Multisystem Inflammatory Syndrome in Neonates Born to Mothers with SARS-CoV-2 Infection (MIS-N) and in Neonates and Infants Younger Than 6 Months with Acquired COVID-19 (MIS-C): A Systematic Review

Abstract

(1) Introduction: There is an increasing literature describing neonates born to mothers with SARS-CoV-2 infection (MIS-N) and infants infected with SARS-CoV-2 who presented with a severe disease (MIS-C). (2) Methods: To investigate clinical features of multisystem inflammatory syndrome in neonates and infants under six months of age, we used a systematic search to retrieve all relevant publications in the field. We screened in PubMed, EMBASE and Scopus for data published until 10 October 2021. (3) Results: Forty-eight articles were considered, including 29 case reports, six case series and 13 cohort studies. Regarding clinical features, only 18.2% of MIS-N neonates presented with fever; differently from older children with MIS-C, in which gastrointestinal symptoms were the most common manifestation, we displayed that cardiovascular dysfunction and respiratory distress are the prevalent findings both in neonates with MIS-N and in neonates/infants with MIS-C. (4) Conclusions: We suggest that all infants with suspected inflammatory disease should undergo echocardiography, due to the possibility of myocardial dysfunction and damage to the coronary arteries observed both in neonates with MIS-N and in neonates/infants with MIS-C. Moreover, we also summarize how they were treated and provide a therapeutic algorithm to suggest best management of these fragile infants.

Maternal COVID-19 Vaccine May Reduce the Risk of MIS-C in Infants: A Narrative Review

“…[4] Incidence in newborns and infants is unknown due to scarcity of data and difficulty in diagnosis as newborns could be afebrile and due to many overlapping symptoms, it can be difficult to differentiate MIS-C from sepsis in early infancy. [8]Although there are only a few cases reported so far, risk of cardiac complications and critical illness is high in this population, with very high mortality of 12.5% reported in infants 0-6 months. [4,8] MIS-C is temporally associated with current or prior SARS-Cov-2 infection, but the exact pathogenesis of MIS-C is not fully understood.…”

“…[45] In a systematic meta-analysis, DeRose et al analyzed 48 studies which include 29 case reports, 6 case series and 13 cohort studies. [8] They identified 25 papers which included a total 32 cases of MIS-C in the form of case studies in infants aged 0-6 months. Additionally, 31 infants 0-6 months with MIS-C were identified in existing 12 cohort studies which included total 1062 children 0-18 years old.…”

“…[46] MIS-N is the proposed definition for infants born to mothers with SARS Cov-2 infection by some clinicians but there is no formal definition of MIS-N. Based on this proposed definition, Del Rose et al identified 33 neonates with MIS-N and interestingly only 18.2% had fever as compared to fever as a major criterion in diagnosis of MIS-C in children. [8] The true incidence of MIS-C is not known. Based on a multicenter study of a large cohort in the United States, the cumulative incidence of MIS-C in those younger than 21 years of age was 2.1 per 100,000 persons, with a mortality rate of 1.4%.…”

“…As per the latest systematic analysis, a total 90 cases of MIS-C and MIS-N were identified in 0-6 months infants. [8]. However, there is no formal definition of MIS-N, and this term is used by some clinicians for case identification in neonates born to SARS-CoV 2 positive mothers.…”

“…However, there is no formal definition of MIS-N, and this term is used by some clinicians for case identification in neonates born to SARS-CoV 2 positive mothers. [8,9] Both vertical and horizontal transmission of SARS-CoV-2 virus is the proposed etiology for MIS-C in infants.…”