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 Table of Contents  
CASE SERIES
Year : 2022  |  Volume : 9  |  Issue : 3  |  Page : 100-103

Overlap of severe dengue with multisystem inflammatory syndrome in children due to SARS-CoV-2 infection: A case series from a tertiary care center of Central India


1 Department of PICU, Ankura Hospitals for Women and Children, Hyderabad, Telangana, India
2 Department of Pediatrics, MRIMS, Hyderabad, Telangana, India
3 Department of PICU and Pediatrics, Ankura Hospitals for Women and Children, Hyderabad, Telangana, India

Date of Submission24-Jan-2022
Date of Decision30-Mar-2022
Date of Acceptance08-Apr-2022
Date of Web Publication12-May-2022

Correspondence Address:
Dr. Krishna Chaitanya
Department of PICU, Ankura Children's Hospital, LB Nagar, Hyderabad - 500 074, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcc.jpcc_12_22

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  Abstract 


India is currently facing a double burden of severe dengue and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Co-infection/complication due to these viruses can result in severe morbidity. We present five cases of severe dengue with multisystem inflammatory syndrome in children (MIS-C) due to SARS-CoV-2 infection in children. All children presented with shock with variable degrees of plasma leakage. They were treated initially as severe dengue cases; however, due to refractory symptoms such as persistent fever and inotropic requirement, an alternate diagnosis was suspected and established. They were successfully managed according to the World Health Organization Dengue Shock Syndrome and MIS-C Guidelines with intravenous (IV) fluids, methylprednisolone, aspirin, and IV immunoglobulin. Severe dengue in endemic regions overlapping with MIS-C makes it difficult to diagnose which needs early recognition and appropriate management.

Keywords: Multisystem inflammatory syndrome in children, severe acute respiratory syndrome coronavirus 2, severe dengue


How to cite this article:
Chaitanya K, Avani D, Keerty R, Srinidhi T. Overlap of severe dengue with multisystem inflammatory syndrome in children due to SARS-CoV-2 infection: A case series from a tertiary care center of Central India. J Pediatr Crit Care 2022;9:100-3

How to cite this URL:
Chaitanya K, Avani D, Keerty R, Srinidhi T. Overlap of severe dengue with multisystem inflammatory syndrome in children due to SARS-CoV-2 infection: A case series from a tertiary care center of Central India. J Pediatr Crit Care [serial online] 2022 [cited 2022 Dec 6];9:100-3. Available from: http://www.jpcc.org.in/text.asp?2022/9/3/100/345091




  Introduction Top


The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) is a currently ongoing global pandemic. The Centers for Disease Control and Prevention[1] together with the World Health Organization (WHO)[2] released a Health Advisory on severe complications of SARS-CoV-2 infection in children called as multisystem inflammatory syndrome in children (MIS-C).

Severe dengue with MIS-C can be difficult to diagnose as both diseases have similar symptoms and laboratory findings. India is currently facing a double burden of severe dengue and SARS-CoV-2 infection. Overlap of MIS-C with severe dengue can result in severe morbidity. Here, we present five such overlap cases.


  Case Series Top


Over a period of 1 year from November 2020 to October 2021 with the data collected from a single tertiary care center at Telangana state of Central India, we present five children who had overlap of severe dengue and MIS-C due to SARS-CoV-2. Data was collected with informed consent form duly signed from the parents of all the patients. Data were tabulated and analyzed after obtaining institutional ethical committee approval (No: 01/HREC/ANK dated January 21, 2022).

All the children presented with shock with variable degrees of plasma leakage and mucocutaneous and gastrointestinal involvement. Four of them tested positive for dengue nonstructural protein 1 antigen on the 3rd–4th day of fever, and all of them tested positive for dengue IgM by the 6th day of illness.

They were treated initially as severe dengue; however, due to refractory symptoms such as persistent fever and requirement of inotropic support, an alternate diagnosis was thought of by day 9 of illness. On further inquiry, all of them gave a clinical history of having been exposed to or infected with COVID-19 few months prior. Suspecting MIS-C, anti-SARS-CoV-2 IgG by ELISA was tested and turned to be positive. Inflammatory markers such as ferritin, lactate dehydrogenase, C-reactive protein, erythrocyte sedimentation rate, interleukin 6, and D-dimer were sent and found to be raised. The peak values of all of these markers are tabulated in [Table 1]. Three of them required inotropic support [vasoactive-inotropic score is mentioned in Table 1]. On echocardiographic evaluation, four of them showed coronary arterial dilatations with Z scores more than 2.5. Two of them had moderate left ventricular (LV) dysfunction (ejection fraction [EF] <40%) and one had severe LV dysfunction (EF <30%).
Table 1: Severe dengue with multisystem inflammatory syndrome in children

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They were successfully managed according to the WHO[1],[3] dengue shock syndrome and SARS-CoV-2 infection MIS-C guidelines. Injection methylprednisolone intravenous (IV) 2 mg/kg/day was given for 3 days followed by oral prednisolone. Aspirin was started only after once platelet count reached more than 1 lakh/μl. IV immunoglobulin (IVIG) was used for only one case with severe LV dysfunction, and for rest of the cases, we could not use IVIG due to lack of consent and support from parents.

Initial clinical picture in all cases was of severe dengue. In spite of managing under severe dengue protocol, leaky phase symptoms persisted beyond day 9 triggering suspicion of alternate diagnosis and found out to be as due to MIS-C. There was a dramatic clinical response in all of them within 48 h of starting steroids. Enzymes and all other inflammatory markers came down on repeat testing. Mean duration of intensive care unit stay was 6 days. There was no death in our case series.


  Discussion Top


This case series aims to describe the possibility of overlap of severe dengue with MIS-C due to SARS-CoV-2 infection in a dengue-endemic region. Severe dengue with the MIS-C can be difficult to diagnose as both diseases have similar symptoms and laboratory findings. It needs early recognition and appropriate protocolized management.

Several studies[4],[5],[6] described clusters of children and adolescents with SARS-CoV-2 infection triggered MIS-C presenting with an acute illness accompanied by a hyperinflammatory syndrome, leading to multiorgan failure and shock.

Children with SARS-CoV-2 infection typically will have a mild-to-moderate course of illness. However, MIS-C associated with SARS-CoV-2 infection is characterized by hyperinflammation, fever, abdominal symptoms, conjunctivitis and rash, and multiple organ dysfunction.[5],[7] The MIS-C has a clinical profile that is similar to inflammation found in moderate-to-severe Kawasaki disease with shock, staphylococcal and streptococcal toxic shock syndromes, bacterial sepsis, and macrophage activation syndrome.[2],[8]

Amid the SARS-CoV-2 pandemic, South East Asia is also experiencing a dengue virus outbreak. Dengue fever is the most rapidly spreading mosquito-borne viral disease worldwide, with an unpredictable clinical course.[3],[9],[10] Most cases are usually mild and do not require hospitalization; however, some patients develop severe complications, including shock, bleeding manifestations, encephalopathy, hepatic failure, renal failure, cardiac arrhythmia, and myocarditis.[9] Missing a case due to the overlapping symptoms and signs, pathological similarities, and immunological cross-reactivity of MIS-C with severe dengue poses a major health problem and can lead to fatal outcome.

Ferdous et al.[11] reported similar case series from Bangladesh. Dhooria et al.[12] described comparison of clinical features and outcome of dengue fever and MIS-C associated with SARS-CoV-2.

Government of India has laid down specific recommendations[13] for co-infection possibilities with SARS-CoV-2. According to it, co-infection should be ruled out when suspected with proper diagnostic method at the early stage to initiate proper specific management to reduce morbidity and mortality.

Fluids can be given according to national guidelines[14] for clinical management of most cases with severe dengue. Low-molecular-weight heparin (LMWH) has been included in the national guidelines for the management of moderate-to-severe SARS-CoV-2 cases with high D-dimer levels.[15] However, in cases with dengue, it is not indicated with platelet count less than 1 lakh. In any case with active bleeding, LMWH needs to be stopped immediately. Anti-inflammatory drugs such as tocilizumab, antivirals such as remdesivir, and all other supportive therapies can be used as per the national guidelines for SARS-CoV-2 infection management.[15]

However, there are no specific guidelines mentioned for those overlap cases of MIS-C with severe dengue. Probably, more research and literature support need to be considered in this aspect. To the best of our knowledge, this is the first case series from India demonstrating severe dengue and MIS-C in pediatric patients.

Concomitant severe dengue with MIS-C due to SARS-CoV-2 is not usually thought for which increases the chance of missing the diagnosis and delaying the start of appropriate management. We believe that this case series may help pediatricians considering the possibility of overlap of severe dengue and MIS-C due to SARS-CoV-2, rather than focusing on a single disease in patients with sick presentations who are refractory and atypical. Early initiation of steroids or IVIG could alter the course of illness, duration of stay in hospital, and morbidity and mortality.

In our study, none of them were active cases (reverse transcription polymerase chain reaction [RTPCR] positive) for SARS-CoV-2. Need further research and literature support to know the clinical spectrum and propose management guidelines for the overlap of severe dengue with MIS-C due to SARS-COV-2 RTPCR-positive versus RTPCR-negative cases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Centers for Disease Control and Prevention. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019. SARS-COV-2 INFECTION): Centers for Disease Control and Prevention. Centers for Disease Control and Prevention; 2020. Available from: https://emergency.cdc.gov/han/2020/han00432.asp. [Last accessed on 2022 Feb 17].  Back to cited text no. 1
    
2.
World Health Organization. Multisystem Inflammatory Syndrome in Children and Adolescents Temporally Related to SARS-COV-2 Infection. WHO; 2020. Available from: https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-withSARS-CoV-2.Infection. [Last accessed on 2022 Feb 17].  Back to cited text no. 2
    
3.
World Health Organization: Dengue Guidelines for Diagnosis, Treatment, Prevention and Control. Geneva: WHO; 2011. Available from: https://apps.who.int/iris/handle/10665/44188. [Last accessed on 2022 Feb 17].  Back to cited text no. 3
    
4.
Rapid Risk Assessment: Paediatric Inflammatory Multisystem Syndrome and SARS-CoV-2 Infection in Children; 2020. Available from: https://www.ecdc.europa.eu/en/publicationsdata/pediatric-inflammatory-multisystem-syndrome-and-sars-cov-2-rapid-risk.assessment.Asp. [Last accessed on 2022 Feb 17].  Back to cited text no. 4
    
5.
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. 5
    
6.
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. 6
    
7.
Dallan C, Romano F, Siebert J, Politi S, Lacroix L, Sahyoun C. Septic shock presentation in adolescents with COVID-19. Lancet Child Adolesc Health 2020;4:e21-3.  Back to cited text no. 7
    
8.
Pouletty M, Borocco C, Ouldali N, Caseris M, Basmaci R, Lachaume N, et al. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): A multicentre cohort. Ann Rheum Dis 2020;79:999-1006.  Back to cited text no. 8
    
9.
Chacko B, Subramanian G. Clinical, laboratory and radiological parameters in children with dengue fever and predictive factors for dengue shock syndrome. J Trop Pediatr 2008;54:137-40.  Back to cited text no. 9
    
10.
Dengue amid SARS-COV-2 Infection Outbreak: With Rain Comes Risk; 2020. Available from: https://www.thedailystar.net/backpage/news/dengue-amid-SARS-CoV-2-Infection-outbreak-rain-comes-risk-1897489. [Last accessed on 2022 Feb 17].  Back to cited text no. 10
    
11.
Ferdous A, Hossain MM, Afrin M. Severe dengue with multisystem inflammatory syndrome in children due to COVID-19: A co-infection case series. Cureus 2021;13:e19516.  Back to cited text no. 11
    
12.
Dhooria GS, Kakkar S, Pooni PA, Bhat D, Bhargava S, Arora K, et al. Comparison of clinical features and outcome of dengue fever and multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C). Indian Pediatr 2021;58:951-4.  Back to cited text no. 12
    
13.
Government of India Ministry of Health & Family Welfare Directorate General of Health Services (EMR Division). Guidelines for Management of Co-Infection of COVID-19 with other Seasonal Epidemic Prone Diseases. New Delhi; 2020. Available from: http://www.mohfw.gov.in. [Last accessed on 2022 Feb 17].  Back to cited text no. 13
    
14.
National Guidelines for Dengue Management during COVID-19 Pandemic. NVBDCP, DGHS, MOHWF, Government of India. New Delhi; 2020. Available from: http://www.mohfw.gov.in. [Last accessed on 2022 Feb 17].  Back to cited text no. 14
    
15.
Guidelines for Management of COVID-19 in Children. MOHFW. Government of India. New Delhi; 2021. Available from: http://www.mohfw.gov.in. [Last accessed on 2022 Feb 17].  Back to cited text no. 15
    



 
 
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