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

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.

COVID 19 in neonates

Corona virus disease 2019 started in December 2019 as an outbreak of unexplained pneumonias in Wuhan, a city in Hubei province of China. This illness emerged as an epidemic in China and later spread to almost all countries over the globe except Antarctica. This is caused by a beta Corona virus, which is genetically similar to SARS virus. The predominant mode of transmission is via droplet spread, when the infected person coughs, sneezes or talks the virus is released in the respiratory secretions. As there are only a few cases of COVID 19 in neonates, there is no convincing evidence to support the possibility of vertical transmission. Clinical presentation in neonates is nonspecific, commonly observed are temperature instability, respiratory distress, poor feeding, lethargy, vomiting and diarrhea. Laboratory examinations may be nonspecific. Definitive test for 2019-nCoV is the detection of viral nucleic acid by real-time fluorescence polymerase chain reaction (RT-PCR). Suspected and confirmed COVID positive mothers should be delivered in separate delivery rooms and operation theaters. Since there is no approved treatment or drug for this disease, prevention of infection and breaking the chain of transmission plays a crucial role.