Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 - PowerPoint PPT Presentation

Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 ALLISON AGWU, MD, ScM Associate Professor of Pediatric and Adult Infectious Diseases NICOLE SALAZAR-AUSTIN, MD Assistant Professor of Pediatrics JODY HOOPER, MD Associate Professor of Pathology

Session Overview • Epidemiology of COVID-19 in children • Clinical case presentation • Review of MIS-C clinical characteristics • Discussion of therapeutic options for MIS-C • Pathology presentation • Discussion

Epidemiology of COVID-19 in Children

Data in Children: China • Nationwide case series of 2135 pediatric cases of SARS-CoV-2 infection reported to Chinese CDC from 1/16/20 through 2/8/20 • Children = <18 years old • 728 (34.1%) laboratory-confirmed • 1407 (65.9%) suspected • Exposed to COVID-19 patient or living in an epidemic area + two of the following: • Fever, respiratory or GI symptoms, or fatigue • WBC normal or decreased or CRP elevated • Abnormal chest radiograph Dong Y et al. Pediatrics. 2020 Jun;145(6):e20200702. doi: 10.1542/peds.2020-0702. Epub 2020 Mar 16.

Data in Children: China • Illness severity definitions • Asymptomatic: + SARS-CoV-2 PCR, no signs/symptoms, normal CXR • Mild: Upper respiratory tract symptoms OR only digestive symptoms without fever, normal lung exam • Moderate: Pneumonia, not hypoxic, no SOB, abnormal lung exam OR no signs or symptoms but CT findings of lung lesions • Severe: Symptoms + oxygen saturation is <92% with other hypoxia manifestations. • Critical: ARDS or respiratory failure, or shock, encephalopathy, myocardial injury or heart failure, coagulation dysfunction, acute kidney injury, other end- organ damage Dong Y et al. Pediatrics. 2020 Jun;145(6):e20200702. doi: 10.1542/peds.2020-0702. Epub 2020 Mar 16.

Data in Children: China • Median age 7y [IQR 2-13 years] • 1208 (56.6%) male • >90% asymptomatic, mild, or moderate disease • 94 (4.4%) asymptomatic, 1088 (51.0%) mild, 826 (38.7%) moderate • 5.9% severe or critical (18.5% of adult cases in China severe or critical as of Feb) • 1 death • Severe and critical cases by age group • 10.6% <1 year of age • 7.3% ages 1 to 5 • 4.2% ages 6 to 10 • 4.1% ages 11 to 15 • 3.0% aged ≥ 16 Dong Y et al. Pediatrics. 2020 Jun;145(6):e20200702. doi: 10.1542/peds.2020-0702. Epub 2020 Mar 16.

Data in Children: China Dong Y et al. Pediatrics. 2020 Jun;145(6):e20200702. doi: 10.1542/peds.2020-0702. Epub 2020 Mar 16.

Data in Children: China • Median number of days from illness onset to diagnosis = 2 days (range: 0–42 days) • Most cases diagnosed in the first week after illness onset occurred Dong Y et al. Pediatrics. 2020 Jun;145(6):e20200702. doi: 10.1542/peds.2020-0702. Epub 2020 Mar 16.

Data in Children: United States • Baseline US demographics • 22% of population comprised of infants, children and adolescents <18y • COVID-19 data through 4/2/20 • >890,000 cases and >45,000 deaths worldwide • 239,279 cases and 5443 deaths in the US • Analysis of 149,760 laboratory-confirmed cases 2/12 through 4/2 • 2572 (1.7%) among children aged <18y • Voluntary reporting via standardized case report form • Data available for only small proportion of patients on many variables MMWR Morb Mortal Wkly Rep 2020;69:422–426. DOI: http://dx.doi.org/10.15585/mmwr.mm6914e4

Data in Children: United States • 2572 pediatric cases • Median age 11 years • 850 (33%) from New York City • 813 (32%) reported cases in children 15-17y • 584 (23%) from the rest of New York state • 682 (27%) in children 10-14y • 393 (15%) from New Jersey • 398 (15%) in children aged <1 year • 745 (29%) from other jurisdictions • 388 (15%) in children aged 5-9y • 291 (11%) in children aged 1-4y • Similar to adult cases save lower proportion (14%) from NY state MMWR Morb Mortal Wkly Rep 2020;69:422–426. DOI: http://dx.doi.org/10.15585/mmwr.mm6914e4

Data in Children: US Demographics • 1408 (57%) in males (vs 53% in adults aged ≥ 18y) • Predominance of males in all pediatric age groups • Among the 184 (7.2%) with known exposure information: • 168 (91%) had exposure to a COVID-19 patient • 16 (9%) associated with travel • Underlying conditions (data available on 13%) • 23% had at least one, including all six admitted to ICU • Most common: chronic lung disease, cardiovascular disease, immunosuppression MMWR Morb Mortal Wkly Rep 2020;69:422–426. DOI: http://dx.doi.org/10.15585/mmwr.mm6914e4

Pediatric Clinical Data • Signs and symptoms (data available on 11% of patients) • 73% had fever, cough, or dyspnea (vs. 93% adults 18-64y) • 56% fever; 54% cough; 13% dyspnea • Versus 71%, 80%, and 43% among adults 18-64y MMWR Morb Mortal Wkly Rep 2020;69:422–426. DOI: http://dx.doi.org/10.15585/mmwr.mm6914e4

Pediatric Clinical Data: U.S. • Hospitalization status (data available on 29%) • 5.7% hospitalized (vs 10% adults 18-64y) • 0.58% to ICU (vs 1.4%) • 20% of those for whom status known (vs. 33% adults) • 2% to ICU (vs. 4.5%) • Children <1 year accounted for highest proportion of hospitalized children • Three deaths MMWR Morb Mortal Wkly Rep 2020;69:422–426. DOI: http://dx.doi.org/10.15585/mmwr.mm6914e4

Take-Home Points • COVID-19 is typically less severe in children than adults • Serious illness resulting in hospitalization still occurs • Slight preponderance of cases in boys • Physical distancing and other measures remain important given concern that less symptomatic persons may still contribute to disease transmission

Multisystem Inflammatory Syndrome in Children (MIS-C)

Clinical Case

Case Presentation • 15 year old previously healthy African American female presented to another hospital with one week of epigastric pain, initially waxing and waning, then progressively worsening with loss of appetite. • 2 days prior to admission developed nasal congestion and rhinorrhea without sore throat, dyspnea, or cough. She also endorsed loss of smell and taste, which she attributed to nasal congestion. • One day prior to presentation developed myalgia • ROS: negative for fever, headache, nausea, vomiting, diarrhea, vaginal discharge (LMP 1 week prior to symptoms), urinary symptoms

History • PMH: none • SH: lives with mother and 2 sisters (both had sore throat and cold- like symptoms the week prior); +social distancing • FH: MGM hypothyroid

At the First Hospital • PE: T 36.5°C HR 88 RR 18 O2 Sat 100% on RA • mild epigastric tenderness without rebound/guarding • WBC 18.9 S15.7% • Urinalysis negative, urine pregnancy test negative • SARS-CoV-2 PCR NEGATIVE • Abdominal CT: Fat stranding and prominent lymph nodes (<1 cm) in the epigastric region surrounding a loop of proximal jejunum. Mildly prominent lymph nodes (<1 cm) in the left retroperitoneum. • Transferred to JHU for further surgical evaluation

JHU ED course • Tm 38.1°C HR 90s-110s BP 110s/50s Weight 95.7 kg (BMI 31) • PE: RUQ tenderness without rebound or guarding. • Labs: WBC 16.2 (S-91% L-5% M-1.5%), ALC 790 • Chemistries, urinalysis: unremarkable • ESR 74 CRP 24.3 • SARS-CoV-2 PCR NEGATIVE • GC/CT NEGATIVE • GI cocktail à unclear improvement, admitted for observation

Hospital Course • HD #1-2 (illness day 8-9): abdominal pain and fluid intake improved, but continued to have fever and tachycardia • Tm 38.9°C CRP 24.3 ESR 74 • HD #3 (illness day 10): worsening abdominal pain, diffuse myalgia (diffuse paraspinal), throat discomfort (L>R), pleuritic chest discomfort without shortness of breath. Faint erythematous maculopapular rash noted on chest, back, palms, and soles. • Tm 37.7°C, d-dimer 1.09, CRP 30.4, LFTs nl, troponin <.04, ferritin 137 • WBC 18.8, B-24%, Plt 272K

Hospital Course • HD#4 (illness day 11): developed worsened fever (39.9°C), continued abdominal discomfort, tachycardia, hypotension requiring fluid boluses, and increased work of breathing. Transferred to PICU • CRP 33.7 ESR 107 d-dimer 1.55 • WBC 27.7 B-43% • Troponin >.04, proBNP 652, Fibrinogen 965 mg/dL (170-422) • Repeat imaging à

HD #1 HD #4 A Figure 1. Imaging at hospital admission (Panels A and B) C and at admission to the PICU (Panels C and D). Axial CT of the chest showed normal lungs (Panel A) with coronal IV contrast enhanced CT (Panel B) showing enlarged mesenteric and retroperitoneal nodes (arrows) and normal bowel. On HD 4, repeat chest CT (Panel C) showed bilateral lower lobe consolidation without pulmonary embolism and coronal IV contrast enhanced CT (Panel D) demonstrated new wall thickening of the distal transverse colon, gallbladder wall edema, and mesenteric stranding (arrows). Both chest and abdominal CT at that time showed prominent diffuse supraclavicular, hilar, B D mediastinal, abdominal, and retroperitoneal lymphadenopathy (Panels C and D).

MIS-C: Clinical Characteristics