COVID-19 vaccination can greatly reduce multisystem inflammatory syndrome in children (MIS-C), a rare but serious complication associated with SARS-CoV-2 infection, researchers are finding.
MIS-C can cause inflammation in multiple body systems and is threatening to become the leading cause of pediatric heart disease, said Emily Jacoby, MSN, RN, infection prevention specialist at St. Louis Children’s Hospital.
Speaking recently in Indianapolis at the 2022 conference of the Association for Professionals in Infection Control and Epidemiology (APIC), Jacoby urged infection preventionists (IPs) to spread the word about preventing MIS-C through vaccination. “This is really important for us to share with our families, with our healthcare teams, and the public,” she said. “[If] we can increase vaccination, we won’t have families having to go through this situation with their child developing MIS-C.”
The syndrome is serious, since MIS-C pediatric patients often have to be admitted to intensive care. As of July 31, 2022, there have been 8,798 MIS-C cases and 71 deaths in the United States since mid-May 2020, the Centers for Disease Control and Prevention (CDC) reports.1 MIS-C onset usually is two to six weeks after COVID-19 infection, which may go undiagnosed in children. The median age of patients with MIS-C is 9 years, and the inflammatory syndrome has a disproportionate effect on Black and Hispanic children. Overall, 98% of case patients have had a positive test result for SARS CoV-2, and the remaining 2% had contact with someone with COVID-19, the CDC reported.
The Case for Vaccination
In making the case for vaccination to prevent MIS-C, Jacoby cited a 2022 study that found only one case of MIS-C per million immunized children.2 In contrast, a 2021 study on unvaccinated children found a rate of MIS-C of more than 300 children per million.3
“About 312 [children] went on to develop MIS-C in that study compared to one per 1 million vaccinated children,” she said. “So, again, it just really highlights the importance that vaccination can play in helping to prevent this severe complication from a COVID infection.”
Although the CDC estimates COVID-19 immunization is 91% protective against MIS-C in children ages 12 to 18 years, vaccinating younger children has been delayed because of comprehensive safety investigations.4 The CDC recommended vaccination of children ages 5 to 12 years for COVID-19 in November 2021. The final step came on June 18, 2022, when the CDC recommended that children 6 months through 5 years of age should receive a COVID-19 vaccine.
In greenlighting vaccination of children, the CDC emphasized that everyone in the United States older than 6 months of age now can be immunized. “COVID-19 vaccines have undergone — and will continue to undergo — the most intensive safety monitoring in U.S. history,” the CDC stated.5
MIS-C is a diagnosis of exclusion, and isolating these patients may come down to a local judgment call.
“If they come in and they do not have a prior noted positive PCR (polymerase chain reaction) or antigen test [for SARS-CoV-2], but test positive by PCR in our hospital, then we’re going to isolate them,” Jacoby said. “Even if they have IgG (immunoglobulin G) antibodies, we’re still going to isolate them.”
However, 63% of the hospital’s MIS-C cases had positive IgG antibodies but tested negative by PCR for COVID-19. “Those are easy — they didn’t have positive PCR tests, so no isolation for them,” she said.
However, the diagnosis itself and resulting isolation decisions may involve discussions with specialists because MIS-C can affect multiple organs, including the heart, lungs, blood vessels, kidneys, digestive system, brain, skin, and eyes.
“There’s no specific biomarker, so that makes it hard,” Jacoby said. “You can’t run a specific report in your electronic medical records to pull one particular lab result. It’s a lot of lab results and the clinical presentation all put together. It is challenging. “
Jacoby consults with infectious disease, rheumatology, and cardiology physicians. MIS-C can be misdiagnosed as Kawasaki’s disease, but it is a syndrome with multiple manifestations. Patients with MIS-C generally present with persistent fever, abdominal pain, vomiting, diarrhea, skin rash, mucocutaneous lesions and, in severe cases, with hypotension and shock, the CDC notes.6 The CDC case definition for MIS-C is:
- an individual aged < 21 years presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (> 2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurological); AND
- no alternative plausible diagnoses; AND
- positive for current or recent SARS-CoV-2 infection by RT (reverse transcription)-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the four weeks prior to the onset of symptoms.
Concerning isolation for MIS-C, the Society for Healthcare Epidemiology of America (SHEA) generally recommends it for those PCR-positive for SARS-CoV-2, with a negative test indicating no patient isolation is needed or can be discontinued. “For care of [MIS-C] patients not requiring aerosol-generating procedures, the minimum level of PPE (personal protective equipment) that should be used includes surgical mask, eye protection, gloves, and gown to care for patients,” the SHEA Pediatric Leadership Council recommends.7 “Notably, specific hospital policy should be followed because some hospitals may require N95 or similar type of respirator for all persons under investigation for COVID-19.”
Data from St. Louis Children’s Hospital
As of April 2022, St. Louis Children’s Hospital has admitted 87 children with MIS-C, and 85 of them were not vaccinated, Jacoby said.
“We had one patient who was fully vaccinated and one patient who was partially vaccinated,” she said. “We had 34 who were eligible for vaccination at the time of their MIS-C illness onset.” Another 53 cases were not vaccine-eligible, primarily because the 6-month to 5-year vaccine recommendation had not yet been issued.
When the first Omicron variant hit St. Louis in December 2021, the hospital admitted 17 cases of MIS-C that month.
“It was a huge number, but it is interesting that it just completely dropped back off as that wave went through,” Jacoby said. “We’re down to about one case a month, which is manageable — 17 a month was not very manageable.”
A majority of patients had to be admitted to the intensive care unit (ICU), including many with no underlying risk factors.
“We had 67 (77%) of our 87 cases require ICU level of care and we had one death associated with MIS-C,” she said. “It is just really astonishing to me that 59 (68%) of our [MIS-C patients] had absolutely no underlying past medical history. Keep that in mind when you’re thinking 77% of them required an ICU level of care. That’s pretty significant and it stands out a lot to me.”
Overall, 16 of the hospital’s MIS-C patients were obese, a known risk factor. MIS-C is a reportable condition, but health departments may ask clinicians to wait and report when the patient has been discharged or has died. This is to better determine the long-term course of MIS-C, but it also means the data available are a lagging indicator.
“Sometimes I may have patients admitted for a very long time before I can report them,” Jacoby said. “I also look for any COVID-19 patients who stay admitted for a long time, specifically in our ICU. I periodically get back into their charts to read and update and see if they’ve maybe shifted. It’s challenging. When they have a severe acute case of COVID-19 — at what point does that turn into MIS-C?”
- Centers for Disease Control and Prevention. Health department-reported cases of multisystem inflammatory syndrome in children (MIS-C) in the United States. https://covid.cdc.gov/covid-data-tracker/#mis-national-surveillance
- Yousaf AR, Cortese MM, Taylor AW, et al. Reported cases of multisystem inflammatory syndrome in children aged 12-20 years in the USA who received a COVID-19 vaccine, December, 2020, through August, 2021: A surveillance investigation. Lancet Child Adolesc Health 2022;6:303-312.
- Payne AB, Gilani Z, Godfred-Cato S, et al. Incidence of multisystem inflammatory syndrome in children among US persons infected with SARS-CoV2. JAMA Netw Open 2021;4:e2116420.
- Zambrano LD, Newhams MM, Olson SM, et al. Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA vaccination against multisystem inflammatory syndrome in children among persons aged 12-18 years – United States, July-December 2021. MMWR Morb Mortal Wkly Rep 2022:71:52-58.
- Centers for Disease Control and Prevention. CDC recommends COVID-19 vaccines for young children. Published June 18, 2022. https://www.cdc.gov/media/releases/2022/s0618-children-vaccine.html#:~:text=Today%2C%20CDC%20Director%20Rochelle%20P,receive%20a%20COVID%2D19%20vaccine
- Centers for Disease Control and Prevention. Information for healthcare providers about multisystem inflammatory syndrome in children (MIS-C). Last reviewed May 20, 2021. https://www.cdc.gov/mis/mis-c/hcp/index.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fmis%2Fhcp%2Findex.html
- Muller ML, Logan LK, Kociolek LK, et al. SHEA Pediatric Leadership Council commentary: Personal protective equipment during care of children with multisystem inflammatory syndrome in children (MIS-C). Infect Control Hosp Epidemiol 2021;42:1108-1110.
