Neonatal Multisystem Inflammatory Syndrome (MIS-N) Associated with Prenatal Maternal SARS-CoV-2: A Case Series

Abstract

Multisystem inflammatory syndrome in children (MIS-C) is a post-infectious immune-mediated condition, seen 3-5 weeks after COVID-19. Maternal SARS-CoV-2 may potentially cause a similar hyperinflammatory syndrome in neonates due to transplacental transfer of antibodies. We reviewed the perinatal history, clinical features, and outcomes of 20 neonates with features consistent with MIS-C related to maternal SARS-CoV-2 in Kolhapur, India, from 1 September 2020 to 30 April 2021. Anti-SARS-CoV-2 IgG and IgM antibodies were tested in all neonates. Fifteen singletons and five twins born to eighteen mothers with a history of COVID-19 disease or exposure during pregnancy presented with features consistent with MIS-C during the first 5 days after birth. Nineteen were positive for anti-SARS-CoV-2 IgG and all were negative for IgM antibodies. All mothers were asymptomatic and therefore not tested by RTPCR-SARS-CoV-2 at delivery. Eighteen neonates (90%) had cardiac involvement with prolonged QTc, 2:1 AV block, cardiogenic shock, or coronary dilatation. Other findings included respiratory failure (40%), fever (10%), feeding intolerance (30%), melena (10%), and renal failure (5%). All infants had elevated inflammatory biomarkers and received steroids and IVIG. Two infants died. We speculate that maternal SARS-CoV-2 and transplacental antibodies cause multisystem inflammatory syndrome in neonates (MIS-N). Immunomodulation may be beneficial in some cases, but further studies are needed.

Keywords: COVID-19; anti SARS-CoV-2 antibodies; multisystem inflammatory syndrome in children (MIS-C); neonate.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Various presentations of SARS-CoV-2 infection and its sequences in the neonatal period. Red colored subjects with a ‘+’ sign indicate COVID-19 positive patients. Pregnant mother A has COVID-19 and her baby is negative at birth but contracts late-onset COVID-19 due to transmission from the mother. Pregnant mother B has no COVID-19 but her neonate develops late-onset neonatal infection due to exposure to a family member 2–4 weeks after birth. Pregnant mother C is COVID-19 positive during the perinatal period and transmits the virus to her offspring during birth leading to early-onset infection in the neonate. This baby can potentially develop MIS-C 2–4 weeks later (a rare occurrence) [16]. Pregnant mother D has COVID-19 during pregnancy but the neonate remains healthy. Pregnant mother E has COVID-19 disease or exposure to SARS-COV-2 during pregnancy and the baby develops multisystem inflammation secondary to passive transfer of antibodies leading to MIS-N (multisystem inflammatory syndrome in neonates) [14].

Figure 2

Representative EKGs of neonates presenting with bradycardia. Baby number sequence is the same as in Table 3. The first column showing EKGs at presentation (A,D,G,J,M), with sinus rhythm, prolonged QT interval and atrio-ventricular block. Middle column showing sinus rhythm and prolonged QT interval (B,E,H,K,N). The last column showing sinus rhythm with normal QT interval (C,F,I,L,O). Black arrows = atrial beats; horizontal square bracket = QT interval; QTc = corrected QT interval; ms = milliseconds. QTc values in the figure are derived by the formula QTc = QT/√RR.

Figure 3

Echocardiography and clinical findings in neonates with MIS-C. Baby number sequence is the same as in Table 3. Transthoracic echocardiography, parasternal short axis view in Baby #14 (A) and Baby #19 (B,C). The left main and left anterior descending coronary artery (yellow arrow) and the right coronary artery (blue arrow) are significantly dilated. AV = aortic valve. Transthoracic echocardiography and color doppler, parasternal short axis view in Baby #4 (D), showing aorta (Ao) and main pulmonary artery (MPA) bifurcation, with a large thrombus (red arrow) obstructing the left pulmonary artery (yellow star) origin and causing flow turbulence on color doppler (E), but normal flows across right pulmonary artery (green star). Transthoracic echocardiography subcostal bi-caval view in Baby # 20 (F), showing a thrombus (red arrow) in right atrium (RA). Baby #6, showing oral and muco-cutaneous lesions (G) and, pedal edema and skin peeling (H) and Baby #7 with black, tarry stools (melena, I).