Pediatrics

MIS-C among return visits for fever in a pediatric emergency department during the COVID-19 pandemic

a b s t r a c t

Return visits (RV) to a pediatric emergency department (PED) can be secondary to illness progression, parental concerns, call backs or rarely due to a diagnostic error during the First visit. Fever accounts for nearly half of these RVs and is also one of the most common Presenting complaints of Corona Virus Disease 2019 (COVID- 19) due to severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection in children. Although majority of chil- dren with COVID 19 have a mild illness, severe complications such as multisystem inflammatory syndrome in children can occur. These children are often critically ill with a mortality rate of 2-4%. initial symptoms of MIS- C are non- specific and mimic other Viral illness making early diagnosis challenging. We report five pa- tients who were evaluated for fever and discharged from our PED and were subsequently diagnosed with MIS- C (n = 3) or Kawasaki disease (n = 2) during their RV within 7 days. All patients presented with fever during the initial visit and three of the five children had Gastrointestinal symptoms. They were all noted have persistent tachycardia during the index visit. Three patients presented in cardiogenic shock and echocardiographic abnor- malities were noted in four patients during the RV. Significant interventions were required in majority of these children (PICU admission: 4, inotropes: 3, mechanical ventilation:2). Clinicians need to maintain a high index of suspicion for diagnosis of MIS-C especially in those who present with persistent fever and have Abnormal vital signs during the COVID-19 pandemic.

(C) 2021

  1. Case report

Fever is the most common symptom associated with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infections in chil- dren. Although majority of cases in children have been mild, severe dis- eases such as multisystem inflammatory syndrome in children have occurred. The return visits(RV) of children who were evaluated for fever and discharged home during the pandemic is unknown. We performed a retrospective chart review of RV of children <=18 years of age who were evaluated for fever and discharged from our pediatric emergency department (PED) during the first six months (4/1/ 2020-12/31/2020) of the Corona Virus Disease 2019 (COVID 19) pan- demic to identify those children who were diagnosed with Multisystem

* Corresponding author.

E-mail addresses: [email protected] (N. Kannikeswaran), [email protected] (D.M. Merolla), [email protected] (K. Bond), [email protected] (L. Philip), [email protected] (U. Sethuraman).

Inflammatory Syndrome in children (MIS-C) or Kawasaki Disease during the RV. Our PED is an Inner city, level 1 trauma center attached to a free standing children’s hospital with approximately 85,000 visits/ year.

Among the seventy seven children who had a seven day RV after an index visit for fever, five children (5/77; 0.6%) were diagnosed with MIS-C (n = 3) and Kawasaki disease (n = 2). (Table 1a) These children ranged in age from 1 to 15 years. Sixty percent were male and African American. Three children had gastrointestinal symptoms and one child had a rash. All children had persistent tachycardia during the index visit. One of these children had a screening evaluation for MIS-C during the index visit which was only abnormal during the RV (Table 1b). All children were noted to be tachycardic and shock (defined as presence of hypotension with vasopressor support requirement) was noted in three children during the RV. The laboratory results are noted in Table 1b. All children had elevated CRP (median: 263; IQR: 279.85) and D- Dimer (median: 2.29; IQR:17.81). Lymphopenia was noted in three children. serum troponin was abnormal in four children and

https://doi.org/10.1016/j.ajem.2021.12.022

0735-6757/(C) 2021

Table 1a

N. Kannikeswaran, D.M. Merolla, K. Bond et al.

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Description of children with a return visit diagnosis of MIS-C/Kawasaki Disease (KD).

ID

Age in years

Sex

Past medical history

First visit symptoms

Physical exam-first visit

Physical exam-return visit

Admit to PICU

Treatment

COVID PCR

COVID IgG

Diagnosis

Hopsital LOS

1

3

Female

None

Fever (2 days)

Fever Tachycardia

Ill-appearing

Yes

IVIG inotropic support

Negative

Not performed

MIS-C

4 days

2

15

Male

Asthma

Vomiting Diarrhea Rash

Fever (2 days)

Fever

Rash

Tachycardia Shock with depressed myocardial function

Shock with severely depressed

Yes

(epinephrine-1 day)

IVIG Infliximab

Negative

Not performed

MIS-C

8 days

3

11

Male

Obesity

Asthma

Vomiting Diarrhea

Fever (2 days)

Tachycardia Pharyngeal erythema

Tachycardia Pharyngeal

myocardial function

Ill-appearing Tachycardia

Yes

Inotrophic support

(epinephrine -4 days), Mechanical ventilation -4 days

IVIG

Negative

Not performed

MIS-C

9 days

4

1

Male

Eczema

None

Vomiting Diarrhea

Fever (2 days)

erythema

Fever Tachycardia

Tachypnea Rash Shock

Ill-appearing Tachycardia

No

Infliximab

Inotrophic support (dopamine and epinephrine -4 days)

Mechanical ventilation – 6 days

IVIG

Negative

Negative

Kawasaki Disease

6 days

Fussiness

Poor oral

Aspirin

5

5

Female

None

intake

Fever (3 days)

Fever Tachycardia Cervical

Ill-appearing, Tachycardia

Yes

IVIG (twice) Infliximab

Negative

Negative

Kawasaki Disease

6 days

lymphadenitis

Red eyes

Dry cracked lips Rash

Cervical lymphadenitis

Aspirin

Table 1b

Laboratory, electrocardiogram, and echocardiogram findings on initial and return visits of patients ultimately diagnosed with MISC or Kawasaki.

American Journal of Emergency Medicine 52 (2022) 184186

Type

Patient 1

Patient 2

Patient 3

Patient

4

Patient 5

Visit

Return

Return

Return

Initial

Return

Return

CRP mg/L

39.3

263

322

16.2

20

297

Sodium mMol/L

136

126

137

135

134

124

ALT Units/L

20

35

77

16

14

225

Albumin gm/dl

3.5

3.3

4

4.7

4.6

3.5

Ferritin ng/ml

101.5

860

615

37.4

45.2

390

Troponin ng/L

22

119

1797

5

24

10

BNP pg/ml

858

n/a

1090

n/a

n/a

21

ALC Units/L

1.6

1.1

0.6

2

3.5

0.9

D Dimer mg/L

2.29

2.95

1.68

0.46

0.64

3.5

Electrocardiogram

Sinus

ST- T wave changes

Junctional rhythm or ventricular

NA

Normal

Normal

tachycardia

rhythm

Echocardiogram

Normal

Mild left ventricular dysfunction and mitral

Severe left ventricular dysfunction

NA

Mitral regurgitation and pulmonary

Mild left ventricular dysfunction and mitral

regurgitation

regurgitation

regurgitation

N. Kannikeswaran, D.M. Merolla, K. Bond et al. American Journal of Emergency Medicine 52 (2022) 184186

brain natriuretic peptide was abnormal in three children. EKG abnor- malities were noted in two children with MIS-C and included junctional rhythm in one and ST-T wave changes in another. Echocardiogram was abnormal in four children and included mitral regurgitation in three pa- tients, mild left ventricular dysfunction in two patients, severe left ven- tricular dysfunction in one patient and pulmonary regurgitation in one patient. Four children required admission to the intensive care unit, three required inotropic support and two required mechanical ventila- tion (table 1a). There were no deaths in our cohort.

  1. Discussion

The World Health Organization (WHO) declared COVID-19 caused by SARS-CoV-2 as a pandemic on March 11, 2020. As of early December 2021, 7 million children have tested positive for COVID-19 [1]. MIS-C is a rare complication of children with Covid-19 with a reported incidence of 2 per 100,000 [2]. It is associated with a mortality of 2-4% [3]and with cardiogenic shock and coronary artery aneurysms in 20% of patients [4,5]. The Center for Disease Control (CDC) and WHO have published guidelines for diagnosis and work up of children with suspected MISC. [6,7] Early recognition and timely management is critical for favorable outcomes in children with MIS-C.

Presenting symptoms of MIS-C include fever, gastrointestinal symp- toms such as abdominal pain vomiting and diarrhea, rash and conjunc- tival injection. Since these symptoms often mimic other common viral illness clinical distinction is often difficult. However, children diagnosed with MIS-C in our case series demonstrated persistent tachycardia and nearly two thirds of them presented in cardiogenic shock. Thus, it is crit- ical for clinicians to be vigilant of abnormal vital signs and maintain a high index of suspicion for diagnosis of MIS-C especially in those who present with persistent fever and elevated inflammatory markers. Com- mon laboratory findings noted in children with MIS-C include elevated inflammatory markers such as C reactive protein, ferritin, and lactate dehydrogenase as well as hyponatremia, acute kidney injury and ele- vated D-dimers. Since MIS-C often develops a few weeks after SARS- CoV-2 infection or exposure, serology testing is often recommended in addition to rt-PCR testing. Though children with MIS-C often have ele- vated inflammatory markers, it is important to note that the screening evaluation for MIS-C can be misleadingly normal if the children have been symptomatic only for a Short duration (<=24 h). Hence, it is critical to arrange for a timely follow up as well repeat the screening labs for MIS-C for the subset of children who continue to be symptomatic.

The major morbidity noted in children with MIS-C results from Cardiac abnormalities which include ventricular dysfunction, coronary artery dilation and aneurysms, arrhythmia, and conduction abnormali- ties [8]. Patients with severe illness often present in cardiogenic shock requiring inotropic support, mechanical ventilation and extracorporeal membrane oxygenation. Given the frequent association with cardiac abnormalities, all patients with suspected MIS-C should undergo evalu- ation with an electrocardiogram, echocardiogram as well serial moni- toring of troponin and BNP. Prompt recognition and admission to a pediatric intensive care unit of children with cardiac involvement at risk for Hemodynamic compromise is essential to improve mortality and morbidity.

Funding and disclosures

None.

Declaration of Competing Interest

None.

References

  1. Children and COVID-19. State level data report – American Academy of Pediatrics. https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/ children-and-covid-19-state-level-data-report; 2021. [Accessed December 6th 2021].
  2. Dufort EM, Koumans EH, Chow EJ, et al. Multisystem Inflammatory Syndrome in Chil- dren in New York State. New York State and Centers for Disease Control and preven- tion Multisystem Inflammatory Syndrome in Children Investigation Team. N Engl J Med. 2020;383(4):347.
  3. Levin M. N childhood multisystem inflammatory syndrome — a new challenge in the pandemic. N Engl J Med. 2020;383:393-5.
  4. Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. Overcoming COVID-19 investigators, CDC COVID-19 re- sponse team. N Engl J Med. 2020;383(4):334-46.
  5. Davies P, Evans C, Kanthimathinathan HK, et al. intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a Multicenter observational study. Lancet Child Adolesc Health. 2020;4(9):669-77.
  6. https://www.cdc.gov/mis/mis-cindex; 2021. [Accessed December 6thth 2021].
  7. https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory- syndrome-in-children-and-adolescents-with-covid-19. [Accessed December 6th 2021].
  8. Alsaied T, Tremoulet AH, Burns JC, et al. Review of cardiac involvement in multisys- tem inflammatory syndrome in children. Circulation. 2021;143:78-88.

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