Is Multi System Inflammatory Syndrome Secondary to Covid (Mis-C) Same as Sepsis Associated Secondary Hlh?

ABSTRACT

Purpose: COVID 19 infection in children is generally mild,however some of them develop an unique immunological phenomenon called MIS-C(multi-system inflammatory syndrome, which is a hyperimmune state resulting in vasculitis,mycarditis and end organ damage.We compared immune status of MIS-C with another viral infection triggered hyperinflammtory state;sepsis hemophagocyticlymphohistiocytosis (SHLH) to understand the pathogenses of this novel clinical syndrome Methods: We included patients with MIS-C, SHLH and viral sepsis(S) Blood samples were collected after written informed consent, utilizing protocols approved by our institution. We evaluated differential leukocyte counts, soluble markers of T cell and macrophage activation (sIL-2R, sCD163 and Ferritin) in plasma and did immunophenotyping of T cells and monocytes on cryopreserved peripheral blood mononuclear cells Results: Total of 62 children (MIS-C 27, Sepsis 27 &SHLH 8) were included with age ranging from 1 to 16 years. Total leukocyte counts did not differ across the groups. MISC had higher neutrophil counts as compared to SHLH and sepsis.(Median cu/mm MIS-C -10062 SHLH-4434, S- 3138). Monocyte(M)and lymphocyte (L)numbers were comparable with SHLH but lesser than sepsis(Median M/L cummMISC- 390/1488, SHLH-252/1565, S-795/2841). Plasma levels of sIL-2R in MIS-C and SHLH were similarly elevated as opposed to sepsis(Median pg/ml MIS-C- 17824, SHLH- 25702, S - 3653). sCD163 levels was elevated highest in SHLH, followed by MIS-C and Sepsis (Median ng/ml SHLH- 2.18, MIS-C 0-96,S- 0.25). Similar trend was seen in proportions of activated T cells (HLADR+CD38+) across the groups (Median % SHLH 32.5, MIS-C- 4.31, S 1.14). Median CD4CD8 in MIS-C (2.5) is comparable to sepsis (1.2) but significantly higher than SHLH (0.75) There was no difference inmonocyte activation Conclusion(s)MIS-C is a hyperimmune state but the immune profile has features overlapping with SHLH and sepsis. It is a different hyperimmune syndrome as compared to SHLH and needs more mechanistic studies.