Inflammatory parameters distinguish severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pediatric presentations, coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C)

ABSTRACT

Purpose: Pediatric SARS-CoV-2 infections result in at least three distinct disease manifestations. Most children infected acutely remain asymptomatic or develop only mild symptoms of COVID-19;however, small proportion of acutely infected children, develop progressive respiratory illness, multi-organ involvement, and an associated hyperinflammatory syndrome. These COVID-19 presentations are contrasted by MIS-C, a post-infectious hyperinflammatory condition characterized by fever, shock, and multi-organ dysfunction. We sought to characterize the hyperinflammatory syndromes of SARS-CoV-2 infections, in order to identify biomarkers that may distinguish the hyperinflammation seen in these conditions from that of HLH. Methods:We enrolled children admitted to the Children's Hospital of Philadelphia who had positive SARS-CoV-2 RT-PCR tests or met clinical criteria for MIS-C.We measured plasma levels of 10 cytokines on a MesoScale Discovery platform and correlated these values with available clinical parameters of inflammation. Results: Fifty patients were classified into asymptomatic/mild COVID- 19 (amC19;N = 18), severe COVID-19 (sevC19;N = 11), or MISC (MIS-C;N = 21). Five cytokines (IL-1beta, IL-2, IL-4, IL-12p70 and IL-13) were excluded from further analyses, as their levels were not abnormal. Of the remaining (IL-6, IL-8, IL-10, TNF-alpha and IFNgamma) thatwere often elevated, we found statistically significant elevations in IL-10 in both sevC19 andMIS-C, when compared to amC19 patients. Some patients in each cohort had markedly elevated IFNgamma, but the cohort means were not statistically different. While the maximal C-reactive protein levels were elevated in both sevC19 and MIS-C, these were not statistically different,while maximal ferritin levels differentiated sevC19 from amC19 andMIS-C. Conclusion: While the pathogenesis of pediatric COVID-19 andMIS-C are not fully elucidated, differences between observed biomarkers suggest that the immune pathogenesis of the hyperinflammation in these syndromes is likely to be mechanistically different, although overlap may exist with HLH in some patients.