, the CDC had reported 1,027 confirmed cases of MIS-C with several cases under investigation. Twenty children are dead.

In some cases, the children developed rashes as Femia noticed in her adult patient.

Femia and colleagues published details of the case in The Lancet in July to warn other doctors to be on the lookout for similar patients.

“The skin is right in front of your eyes,” Femia said. “You can not see it.”

However, many doctors may not recognize the condition in adults. Just a few dozen cases of MIS-A have been reported. And not all patients have obvious rashes.

Dr. Sapna Bamrah Morris, clinical director of the Health Care Systems and Worker Safety Task Force, part of the CDC’s COVID-19 response, detailed 27 cases in a report released by the agency last week.

MIS-A’s “true prevalence is unknown,” Morris said. “We need to make doctors realize that. It may be rare, but we do not know. It may be more common than we think.”

Negative tests

Part of the problem is that the virus has been circulating among humans for less than a year. Doctors around the world are still learning about how SARS-CoV-2 works in patients.

Typically, seriously ill COVID-19 patients tend to arrive at the hospital because they have difficulty breathing. This has not been the case with MIS-A.

Many MIS-A patients report fever, chest pain or other heart problems, diarrhea or other gastrointestinal problems – but not shortness of breath. And diagnostic tests for COVID-19 tend to be negative.

Instead, patients will test positive for COVID-19 antibodies, meaning they were infected two to six weeks earlier, even though they never had symptoms.

“Just because someone does not have respiratory symptoms as their primary manifestation does not mean that what they are experiencing is not a result of COVID-19,” Morris said.

The disease can be life threatening. Patients usually have some form of severe dysfunction of at least one organ, such as the heart or liver.

Ten patients in the CDC report were to be admitted to intensive care units. Some had to be put on fans. Two are dead.

What’s more, the CDC report showed that members of racial and ethnic minority groups appear to be disproportionately affected. Almost all patients with MIS-A were African American or Hispanic. But far too few cases have been reported to fully understand the underlying mechanisms at play.

While some kind of genetic link may be possible, COVID-19 has been shown to “disproportionately affect underrepresented minorities, probably due to socioeconomic factors,” Femia said. Underlying health conditions that increase the risk of COVID-19 complications, such as obesity and type 2 diabetes, also tend to be more prevalent among members of race and ethnic minority groups.

Over the summer, doctors in Florida began to see increases in COVID-19 cases. Dr. Lilian Abbo, head of infection prevention for the Jackson Health System in Miami, recalls a “very large amount of people coming through our emergency departments or hospitals who become very ill.”

The most sensitive and reliable test for COVID-19, called a PCR test, was not always available and could take several days to return results. Abbo turned to antibody testing to get the influx of patients triaged to a COVID-19 device or elsewhere in the healthcare system.

People generally develop antibodies to an infection within about a week or so. At the very least, it would give Abbo and her colleagues an indication that COVID-19 was somehow involved in their patient’s symptoms, she reasoned.

It was then that Abbo discovered a subset of patients who were critically ill after having COVID-19, but without the revealing lung problems with an acute infection.

“We were a little worried,” Abbo said. “We would perform the molecular PCR tests and they would be negative. Then the antibody tests were positive.”

Additional blood tests revealed extremely high levels of inflammation in the body.

What’s more, while the most severely ill COVID-19 patients tend to be over 65 or have more underlying health issues, these patients were “younger people who would be expected not to get sick,” Abbo said.

“That was what caught our attention.”

MIS-A treatment

There is no documented treatment for MIS-A. “We need to recognize this syndrome and develop data” to find out which therapies can be most effective, “Abbo said. We all just shoot blind. “

Dr. Jill Weatherhead, an assistant professor of infectious diseases and tropical medicine at Baylor College of Medicine in Houston, points out that CDC case reports show that doctors have tried a number of drugs for MIS-A patients, including steroids and drugs that may be affects the immune system, called interleukin-6 inhibitors.

“The problem with these diseases is that we do not know the mechanisms that cause MIS-A and MIS-C,” Weatherhead said. “It’s hard to know what the standard treatment should be until we have more information.”

In children, MIS-C is generally treated with intravenous immunoglobulin, a blood product that contains a variety of antibodies. It can also be used in adults, but the effects are largely untested.

Intravenous immunoglobulin or IVIG differs from another blood-derived antibody therapy, convalescent plasma. The latter is taken from patients who have recovered from COVID-19 and have antibodies specifically targeted to the virus in their blood. IVIG, on the other hand, is more of a mass of antibodies that are not specific to coronavirus.

The idea is that MIS-A patients already have COVID-19 antibodies, so adding more with restorative plasma is unlikely to help.

The current theory for MIS-A patients is that “the infection, as far as we know, is gone,” said Dr. Hugh Cassiere, Director of Critical Care at Sandra Atlas Bass Heart Hospital at North Shore University Hospital, part of Northwell Health on Long Island, New York.

“It’s the antibodies that are produced that seem to cause a problem,” he said.

Cassiere was part of a large team of physicians treating the wave of COVID-19 patients in New York this spring. Although MIS-A had not been identified at the time, Cassiere is convinced that such patients existed throughout.

“We saw patients admitted to the ICU with organ failure,” Cassiere said. They would test negative for COVID-19, he said, but test positive for COVID-19 antibodies, suggesting they had been infected previously.

“You look back and they probably had this multi-system inflammatory syndrome,” Cassiere said. “We did not have all the pieces to put together.”

Months later, the puzzle begins to unfold. But it will take an all-hands-on-deck approach to identifying patients with MIS-A.

“This should be at the forefront of any intensive care unit physician who sees patients, especially when they have COVID-19 antibodies,” Cassiere said.

Given Femia’s experience, this includes those who specialize in dermatology.

“This is truly the beauty of medicine, where many different specialists for this syndrome need to come together to help make the diagnosis,” Femia said.

Doctors are afraid that many MIS-A patients will not be detected – and perhaps untreated.

“There is not enough data for me to tell you what the long-term effects of this may be,” Cassiere said. “This could be the tip of the iceberg. That’s what I’m worried about.”

This story was originally published on NBC News.

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