Published: 2022-03-24

Neonatal multisystem inflammatory syndrome associated with prenatal maternal SARS-CoV-2 exposure: a case series

Harish J. Tambekar, Satish D. Ashtekar, Shishir P. Mirgunde, Swati Khot, Shrikant Mane


Multisystem inflammatory syndrome (MIS-C) in children (MIS-C) associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) is well recognised in children, however, rarely reported in newborns. It usually presents as fever and multiorgan involvement, with blood investigations showing increased inflammatory markers weeks after exposure to SARS-CoV-2. Unlike older children, the mechanism is unique in neonates as COVID-19 infection and the subsequent inflammatory reaction leading to MIS-C occur in two different individuals. We reviewed the perinatal history, clinical features, and outcomes of 3 neonates with features consistent with MIS-N related to maternal SARS-CoV-2, from August 2021 to December 2021. Anti-SARS-CoV-2 IgG and IgM antibodies were tested in all neonates. Clinical picture comprised multiorgan dysfunction (gastrointestinal, cardiorespiratory, haematological and dermatological), positive inflammatory markers, high ferritin and high D-dimer levels, elevated Cardiac enzymes. Blood cultures were sterile. Positive anti-SARS-CoV-2 IgG in both the mother and the infant, along with epidemiological evidence of maternal contact with COVID-19, clinched the diagnosis of MIS-C. Immunomodulatory drugs (intravenous immunoglobulin and systemic steroids) were administered. Multisystem inflammatory syndrome should be considered as a differential diagnosis in all critically ill neonates, particularly with maternal history of COVID-19 infection or epidemiological contact. This neonatal presentation is the reflection of fetal inflammatory response syndrome associated with maternal SARS-CoV-2 infection. Having no fever throughout the course of illness, in some neonates, suggests that neonates respond differently compared with children.


SARS-CoV2, Antibodies, Intravenous immunoglobulin

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Hoste L, Van Paemel R, Haerynck F. Multisystem inflammatory syndrome in children related to COVID-19: a systematic review. Eur J Pediatr. 2021;180(7):2019-34.

Sally A, Madsen-Bouterse. The Transcriptome of the Fetal Inflammatory Response Syndrome Am J Reprod Immunol. 2010;63(1):73-92.

Shaiba LA, Hadid A, Altirkawi KA, Bakheet HM, Alherz AM, Hussain SA et al. Case Report: Neonatal Multi-System Inflammatory Syndrome Associated With SARS-CoV-2 Exposure in Two Cases from Saudi Arabia. Front Pediatr. 2021;9:652857.

McCrindle BW, Manlhiot C. SARS-CoV-2-Related inflammatory multisystem syndrome in children: different or shared etiology and Pathophysiology as Kawasaki Disease? JAMA. 2020;324(3):246-8.

Song YW, Ng QX. Distinguishing between typical Kawasaki disease and multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2. Med hypotheses vol. 2020;144:110263.

Pawar R, Gavade V, Patil N, Mali V, Girwalkar A, Tarkasband V et al. Neonatal Multisystem Inflammatory Syndrome (MIS-N) Associated with Prenatal Maternal SARS-CoV-2: A Case Series. Children. 2021;8:572.

Agrawal G, Wazir S, Arora A. Multisystem inflammatory syndrome in a neonate masquerading as surgical abdomen BMJ Case Reports CP. 2021;14:e246579.

Sankaran D, Nakra N, Cheema R, Blumberg D, Lakshminrusimha S. Perinatal SARS-CoV-2 Infection and Neonatal COVID-19: A 2021 Update Neo-Reviews. 2021;22(5):e284-95.

Karimi-Zarchi M, Neamatzadeh H, Dastgheib SA. Vertical transmission of coronavirus disease 19 (COVID-19) from infected pregnant mothers to neonates: a review. Fetal Pediatr Pathol. 2020;39:246-50.

Schoenmakers S. SARS-CoV-2 placental infection and inflammation leading to fetal distress and neonatal multi-organ failure in an asymptomatic woman. Med Rxiv. 2020.

Diriba K, Awulachew E, Getu E. The effect of coronavirus infection (SARS-CoV-2, MERS-CoV, and SARS-CoV) during pregnancy and the possibility of vertical maternal-fetal transmission: a systematic review and meta-analysis. Eur J Med Res. 2020;25:39.

World Health Organization. Multisystem Inflammatory Syndrome in Children and Adolescents with COVID 19. Available at: care readiness clinical unit/covid 19. Accessed on 10 Feb, 2021.

Consiglio CR, Cotugno N, Sardh F. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020;183:968-81.

Kappanayil M. Multisystem inflammatory syndrome in a neonate, temporally associated with prenatal exposure to SARS-CoV-2: a case report Lancet Child Adolesc Health. 2021;5:304-08.

Nakra NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S. Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management. Children (Basel). 2020;7(7).

More K, Aiyer S, Goti A. Multisystem inflammatory syndrome in neonates associated with SARS-Co-V2 infection; a case series, research square. Research square. 2021;1-13.

Shivshankar D, Nanjegowda R, Kumar A, Kumar V, Kulkarni S, Venkatagiri P. Neonatal Multisystem Inflammatory Syndrome secondary to SARS-CoV-2 infection. J paediatr child health. 2021;13:10.1111/jpc.15696.

Magboul S, Khalil A, Al Shami A. Refractory Multi-Inflammatory Syndrome in a two weeks old neonate with COVID-19 Treated Successfully with Intravenous Immunoglobulin, Steroids and Anakinra, 24 August 2020. Research Square. 2020.

Manlhiot C, Millar K, Golding F, McCrindle B. Improved classification of coronary artery abnormalities based only on coronary artery zscores after Kawasaki disease. Pediatr. Cardiol. 2009;31:242-9.

Kappanayil M, Balan S, Alawani S. Multisystem inflammatory syndrome in a neonate, temporally associated with prenatal exposure to SARS-CoV-2: a case report. Lancet Child Adolesc Health. 2021;5:304-8.

Divekar AA, Patamasucon P, Benjamin JS. Presumptive Neonatal Multisystem Inflammatory Syndrome in Children Associated with Coronavirus Disease 2019. Am J Perinatol. 2021;38(6):632-6.

Alsaleem M. Intravenous Immune Globulin Uses in the Fetus and Neonate: A Review. Antibodies (Basel). 2020;9(4):60.

Jain S, Sen S, Lakshmivenkateshiah S, et al. Multisystem Inflammatory Syndrome in Children With COVID-19 in Mumbai, India. Indian Pediatr. 2020;57(11):1015-9.

McCarty KL, Tucker M, Lee G, Pandey V. Fetal inflammatory response syndrome associated with maternalSARS-CoV-2 infection. Pediatrics. 2020.

Khaund Borkotoky, Rekha MD*; Banerjee Barua, Puja MD*; Paul, Siba Prosad MRCPCH*, †; Heaton, Paul Anthony FRCPCH† COVID-19-Related Potential Multisystem Inflammatory Syndrome in Childhood in a Neonate Presenting as Persistent Pulmonary Hypertension of the Newborn. Pediatr Infect Dis J. 2021;40(4):e162-4.