Multi-System Inflammatory Syndrome in Neonates (MIS-N) - Clinical Profile and Outcomes - A Prospective Cohort Study

Authors

  • Yalaguraswami Kolkar Department of Paediatrics, BLDE (DU) Shri B M Patil Medical College Hospital and Research Centre, Vijayapura, Karnataka, India
  • P. Lavanya Department of Paediatrics, BLDE (DU) Shri B M Patil Medical College Hospital and Research Centre, Vijayapura, Karnataka, India
  • Vijayakumar S. Biradar Department of Paediatrics, BLDE (DU) Shri B M Patil Medical College Hospital and Research Centre, Vijayapura, Karnataka, India
  • K. Nandakishore Department of Paediatrics, BLDE (DU) Shri B M Patil Medical College Hospital and Research Centre, Vijayapura, Karnataka, India
  • Siddu Charki Department of Paediatrics, BLDE (DU) Shri B M Patil Medical College Hospital and Research Centre, Vijayapura, Karnataka, India
  • S.V. Patil Department of Paediatrics, BLDE (DU) Shri B M Patil Medical College Hospital and Research Centre, Vijayapura, Karnataka, India

DOI:

https://doi.org/10.6000/1929-4247.2023.12.03.2

Keywords:

MIS-N, COVID-19, Neonate, immunomodulators

Abstract

Aims: To analyze the clinical spectrum in Neonates with MIS-N based on the time of presentation and also to assess the use of immunomodulator therapy in MIS-N.

Subjects and Methods: We studied 100 neonates delivered at BLDE (DU) Shri B M Patil Medical College Hospital admitted to Level III-A NICU from JULY 2020 to MAY 2021. 98 neonates had high titers of IG G antibodies and were negative for COVID Antigen. We categorized the cohorts into EARLY MIS-N (<72 hrs) and LATE MIS-N (>72 hrs).

Results: 58 presented as EARLY MIS-N with Respiratory distress (RD) in 40 (70%), cardiac dysfunction 34 (60%), PPHN 12(20%), Fever 12(20%), seizures 12(20%), encephalopathy in 6(10%), sepsis-like features 6(10%), had elevated inflammatory markers like CRP (30%), D-Dimer (70%), Ferritin (30%), cardiac biomarkers like BNP (60%), LDH (30%) and ECHO showing LV dysfunction in 50%. LATE MIS-N presented mostly with fever 28(70%), sepsis-like features 24(60%), Respiratory Distress in 16(40%), cardiac dysfunction 12 (30%), hypoglycemia 4(10%), parotitis 4(10%), had significantly elevated inflammatory markers like CRP (70%), D-Dimer (50%), Ferritin (70%), cardiac biomarkers like BNP (40%), LDH (20%) and ECHO showing LV dysfunction in 20%, dilated coronaries in 20 %, PPHN in 10%. Oxygen and respiratory support requirements were higher in EARLY presenters and IVIG and steroid requirements were more in LATE presenters.

Conclusion: We observed that maternal SARS-COV-2 antibodies transferred transplacentally and neonatal antibodies acquired after COVID-19 infection can cause MIS-N in neonates. Immunomodulator therapy is required in severe cases of MIS-N only.

References

Al Ameer HH, Al Kadhem SM, Busaleh F, Al Khwaitm S, Llaguno MBB. Multi-system inflammatory syndrome in children temporally related to COVID-19: a case report from Saudi Arabia. Cureus 2020; 12(9): e10589. https://doi.org/10.7759/cureus.10589 DOI: https://doi.org/10.7759/cureus.10589

Radia T, Williams N, Agrawal P, Harman K, Weale J, Cook J, Gupta A. Multi-system inflammatory syndrome in children & adolescents (MIS-C): A systematic review of clinical features and presentation. Paediatr Respir Rev 2021; 38: 51-57. https://doi.org/10.1016/j.prrv.2020.08.001 DOI: https://doi.org/10.1016/j.prrv.2020.08.001

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): 69. https://doi.org/10.3390/children7070069 DOI: https://doi.org/10.3390/children7070069

Flannery DD, Gouma S, Dhudasia MB, Mukhopadhyay S, Pfeifer MR, Woodford EC, Triebwasser JE, Gerber JS, Morris JS, Weirick ME, et al. Assessment of Maternal and Neonatal CoRD Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios. JAMA Pediatr 2021. https://doi.org/10.1001/jamapediatrics.2021.0038 DOI: https://doi.org/10.1001/jamapediatrics.2021.0038

Pawar R, Gavade V, Patil N, Mali V, Girwalkar A, Tarkasband V, et al. Neonatal Multi-system Inflammatory Syndrome (MIS-N) associated with prenatal maternal SARS-CoV-2: a case series. Children 2021; 8(7): 572. https://doi.org/10.3390/children8070572 DOI: https://doi.org/10.3390/children8070572

Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, Chen YK, et al. Antibody responses to SARS-CoV-2 in patient's withCOVID-19. Nat Med 2020; 26(6): 845-848. https://doi.org/10.1038/s41591-020-0897-1 DOI: https://doi.org/10.1038/s41591-020-0897-1

Orlanski-Meyer E, Yogev D, Auerbach A, et al. Multi-system Inflammatory Syndrome in Children associated with severe acute respiratory syndrome coronavirus-2 in an 8-week-old infant. J Pediatric Infect Dis Soc 2020; 9(6): 781-784. https://doi.org/10.1093/jpids/piaa137 DOI: https://doi.org/10.1093/jpids/piaa137

Abrams JY, Oster ME, Godfred-Cato SE, Bryant B, Datta SD, Campbell AP, et al. Factors linked to severe outcomes in multi-system inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study. Lancet Child Adolesc Health 2021; 5(5): 323-331. https://doi.org/10.1016/S2352-4642(21)00050-X DOI: https://doi.org/10.1016/S2352-4642(21)00050-X

Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, et al. Multi-system Inflammatory Syndrome in Children in New York State. N Engl J Med 2020; 383(4): 347-358. https://doi.org/10.1056/NEJMoa2021756 DOI: https://doi.org/10.1056/NEJMoa2021756

Lima ARO, CaRDoso CC, Bentim PRB, Voloch CM, Rossi ÁD, da Costa RMMSC, et al. Maternal SARS-CoV-2 infection associated to systemic inflammatory response and pericaRDial effusion in the neonate: a case report. J Pediatric Infect Dis Soc 2021; 10(4): 536-539. https://doi.org/10.1093/jpids/piaa133 DOI: https://doi.org/10.1093/jpids/piaa133

Kappanayil M, Balan S, Alawani S, et al. Multi-system inflammatory syndrome in a neonate, temporally associated with prenatal exposure to SARS-CoV-2: a case report. Lancet Child Adolesc Health 2021; 5(4): 304-308. https://doi.org/10.1016/S2352-4642(21)00055-9 DOI: https://doi.org/10.1016/S2352-4642(21)00055-9

Khaund Borkotoky R, Banerjee Barua P, Paul SP, Heaton PA. COVID-19-Related Potential Multi-system Inflammatory Syndrome in Childhood in a Neonate Presenting as Persistent Pulmonary Hypertension of the Neonate. Pediatr Infect Dis J 2021; 40(4): e162-e164. https://doi.org/10.1097/INF.0000000000003054 DOI: https://doi.org/10.1097/INF.0000000000003054

Divekar AA, Patamasucon P, Benjamin JS. Presumptive neonatal multi-system inflammatory syndrome in children associated with coronavirus disease 2019. Am J Perinatol 2021; 38: 632-636. https://doi.org/10.1055/s-0041-1726318 DOI: https://doi.org/10.1055/s-0041-1726318

Shaiba LA, Hadid A, Altirkawi KA, et al. Case report: Neonatal multi-system inflammatory syndrome associated with SARS-CoV-2 exposure in two cases from Saudi Arabia. Front Pediatr 2021; 13(9): 652857. https://doi.org/10.3389/fped.2021.652857 DOI: https://doi.org/10.3389/fped.2021.652857

DIG Gikar S, Nanjegowda R, Kumar A, Kumar V, Kulkarni S, Venkatagiri P. Neonatal Multi-system Inflammatory Syndrome secondary to SARS-CoV-2 infection. J Paediatr Child Health 2021; 13. https://doi.org/10.1111/jpc.15696 DOI: https://doi.org/10.1111/jpc.15696

Diwakar K, Gupta BK, Uddin MW, Sharma A, Jhajra S. Multi-system inflammatory syndrome with persistent neutropenia in neonate exposed to SARS-CoV-2 virus: A case report and review of literature. J Neonatal Perinatal Med 2021. https://doi.org/10.3233/NPM-210839 DOI: https://doi.org/10.3233/NPM-210839

More K, Chawla D, Murki S, Tandur B, Deorari AK, Kumar P. National Neonatology Forum (NNF) COVID-19 Registry Group. Outcomes of neonates born to mothers with coronavirus disease 2019(COVID-19)—National Neonatology Forum (NNF) India COVID-19 Registry. Indian Pediatr 2021; 58(6): 525-531. https://doi.org/10.1007/s13312-021-2234-2 DOI: https://doi.org/10.1007/s13312-021-2234-2

Chawla D, Chirla D, Dalwai S, Deorari AK, Ganatra A, Gandhi A, Kabra NS, Kumar P, Mittal P, Parekh BJ, Sankar MJ, Singhal T, Sivanandan S, Tank P. Federation of Obstetric and Gynaecological Societies of India (FOGSI), National Neonatology Forum of India (NNF) and Indian Academy of Pediatrics (IAP). Perinatal-Neonatal Management of COVID-19Infection-Guidelines of the Federation of Obstetric and Gynaecological Societies of India (FOGSI), National Neonatology Forum of India (NNF), and Indian Academy of Pediatrics (IAP). Indian Pediatr 2020; 57(6): 536-548. https://doi.org/10.1007/s13312-020-1852-4 DOI: https://doi.org/10.1007/s13312-020-1852-4

MOHFW Clinical management protocol: COVID 19 Version 3: 13/06/2020. https://www.mohfw.gov.in/pdf/Clinical Management Protocol for COVID-19.pdf

Centers for Disease Control and Prevention (2020) Multi-system inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). CDC Health Alert Net- work. https://www.cdc.gov/mis/about.html

Raschetti R, Vivanti AJ, Vauloup-Fellous C, Loi B, Benachi A, De Luca D. Synthesis and systematic review of reported neonatal SARS-CoV-2 infections. Nat Commun 2020; 11(1): 5164. https://doi.org/10.1038/s41467-020-18982-9 DOI: https://doi.org/10.1038/s41467-020-18982-9

Kobayashi T, Fuse S, Sakamoto N, Mikami M, Ogawa S, Hamaoka K, Arakaki Y, Nakamura T, Nagasawa H, Kato T, et al. A New Z Score Curve of the Coronary Arterial Internal Diameter Using the Lambda-Mu-Sigma Method in a Pediatric Population. J Am Soc EchocaRDiogr Off Publ Am Soc EchocaRDiogr 2016; 29: 794-801.e29. https://doi.org/10.1016/j.echo.2016.03.017 DOI: https://doi.org/10.1016/j.echo.2016.03.017

Alsaleem M. Intravenous Immune Globulin Uses in the Fetus and Neonate: A Review. Antibodies (Basel) 2020; 9(4): 60. https://doi.org/10.3390/antib9040060 DOI: https://doi.org/10.3390/antib9040060

Navarro M, Negre S, Matoses ML, Golombek SG, Vento M. Necrotizing enterocolitis following the use of intravenous immunoglobulin for haemolytic disease of the neonate. Acta Paediatr 2009; 98: 1214-1217. https://doi.org/10.1111/j.1651-2227.2009.01279.x DOI: https://doi.org/10.1111/j.1651-2227.2009.01279.x

Whitworth HB, Sartain SE, Kumar R, Armstrong K, Ballester L, Betensky M, Cohen C, Diaz R, Diorio C, Goldenberg NA, et al. Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C. Blood 2021. https://doi.org/10.1182/blood.2020010218 DOI: https://doi.org/10.1182/blood.2020010218

Lakshminrusimha S, Hudak M, Dimitriades V, HIG Gins RD. Multi-system Inflammatory Syndrome (MIS-C) in Neonates (MIS-N) Following Maternal SARS CoV-2 COVID-19 Infection. Am J Perinatol 2021. https://doi.org/10.1055/a-1682-3075 DOI: https://doi.org/10.1055/a-1682-3075

Gray KJ, BoRDt EA, Atyeo C, Deriso E, Akinwunmi B, Young N, Medina Baez A, Shook LL, Cvrk D, James K, et al. COVID-19 vaccine response in pregnant and lactating women: A cohort study. Am J Obstet Gynecol 2021. https://doi.org/10.1101/2021.03.07.21253094 DOI: https://doi.org/10.1101/2021.03.07.21253094

KabeeRDoss J, Pilania RK, Karkhele R, Kumar TS, Danda D, Singh S. Severe COVID-19, multi-system inflammatory syndrome in children, and Kawasaki disease: Immunological mechanisms, clinical manifestations, and management. Rheumatol Int 2021; 41: 19-32. https://doi.org/10.1007/s00296-020-04749-4 DOI: https://doi.org/10.1007/s00296-020-04749-4

Anderson EM, Diorio C, Goodwin EC, McNerney KO, Weirick ME, Gouma S, Bolton MJ, Arevalo CP, Chase J, Hicks P, et al. SARS-CoV-2 antibody responses in children with MIS-C and mild and severe COVID-19. J Pediatric Infect Dis Soc 2020. https://doi.org/10.1101/2020.08.17.20176552 DOI: https://doi.org/10.1101/2020.08.17.20176552

Vella LA, Giles JR, Baxter AE, Oldridge DA, Diorio C, Kuri-Cervantes L, Alanio C, Pampena MB, Wu JE, Chen Z, et al. Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19. Sci Immunol 2021; 6. https://doi.org/10.1101/2020.09.25.20201863 DOI: https://doi.org/10.1101/2020.09.25.20201863

Gruber CN, Patel RS, Trachtman R, Lepow L, Amanat F, Krammer F, Wilson KM, Onel K, Geanon D, Tuballes K, et al. Mapping Systemic Inflammation and Antibody Responses in Multi-system Inflammatory Syndrome in Children (MIS-C). Cell 2020; 183: 982-995. https://doi.org/10.1016/j.cell.2020.09.034 DOI: https://doi.org/10.1016/j.cell.2020.09.034

Zeng H, Xu C, Fan J, Tang Y, Deng Q, Zhang W, Long X. Antibodies in Infants Born to Mothers With COVID-19 Pneumonia. JAMA J Am Med Assoc 2020. https://doi.org/10.1001/jama.2020.4861 DOI: https://doi.org/10.1001/jama.2020.4861

Atyeo C, Pullen KM, BoRDt EA, Fischinger S, Burke J, Michell A, Slein MD, Loos C, Shook LL, Boatin AA, et al. Compromised SARS-CoV-2-specific placental antibody transfer. Cell 2021; 184: 628-642.e10. https://doi.org/10.1016/j.cell.2020.12.027 DOI: https://doi.org/10.1016/j.cell.2020.12.027

Blumberg D, Sridhar A, Lakshminrusimha S, HIG Gins RD, Saade G. COVID-19 Vaccine Considerations during Pregnancy and Lactation. Am J Perinatol 2021; 38: 523-528. https://doi.org/10.1055/s-0041-1726390 DOI: https://doi.org/10.1055/s-0041-1726390

Shimabukuro TT, Kim SY, Myers TR, Moro PL, Oduyebo T, Panagiotakopoulos L, Marquez PL, Olson CK, Liu R, Chang KT, et al. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N Engl J Med 2021. https://doi.org/10.1097/01.aoa.0000796052.11696.42 DOI: https://doi.org/10.1097/01.aoa.0000796052.11696.42

Metz TD, Clifton RG, Hughes BL, Sandoval G, Saade GR, Grobman WA, Manuck TA, Miodovnik M, Sowles A, Clark K, et al. Disease Severity and Perinatal Outcomes of Pregnant Patients With Coronavirus Disease 2019 (COVID-19). Obstet Gynecol 2021; 137: 571-580. https://doi.org/10.1097/AOG.0000000000004339 DOI: https://doi.org/10.1097/AOG.0000000000004339

Published

2023-08-18

How to Cite

Kolkar, Y. ., Lavanya, P. ., Biradar, V. S. ., Nandakishore, K. ., Charki, S. ., & Patil, S. . (2023). Multi-System Inflammatory Syndrome in Neonates (MIS-N) - Clinical Profile and Outcomes - A Prospective Cohort Study. International Journal of Child Health and Nutrition, 12(3), 83–90. https://doi.org/10.6000/1929-4247.2023.12.03.2

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