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 Table of Contents  
Year : 2021  |  Volume : 8  |  Issue : 3  |  Page : 197-200

Multisystem inflammatory syndrome in children associated with 2019 novel coronavirus (SARS-CoV-2) infection

Department of Pediatric Medicine, SMS Medical College, Jaipur, Rajasthan, India

Date of Submission03-Feb-2021
Date of Decision29-Jul-2021
Date of Acceptance09-Sep-2021
Date of Web Publication04-Mar-2022

Correspondence Address:
Gayatri Dhanger
F-3 Gangwal Park, Doctor's Flat, JLN Marg, Jaipur, Rajasthan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cjhr.cjhr_19_21

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Background: MIS-C is a serious condition that appears to be linked to novel coronavirus disease 2019, which is increasingly being reported worldwide. Here we report 10 children diagnosed with MIS-C. Aims and Objective: To describe the clinical and laboratory findings along with treatment and outcome of hospitalized children with multisystem inflammatory syndrome in children (MIS-C) associated with 2019 novel corona virus at SPMCHI, Jaipur. Methods: This was an observational study of 10 children who presented with MIS-C during 10-week duration from 1 October to 20 December 2020. Results: The median age of study was7 years. 8 patients had antibody test positive, 1 antigen by RTPCR was positive and 1 patient was negative. 4(40%) required intensive care unit admission and inotropic support. All patients received steroids, 4 (40%) IVIg, out of 10, 8(80%) survived and 2 (20%) expired. Conclusion: Children with MIS-C present with varied clinical presentation. There was a low RT-PCR positivity with high SARS-CoV-2 antibodies positivity. High index of suspicion is required for this clinical emerging complication of corona in children.

Keywords: Coronavirus, multisystem inflammatory syndrome in children, reverse transcription-polymerase chain reaction

How to cite this article:
Gupta RK, Dhanger G, Gupta V, Gupta ML, Goyal A. Multisystem inflammatory syndrome in children associated with 2019 novel coronavirus (SARS-CoV-2) infection. CHRISMED J Health Res 2021;8:197-200

How to cite this URL:
Gupta RK, Dhanger G, Gupta V, Gupta ML, Goyal A. Multisystem inflammatory syndrome in children associated with 2019 novel coronavirus (SARS-CoV-2) infection. CHRISMED J Health Res [serial online] 2021 [cited 2022 Jul 7];8:197-200. Available from: https://www.cjhr.org/text.asp?2021/8/3/197/339047

  Introduction Top

Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely leading to a pandemic. Early data suggested that children were relatively less affected.[1],[2] Several countries have noticed a new hyper-inflammatory syndrome affecting children.[3] The first case of Kawasaki Disease with concurrent COVID-19 in the pediatric population was reported from the United States.[4] Thereafter, health authorities from the United Kingdom (UK) issued a health alert describing a serious illness requiring intensive care in children. The Royal College of Pediatrics and Child Health published guidelines to raise awareness among clinicians for this newly recognized entity called Pediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2.[5] This clinical condition was named as the multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19 (MIS-C) by the World Health Organization and Centers for Disease Control and Prevention (CDC).[6],[7] The first published report of MIS-C was reported from India in May 2020.[8] This is beginning to be recognized in India, although published reports from India are limited.[8],[9],[10] We are describing ten patients with the spectrum of MIS-C associated with SARS CoV-2 infection presenting to a single center in north India.

  Methods Top

This was an observational study, conducted at a tertiary care hospital attached with a Government Medical College in children <18 years of age, who fulfilled the CDC case definition of MIS-C after taking approval from the ethics committee (IEC-423/MC/2020 dated 27.06.2020 SMS Medical College, Jaipur).[7]

Case definition

The MIS-C case definition provided by the US CDC was used in this study, which considers the following criteria: (1) an individual aged <21 years presenting with fever (temperature ≥38.0°C for ≥24 h, or report of subjective fever lasting ≥24 h), (2) laboratory evidence of inflammation, including, but not limited to, one or more of the following: An elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, D-dimer, ferritin, lactate dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes, and low albumin, (3) evidence of a clinically severe illness requiring hospitalization, with multisystem (two or more) organ involvement (cardiac, renal, respiratory, hematological, gastrointestinal, dermatological, or neurological), (4) a lack of an alternative plausible diagnoses, and (5) positivity for current or recent SARS-CoV-2 infection by reverse transcription-polymerase chain reaction (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.[7]

We analyzed patients presenting to our hospital from October 1, 2020 to December 20, 2020. Patients were investigated for MIS-C if presented with unresolved fever, fever with raised inflammatory marker, shock, and Kawasaki Disease symptoms. Data about clinical findings, radiological findings, underlying co-morbidities, echocardiography findings, laboratory investigations, treatment received, and the outcome were entered into the Microsoft Excel spreadsheet and analyzed.

Confirmed COVID-19 case was defined as either positive for SARS CoV-2 by real-time RT-PCR approved by ICMR or Covid-19 antibody-positive test performed with ICMR approved SARS-CoV-2 IgG/total antibody titer assay.

Statistical analyses

Demographic and clinical characteristics were described using frequencies or percentages for categorical variables.

  Results Top

A total of ten patients with a median age of 7 years (range: 4 month–11 years), who met the criteria of MIS-C as per the definition of CDC were included in the study. Six were male (60%) and five children were <7 years.

As shown in [Table 1], all patients had fever >3 days duration. In all children, two or more systems were involved: respiratory (50%), neurological (40%), mucocutaneous (40%), gastrointestinal (30%), cardiovascular (30%), cervical lymphadenopathy (20%), and musculoskeletal (10%).
Table 1: Serology/RT-PCR

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Antibody against SARS-CoV-2 was positive in eight (80%) patients and negative in the rest two (20%) patients. Nasopharyngeal swab for SARS-CoV-2 RT-PCR was positive in one and negative in rest all. In one patient, both RT-PCR and antibody were negative but had a history of contact with COVID-positive patient 15 days back so met the criteria specified by CDC MIS-C definition.

At admission, laboratory parameters were compatible with acute inflammation in most children, with neutrophilia 80% (8/10), lymphopenia 10% (1/10), and increased ESR 80% (8/10). CRP and D-dimer were increased in all patients. Serum LDH and ferritin were elevated in 80% (8/10) and 70% (7/10), respectively. Creatine phosphokinase-MB was elevated in 30% (3/10) of patients and Troponin-T was positive in 50% (2/4). Echocardiography was done in four children, and abnormality was noted in one patient as left ventricular global hypokinesia (left ventricular ejection fraction-35%). High-resolution computed tomography thorax was done in six patients. Ground-glass haziness was reported in three patients, tree in bud appearance in one patient, both ground-glass haziness and tree in bud appearance in one patient, and one was normal. Prothrombin time/international normalized ratio was abnormal in three patients.

Four (40%) patients required intensive care unit admission and inotropic support. All cases were started on intravenous (IV) methylprednisolone, four (40%) were given IV immunoglobulin (IVIG). All of our patients received broad-spectrum antibiotics which were discontinued after negative blood and urine culture reports. Biological such as tocilizumab, infliximab, or anakinra was not used in our study. Three patients presented with underlying comorbidity (one B-cell acute lymphoblastic leukemia, one global developmental delay, and one with epilepsy); the first two patients expired.

  Discussion Top

In our study, children presented with a varied spectrum of signs and symptoms. The respiratory system was most commonly involved. Fewer children (40%) in our series presented with gastrointestinal symptoms in contrast to 80% in the literature.[11],[12],[13],[14] We have found fewer echocardiograph abnormalities 25% (1/4) similar to Dhanalakshmi et al. 16% (3/19), whereas cardiac dysfunction was the most common finding in international studies.[6],[9],[12],[15] We found notable findings of neurologic symptoms including seizure in three and altered mental status in two patients.

A positive serologic assay for SARS-CoV-2 or RT-PCR has been a consistent finding in the literature; although there have also been published reports with negative results for SARS-CoV-2 infection.[15],[16],[17] Most of the children in our study (90%) had laboratory-confirmed SARS-CoV2 infections. We also report low RT-PCR positivity with high SARS-CoV-2 antibodies positivity. One patient had both covid Ag and Antibody test negative, but she had a history of contact with covid positive patient 15 days back and presented with a raised inflammatory marker with no microbiological evidence for other infections. She had multi-organ dysfunction with elevated inflammatory markers (CRP, D-Dimer, and ESR) in addition to neutrophilia. However, we plan to perform a repeat serological assay in this patient during their follow-up to establish a link between their symptoms and SARS-CoV-2.

Laboratory testing in our group generally showed neutrophilia, significant elevation of inflammatory markers, as reported earlier.[13],[18] Coagulation profile was abnormal in three (30%) patients, out of which two (20%) died. D-dimer and CRP were raised in all patients.

Currently, there is no consensus regarding the management of children with MIS-C. A study was done in the central part of India (Mumbai), conducted by Jain et al. used inotropic support in 65%, steroids in 96%, and IVIg in 65%.[10] Dhanalakshmi et al. used IVIG in 26% alone, 16% were treated with steroids alone; 42% received both IVIG and steroids and one child received IVIG and tocilizumab. Aspirin was given in sixteen (84.2%) children and two children were not given any immunomodulatory agents in a study done at Chennai In the MIS-C series from the United States, IVIG (77%) and systemic glucocorticoids (49%) were used in most patients.[9],[12] In another case series from the UK, 71% received IVIG and 64% corticosteroids. Three patients received Anakinra and eight received Infliximab. Inotropic support was required in 47%.[13] In our series, we have used relatively less inotropic support and IVIG. Biological such as tocilizumab/infliximab was not used in our study. Mortality in our series was 20%, which is comparable to international studies.[13]

Epidemiologic evidence suggests SARS-CoV-2 as the likely cause of MIS-C. The emergence of clusters of cases in locations that have been heavily impacted by COVID-19, such as Italy, the UK, and New York City, is highly suggestive of a linkage to infection with SARS-CoV-2.[12],[13],[14],[15] The epidemic curve of MIS-C cases followed that of COVID-19 with a lag time of 2–4 weeks is supporting the hypothesis of postinfectious manifestation. Immune dysregulation is considered to be the main pathogenesis and is characterized by sustained production of pro-inflammatory cytokines such as tumor necrosis factor-α and IL-6.[19]

This study is the first case series from Rajasthan, describing children presenting with MIS-C. Within India, Jaipur, was one of the hotspots of the pandemic, and we believe this was one of the reasons that we have seen clustering of MIS-C.

The main limitation of our study was a relatively small number of the patient and short duration of the study. There is underreporting of cases as reporting of MIS-C is not mandatory, and there is no active and passive surveillance. Long-term follow-up with cardiac and neurologic evaluations is needed. Further studies and longer surveillance of patients diagnosed with MIS-C are required to improve our diagnostic, treatment, and surveillance criteria.

Our study will help in establishing the database of clinical, laboratory findings, and outcomes of MIS-C patients in our country. As knowledge about manifestations of COVID-19 in children is evolving, reporting is essential to equip clinicians in recognizing the spectrum of MIS-C which is necessary for timely initiation of appropriate management.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Balasubramanian S, Rao NM, Goenka A, Roderick M, Ramanan AV. Coronavirus disease 2019 (COVID-19) in children – What we know so far and what we do not. Indian Pediatr 2020;57:435-42.  Back to cited text no. 1
Meena J, Yadav J, Saini L, Yadav A, Kumar J. Clinical features and outcome of SARS-CoV-2 infection in children: A systematic review and meta-analysis. Indian Pediatr 2020;57:820-6.  Back to cited text no. 2
European Centre for Disease Prevention and Control. Pediatric Inflammatory Multisystem Syndrome and SARS-CoV-2 Infection in Children – 15 May 2020. Stockholm: ECDC; 2020.  Back to cited text no. 3
Jones VG, Mills M, Suarez D, Hogan CA, Yeh D, Segal JB, et al. COVID-19 and Kawasaki disease: Novel virus and novel case. Hosp Pediatr 2020;10:537-40.  Back to cited text no. 4
Royal College of Pediatrics and Child Health. Guidance-Pediatric Multisystem Inflammatory Syndrome Temporally Associated with COVID-19; 2020. Available from: https://www.rcpch.ac.uk/resources/guidance-pediatric-multisystem-inflammatory-syndrome temporally-associated-covid-19. [Last accessed on 2020 Dec 20].  Back to cited text no. 5
Multisystem Inflammatory Syndrome in Children and Adolescents with COVID-19. Scientific Brief: World Health Organisation; May 15, 2020. Available from: https://www.who.int/publications-detail/multisysteminflam-matory-syndrome-in-children-and adolescents-with-covid-19. [Last accessed on 2020 Dec 20].  Back to cited text no. 6
Centers for Disease Control and Prevention. Emergency Preparedness and Response: Health alert Network; May 14, 2020. Available from: https://emergency.cdc.gov/han/2020/han00432.asp. [Last accessed on 2020 Dec 20].  Back to cited text no. 7
Balasubramanian S, Nagendran TM, Ramachandran B, Ramanan AV. Hyper-inflammatory syndrome in a child with COVID-19 treated successfully with intravenous immuno-globulin and tocilizumab. Indian Pediatr 2020;57:681-3.  Back to cited text no. 8
Dhanalakshmi K, Venkataraman A, Balasubramanian S, Madhusudan M, Amperayani S, Putilibai S, et al. Epidemio-logical and clinical profile of pediatric inflammatory multisystem syndrome – Temporally associated with SARS-CoV-2 (PIMS-TS) in Indian children. Indian Pediatr 2020;57:1010-4.  Back to cited text no. 9
Jain S, Sen S, Lakshmivenkateshiah S, Bobhate P, Venkatesh S, Udani S, et al. Multisystem inflammatory syndrome in children with COVID-19 in Mumbai, India. Indian Pediatr 2020;57:1015-9.  Back to cited text no. 10
Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, et al. Multisystem inflammatory syndrome in children in New York state. N Engl J Med 2020;383:347-58.  Back to cited text no. 11
Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MB, et al. Multisystem inflammatory syndrome in U.S. Children and adolescents. N Engl J Med 2020;383:334-46.  Back to cited text no. 12
Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, et al. Clinical Characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA 2020;324:259-69.  Back to cited text no. 13
Davies P, Evans C, Kanthimathinathan HK, Lillie J, Brierley J, Waters G, et al. Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study. Lancet Child Adolesc Health. 2020;4:669-77.  Back to cited text no. 14
Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, 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.  Back to cited text no. 15
Cabrero-Hernández M, García-Salido A, Leoz-Gordillo I, Alonso-Cadenas JA, Gochi-Valdovinos A, González Brabin A, et al. Severe SARS-CoV-2 infection in children with suspected acute abdomen: A case series from a tertiary hospital in Spain. Pediatr Infect Dis J 2020;39:e195-8.  Back to cited text no. 16
Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020;395:1607-8.  Back to cited text no. 17
Wu H, Zhu H, Yuan C, Yao C, Luo W, Shen X, et al. Clinical and immune features of hospitalized pediatric patients with coronavirus disease 2019 (COVID-19) in Wuhan, China. JAMA Netw Open 2020;3:e2010895.  Back to cited text no. 18
Lee PY, Day-Lewis M, Henderson LA, Friedman KG, Lo J, Roberts JE, et al. Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children. J Clin Invest 2020;130:5942-50.  Back to cited text no. 19


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