Discussion

This case report presents a neonate with prenatal exposure to the SARS-CoV2 virus, leading to fulminant myocarditis, cardiac arrhythmia, acute hepatic injury, and renal failure. The excellent response to immunotherapy is consistent with the current definition of multisystem inflammatory syndrome.

Currently, the diagnosis of PIMS-TS is complicated for two main reasons: firstly, there are no unified case definitions casting speculation on reported diagnoses. ^{Reference Rhys-Evans3} Secondly, vertical transmission in neonates has been reported, but confirmation is complex. The diagnostic criteria for the confirmation of congenital infection in neonates include clinical features of infection in neonates and mothers with SARS-CoV2 infection or detection of the virus by polymerase chain reaction in umbilical cord blood or neonatal blood collected within the first 12 hours of birth or amniotic fluid collected prior to rupture of the membrane. ^{Reference Shah, Diambomba and Acharya4} The case we are presenting does not meet these criteria. However, since there was a known asymptomatic infection diagnosed in the mother in the late third trimester and no other SARS-CoV2-positive contacts were reported, the possibility of vertical transmission in this case still needs to be discussed.

A recent report summarises direct and serological evidence of vertical transmission in more than 40 neonatal cases consistent with the definition criteria for PIMS-TS, mainly presenting with features of severe cardiogenic shock due to structural damage to the myocardium. ^{Reference Lakshminrusimha, Hudak, Dimitriades and Higgins5} Given the emerging evidence, the term PIMS-TS is gaining interest amongst researchers and may have future implications, since it reflects immune-mediated effects of previous in utero COVID-19 infection, clearly distinguishing the former from postpartum viral transmission. It is important to differentiate the two, since paediatric inflammatory multisystem syndrome may have different time frames and different presentations in cases of SARS-CoV2 exposure in utero compared to postpartum exposure. ^{Reference Lakshminrusimha, Hudak, Dimitriades and Higgins5,Reference More, Aiyer and Goti6} According to the British Congenital Cardiac Association recommendations, stable at birth, not requiring surgery, or catheter intervention CHD infants are not estimated to be at a higher risk of cardiac compromise due to COVID-19 infection but have an increased risk for a negative outcome. ^{Reference Sendzikaite, Heying and Milanesi7} However, in the context of PIMS-TS, where the majority of affected infants seem to be prone to cardiac dysfunction, ^{Reference Lakshminrusimha, Hudak, Dimitriades and Higgins5,Reference More, Aiyer and Goti6,Reference Pawar, Gavade and Patil8} neonates with CHD previously exposed to SARS-CoV2 infection should be monitored with more caution.

The pathogenesis of PIMS-TS is also poorly understood. SARS-CoV-2 infection causes the production of virus-specific antibodies. However, in genetically susceptible individuals, cross-reactive antibodies may form, leading to the activation and secretion of pro-inflammatory cytokines and resulting in the development of PIMS-TS. ^{Reference Kabeerdoss, Pilania and Karkhele9} This explains in part the efficacy of immunomodulation. However, some aspects of susceptibility and prevention are currently unknown.

Although the use of maternal SARS-CoV2 vaccines prior to or during pregnancy has not been systemically evaluated, it may have a role in the prevention of paediatric inflammatory multisystem syndrome. A large case series of PIMS-TS reported that none of the mothers of the ill neonates had been vaccinated. ^{Reference Pawar, Gavade and Patil8} In contrast, preliminary safety reports of vaccinated mothers during pregnancy reported no PIMS-TS cases and no neonatal deaths related to COVID-19 and its mediated syndromes. ^{Reference Shimabukuro, Kim and Myers10} On the other hand, transplacental transmission of antibodies against SARS-CoV2 may encourage the overdiagnosis of PIMS-TS and miss out on other neonatal diseases leading to poor outcomes, especially when immunomodulation is considered. Therefore, more longitudinal clinical trials might be helpful to create a unified protocol with new diagnostic aids specific to neonates with CHD. ^{Reference Rhys-Evans3}