P4A220: Understanding Inflammatory Response in Non-covid Viral Infections

Background: Viral pathogens are a major cause of illness in the pediatric population. Prior to 2020, extensive lab workups were rare as most viral illnesses resolve with supportive care. After the emergence of COVID-19, there was a small subset of patients who developed Multisystem Inflammatory Syndrome in Children (MIS-C). Due to severity of expected sequelae of MIS-C, laboratory and clinical biomarkers for this inflammatory syndrome were obtained more regularly, often prior to confirming current or prior SARS CoV2 infection. Many of these tests are shared with septic workups due to the inflammatory nature of sepsis regardless of the original pathogen, viral, bacterial, or fungal. Importantly, not all systems may be impacted at the time of presentation of both classical viral sepsis and MIS-C.

Methods: We did a retrospective chart analysis and received all positive BioFire respiratory pathogen panel (RPP) results with no other identified sources of infection from March 2020-October 2022 in pediatric patients.

Our institution separated suspected MIS-C workup into tier 1 and tier 2 labs after identifying patients with one or more days of fever, more than one system of involvement, and no otherwise identified source of infection. Our tier one labs included CRP or ESR, ALC, ANC, platelets, sodium, and albumin. Our tier two labs included troponin, BNP, ferritin, d-dimer, fibrinogen, hemoglobin, ALT, INR, aPTT, and Cr. Figure 1 provides our institution’s guidelines and cutoffs for MIS-C test criteria.

A patient was considered hyperinflammatory if they had > 3 markers of inflammation. Individual patient workups were directed by the patient’s clinical status, therefore not all labs or markers were obtained for all patients. The study received IRB approval from all relevant institutions.

Results: We received 5,421 samples who had a positive RPP. Samples were separated out if they were co-positive with COVID-19 or were COVID-IgG +. Table 1 shows the number of samples for each virus (or the total sample pool) that reached >3 inflammatory markers. Only pathogens with greater than 50 samples are reported.

COVID + showed >3 inflammatory markers 17% of the time in this sample set. Three collections of viruses on the panel (Human metapneumovirus, Adenovirus, and Rhinovirus/Enterovirus) all showed higher propensity to have a hyper-inflammatory state relative to the entire sample. Due to the prevalence of Rhinovirus/Enterovirus, this class had the highest actual number of samples flagged for hyperinflammation. Our data also shows that previous seasonal Coronaviruses NL63 and OC43 were not frequently hyperinflammatory.

Conclusion: This work helps lay the groundwork for assessing expected levels of inflammation triggered by acute infection of “common cold” viruses. This will help separate future novel viral illnesses and their potential sequelae from the more well-known viral illnesses that occur every year.