Multisystem inflammatory syndrome in neonates (MIS-N) associated with SARS-CoV2 infection: a case series.

ABSTRACT

Multisystem inflammatory syndrome in neonates (MIS-N) is hypothesised to be caused either following transplacental transfer of SARS-CoV2 antibodies or antibodies developed in the neonate after infection with SARS-CoV-2. In this paper, we aim to discuss the clinical manifestations, laboratory features, and management of neonates diagnosed with MIS-N. We collated information from five participating hospitals in western India. A cohort of newborn infants presenting with multi-system involvement, along with the presence of SARS-CoV2 antibodies, was identified. Current proposed international diagnostic criteria for MIS-N were used to group the cases into three categories of Most likely, Possible, and Unlikely MIS-N. A total of 20 cases were reported with a diagnosis of MIS-N, all having high titres of SARS CoV2 IgG antibodies and negative for SARS CoV2 antigens. Most likely MIS (n = 5) cases presented with respiratory distress (4/5), hypotension and shock (4/5), and encephalopathy (2/5). Inflammatory markers like CRP (1/5), Procalcitonin (1/5), Ferritin (3/5), D-dimer (4/5), and LDH (2/5) were found to be elevated, and four of them had significantly high levels of proBNP. The majority of them (4/5) responded to immunomodulators, three neonates were discharged home, and two died. Possible MIS infants (n = 9) presented with fever (7/9), respiratory distress (4/9), refusal to feed (6/9), lethargy (5/9), and tachycardia (3/9). ProBNP as a marker of cardiac dysfunction was noted to be elevated in four (4/9) infants, correlating with abnormal echocardiography findings in two. In the Unlikely MIS (n = 6) category, three (3/6) infants presented with respiratory distress, one (1/6) with shock and cardiac dysfunction, and only one (1/6) with fever. All of them had elevated inflammatory markers. However, there were other potential diagnoses that could have been responsible for the clinical scenarios in these six cases.   Conclusion: MIS-N requires a high index of suspicion and should be considered in a neonate presenting with two or more systems involvement, in the presence of SARS-CoV2 antibodies, along with elevated inflammatory markers, once other common neonatal conditions have been ruled out. What is Known • Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) associated multisystem inflammatory syndrome in children (MIS-C) is  widely reported in paediatric population, however only few reports of newborn affection. • MIS-C is known to cause by virus-induced post-infective antibody mediated immune dysregulation with severe multi-system affection. What is New • MIS-N may present with varied clinical manifestations with multi-system involvement of variable severity with milder disease in term and severe disease with cardiac dysfunction in preterm newborns. • Multisystem inflammatory syndrome in newborns (MIS-N) is postulated to occur following immune dysregulation associated with transplacental transfer of SARS-CoV2 antibodies or antibodies developed in the neonate after infection with SARS-CoV-2.