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Multisystem Inflammatory Syndrome in Children in New York State

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Study Population and SARS-CoV-2 Testing

From March 1 through May 10, 2020, there were 191 reports submitted to the NYSDOH regarding admitted patients younger than 21 years of age. A total of 189 medical records were received, and 161 were abstracted (Fig. S2). Of these 161 patients, 99 met the NYSDOH interim case definition of MIS-C (for comparison of included and excluded patients, see Table S1); 95 patients (96%) were classified as having a confirmed case and 4 (4%) as having a suspected case. Of the 99 patients, 29 (29%) met clinical criteria with one or more of the following: hypotension or shock, severe cardiac illness, or other severe end-organ illness; 6 (6%) met clinical criteria with two or more of the following: rash, conjunctivitis, mucocutaneous signs, or gastrointestinal symptoms; and 64 (65%) met both types of clinical criteria. Between March 1 to May 10, of the 95 patients with confirmed cases, 94 (99%) were tested for SARS-CoV-2 infection with an RT-PCR assay and 77 (81%) were tested for the presence of SARS-CoV-2 antibodies with a serologic assay; 19 (20%) had evidence of SARS-CoV-2 infection from an RT-PCR assay alone, 45 (47%) had evidence of SARS-CoV-2 infection from a serologic assay alone (1 of whom was never tested for SARS-CoV-2 infection with an RT-PCR assay), and 31 (33%) had evidence of SARS-CoV-2 from both RT-PCR and serologic assays. Of the 77 patients tested for the presence of IgG, 76 (99%) were reactive; 3 patients were reactive for IgA, 3 were reactive for IgM, and 21 were nonreactive for IgM. There were no patients with IgM or IgA reactivity alone. Of the 76 patients with serologic evidence of SARS-CoV-2 infection, 40 (53%) had reactive IgG before or on the first day of admission.

All four patients with suspected cases had negative molecular testing; none underwent serologic testing. Two (50%) had Covid-19–like illness in the 6 weeks before MIS-C symptom onset. Because the characteristics of the patients with confirmed cases and of the patients with suspected cases were similar (data not shown), the two groups were combined for further analyses.

Characteristics of the Patients

Patients at Hospital Admission with Confirmed or Suspected Multisystem Inflammatory Syndrome in Children (MIS-C). Demographic and Clinical Characteristics of the Patients at Hospital Admission, According to Age Group. Syndrome Clusters According to Age Group among Patients with Multisystem Inflammatory Syndrome in Children (MIS-C).

Color ranges were determined at quintiles of the observed percentages. Dermatologic or mucocutaneous included the following symptoms: rash, conjunctivitis, swollen hands or feet, and mucosal changes. Gastrointestinal included the following symptoms: abdominal pain, nausea or vomiting, and diarrhea. Kawasaki’s disease (KD) or atypical KD was determined by discharge diagnosis or code in the International Classification of Diseases, 10th Revision (ICD-10). Myocarditis was determined by discharge diagnosis or ICD-10 code. Clinical myocarditis was defined as cardiac dysfunction on echocardiography with an elevated troponin level; if the troponin value was missing, clinical myocarditis was defined as an elevated level of pro–brain natriuretic peptide or brain natriuretic peptide and cardiac dysfunction or arrhythmia on electrocardiography in the context of an inflammatory process. Neurologic included the following symptoms: headache, altered mental status, and confusion.

Of the 99 patients with MIS-C, 53 (54%) were male. A total of 31 patients (31%) were 0 to 5 years of age, 42 (42%) were 6 to 12 years of age, and 26 (26%) were 13 to 20 years of age (Table 1). Of 78 patients with data on race, 29 (37%) were white, 31 (40%) were black, 4 (5%) were Asian, and 14 (18%) were of other races; of 85 patients with data on ethnic group, 31 (36%) were Hispanic (Table 2). Of the 36 patients with a preexisting condition, 29 had obesity. All the patients had fever or chills at admission. Other common presenting symptoms were gastrointestinal (80%), dermatologic (62%), mucocutaneous (61%), and lower respiratory (40%). A total of 60 patients (61%) had gastrointestinal and either dermatologic or mucocutaneous symptoms. Figure 1 shows symptom categories according to age group. Neurologic symptoms, predominantly headache, were present in 13% of the patients 0 to 5 years of age and 38% of those 13 to 20 years of age. A total of 48% of the patients 0 to 5 years of age and 43% of those 6 to 12 years of age presented with Kawasaki’s disease or atypical Kawasaki’s disease, whereas 12% of those 13 to 20 years of age had such a presentation.

One neonate, who was classified as having a suspected case and whose mother had asymptomatic SARS-CoV-2 infection at delivery, presented with fever and left breast cellulitis between 14 and 28 days of age. Laboratory assessment showed increasing troponin levels (increasing from 43 ng per liter to 51 ng per liter in 10 hours); cardiac two-dimensional ultrasonography showed good ventricular function and unremarkable coronary arteries. Two molecular tests for SARS-CoV-2 were negative. The discharge diagnoses were cellulitis, myocarditis, and shock. One adolescent who was pregnant (between 23 and 26 weeks of gestation), classified as having a confirmed case, was admitted with fever, headache, and chest pain. She had hypotension, and laboratory assessment showed elevated levels of troponin and other inflammatory markers. The discharge diagnoses were acute respiratory distress syndrome, perimyocarditis, and pneumonia.

Vital Signs and Laboratory Values of the Patients at Hospital Admission, According to Age Group.

On admission, 63% of the patients had fever of 38.0°C (100.4°F) or higher, 97% had tachycardia, 78% had tachypnea, and 32% had hypotension (Table 3). The median temperature on admission was 38.3°C, and the median oxygen saturation was 98%. Median and interquartile ranges for systolic and diastolic blood-pressure measurements at admission, according to age, are presented in Table S2. On admission, among patients with suspected or confirmed MIS-C, the median white-cell count was 10,400 per microliter, and 59 of 89 (66%) had lymphopenia; 74 of 82 (90%) had elevated proBNP levels, 63 of 89 (71%) had elevated troponin levels, 98 of 98 had elevated C-reactive protein levels, and 86 of 94 (91%) had elevated d-dimer levels (Table 3). Additional clinical and laboratory findings on admission, according to age group, are provided in Table 2 and Table 3.

Antecedent Illness and Viral and Bacterial Testing on Admission

In the 6 weeks before admission, of the 99 patients with MIS-C, 24 (24%) had a Covid-19–compatible illness a median of 21 days (interquartile range, 10 to 31) before hospitalization, 38 (38%) had exposure to a person with confirmed Covid-19, and 22 (22%) had direct contact with a person who had a clinically compatible Covid-19–like illness. Testing for respiratory viruses, including influenza A and B, and for respiratory syncytial virus was performed in 57 patients (58%). Of the 57 patients tested for respiratory viruses, 2 had evidence of viral infection: coronavirus 229e and SARS-CoV-2 were detected in 1 patient, and adenovirus, a nontyped coronavirus, and SARS-CoV-2 were detected in 1 patient. Bacterial cultures were reported for 77 patients (78%); none showed evidence of a bacterial blood infection. A total of 71 patients (72%) received empiric systemic antibacterial therapy.

Clinical Course, Treatment, and Outcomes

Clinical Course and Outcomes, According to Age Group.

Overall, 79 patients (80%) were admitted to an intensive care unit (ICU) (median time from admission to ICU entry, <1 day; interquartile range, 0 to 1), and 10 (10%) received mechanical ventilation. The median time from symptom onset to hospital admission was 4 days (interquartile range, 3 to 6) (Table 4). A total of 69 patients (70%) received intravenous immune globulin (IVIG), 63 (64%) received systemic glucocorticoids, and 61 (62%) received vasopressor support; 48 (48%) received both systemic glucocorticoids and IVIG. During hospitalization, at least one echocardiogram was obtained for 93 patients (94%); 51 (52%) had some degree of ventricular dysfunction, 32 (32%) had pericardial effusion, and 9 (9%) had a documented coronary-artery aneurysm. The z scores were reported for 7 of the 9 patients with coronary-artery aneurysms, with 4 (57%) having a score of 2.5 to less than 5. Of 60 patients with examinations for troponin and proBNP levels, an electrocardiogram, and an echocardiogram, 59 had evidence of cardiac abnormalities. Of 90 patients who underwent computed tomography (CT) or radiography of the chest, 35 (39%) had at least one opacity noted. Of 44 patients who underwent CT of the abdomen, ultrasonography of the abdomen, or both, 34 (77%) had abnormal findings; 4 (9%) had hepatomegaly, splenomegaly, or hepatosplenomegaly, 8 (18%) had mesenteric adenopathy, 16 (36%) had ascites, pleural effusions, or pelvic fluid, and 17 (39%) had inflammation or enlargement of the appendix (in 2 patients) or the gallbladder (in 5), enteritis or enterocolitis (in 3), bowel-wall thickening (in 7), or fluid-filled bowel loops (in 4).

A total of 36 patients (36%) received a diagnosis of Kawasaki’s disease or atypical (or incomplete) Kawasaki’s disease; 7 of the 9 patients with coronary-artery aneurysms also received a diagnosis of Kawasaki’s disease. A total of 36 patients (36%) received a diagnosis of myocarditis, and an additional 16 (16%) had clinical myocarditis. As of May 15, a total of 76 patients (77%) had been discharged and 21 (21%) were still hospitalized; 2 (2%) died in the hospital. The median length of stay was 6 days (interquartile range, 4 to 9) overall, 6 days (interquartile range, 4 to 8) among patients who were discharged, and 7 days (interquartile range, 3 to 11) among those who died.

Death occurred in two children 0 to 12 years of age. Both were admitted with abdominal pain and fever, had tachycardia and hypotension on presentation, and during the course of their hospitalization received vasopressor support and underwent intubation; one received extracorporeal membrane oxygenation. Neither received IVIG, systemic glucocorticoids, or immunomodulators. The contributing cause of death for both children included complications of a possibly inflammatory, coagulopathic, or neurologic process.

Epidemic Curve

Pediatric Cases of Coronavirus Disease 2019 (Covid-19) and of MIS-C.

All data are for patients younger than 21 years of age in New York State from March through May, 2020. Covid-19 was defined by a positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Cases of laboratory-confirmed SARS-CoV-2 infection among persons younger than 21 years of age in New York State, according to date of specimen collection, and cases of confirmed and suspected MIS-C in our study, according to date of admission, are shown in Figure 2. The peak in the number of MIS-C cases followed the peak in the number of cases of laboratory-confirmed SARS-CoV-2 infection by 31 days. From March 1 through May 10, 2020, the incidence of laboratory-confirmed SARS-CoV-2 infection was 322 per 100,000 persons younger than 21 years of age, and the incidence of MIS-C was 2 per 100,000 persons younger than 21 years of age.

https://www.nejm.org/doi/full/10.1056/NEJMoa2021756

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