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Year : 2022  |  Volume : 11  |  Issue : 2  |  Page : 139-142

The clinical dilemma of sick neonates with positive COVID antibodies – A case series from India

Department of Neonatology, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India

Date of Submission16-Jul-2021
Date of Decision03-Feb-2022
Date of Acceptance06-Feb-2022
Date of Web Publication20-Apr-2022

Correspondence Address:
Shilpa Kalane
NICU, 3rd Floor, SS Building, Deenanath Mangeshkar Hospital, Pune - 411 004, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcn.jcn_89_21

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In the face of the emergence of COVID-19, the multisystem inflammatory syndrome in neonates, which is associated with severe acute respiratory syndrome-related coronavirus, has increasingly been reported. The clinical presentation and evolution of multisystem inflammatory syndrome (MIS) mimics neonatal diseases such as sepsis. Because of the similarities, these cases present clinical and laboratory peculiarities that necessitate distinguishing them from more common neonatal illnesses to reach a consensus on this new disease in the future. Here, we present two cases from India in which neonates had MIS-like manifestations but were later diagnosed with sepsis and metabolic disorder, posing a management dilemma.

Keywords: Cardiovascular system, inborn errors of metabolism, multisystem inflammatory syndrome in neonates, neonate, sepsis, supraventricular tachycardia

How to cite this article:
Kalane S, Shah D, Joshi S, Wakankar A, Rajhans A, Joshi R. The clinical dilemma of sick neonates with positive COVID antibodies – A case series from India. J Clin Neonatol 2022;11:139-42

How to cite this URL:
Kalane S, Shah D, Joshi S, Wakankar A, Rajhans A, Joshi R. The clinical dilemma of sick neonates with positive COVID antibodies – A case series from India. J Clin Neonatol [serial online] 2022 [cited 2023 Mar 21];11:139-42. Available from: https://www.jcnonweb.com/text.asp?2022/11/2/139/343424

  Introduction Top

Increasing case reports of children suffering from potentially life-threatening pediatric inflammatory multisystem syndrome, also known as multisystem inflammatory syndrome in children (MIS-C), have been described amid the COVID pandemic. MIS-C is a new disease in children, with no known cause. It is thought to be the result of immune dysregulation caused by severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) exposure. In contrast to MIS-C, where SARS-CoV-2 infection and multisystem inflammation occur in the same patient, a few case reports suggest neonatal multisystem inflammation (MIS-N) occurs because of maternal SARS-CoV-2 infection.[1] A case series of twenty neonates with multisystem involvement, hyperinflammatory syndrome, and positive anti-SARS-CoV-2 Immunoglobulin G (IgG) antibodies was recently published, emphasizing the severity of the disease.[1] Diagnosis and management of MIS-N remain a huge gray area, which could lead to overdiagnosis and overtreatment of neonates with clinical manifestations of MIS.[1],[2],[3],[4] Hence, differentiating MIS-N from other causes is utmost important for providing the quality neonatal care. We present a case series of two neonates from India who had clinical manifestations such as MIS-N but a different underlying cause.

  Case Reports Top

Case 1

A male baby born to a primigravida mother by premature onset of spontaneous labor (gestation: 34 + 4 weeks and weight: 1954 g) was admitted to the newborn intensive care unit for transient tachypnea of the newborn, which resolved in 4 h. The mother had a history of COVID-19 infection 2 months before delivery. There was no history of chorioamnionitis or prolonged rupture of membranes. APGAR score at 1 and 5 min was 8/10 and 9/10, respectively. The neonate did well during the first 2 days of life and accepted oral feeds. On day 3, he developed tachycardia (heart rate: 230–250 beats per minute [BPM]). Electrocardiogram showed supraventricular tachycardia (SVT). There was no response to adenosine. The baby was cardioverted because of his cardiovascular instability (poor peripheral pulses, mottling, and significant cardiac dysfunction). For 3 h, sinus tachycardia (HR: 200–220 BPM) was maintained. Meanwhile, blood investigations revealed elevated inflammatory markers (C-reactive protein, procalcitonin, ferritin, and D-dimer), as well as positive serology for COVID antibodies [Table 1] and [Table 2]. IgG and total against SARS-CoV-2 were detected using VIDAS® SARS-COV-2 kits (BioMerieux SA, Marcy-I'Etioile, France), with MINIVIDAS using enzyme-linked fluorescent assay (ELFA). The neonate had generalized tonic convulsions hence was administered phenobarbitone.
Table 1: Clinical manifestations and comparison with multisystem inflammatory syndrome in children versus sepsis criteria on the day of clinical illness

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Table 2: Laboratory parameters on the day of clinical deterioration

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The fever and underlying metabolic disturbance, that is, metabolic acidosis, were treated. Intravenous immunoglobulin (IVIG) was administered due to the likely diagnosis of MIS-N. Because sepsis could not be ruled out, intravenous (IV) methylprednisolone was not administered. The neonate did, however, develop tachyarrhythmia again, and this time, it did not respond to adenosine or cardioversion. Because of the refractory SVT, IV amiodarone was administered. As no clinical benefit was observed 2 h after amiodarone administration, IV methylprednisolone was given under the cover of broad-spectrum antibiotics – meropenem and vancomycin. Within 3 h, sinus rhythm was established, and hemodynamic stability improved significantly. Because clinical sepsis remained a possibility, additional methylprednisolone doses were withheld. Patient's blood and cerebrospinal fluid culture grew Group B Streptococcus (GBS). The final diagnosis was early-onset sepsis. The neonate was extubated on day 5, weaned off respiratory support by day 16, and discharged on day 25. [Figure 1] depicts a detailed timeline of clinical presentation and management.
Figure 1: Clinical progress and management of the case 1

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Case 2

A male newborn with asphyxia was referred for further management. He was delivered by emergency cesarean section at 36-week gestation due to fetal distress. At 1 and 5 min, the APGAR score was 3/10 and 5/10, respectively. Mother was gravida 4, had two spontaneous abortions and had a history of intrauterine death. The baby had moderate hypoxic ischemic encephalopathy (HIE) at the time of admission. Therapeutic hypothermia (TH) was started within 6 h of birth. The neurology improved from moderate stage of HIE to mild over the next 24 h, but there was an increased need for respiratory support, progressive metabolic acidosis, and hemodynamic instability in the form of hypotension. Hence, TH was discontinued, and controlled rewarming was done. The laboratory parameters were suggestive of multi-organ dysfunction. The neonate's serology for COVID antibodies was positive. IgG and total against SARS-CoV-2 were detected using VIDAS® SARS-COV-2 kits (BioMerieux SA, Marcy-I'Etioile, France), with MINIVIDAS using ELFA. The blood culture was negative. The neonate clinically was diagnosed to have MIS [Table 1] and [Table 2]. IVIG was administered. However, possibility of sepsis and inborn errors of metabolism (IEM) could not be ruled out, hence, methylprednisolone was not administered. The metabolic workup, which included blood for tandem mass spectroscopy and urine for gas chromatography–mass spectrometry, was ordered. The baby's clinical condition worsened over time, and he died on the 4th day of life. He was later diagnosed with 3-methyl glutaconic aciduria.

  Discussion Top

Traditionally, any sick neonate with positive septic screen or raised inflammatory markers is considered to have probable sepsis or sepsis mimic-like IEM, etc.[5] However, today amid pandemic, MIS-N appears to be the closest differential.[1],[2],[3] Because the management for these two conditions is so different, distinguishing between MIS and sepsis or sepsis mimics becomes critical. The practical issue is that laboratory results supporting the MIS diagnosis are available within a few hours, whereas blood culture takes days, and the yield is also dependent on many factors.[5]

The most difficult situation arises when the neonate suffers from a life-threatening emergency, as in the two cases described here. The neonate in first case had SVT, developed fever, and had positive inflammatory markers [Table 1]. The second case had progressive organ dysfunction and raised inflammatory markers. Both neonates were managed as per the standard protocol.[6] Anti-SARS-CoV-2 IgG antibodies were positive in both the cases. In the MIS-N case series published by Pawar et al., 90% of the neonates had cardiac manifestations. Arrhythmia was observed in 44% and one neonate had asphyxia and died of multi-organ dysfunction.[1] In both cases, there was no conclusive point-of-care test to rule out sepsis or metabolic disorder, and the only evidence was positive anti-SARS-CoV-2 antibodies.[1]

Clinical improvement was seen in first case, whereas the neonate in second case had rapid downhill. The neonate in first case was later diagnosed with GBS sepsis and that in the second case was diagnosed with 3-methyl glutaconic aciduria. Both neonates had life-threatening clinical features warranting urgent treatment in the form of IVIG and methylprednisolone. It was not possible to rule out sepsis or metabolic disorder on the day of clinical deterioration. Diagnosis of GBS needs advanced microbiology facilities. Many centers in India may not have the advanced culture techniques, so GBS infection could have easily been missed and mislabeled as MIS-N.[7] Similarly, in the second case, the result of metabolic work up was available after 7 days. As the clinical progress and history pointed toward probability of metabolic disorder, the work up was sent.

In both cases, although the clinical features and laboratory investigations were initially pointing toward diagnosis of MIS-N, we treated both babies as sepsis mimics, with close watch on the clinical progression.

  Conclusion Top

Differentiating MIS from sepsis mimics (e.g., asphyxia, IEM, etc.) in newborns is difficult. Although methylprednisolone has been recommended in potentially life-threatening cases, the decision to continue should be reviewed on a regular basis based on the patient's clinical progress.

Patient's consent

A full and detailed consent from the patient/guardian has been taken. The patient's identity has been adequately anonymized.


We sincerely thank Dr Usha Pratap and Dr Sampada Patwardhan for her valuable inputs while managing the case.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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 (Basel) 2021;8:572.  Back to cited text no. 1
World Health Organization. Multisystem Inflammatory Syndrome in Children and Adolescents with COVID-19: Scientific Brief; 2020. Available from: https://www.who.int/publications-detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19. [Last accessed on 2020 May 17].  Back to cited text no. 2
Centers for Disease Control and Prevention Health Alert Network (HAN). Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19). Available from: https://emergency.cdc.gov/han/2020/han00432.asp. [Last accessed on 2020 May 15].  Back to cited text no. 3
Wastnedge EA, Reynolds RM, van Boeckel SR, Stock SJ, Denison FC, Maybin JA, et al. Pregnancy and COVID-19. Physiol Rev 2021;101:303-18.  Back to cited text no. 4
Sharma D, Farahbakhsh N, Shastri S, Sharma P. Biomarkers for diagnosis of neonatal sepsis: A literature review. J Matern Fetal Neonatal Med 2018;31:1646-59.  Back to cited text no. 5
Topjian AA, Raymond TT, Atkins D, Chan M, Duff JP, Joyner BL, et al. Pediatric basic and advanced life support collaborators. Part 4: Pediatric basic and advanced life support 2020 american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Pediatrics 2021;147 Suppl 1:e2020038505D.  Back to cited text no. 6
Goel N, Wattal C, Gujral K, Dhaduk N, Mansukhani C, Garg P. Group B Streptococcus in Indian pregnant women: Its prevalence and risk factors. Indian J Med Microbiol 2020;38:357-61.  Back to cited text no. 7
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  [Figure 1]

  [Table 1], [Table 2]


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