193 - VIROME ANALYSIS OF PLASMA FROM KAWASAKI DISEASE PATIENTS

BACKGROUND: Viral infections are suggested to contribute to Kawasaki disease (KD). Viral high-throughput sequencing (HTS) was employed on plasma samples from KD patients to identify potential viral agents. Plasma samples from children with febrile illness (FC) and Multisystem Inflammatory Syndrome in Children (MIS-C) were used as matched control groups in the study.

METHODS: Viral HTS was performed using the VirCapSeq-VERT (VCS) platform; a capture probes based viral enrichment method for sequencing all viruses of vertebrate origin. VCS provides 100-1000-folds sensitivity compared to traditional viral metagenomics HTS. We analyzed pre-treatment plasma from 43 KD patients [median age: 7.1y (5.8-8.3y), days post fever onset (DPFO): 5d (4.5d-7.0d)], 52 FC patients [median age: 6.1y (4.7y-8.2y), DPFO: 5d (3.8d-6.0d)], and 89 MISC patients [median age: 9.2y (5.7y-12.7y), DPFO: 5d (4d-6d)]. FC diagnoses included adenovirus (ADV) (n=17), other viral infections (n=6) and self-limited unexplained febrile illness (n=29). After sequencing (Illumina NextSeq2000) reads were preprocessed, host-genome-subtracted, assembled for contigs, and used for NCBI Megablast.

RESULTS: Approximately 7.6 million reads were generated for each sample. In the KD-group, 2 patients were positive for human herpesviruses (HHVs), 2 patients were positive for parvoviruses, 1 patient was positive for adenovirus (ADV), 1 patient was positive for human pegivirus (HPgV), and 1 patient was positive for human papillomavirus (HPV) (Table). The FC-group revealed the presence of ADV in 28 patients, enteroviruses in 2 patients, HHVs in 12 patients, HPV in 1 patient, parvoviruses in 2 patients, and Merkel-cell polyomavirus in 2 patients. In the MIS-C-group, plasma had reads for HHVs in 63 patients, HPV in 13 patients, parvovirus in 3 patients, HPgV in 3 patients, polyomaviruses in 10 patients, and vesicular stomatitis Indiana virus in 1 patient.
CONCLUSION: Viral detection in the KD group was lower than FC and MISC groups. No consistent viral sequences of known or a novel virus were detected in KD patients. We identified viral agents in plasma samples from 19 out of 23 (82.6%) FC patients with a previous viral diagnosis by PCR in respiratory swabs, and discovered viral agents in 16 out of 29 (55.2%) FC patients with unexplained febrile illness. The FC group showed a high rate of ADV viremia. MIS-C group had reads for HHVs, notably for Epstein Barr Virus, suggesting reactivation of latent HHVs in these patients. Viremia with a known human virus or novel virus with homology to a known virus is not a feature of acute KD.