Saturday, August 08, 2020

MMWR: COVID-19–Associated Multisystem Inflammatory Syndrome in Children — U.S., March–July 2020


#15,404

After six months of economic and societal upheaval due to COVID-19, our nation - and many others around the world - continue to debate over how and when it will be `safe' to send kids back to the classroom.
 
Yesterday we looked at the ECDC's Technical Report: COVID-19 In Children & The Role Of School Transmission, which - while finding school closures have little impact on community spread of the pandemic - acknowledged `. . . . . the role of children in SARS-CoV-2 transmission remains unclear, especially in the context of educational settings.'

Although children and adolescents are less likely to experience severe illness with COVID-19 than an adult, they are hardly immune.  And when they do get sick enough to be hospitalized, they often end up in intensive care (see MMWR Hospitalization Rates and Characteristics of Children Aged <18 Years Hospitalized with Laboratory-Confirmed COVID-19).

(EXCERPT)

Analysis of pediatric COVID-19 hospitalization data from 14 states found that although the cumulative rate of COVID-19–associated hospitalization among children (8.0 per 100,000 population) is low compared with that in adults (164.5), one in three hospitalized children was admitted to an intensive care unit.

Children are at risk for severe COVID-19. Public health authorities and clinicians should continue to track pediatric SARS-CoV-2 infections. Reinforcement of prevention efforts is essential in congregate settings that serve children, including childcare centers and schools.

While many of these very sick kids are suffering from severe COVID-19, a subset of them go on to develop a Kawasaki-like life threatening syndrome called MIS-C (Multisystem Inflammatory Syndrome in Children), which we first saw described in the UK back in April (see PICS: NHS Alert On Possible Severe Pediatric COVID-19 Complication).

A week later the CDC would issue their first alert (see CDC HAN: Multisystem Inflammatory Syndrome In Children (MIS-C)), which was followed up with a CDC COCA Call : Multisystem Inflammatory Syndrome in Children (MIS-C) four days later. 

Since then, this syndrome has been identified in hundreds of children around the world - and while the numbers remain small - surveillance and reporting are still in their infancy. 

The CDC describes the syndrome on their MIS-C website as:
What is MIS-C?

Multisystem inflammatory syndrome in children (MIS-C) is a condition where different body parts can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. Children with MIS-C may have a fever and various symptoms, including abdominal (gut) pain, vomiting, diarrhea, neck pain, rash, bloodshot eyes, or feeling extra tired. We do not yet know what causes MIS-C. However, many children with MIS-C had the virus that causes COVID-19, or had been around someone with COVID-19.

Up until yesterday, the number of U.S. cases reported on the CDC's website (current through May 20th) was 186, reported across 26 states.  According to the following MMWR report, that number has since tripled to nearly 600 known cases across 40 states (through July 29th)

Once again, we see stark racial disparities in the numbers, with Hispanic and black patients accounting for 73.6% of reported MIS-C patients.  The median age was 8, and two-thirds of these cases did not have preexisting underlying medical conditions.

While the percentage of COVID-19 cases that go on to develop MIS-C is minuscule, to put it in some kind of perspective - compared to the total number of Acute Flaccid Myelitis cases reported in the United States (see CDC MMWR/Vital Signs) - we've seen more MIS-C cases in the past 6 months than AFM cases over the past 6 years.

Due to its length I've only posted some excepts from yesterday's report.  Follow the link to read it in its entirety. 

COVID-19–Associated Multisystem Inflammatory Syndrome in Children — United States, March–July 2020

Early Release / August 7, 2020 / 69


Shana Godfred-Cato, DO1; Bobbi Bryant, MPH1,2; Jessica Leung, MPH1; Matthew E. Oster, MD1; Laura Conklin, MD1; Joseph Abrams, PhD1; Katherine Roguski, MPH1; Bailey Wallace, MPH1,2; Emily Prezzato, MPH1; Emilia H. Koumans, MD1; Ellen H. Lee, MD3; Anita Geevarughese, MD3; Maura K. Lash, MPH3; Kathleen H. Reilly, PhD3; Wendy P. Pulver, MS4; Deepam Thomas, MPH5; Kenneth A. Feder, PhD6; Katherine K. Hsu, MD7; Nottasorn Plipat, MD, PhD8; Gillian Richardson, MPH9; Heather Reid10; Sarah Lim, MBBCh11; Ann Schmitz, DVM12,13; Timmy Pierce, MPH1,2; Susan Hrapcak, MD1; Deblina Datta, MD1; Sapna Bamrah Morris, MD1; Kevin Clarke, MD1; Ermias Belay, MD1; California MIS-C Response Team (View author affiliations)View suggested citation


Summary

What is already known about this topic?

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition that has been reported approximately 2–4 weeks after the onset of COVID-19 in children and adolescents.

What is added by this report?

Most cases of MIS-C have features of shock, with cardiac involvement, gastrointestinal symptoms, and significantly elevated markers of inflammation, with positive laboratory test results for SARS-CoV-2. Of the 565 patients who underwent SARS-CoV-2 testing, all had a positive test result by RT-PCR or serology.

What are the implications for public health practice?

Distinguishing MIS-C from other severe infectious or inflammatory conditions poses a challenge to clinicians caring for children and adolescents. As the COVID-19 pandemic continues to expand in many jurisdictions, health care provider awareness of MIS-C will facilitate early recognition, early diagnosis, and prompt treatment.

PDF pdf icon[195K]


(EXCERPT)

As of July 29, 2020, a total of 570 MIS-C patients with onset dates from March 2 to July 18, 2020, had been reported from 40 state health departments, the District of Columbia, and New York City (Figure). The median patient age was 8 years (range = 2 weeks–20 years); 55.4% were male, 40.5% were Hispanic or Latino (Hispanic), 33.1% were non-Hispanic black (black), and 13.2% non-Hispanic white (white) (Table 1). Obesity was the most commonly reported underlying medical condition, occurring in 30.5% of Hispanic, 27.5% of black, and 6.6% of white MIS-C patients.

Overall, the illness in 490 (86.0%) patients involved four or more organ systems. Approximately two thirds did not have preexisting underlying medical conditions before MIS-C onset. The most common signs and symptoms reported during illness course were abdominal pain (61.9%), vomiting (61.8%), skin rash (55.3%), diarrhea (53.2%), hypotension (49.5%), and conjunctival injection (48.4%). Most patients had gastrointestinal (90.9%), cardiovascular (86.5%), or dermatologic or mucocutaneous (70.9%) involvement. Substantial numbers of MIS-C patients had severe complications, including cardiac dysfunction (40.6%), shock (35.4%), myocarditis (22.8%), coronary artery dilatation or aneurysm (18.6%), and acute kidney injury (18.4%). The majority of patients (63.9%) were admitted to an ICU. The median length of ICU stay was 5 days (interquartile range = 3–7 days).

Of the 565 (99.1%) patients who underwent SARS-CoV-2 testing, all had a positive test result by RT-PCR or serology; 46.1% had only serologic evidence of infection and 25.8% had only positive RT-PCR test results. Five patients (0.9%) did not have testing performed but had an epidemiologic link as indicated in the MIS-C case definition.

Among all 570 patients, 527 (92.5%) were treated, including 424 (80.5%) who received intravenous immunoglobulin (IVIG), 331 (62.8%) who received steroids, 309 (58.6%) who received antiplatelet medication, 233 (44.2%) who received anticoagulation medication, and 221 (41.9%) who were treated with vasoactive medication. Ten (1.8%) patients were reported to have died (Table 1).

(SNIP) 
Discussion

Initial reports of MIS-C patients described varied clinical signs and symptoms at initial evaluation, but most cases included features of shock, cardiac dysfunction, gastrointestinal symptoms, significantly elevated markers of inflammation and cardiac damage, and positive test results for SARS-CoV-2 by serology (3,6–8).
Because the case definition is nonspecific and confirmatory laboratory testing does not exist, it might be difficult to distinguish MIS-C from other conditions with overlapping clinical manifestations such as severe acute COVID-19 and Kawasaki disease (9). Latent class analysis is particularly well-suited to describe differing manifestations of a novel clinical syndrome. It divides patients into groups that might have been previously unrecognized, based on shared characteristics, allowing for an unbiased determination of disease manifestations.
Patients identified in class 1 had little overlap with acute COVID-19 or Kawasaki disease, whereas patients in class 2 had clinical and laboratory manifestations that overlapped with acute COVID-19. This overlap might result from the development of MIS-C soon after symptomatic acute COVID-19 illness. However, the presence of isolated severe acute COVID-19 illness cannot be ruled out in some of these patients. Patients in class 3 generally seemed to have less severe MIS-C illness and clinical manifestations that overlapped with Kawasaki disease, and distinguishing class 3 patients from those with true Kawasaki disease could be difficult (4). As the COVID-19 pandemic spreads, and more children are exposed to SARS-CoV-2 with subsequent seroconversion, patients with Kawasaki disease might be misidentified as MIS-C because of an incidental finding of antibodies to SARS-CoV-2.

Overall, the age distribution of the patients in this analysis is similar to that described elsewhere, but there are differences in the clinical manifestations and laboratory findings, perhaps due to differences in inclusion criteria (6,7). Increases in COVID-19 incidence might result in increased occurrence of MIS-C which might not be apparent immediately because of the 2–4-week delay in the development of MIS-C after acute SARS-CoV-2 infection (8). The proportion of Hispanic, black, and white MIS-C patients with obesity is slightly higher than that reported in the general pediatric population.¶
Hispanic and black patients accounted for the largest proportion (73.6%) of reported MIS-C patients. Acute COVID-19 has been reported to disproportionately affect Hispanics and blacks (10). Long-standing inequities in the social determinants of health, such as housing, economic instability, insurance status, and work circumstances of patients and their family members have systematically placed social, racial, and ethnic minority populations at higher risk for COVID-19 and more severe illness, possibly including MIS-C.**

The findings in this report are subject to at least four limitations. First, there is a possibility of case identification and reporting bias, including variability in diagnosis, testing, and management of patients by different jurisdictions. Second, inconsistency in completion of case report forms, with some patients still hospitalized at the time of reporting, might have affected data completeness (e.g., race and ethnicity were not reported for 18.9% of cases). Third, access to SARS-CoV-2 testing at the time of onset might have varied by regions, hospitals, and time. Finally, CDC’s case definition was broad, with the intention of being more inclusive, which might have led to the unintentional inclusion of patients whose illnesses overlapped with acute COVID-19 and Kawasaki disease.

As the COVID-19 pandemic continues, with the number of cases increasing in many jurisdictions, health care providers should continue to monitor patients to identify children with a hyperinflammatory syndrome with shock and cardiac involvement. Suspected MIS-C patients should be reported to local and state health departments. Distinguishing patients with MIS-C from those with acute COVID-19 and other hyperinflammatory conditions is critical for early diagnosis and appropriate management. It is also critical for monitoring potential adverse events of a COVID-19 vaccine when one becomes widely available. Studies to define the clinical and laboratory characteristics of MIS-C should continue, including identification of parameters that will help distinguish the illness from other similar conditions.
(Continue . . . )