It was a rash that pushed Dr. Alice Femia.
Femia, director of inpatient dermatology at NYU Langone Health in New York, reviewed a patient chart that included several photos of a 45-year-old man caring for his wife in recent weeks when she was suffering from COVID-19. The man had dark red circular spots on his hands and soles. His eyes were pink and his lips were extremely chapped.
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His body erupted with such strong inflammation that it was observed almost exclusively in children at that time.
“Before I saw the patient,”; Fema recalled, “I said, ‘It hasn’t been reported.’ This is probably MIS-A “.”
MIS-A means “multisystem inflammatory syndrome in adults”. When the condition was found in children this spring, it was called MIS-C, and C means “children.”
Children developed dangerous inflammation around the heart and other organs, often weeks after the initial infection with SARS-CoV-2, the virus that causes Covid-19.
Centers for Disease Control and Prevention warned doctors about MIS-C in May. As of October 1, the CDC has reported 1,027 confirmed MIS-C cases, with even more cases being investigated. Twenty children died.
In some cases, children developed rashes similar to those noted by Fema 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’t help but see this.”
But in reality, many doctors cannot recognize the condition in adults. Only a few dozen cases of MIS-A have been reported. And not all patients have obvious rashes.
Dr. Sapna Bamra Morris, clinical chair of the Occupational Health and Safety Working Group, which is part of the CDC Committee-19’s response, detailed 27 cases in a report published by the agency last week.
“The true spread of MIS-A is unknown,” Morris said. “We need to get doctors to understand this. It may be rare, but we don’t know. It may be more often than we think.”
Part of the problem is that the virus has been circulating among people for less than a year. Doctors around the world are still learning about how SARS-CoV-2 works in patients.
As a rule, seriously ill patients with Covid-19 usually go to the hospital because they have breathing problems. This was not the case with MIS-A.
Many patients with MIS-A report fever, chest pain, or other heart problems, diarrhea, or other gastrointestinal problems – but not shortness of breath. And diagnostic tests for Covid-19 are usually negative.
Instead, patients will test positive for antibodies to Covid-19, meaning they have been infected two to six weeks before, even if they have never had symptoms.
It may be rare, but we don’t know. It may be more often than we think.
“Just because someone doesn’t have respiratory symptoms as their main manifestation doesn’t mean that what they’re experiencing isn’t the result of Covid-19,” Morris said.
The disease can be life threatening. Patients usually have some kind of severe dysfunction of at least one organ, such as the heart or liver.
Ten patients in the CDC report required hospitalization in the intensive care unit. Some had to be put on fans. Two died.
Moreover, the CDC report found that members of racial and ethnic minorities appear to be disproportionately affected. Almost all patients with MIS-A were African American or Latin American. But too few cases have been reported to fully understand the underlying mechanisms at work.
While some genetic link may be possible, Covid-19 has been shown to “disproportionately affect underrepresented minorities, probably due to socioeconomic factors,” Femia said. Major health conditions that increase the risk of Covid-19 complications, such as obesity and type 2 diabetes, are also generally more common among racial and ethnic minorities.
In the summer, doctors in Florida began to see outbreaks in Covid-19 cases. Dr. Lillian Abbo, head of Jackson’s Miami Health Infections Prevention Department, recalls that “a very large number of people who go through our emergency departments or hospitals are very ill.”
The most sensitive and reliable test for Covid-19, called the PCR test, was not always available, and it may take several days for the results to return. Abbo turned to antibody testing to get an influx of patients who were tested at the Covid-19 unit or elsewhere in the health care system.
Typically, people produce antibodies to the infection in about a week or so. At the very least, it would give Ebbo and her colleagues an indication that Covid-19 was somehow involved in their patients’ symptoms, she reasoned.
Abbo then identified a subset of patients who were seriously ill after suffering from Covid-19, but without the obvious pulmonary problems of acute infection.
“We were a little embarrassed,” Abbo said. “We would do molecular PCR tests and they would be negative. Then the antibody tests were positive.”
Subsequent blood tests revealed an extremely high level of inflammation in the body.
Moreover, although most seriously ill patients with Covid-19 tend to be over the age of 65 or have several major health problems, these patients “were younger people who you expected not to get sick,” Abbo said. .
“That’s what caught our attention.”
There is no proven treatment for MIS-A. “We need to recognize this syndrome and develop data,” to find out which therapies may be most effective, Abbo said. “We all just shoot blindly.”
Dr. Jill Weatherhead, an associate professor of infectious diseases and tropical medicine at Baylor Medical College in Houston, notes that reports of CDC cases show that doctors have tried various medications for patients with MIS-A, including steroids and drugs that may affect immune system, called interleukin-6 inhibitors.
“The problem with these diseases is that we don’t know the mechanisms that cause MIS-A and MIS-C,” Weatherhead said. “It’s hard to understand what standard treatment should be until we get more information.”
In children, MIS-C is usually treated with intravenous immunoglobulin, a blood product that contains a variety of antibodies. It can be used for adults, but the effects are largely unproven.
Intravenous immunoglobulin, or IVIG, differs from other treatment with antibodies derived from blood, 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. On the other hand, IVIG is rather a mixture of antibodies that are not specific for the coronavirus.
Patients with MIS-A are thought to already have Covid-19 antibodies, so adding extra convalescent plasma is unlikely to help.
The current theory for patients with MIS-A is that “as far as we know, the infection has disappeared,” said Dr. Hugh Cassierre, director of critical care services at Sandra Atlas Bass Heart Hospital at North Shore University Hospital, part Northwell. Health, on Long Island, New York.
“These seem to be antibodies that seem to be causing problems,” he said.
The cashier was part of a large group of doctors who treated a surge of Covid-19 patients in New York in the spring. Although MIS-A was not identified at the time, Cassier is convinced that such patients existed at all times.
“We have seen patients admitted to the intensive care unit with organ failure,” Cassier said. He said they would have tested negative for Covid-19, but tested positive for Covid-19 antibodies, suggesting they had been infected before.
“You look back, and they probably had this multisystem inflammatory syndrome,” Cassier said. “We didn’t have all the parts to put them together.”
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After a few months, the mystery begins to unfold. But to identify patients with MIS-A will require an approach consisting of hands on deck.
“This should be at the forefront of every intensive care physician who visits patients, especially when they have antibodies to Covid-19,” Cassier said.
Given Femia’s experience, this includes those who specialize in dermatology.
“This is truly the beauty of medicine, where for this syndrome you need to gather many different specialists to help make a diagnosis,” said Femia.
Doctors worry that many patients with MIS-A will go undetected – and possibly without treatment.
“I don’t have enough data to tell you what the long-term consequences of this could be,” Cassier said. “It could be the tip of the iceberg. That’s what worries me.”
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