New York State Children’s Multi-Systemic Inflammatory Syndrome

Population study and SARS-CoV-2 tests

From March 1 to May 10, 2020, 191 reports were submitted to the NYSDOH regarding admitted patients under the age of 21. A total of 189 medical records were received and 161 were extracted (Fig. S2). Of these 161 patients, 99 met the NYSDOH provisional 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 suspicious case. Of the 99 patients, 29 (29%) met the clinical criteria with one or more of the following: hypotension or shock, severe heart disease, or other serious terminal organ disease; 6 (6%) met the 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 and 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 to detect the presence of SARS-CoV -2 antibodies with a serological assay; 19 (20%) had evidence of SARS-CoV-2 infection only by an RT-PCR assay, 45 (47%) had evidence of SARS-CoV-2 infection only by a serological test (1 of which never SARS-CoV-2 infection was tested with an RT-PCR assay), and 31 (33%) had evidence of SARS-CoV-2 from both RT-PCR and serological assays. Of the 77 patients analyzed for the presence of IgG, 76 (99%) were reactive; 3 patients were reactive for IgA, 3 were reactive for IgM and 21 were not reactive for IgM. There were no patients with IgM or IgA reactivity alone. Of the 76 patients with serological 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 tests; none underwent serological tests. Two (50%) had Covid-19-like disease in the 6 weeks prior to the onset of MIS-C symptoms. Because the characteristics of patients with confirmed cases and patients with suspected cases were similar (data not shown), the two groups were combined for further analysis.

Characteristics of the patients.

Patients at hospital admission with confirmed or suspected multisystemic inflammatory syndrome in children (MIS-C). Demographic and clinical characteristics of the patients at hospital admission, according to age group. Syndrome groups according to age group among patients with multisystemic inflammatory syndrome in children (MIS-C).

Color ranges were determined in quintiles of the percentages observed. Dermatological or mucocutaneous symptoms included the following symptoms: skin rash, conjunctivitis, swollen hands or feet, and changes in the mucosa. Gastrointestinal included the following symptoms: abdominal pain, nausea or vomiting, and diarrhea. Kawasaki disease (KD) or atypical KD was determined by discharge diagnosis or code in the International Classification of Diseases, Tenth 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 absent, clinical myocarditis was defined as an elevated level of either prorebral natriuretic peptide or cerebral natriuretic peptide and cardiac dysfunction or arrhythmia on electrocardiography in the setting of an inflammatory process. Neurologic included the following symptoms: headache, altered mental status, and confusion.

Of the 99 MIS-C patients, 53 (54%) were male. A total of 31 patients (31%) were between 0 and 5 years old, 42 (42%) were between 6 and 12 years old and 26 (26%) were between 13 and 20 years old (Table 1) Of 78 patients with race data, 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 ethnicity, 31 (36%) were Hispanic (Table 2) Of the 36 patients with a pre-existing condition, 29 were obese. All patients had fever or chills on admission. Other common presenting symptoms were gastrointestinal (80%), dermatological (62%), mucocutaneous (61%) and lower respiratory (40%). A total of 60 patients (61%) had gastrointestinal and dermatological or mucocutaneous symptoms. Figure 1 shows symptom categories according to age group. Neurological symptoms, predominantly headache, were present in 13% of patients 0-5 years of age and 38% of those 13-20 years of age. A total of 48% of patients 0 to 5 years old and 43% of those 6 to 12 years old had Kawasaki disease or atypical Kawasaki disease, while 12% of 13 to 20 years old had that presentation.

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

Vital signs and laboratory values ​​of patients at hospital admission, according to age group.

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

Antecedent disease and viral and bacterial tests upon admission

In the 6 weeks prior to admission, of the 99 MIS-C patients, 24 (24%) had a Covid-19 compatible disease 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 disease. Tests were performed for respiratory viruses, including influenza A and B, and for respiratory syncytial virus in 57 patients (58%). Of the 57 patients evaluated for respiratory viruses, 2 had evidence of viral infection: coronavirus 229e and SARS-CoV-2 were detected in 1 patient, and adenovirus, an untyped coronavirus and SARS-CoV-2 were detected in 1 patient. Bacterial cultures were reported for 77 patients (78%); none showed evidence of a bacterial infection in the blood. A total of 71 patients (72%) received empirical systemic antibacterial therapy.

Clinical course, treatment and results

Clinical course and results, according to age group.

Overall, 79 patients (80%) were admitted to an intensive care unit (ICU) (average 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 immunoglobulin (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. Z scores were reported for 7 of the 9 patients with coronary artery aneurysms, with 4 (57%) with a score of 2.5 to less than 5. Of 60 patients with tests for troponin levels and proBNP, an electrocardiogram, and a echocardiogram, 59 had evidence of cardiac abnormalities. Of 90 patients who underwent computed tomography (CT) or chest radiography, 35 (39%) noted at least one opacity. Of 44 patients who underwent CT of the abdomen, ultrasound 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), thickening of the intestinal wall (in 7) or fluid-filled intestinal loops (in 4).

A total of 36 patients (36%) received a diagnosis of atypical (or incomplete) Kawasaki disease or Kawasaki disease; 7 of the 9 patients with coronary artery aneurysms also received a diagnosis of Kawasaki disease. A total of 36 patients (36%) received a diagnosis of myocarditis, and another 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 discharged patients, and 7 days (interquartile range, 3 to 11) among the deceased.

Death occurred in two children aged 0-12 years. Both were admitted with abdominal pain and fever, had tachycardia and hypotension at presentation, and during the course of their hospitalization received vasopressor support and underwent intubation; one received extracorporeal membrane oxygenation. None received IVIG, systemic glucocorticoids, or immunomodulators. The cause that contributed to the death of both children included complications of a possibly inflammatory, coagulopathic or neurological process.

Epidemic curve

Pediatric cases of coronavirus disease 2019 (Covid-19) and MIS-C.

All data are for patients under 21 years of age in New York State from March to 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 people under 21 years of age in New York State, according to the date of sample collection, and cases of MIS-C confirmed and suspected in our study, according to the date of admission, are shown in Figure 2. The peak in the number of MIS-C cases followed the peak in the number of laboratory-confirmed SARS-CoV-2 infections in 31 days. From March 1 to May 10, 2020, the incidence of laboratory-confirmed SARS-CoV-2 infection was 322 per 100,000 people under the age of 21, and the incidence of MIS-C was 2 per 100,000 people. under 21 years of age.