Introduction: Multisystem inflammatory syndrome in neonates (MIS-N) related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has increasingly been reported worldwide amid the spread of the SARS-CoV-2 pandemic. Methods: We searched PubMed, EMBASE, and CINAHL and preprint servers (BioRxiv.org and MedRxiv.org) using a specified strategy integrating Medical Subject Headings terms and keywords until October 20, 2021. Our aim was to systematically review demographic profiles, clinical features, laboratory parameters, complications, treatments, and outcomes of neonates with MIS-N. Studies were selected when fulfilling the inclusion criteria. Articles were included if they fulfilled the World Health Organization (WHO), Centers for Disease Control (CDC) definitions of MIS-C, or our proposed definition. Results: Sixteen reports of MIS-N including 47 neonates meeting MIS-N criteria were identified. Presentation included cardiovascular compromise (77%), respiratory involvement (55%), and fever in (36%). Eighty-three percent of patients received steroids, and 76% received immunoglobulin. Respiratory support was provided to 60% of patients and inotropes to 45% of patients. Five (11%) neonates died. Conclusion: The common presentation of MIS-N included cardiorespiratory compromise with the possibility of high mortality. Neonates with MIS-N related to SARS-CoV-2 may be at higher risk of adverse outcomes.

1.
Centers for Disease Control and Prevention [Internet]. CDC COVID data tracker. Centers for Disease Control and Prevention. [cited 2022 Feb 26]. Available from: https://covid.cdc.gov/covid-data-tracker/#mis-national-surveillance.
2.
Kaushik
A
,
Gupta
S
,
Sood
M
,
Sharma
S
,
Verma
S
.
A systematic review of multisystem inflammatory syndrome in children associated with SARS-COV-2 infection
.
Pediatr Infect Dis J
.
2020
;
39
(
11
):
e340
. .
3.
Yasuhara
J
,
Watanabe
K
,
Takagi
H
,
Sumitomo
N
,
Kuno
T
.
COVID-19 and multisystem inflammatory syndrome in children: a systematic review and meta-analysis
.
Pediatr Pulmonol
.
2021
;
56
(
5
):
837
48
.
4.
McCarty
KL
,
Tucker
M
,
Lee
G
,
Pandey
V
.
Fetal inflammatory response syndrome associated with maternal SARS-COV-2 infection
.
Pediatrics
.
2020
;
147
(
4
):
e2020010132
. .
5.
Khaund Borkotoky
R
,
Banerjee Barua
P
,
Paul
SP
,
Heaton
PA
.
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
.
6.
Lakshminrusimha
S
,
Hudak
ML
,
Dimitriades
VR
,
Higgins
RD
.
Multisystem inflammatory syndrome in neonates following maternal SARS-COV-2 COVID-19 infection
.
Am J Perinatol
.
2021
. Online ahead of print.
7.
Buonsenso
D
,
Riitano
F
,
Valentini
P
.
Pediatric inflammatory multisystem syndrome temporally related with SARS-COV-2: immunological similarities with acute rheumatic fever and toxic shock syndrome
.
Front Pediatr
.
2020
;
8
:
574
.
8.
Gee
S
,
Chandiramani
M
,
Seow
J
,
Pollock
E
,
Modestini
C
,
Das
A
,
The legacy of maternal SARS-COV-2 infection on the immunology of the Neonate
.
Nat Immunol
.
2021
;
22
(
12
):
1490
502
.
9.
Kaushik
S
,
Aydin
SI
,
Derespina
KR
,
Bansal
PB
,
Kowalsky
S
,
Trachtman
R
,
Multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2 infection (MIS-C): a multi-institutional study from New York City
.
J Pediatr
.
2020
;
224
:
24
9
.
10.
Huang
AT
,
Garcia-Carreras
B
,
Hitchings
MD
,
Yang
B
,
Katzelnick
LC
,
Rattigan
SM
,
A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity
.
Nat Commun
.
2020
;
11
(
1
):
4704
.
11.
Facchetti
F
,
Bugatti
M
,
Drera
E
,
Tripodo
C
,
Sartori
E
,
Cancila
V
,
Sars-cov2 vertical transmission with adverse effects on the newborn revealed through integrated immunohistochemical, electron microscopy and molecular analyses of placenta
.
EBioMedicine
.
2020
;
59
:
102951
.
12.
Multisystem inflammatory syndrome in children and adolescents with COVID-19 [Internet]. World Health Organization. World Health Organization; [cited 2021 Nov 22]. Available from: https://www.who.int/publications-detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19.
13.
Han archive: 00432 [Internet]. Centers for Disease Control and Prevention. 2020 [cited 2021 Nov 22]. Available from: https://emergency.cdc.gov/han/2020/han00432.asp.
14.
More
K
,
Aiyer
S
,
Goti
A
,
Parikh
M
,
Sheikh
S
,
Patel
G
,
Multisystem inflammatory syndrome in neonates (MIS-N) associated with SARS-CoV2 infection: a case series [published online ahead of print, 2022 Jan 14]
.
Eur J Pediatr
.
2022
:
1
16
.
15.
For use in JBI systematic reviews checklist for case reports [Internet]. [cited 2021 Nov 22]. Available from: https://jbi.global/sites/default/files/2019-05/JBI_Critical_Appraisal-Checklist_for_Case_Reports2017_0.pdf.
16.
Pawar
R
,
Gavade
V
,
Patil
N
,
Mali
V
,
Girwalkar
A
,
Tarkasband
V
,
Neonatal multisystem inflammatory syndrome (MIS-N) associated with prenatal maternal SARS-COV-2: a case series
.
Children
.
2021
;
8
(
7
):
572
.
17.
Shaiba
LA
,
Altirkawi
K
,
Hadid
A
,
Alsubaie
S
,
Alharbi
O
,
Alkhalaf
H
,
COVID-19 disease in infants less than 90 days: case series
.
Front Pediatr
.
2021
;
9
:
674899
.
18.
Diggikar
S
,
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
. Online ahead of print.
19.
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
. .
20.
Diwakar
K
,
Gupta
BK
,
Uddin
MW
,
Sharma
A
,
Jhajra
S
.
Multisystem 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
. Online ahead of print. .
21.
Eghbalian
F
,
Sami
G
,
Bashirian
S
,
Jenabi
E
.
A neonate infected with coronavirus disease 2019 with severe symptoms suggestive of multisystem inflammatory syndrome in childhood
.
Clin Exp Pediatr
.
2021
;
64
(
11
):
596
8
. .
22.
Kappanayil
M
,
Balan
S
,
Alawani
S
,
Mohanty
S
,
Leeladharan
SP
,
Gangadharan
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
(
4
):
304
8
.
23.
Lima
AR
,
Cardoso
CC
,
Bentim
PR
,
Voloch
CM
,
Rossi
ÁD
,
da Costa
RM
,
MATERNAL SARS-COV-2 infection associated to systemic inflammatory response and pericardial effusion in the newborn: a case report
.
J Pediatr Infect Dis Soc
.
2020
;
10
(
4
):
536
9
.
24.
Magboul
S
,
Hassan
M
,
Al Amri
M
,
Alhothy
A
,
Almaslamani
E
,
Ellithy
K
,
Refractory multi-inflammatory syndrome in a two weeks old neonate with COVID-19 treated successfully with intravenous immunoglobulin, steroids and anakinra
.
Open Access J Microbiol Biotechnol
.
2020
;
5
(
4)
.
25.
Orlanski-Meyer
E
,
Yogev
D
,
Auerbach
A
,
Megged
O
,
Glikman
D
,
Hashkes
PJ
,
Multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus-2 in an 8-week-old infant
.
J Pediatr Infect Dis Soc
.
2020
;
9
(
6
):
781
4
.
26.
Saha
S
,
Pal
P
,
Mukherjee
D
.
Neonatal MIS-C: managing the cytokine storm
.
Pediatrics
.
2021
;
148
(
5
):
e2020042093
. .
27.
Schoenmakers
S
,
Snijder
P
,
Verdijk
RM
,
Kuiken
T
,
Kamphuis
SS
,
Koopman
LP
,
Severe acute respiratory syndrome coronavirus 2 placental infection and inflammation leading to fetal distress and neonatal multi-organ failure in an asymptomatic woman
.
J Pediatr Infect Dis Soc
.
2020
;
10
(
5
):
556
61
.
28.
Shaiba
LA
,
Hadid
A
,
Altirkawi
KA
,
Bakheet
HM
,
Alherz
AM
,
Hussain
SA
,
Case report: Neonatal multi-system inflammatory syndrome associated with SARS-COV-2 exposure in two cases from Saudi Arabia
.
Front Pediatr
.
2021
;
9
:
652857
.
29.
Yang
J
,
D’Souza
R
,
Kharrat
A
,
Fell
DB
,
Snelgrove
JW
,
Murphy
KE
,
COVID-19 pandemic and population-level pregnancy and neonatal outcomes: a living systematic review and meta-analysis
.
Acta Obstet Gynecol Scand
.
2021
;
100
(
10
):
1756
70
.
30.
Yang
Z
,
Wang
M
,
Zhu
Z
,
Liu
Y
.
Coronavirus disease 2019 (COVID-19) and pregnancy: a systematic review
.
J Matern Fetal Neonatal Med
.
2020
;
35
:
1619
22
. .
31.
McMurray
JC
,
May
JW
,
Cunningham
MW
,
Jones
OY
.
Multisystem inflammatory syndrome in children (MIS-C), a post-viral myocarditis and systemic vasculitis: a critical review of its pathogenesis and treatment
.
Front Pediatr
.
2020
;
8
:
626182
.
32.
Radia
T
,
Williams
N
,
Agrawal
P
,
Harman
K
,
Weale
J
,
Cook
J
,
Multi-system inflammatory syndrome in children & adolescents (MIS-C): a systematic review of clinical features and presentation
.
Paediatr Respir Rev
.
2021
;
38
:
51
7
.
33.
Antúnez-Montes
OY
,
Escamilla
MI
,
Figueroa-Uribe
AF
,
Arteaga-Menchaca
E
,
Lavariega-Sárachaga
M
,
Salcedo-Lozada
P
,
COVID-19 in South American children: a call for action
.
Pediatr Infect Dis J
.
2020
;
39
(
10
):
e332
4
.
34.
Consiglio
CR
,
Cotugno
N
,
Sardh
F
,
Pou
C
,
Amodio
D
,
Rodriguez
L
,
The immunology of multisystem inflammatory syndrome in children with COVID-19
.
Cell
.
2020
;
183
(
4
):
968
81.e7
.
35.
Zambrano
LD
,
Newhams
MM
,
Olson
SM
,
Halasa
NB
,
Price
AM
,
Boom
JA
,
Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA vaccination against multisystem inflammatory syndrome in children among persons aged 12–18 years: United States, July–December 2021
.
MMWR Morb Mortal Wkly Rep
.
2022
;
71
:
52
8
.
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