Neonatal Multisystem Inflammatory Syndrome (MIS-N)

A small subset of pediatric patients develop a newly emerging syndrome associated with post COVID-19 infection. Termed Multisystem Inflammatory Syndrome in Children (MIS-C), this syndrome shares characteristics with Kawasaki Disease (KD), including fever, elevated inflammatory markers and multisystem involvement (cardiac, neurological, ocular, dermatological, mucocutaneous and gastrointestinal). MIS-C can have mixed presentation, creating a diagnostic challenge. We present this case of Neonatal Multisystem Inflammatory Syndrome (MIS-N) to highlight the complication of this syndrome in neonates with an aim to spread awareness of the clinical manifestations of this syndrome among the treating clinician.

Multisystem Inflammatory Syndrome in Children (MIS-C), also called Paediatric Multi-System Inflammatory Syndrome (PMIS or PIMS) [1]. MIS-C has varied symptoms that affect several organs and systems in the body [1]. Multisystem Inflammatory Syndrome in Children (MIS-C) is a condition where different body organs including heart, lungs, kidneys, brain, skin, eyes or gastrointestinal organs can be inflamed [2]. The limited evidence on Neonatal Multisystem Inflammatory Syndrome (MIS-N) Suggests that vertical transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is rare and most neonates seem to acquire the infection postnatally through respiratory droplets and contact [3]. Some children have signs of excessive blood clotting, gastrointestinal symptoms, kidney injury, neurologic symptoms, or heart inflammation with impaired heart function [4]. These symptoms can occur in different combinations [5]. Unlike MIS-C, where SARS-CoV-2 infection and multisystem inflammation occur in the same subject, a few case reports suggest that Neonatal Multisystem Inflammatory Syndrome (MIS-N) occurs secondary to maternal SARS-CoV-2 infection [6].

8 days old male baby vaginally delivered at 38 weeks of gestation with birth weight of 3100 gram to primi mother with birth history uneventful presented to emergency room in view of respiratory distress (RR-80/min, intercostal retraction), and multiple episodes of loose stool. On presentation baby was afebrile, with increased capillary refill time of 5 seconds, cold extremities, weak peripheral pulses. Initial blood gas showed severe metabolic acidosis with pH-7.09, bicarbonate - 3.6 mEq/L, lactate - 7.8 mmol/L. Inotropic support started and upgraded (Dobutamine, Dopamine, Adrenaline, Nor-adrenaline). Soda-bicarbonate correction given in view of severe metabolic acidosis. Emperical antibiotics were started. CPAP support was started in view of respiratory distress. Blood investigation showed CRP - 3.5 mg/dl (Lab Reference range upto 0.5 mg/dl), Covid 19 IgG antibody - 2145 AU/ml (Lab Reference range > 50 AU/ml = positive) positive with raised post-covid inflammatory markers (Pro-BNP - > 25,000 pg/ml, Ferritin- 478 ng/ml, D-Dimer - 923 ng/ml. There was no history of Covid- 19 infection in mother during pregnancy and there was no history of mother vaccinated against Covid-19, but as the baby was positive for Covid-19 IgG antibody hence mother was also tested for Covid -19 IgG antibody which came positive with a value of 1022 AU/ml (Lab Reference range up to 50 AU/ml is negative) which confirmed that mother had Covid-19 Infection during pregnancy. Hence the diagnosis of Neonatal Multisystem Inflammatory Syndrome was made according to the WHO criteria. In spite of giving appropriate antibiotic therapy there was an increase in the CRP value and there was no much clinical improvement hence Inj Methylprednisolone was given in pulse therapy, however despite giving Pulse steroid therapy, inflammatory markers showed rising trends, hence IV immunoglobulin (2 gm/kg) infusion was given. Post IV immunoglobulin infusion there was a decline in the inflammatory markers value and the baby improved clinically. Initial KFT showed BUN-208, creatinine- 4.5, potassium- 2.3. USG KUB was done which was normal. Potassium correction was given and adequate fluid management was given for AKI. Adequate fluid management and electrolyte correction were done along with serial monitoring of KFT, which showed an improving trend with all parameters in a normal range. Ionotropic support gradually weaned off as slowly as the child showed improvement. Blood culture, CSF culture and urine culture were sterile. The baby improved over the next 72 hours. Oral feeds were started gradually increased to full feed which the baby accepted well. Inflammatory markers came back to the normal range over a period of 7 days. The baby was discharged after 8 days of NICU stay. On follow up the baby was doing well, asymptomatic with no positive signs and symptoms.

Neonates born to mothers with a history of SARS-CoV-2 Infection or exposure to a COVID-19 patient during pregnancy and presenting with features that cannot be explained by others causes [2]. Maternal infection with SARS COV-2 results in the development of protective IgG antibodies against the spike protein of the virus [3]. These antibodies cross the placenta to provide passive immunity to newborns [4]. In some susceptible neonates, these autoantibodies triggered by SARS-COV-2 causes activation and secretion of pro-inflammatory cytokines that result in the development of MIS-N [5]. In view of MIS-N, we administered IV immunoglobulin along with systemic steroids [6]. Most of the case reports and case series describing MIS-C in neonates have used the aforementioned drugs and have shown good clinical [7]. However, further studies are needed in this age group to prove their efficacy.

Covid-19 associated MIS-C like the disease has not been well described in neonates. Typical clinical features may be absent, a high index of clinical suspicion is warranted in critically ill neonates born to mothers with Covid-19 infection. The hallmark of MIS-N is widespread inflammation across multiple organ systems. Left untreated, this inflammation can cause long-term morbidity and increased mortality. Hence the need for prompt intensive medical treatment that includes close monitoring and supportive care. This usually involves the delivery of intravenous fluids and medications including prophylactic antibiotics, with the goal of reducing fever, keeping blood pressure and perfusion up and eliminating any underlying bacterial infections. The symptoms of MIS-C are caused by the body’s own exaggerated immune response, there is a need to administer medications to temporarily suppress the body’s immune system. Medication commonly used in neonates with MIS-C includes steroids and IVIG. Prompt diagnosis with an institution of appropriate therapy is the key to a favorable outcome.

Conflict of Interest

The authors have indicated they have no conflicts of interest relevant to this article to disclose.

Article Summary

Multisystem Inflammatory Syndrome in children (MIS-C), this syndrome shares characteristics with Kawasaki Disease (KD), including fever, elevated inflammatory markers and multisystem involvement (cardiac, neurological, ocular, dermatological, mucocutaneous and gastrointestinal). MIS-C can have a mixed presentation, creating a diagnostic challenge. Unlike MIS-C, where SARS-CoV-2 infection and multisystem inflammation occur in the same subject, a few case reports suggest that Neonatal Multisystem Inflammatory Syndrome (MIS-N) occurs secondary to maternal SARS-CoV-2 infection.

Contributors Statement Page

Dr. Sumit Chakravarty, Dr. Vineetranjan Gupta and Dr. Arvind gupta conceptualized and designed, drafted the initial manuscript and reviewed and revised the manuscript.

Dr. Nishu, Dr. Kanika Sain and Dr. Shreyansh Valjiyani collected data, carried out initial analyses and reviewed and revised the manuscript.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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