Transcriptomic analysis of neuroinflammation and occult infection in sudden infant death syndrome

Antemortem infection is a risk factor for sudden infant death syndrome (SIDS) – the leading postneonatal cause of infant mortality in the developed world. Manifestations of infection and attendant inflammation, however, are not always apparent in clinical settings or by standard autopsy, thus enhanced resolution approaches are needed. Here we screened postmortem SIDS tissues and fluids for inflammatory markers and applied metagenomics and transcriptomics to a subset of cases to look for evidence of occult infection and inflammation. Postmortem fluids from a cohort of SIDS and controls collected between 2012 and 2018 were screened for elevated inflammatory markers, specifically cerebrospinal fluid (CSF) neopterin and CSF and serum cytokines. Postmortem brain and liver tissue and CSF from 6 SIDS cases with high levels of neopterin ("inflammatory SIDS"), as well as 3 non-inflammatory SIDS cases were subjected to metagenomic next generation sequencing (mNGS; see BioProject PRJNA1021781 for data). Human parechovirus 3 (HPeV3) was detected in all tissues profiled of a single case (HPeV3+ SIDS), but no pathogens were detected in the other cases or controls. Brainstem tissue (at the level of obex+2mm) from the HPeV3+ SIDS case and 3 non-inflammatory SIDS cases was analyzed by single nucleus RNA sequencing (snRNAseq) to measure cell type-specific gene expression associated with neuroinflammation and infection (the data presented in this submission)