On 31 December 2019, a cluster of pneumonia cases of unknown etiology was reported in Wuhan, Hubei Province, China. On 9 January 2020, China CDC reported a novel coronavirus (now called Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2) as the causative agent.¹ On 11 March 2020, the World Health Organization declared coronavirus disease 2019 (COVID-19) a global pandemic emergency.² SARS-COV-2 affects people across all age groups with a broad range of illness severity from asymptomatic carriers to severe multi-organ dysfunction and death. COVID-19 causes mild to severe respiratory illnesses in humans, with the population at highest risk being older people, especially those with existing ailments like diabetes, cardiac problems, underlying respiratory problems, cancers, or any other immunosuppressing comorbidities.¹ COVID-19 has affected children too. Recent data have suggested that children are more likely to have milder symptoms, However, cases of children who were hospitalized in intensive care due to SARS-CoV-2 related pediatric inflammatory multisystem syndrome (PIMS) were increasingly reported. The presenting signs and symptoms of PIMS are a mix of the ones for Kawasaki disease (KD) and toxic shock syndrome (TSS) and are characterized among others by fever, abdominal pain, and cardiac involvement.² The European Centre for Disease Prevention and Control reported a total of 230 cases of PIMS across Europe as of 12 May 2020.¹

Case definition for multisystem inflammatory syndrome in children (MIS-C)²

"An individual aged <21 years presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND No alternative plausible diagnoses; AND Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms. Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP) produced by a liver response to the inflammatory process, erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes, and low albumin. Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection.”²

Significant numbers of children suffered from multi-organ failure, including:

-acute heart injury, myocarditis, defined as (abnormal troponin >55 ng/L, and/or NT-proBNP >450 ng/mL, and cardiogenic shock or acute left ventricular dysfunction (left ventricular ejection fraction (LVEF) <50%)

-acute kidney injury defined as (an increase in serum creatinine ≥ 1.5 times the upper limit of normal or required treatment)

-respiratory failure defined as the requirement of respiratory assistance by non-invasive ventilation, or invasive ventilation, or extracorporeal membrane oxygenation (ECMO)

-macrophage activation syndrome was defined as ferritin >684 ng/mL and any two of the following platelet counts ≤181 ×10³/μL, aspartate aminotransferase >48 U/L, fibrinogen ≤ 360 mg/dL.¹

A comprehensive search strategy was designed to retrieve all articles published from October 2019 to 30 June 2020, by using the terms COVID-19, SARS-CoV-2, Coronavirus, Kawasaki, multisystem inflammatory syndrome, Kawasaki syndrome, cytokine storm and myocarditis in several electronic databases and Government Agencies Websites (PubMed, Google Scholar, Centers for Disease Control and Prevention, WHO and UK Royal College of Pediatrics and Child Health). Retrospective observational studies, case series, and case report studies about the main clinical characteristics, laboratory results, treatment, and patients' responses were included.

Two investigators independently reviewed and selected studies. We specifically sought studies that reported the main clinical characteristics, laboratory results, treatments, and the response of MIS-C patients during the COVID-19 pandemic.

We developed an analytic framework with four key questions (Figure 1).

For data extraction and quality assessment, one investigator abstracted data from each study (clinical findings, lab results, imaging, treatment, and outcome), entered data in SPSS software 26 (IBM Corp, USA) for statistical analysis. A second investigator checked these data for accuracy. We conducted Dual quality assessments and data abstraction.

Review

Sex: Males were slightly more represented than females within a total of 73 MIS-C patients (40 boys, 54.8% and 33 girls, 45.2%) – Figure 2.

Figure 2. Bar chart demonstrates the percentage of male and female patients affected by MIS-C

Age: Children and young adults from all age groups were affected by MIS-C with a median age of 8.3 years (range 0.2-16 years of age), with a mean age of 8.6 years (SD 3.57) – Figure 3.

Figure 3. Pie chart demonstrates the percentage of different age group affected by MIS-C

Clinical features: All the seventy-three (100%) patients presented with fever. Interestingly, the majority (54/73, 74%) had abdominal pain, whereas only 36 patients (49.3 %) had diarrhea. other manifestations included conjunctivitis (n=34, 46.6%), rash (n=40, 54.8%), cheilitis (n=22, 30.1%), edema (n=9, 12.3%), and lymphadenopathy (n=7, 9.6%). Neurological symptoms were seen (n=20, 27.3%); 5/20 (6.8%) displayed meningeal signs. It is interesting to notice that only 9 (12.3%) patients came to medical attention with respiratory symptoms, including 4 (5.5%) who had shortness of breath, 3 (4.1%) associated with cough, and 2 (2.7 %) had respiratory distress. Other symptoms were also present, namely hypotension (59/70, 84.3%) and vasoplegic shock (61/73, 83.6%) – Figure 4, Table 1.

Laboratory results: Inflammatory markers were elevated with mean CRP 212 mg/dL (SD 145.8), mean ESR was 70 mm/h (SD 22.337), mean ferritin 994 ng/mL (SD 786), and procalcitonin 62 ng/mL (SD 100). Mean fibrinogen was 695 mg/dL (SD 191), and mean d-dimer was 6.5 mg/L (SD 6.5).

Overall, 69 (95.8%) patients had elevated CRP. All patients with available data had elevated ESR. A number of 27 out of 38 (71%) had a high level of ferritin, while fibrinogen was high in 37/38 patients (97.3%) as d-dimer was elevated in all patients 27/27. The mean of platelets was 187.5 103/μL (SD 79); 23 of 61 cases (37.7%) had thrombocytopenia. The absolute lymphocytes mean was 1033 cells/mm3 (SD 1047), with lymphopenia in 33 out of 50 patients (66%). Finally, the mean white blood cell count was 10900 cells/ mm3 (SD 5776) with 23/61 cases having leukocytosis. Mean albumin was 2.4 g/dL (SD 0.64), and hypoalbuminemia was observed in 34/38 cases (89.5% of the patients with available data). Hyponatremia was spotted in 39 cases out of 49 (79.5%), with a mean 130.8 mmol/L (SD 4.3).

Table 2.

Cardiac enzymes were elevated in 65 patients (100% of patients with available data): mean troponin was 647.92 ng/L (SD 1230). A mean prohormone of brain natriuretic peptide (NT-proBNP) was

4965 pg/mL (SD 12666), whereas brain-type natriuretic peptide means was 4965 pg/mL (SD 2555). Elevated troponin was noted in 50/65 patients (76.9%) (Table 2).

Echocardiography was reported abnormal in 58 (90.6%) patients including 14 (21.9%) who had a pericardial effusion, and 2 (3.1%) who had dilated left ventricle. Coronary dilation was reported in 7 cases (11.9%), and aneurysm in 2 cases (3.4%). Left ventricular ejection fraction (LVEF) was decreased in all patients with available data except for three, with a mean LVEF of 40% (SD 11.75) (Table 2).

Abdominal imaging: The most common abnormality was terminal ileitis and mesenteric lymphadenopathy – 7 cases out of 17 (41.2%) (Table 2).

Therapeutic management:

All 73 cases included in this study were managed according to the diagnosis and laboratory results (Table 3). Most of the patients were treated with intravenous immunoglobulin (IVIG) n=65 (89%) and corticosteroids 34 (46.6%); aspirin was given to 13 patients (17.8%). Broad-spectrum antibiotics were given to cover septic shock syndrome n=35 (74.5%). All patients required fluid resuscitation. Inotropic vasopressor support was required for n=51 (69.9%) to treat hypovolemic and cardiogenic shock, 22 (30.1%) children with severe respiratory manifestations required mechanical ventilation and 18 (24.7%) patients received non-invasive ventilation. Four patients received IL-1 receptor antagonist (anakinra) (5.5%), and 6 patients received IL-6 receptor antagonist (tocilizumab) (8.2%). One patient, a known case of Crohn’s disease, received infliximab for its dual effect for treating Crohn’s disease and hyperinflammation (Table 3).

Outcome:

Overall, 54 patients (74%) were discharged from the hospital while 18 (24.7%) were still under ongoing care when we wrote the report. Only one patient had died (1.4%) Table 3.

Complications of MIS-C during COVID-19:

Overall, 59 out of 70 patients (84.3% of the available data) were admitted to the Pediatric Intensive Care Unit (PICU). A significant number of children suffered from multi-organ failure, including 60 out of 69 patients suffering from acute heart injury (87%); 25 of 73 cases had acute kidney injury (34.2%), 38 out of 73 cases (52.1%) had respiratory failure, 18 (25%) required respiratory assistance by non-invasive ventilation, 22 (30.1%) required invasive ventilation, and 3 (4.1%) required ECOM; 7 patients had macrophage activation syndrome (18.4%) whereas 61 patients had toxic shock syndrome (83.6%) (Table 4).

KD is an acute rare febrile illness characterized by systemic medium-vessel vasculitis that occurs most often in children between 5 months and 5 years of age. However, it can occur in children of any age. Given its predilection for the coronary arteries, there is a potential for the development of coronary artery aneurysms (CAAs) and thus sudden death. CAAs develop in approximately 25% of untreated cases; appropriate treatment decreases this risk to 3-5%.⁴ According to our literature study, in contrast to KD, MIS-C is most common in older children between 6 years and 10 years of age.

The association between MIS-C and SARS-CoV-2 has been proposed but attention should be drawn to children with COVID-19 who also have co-infection with other common respiratory pathogens. The high co-infection rate in children can be used to highlight the importance of SARS-CoV-2 screening, especially during the peak season for colds, influenza, and other respiratory ailments.^3,5 Mycoplasma infection has been reported as potentially related to the onset of Kawasaki disease in children,^5-7 available data suggest a possible association. Mycoplasma infection has been shown to function as an inflammatory trigger that can initiate a systemic inflammatory response, which in turn may lead to a systemic inflammatory response similar to hemophagocytic lymphohistiocytosis (HLH). Viral infections in children on the other hand are widely accepted as potential triggers for a cytokine storm leading to the development of a syndrome similar to MIS-C, and this has also been reported in children with COVID-19 in a minority of cases.^8-11 SARS-CoV-2 and Mycoplasma pneumonias may cause rapid clinical deterioration in affected children. In the past few months, in Italy, Bergamo, they found a 30-fold increased incidence of Kawasaki-like disease. Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of macrophage activation syndrome. The SARS-CoV-2 epidemic was associated with a high incidence of a severe form of Kawasaki disease.⁹ This syndrome is not well defined. Furthermore, the CDC case definition of MIS-C is significantly broad and will likely be amended as we move forward and learn more about it. Because of the overlapping clinical features and the lack of a diagnostic test for either KD or MIS-C, distinguishing the two conditions in an individual patient can be difficult.¹²

We found in our literature study that abdominal symptoms with persistent fever were present in the majority of patients with MIS-C, suggesting that MIS-C should be considered in this clinical context of COVID-19 and should guide clinicians to consider MIS-C as a differential diagnosis based on the fact that the majority of patients with MIS-C presented with gastrointestinal symptoms.

We emphasize the importance of recommendations for clinicians and surgeons who assess and manage children with abdominal pain and suspected appendicitis. We stress the importance of abdominal imaging and a swab for SARS-CoV-2 PCR in all children before surgical intervention.

Remarkably, pulmonary symptoms are the least common in MIS-C patients (12.9%). This could be explained due to COVID-19 pneumonia. However, another possible explanation is that MIS-C, like Kawasaki disease, involves various organ systems and pulmonary manifestations can sometimes be seen in children (1.83% of patients).¹³ Kawasaki disease can have abnormal chest X-ray findings in 14.7% of the patients. The reticule-granular pattern was the most frequent abnormality, while peri-bronchial cuffing, pleural effusion, atelectasis, and air trapping were also seen, thus supporting the respiratory symptoms are due to MIC-S or COVID-19.^14,15 In the presence of the above mentioned clinical features, physicians should be extra alert when children between 5 to 15 years old display elevated inflammatory markers (CRP or ESR, ferritin, procalcitonin, fibrinogen, d-dimer, and interleukin-6). All patients should have baseline investigations as described in Table 5.

Clinicians should consider transferring these patients early to a tertiary center as their condition could deteriorate rapidly. Most patients will need supportive care including fluid resuscitation, inotropic support, respiratory support; and rarely, ECMO.

Rheumatologists face hyper inflammation regularly in systemic juvenile idiopathic arthritis (JIA), adult‐onset Still's disease, and systemic lupus erythematosus, among other diseases. Experience from hyperinflammation in hemophagocytic lympho-histiocytosis (HLH), macrophage activation syndrome (MAS), and cytokine release syndrome suggests that early intervention is essential to avoiding life‐threatening tissue damage. In patients with COVID‐19 who exhibit evidence of cytokine storm, treatment with glucocorticoids, IVIG, and/or anti-cytokine therapies should be considered, to revert hyper inflammation.¹⁶

Although our study does not evaluate the efficacy of treatment, we observed that patients were treated as high-risk patients with acute KD guidelines. Patients were treated with intravenous immunoglobulin (IVIG) 2 g/kg as a single infusion, usually given over 10-12 hours. Administration of moderate (30-50 mg/kg/day) to high (80-100 mg/kg/day) dose of aspirin should be continued until the patient is afebrile. Administration of high-dose pulse steroids (usually methylprednisolone 20-30 mg/kg intravenously for days, with or without a subsequent course and taper of oral prednisone). It is reasonable to administer a second dose of IVIG (2 g/kg) to patients with persistent or recrudescent fever at least 36 hours after the end of the first IVIG infusion.⁴ The efficacy of IVIG administered in the acute phase of KD is well established to reduce the prevalence of coronary artery abnormalities. The addition of corticosteroid therapy to IVIG and acetylsalicylic acid in the primary therapy of KD lowers the prevalence of coronary artery abnormalities, duration of fever, and inflammation among those at the highest risk for IVIG resistance.⁴

Alternative treatments include anakinra recombinant IL-1 receptor antagonist (2-6 mg·kg−1·d−1) given by subcutaneous injection or infliximab monoclonal antibody against TNF-α given as single infusion: (5 mg/kg IV given over 2 h).⁴

Other treatments reported in our studies include tocilizumab (8 mg/kg IV); if no clinical improvement in signs and symptoms, up to 3 additional doses may be administered, allowing 8 hours’ interval between consecutive doses. Broad-spectrum antibiotics should be considered in these patients to cover septic shock syndrome until blood culture returns negative.

The most important complication of Kawasaki disease is caused by inflammation of the heart (coronary) arteries supplying blood to the heart muscle. This may lead to immediate heart problems, and damage to the coronary arteries can also have long‐term effects. Salicylate (acetylsalicylate acid, aspirin) and intravenous immunoglobulin (IVIG) are widely used to treat Kawasaki disease, although salicylate is generally avoided in children because of concerns about serious side effects, particularly the risk of Reye's syndrome, it is still used to treat Kawasaki disease as the benefit outweighs the harm.¹⁷

A study titled COVID-19 associated multisystem inflammatory syndrome in children – United States, March–July 2020 included a total of 570 patients with MIS-C included in the case definition by the CDC. According to our literature research (Table 6), the median age was 8.3 years (range: 2 months-16 years), while in the US research, the median age was 8 years (range: 2 weeks-20 years). Regarding gender, the data are remarkably similar. In our literature research (54.8%) were male, whereas in the US research (55.4%) were male. The most common clinical features in both studies were gastrointestinal symptoms. In our literature study, symptoms included abdominal pain (74%), diarrhea (49.3%), conjunctivitis (46.6%), and rash (54.8%), compared to the US study, where symptoms included abdominal pain (61.9%), diarrhea (53.2%), conjunctival injection (48.4%), and skin rash (55.3%). There are similarities in the percentage of complications. In our literature study, most patients had acute heart injury (87%) but only (34.2%) of patients had acute kidney injury. In the US study, most patients had cardiovascular complications (86.5%), and acute kidney injury (18.4%). According to our review, 65 (89%) received intravenous immunoglobulin (IVIG), 34 (46.6%) received steroids, 13 (17.8%) received aspirin, and 51 (69.9%) received inotropic vasopressor. In comparison to the US study, 424 (80.5%) received intravenous immunoglobulin (IVIG), 331 (62.8%) received steroids, 309 (58.6%) received anti-platelet medication, and 221 (41.9%) were treated with vasoactive medication.¹⁸

Study limitations: Not all the studies contained extensive laboratory test results, therefore limiting the value of the laboratory findings.

Study strengths: To the best of our knowledge, this is the first international study that takes into account studies from around the world including Italy, the United Kingdom, India, the United States, and France. The studies contain explicit information about clinical characteristics, complications, treatments, and patient outcomes.

The purpose of this study was to systematically review and summarize the main clinical pictures, define laboratory findings, and illustrate optimal treatment of children with multisystem inflammatory syndrome related to SARS-CoV-2 after a significant increase in numbers of cases was observed, thus supporting the hypothesis that SARS-CoV-2 is associated with MIS-C.

Clinicians should be vigilant to recognize potential cases and implement treatment strategies during this pandemic. Due to lack of knowledge about SARS-CoV-2 and its complications, such as MIS-C, several questions remain open, including long-term complications. Therefore, further studies are needed to obtain sufficient data on children with this infection and to evaluate the effectiveness of various medication modalities.

1. European Centre for Disease Prevention and Control. Paediatric inflammatory multisystem syndrome and SARS-CoV-2 infection in children – 15 May 2020. ECDC: Stockholm; 2020.

2. Center for Disease Control and Prevention. Information for healthcare providers about multisystem inflammatory syndrome in children (MIS-C). 2020. Accessed on: 14 November 2020. Available at: https://www.cdc.gov/mis-c/hcp/

3. Ai JW, Zhang HC, Xu T et al. Optimizing diagnostic strategy for novel coronavirus pneumonia, a multi-center study in Eastern China. medRxiv. 2020;

https://doi.org/10.1101/2020.02.13.20022673

4. McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki Disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135:e927-e999.

https://doi.org/10.1161/CIR.0000000000000484

5. Wang JN, Wang SM, Liu CC, Wu JM. Mycoplasma pneumoniae infection associated with Kawasaki disease. Acta Paediatr. 2001;90:594-5.

https://doi.org/10.1111/j.1651-2227.2001.tb00810.x

6. Ebrahim M, Gabay M, Rivas-Chacon RF. Evidence of acute Mycoplasma infection in a patient with incomplete and atypical Kawasaki disease: a case report. Case Rep Med. 2011;2011:606920.

https://doi.org/10.1155/2011/606920

7. Lee MN, Cha JH, Ahn HM, et al. Mycoplasma pneumoniae infection in patients with Kawasaki disease. Korean J Pediatr. 2011;54:123-7.

https://doi.org/10.3345/kjp.2011.54.3.123

8. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395:1607-8.

https://doi.org/10.1016/S0140-6736(20)31094-1

9. Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395:1771-8.

https://doi.org/10.1016/S0140-6736(20)31103-X

10. Belot A, Antona D, Renolleau S, et al. SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020. Euro Surveill. 2020;25:2001010.

https://doi.org/10.2807/1560-7917.ES.2020.25.22.2001010

11. Dufort EM, Koumans EH, Chow EJ, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med. 2020;383:347-58.

https://doi.org/10.1056/NEJMoa2021756

12. Rowley AH. Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Nat Rev Immunol. 2020;20:453-4.

https://doi.org/10.1038/s41577-020-0367-5

13. Singh S, Gupta A, Jindal AK, et al. Pulmonary presentation of Kawasaki disease-a diagnostic challenge. Pediatr Pulmonol. 2018;53:103-7.

https://doi.org/10.1002/ppul.23885

14. Umezawa T, Saji T, Matsuo N, Odagiri K. Chest x-ray findings in the acute phase of Kawasaki disease. Pediatr Radiol. 1989;20:48-51.

https://doi.org/10.1007/BF02010633

15. Sengler C, Gaedicke G, Wahn U, Keitzer R. Pulmonary symptoms in Kawasaki disease. Pediatr Infect Dis J. 2004;23:782-4.

https://doi.org/10.1097/01.inf.0000134313.86697.20

16. Henderson LA, Canna SW, Schulert GS, et al. On the alert for cytokine storm: immunopathology in COVID-19. Arthritis Rheumatol. 2020;72:1059-63. https://doi.org/10.1002/art.41285

17. Baumer JH, Love SJ, Gupta A, Haines LC, Maconochie I, Dua JS. Salicylate for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2006:CD004175. https://doi.org/10.1002/14651858.CD004175.pub2

18. Godfred-Cato S, Bryant B, Leung J, et al. COVID-19-associated multisystem inflammatory syndrome in children - United States, March-July 2020. MMWR Morb Mortal Wkly Rep. 2020;69:1074-80.

https://doi.org/10.15585/mmwr.mm6932e2

19. Chiotos K, Bassiri H, Behrens EM, et al. Multisystem inflammatory syndrome in children during the coronavirus 2019 pandemic: a case series. J Pediatric Infect Dis Soc. 2020;9:393-8.

https://doi.org/10.1093/jpids/piaa069

20. Labé P, Ly A, Sin C, et al. Erythema multiforme and Kawasaki disease associated with COVID‐19 infection in children. J Eur Acad Dermatol Venereol. 2020;34:e539-41.

https://doi.org/10.1111/jdv.16666

21. Rauf A, Vijayan A, John ST, Krishnan R, Latheef A. Multisystem inflammatory syndrome with features of atypical Kawasaki disease during COVID-19 pandemic. Indian J Pediatr. 2020;87:745-7.

https://doi.org/10.21203/rs.3.rs-29369/v1

22. Licciardi F, Pruccoli G, Denina M, et al. SARS-CoV-2-induced Kawasaki-like hyperinflammatory syndrome: a novel COVID phenotype in children. Pediatrics. 2020;146:e20201711.

https://doi.org/10.1542/peds.2020-1711

23. Deza Leon MP, Redzepi A, McGrath E, et al. COVID- 19-associated pediatric multisystem inflammatory syndrome. J Pediatric Infect Dis Soc. 2020;9:407-8.

https://doi.org/10.1093/jpids/piaa061

24. Greene AG, Saleh M, Roseman E, Sinert R. Toxic shock-like syndrome and COVID-19: a case report of multisystem inflammatory syndrome in children (MIS-C). Am J Emerg Med. 2020;38:2492.e5-6.

https://doi.org/10.1016/j.ajem.2020.05.117

25. Grimaud M, Starck J, Levy M, et al. Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children. Ann Intensive Care. 2020;10:69.

https://doi.org/10.1186/s13613-020-00690-8

26. Wolfler A, Mannarino S, Giacomet V, Camporesi A, Zuccotti G. Acute myocardial injury: a novel clinical pattern in children with COVID-19. Lancet Child Adolesc Health. 2020;4:e26-7.

https://doi.org/10.1016/S2352-4642(20)30168-1

27. Tullie L, Ford K, Bisharat M, et al. Gastrointestinal features in children with COVID-19: an observation of varied presentation in eight children. Lancet Child Adolesc Health. 2020;4:e19-20.

https://doi.org/10.1016/S2352-4642(20)30165-6

28. Blondiaux E, Parisot P, Redheuil A, et al. Cardiac MRI of children with multisystem inflammatory syndrome (MIS-C) associated with COVID-19. Radiology. 2020;297:E283-8.

https://doi.org/10.1148/radiol.2020202288

29. Chiu JS, Lahoud-Rahme M, Schaffer D, Cohen A, Samuels-Kalow M. Kawasaki disease features and myocarditis in a patient with COVID-19. Pediatr Cardiol. 2020;41:1526-8.

https://doi.org/10.1007/s00246-020-02393-0

30. Pain CE, Felsenstein S, Cleary G, et al. Novel paediatric presentation of COVID-19 with ARDS and cytokine storm syndrome without respiratory symptoms. Lancet Rheumatol. 2020;2:e376-9

https://doi.org/10.1016/S2665-9913(20)30137-5

31. Dolinger MT, Person H, Smith R, et al. Pediatric Crohn disease and multisystem inflammatory syndrome in children (MIS-C) and COVID-19 treated with infliximab. J Pediatr Gastroenterol Nutr. 2020;71:153-5.

https://doi.org/10.1097/MPG.0000000000002809

32. Jones VG, Mills M, Suarez D, et al. COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatr. 2020;10:537-40.

https://doi.org/10.1542/hpeds.2020-0123