Neonatal Multisystem Inflammatory Syndrome (MIS-N): The First Case Report in Thailand
Round 1
Reviewer 1 Report
Hypothesis: twin B likely experienced a SARS-CoV-2 infection prior to the development of MIS-N. There is literature indicating that SARS-CoV-2 can persist in patients (i.e., the mother) - this literature is not mentioned or cited. The article notes that the mother was asymptomatic 14 weeks earlier; infection of twin B from the mother can not be excluded. Alternatively, twin B acquired a SARS-CoV-2 infection post birth; this option is less likely with the onset of symptoms as early as 6 DOL.
There is published literature indicating that newborns may develop MIS-C (also MIS-N) with (1) SARS-CoV-2 infection and (2) maternally acquired antibodies. This literature was not cited.
Treatments for twin B included IVIG, methylprednisolone, and finally aspirin. These are the standard treatments that were worked out for Kawasaki Disease treatment. This article does not mention Kawasaki Disease. Published literature has suggested that MIS-N and MIS-C are both Kawasaki Disease associated with the SARS-CoV-2 virus. This literature was not cited. Published literature also indicates that MIS-N and MIS-C may be driven by viral activation of immune cells via Fc receptors. This provides a foundation for why IVIG provides benefits to these patients by diluting the antibodies bound to Fc receptors. Methylprednisolone targets immune cells. Finally, aspirin, which is normally not provided to children, is a known mast cell stabilizer and COX inhibitor.
This reviewer kindly suggests the authors consider relevant literature and if any additional citations should be included.
Author Response
The authors would like to thank the Editors for the suggestion. We have revised the manuscript as described below:
The authors have updated hypothesis in the discussion section (Page 4, line 157-163) include the published literature references [6-12].
The authors have updated published literature and potential management options in the discussion section (Page 4-5, line 192-199) include the references [13,14] as the reviewer suggestions.
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The authors sought to describe the case of a newborn with multisystem inflammatory syndrome. There is limited data in the literature on MIS-N, and this case report is helpful. The manuscript is nicely written. I primarily noticed a few differences between this case and older patients with MIS-C. That may be simply be a true difference between MIS-N and MIS-C, but it may be worth commenting upon: 1- Mother had COVID-19 at 19 weeks. The patient was born at 33 weeks and then developed symptoms on day of life 15. That would indicate symptom onset about 16 weeks after the initial SARS-CoV-2 exposure. That timing is different than in MIS-C when symptoms may represent 2-6 weeks later, often around 4 weeks. Is this timing similar to other reports of MIS-N in the literature? 2 - It's interesting and somewhat unusual that the C-reactive protein was normal in the baby, when it's nearly always elevated (and quite significantly elevated) in older children with MIS-C. Similar to the comment above, it would be helpful to comment about this difference to MIS-C and if this finding is reported in the literature elsewhere. Excellent job!Author Response
The authors would like to thank the Editors for the suggestion. Please see the attachment.
- The authors have updated that “The symptoms onset of twin B was about 15 weeks after the initial SARS-CoV-2 exposure, similar to the case series of MIS-N report that the symptoms may represent 2-20 weeks (median 6 weeks) later.” in the discussion section (Page 4, line 170-172) include the references [3].
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The authors have updated for laboratory testing report from a systematic review of MIS-N that found elevated C-reactive protein in 65% in the discussion section (Page 4, line 173-174) include the references [9].
Author Response File: Author Response.pdf
