Search

Background/Objectives: Multisystem Inflammatory Syndrome in Children (MIS-C) is a post-infectious complication of COVID-19. MIS-C has overlapping features with other pediatric inflammatory disorders including Kawasaki Disease (KD), Macrophage Activation Syndrome (MAS), Toxic Shock Syndrome and sepsis. The exact mechanisms responsible for the clinical overlap between MIS-C and these conditions remain unclear, and biomarkers that could distinguish MIS-C from its clinical mimics are lacking. This study aimed to provide an overview of how proteomic methods, like Mass Spectrometry (MS) and affinity-based proteomics, can offer a detailed understanding of pathophysiology and aid in the diagnosis and prognosis of MIS-C. Methods: A narrative review of relevant studies published up to July 2024 was conducted. Results: We identified 15 studies and summarized their key proteomic findings. These studies investigated the serum or plasma proteome of MIS-C patients using MS, Proximity Extension, or Aptamer-based assays. The studies associated the proteomic profile of MIS-C with laboratory and clinical parameters and/or compared it with that of other diseases including acute COVID-19, KD, MAS, pediatric rheumatic diseases, sepsis and myocarditis or pericarditis following COVID-19 mRNA immunization. Depending on the method and the control group, different proteins were increased or decreased in the MIS-C group. The limitations and challenges in MIS-C proteomic research are also discussed, and future research recommendations are provided. Conclusions: Although proteomics appear to be a promising approach for understanding the pathogenesis and uncovering candidate biomarkers in MIS-C, proteomic studies are still needed to recognize and validate biomarkers that could accurately discriminate MIS-C from its clinical mimics.

This is a SARS-CoV-2 seroepidemiological study in a pediatric population (0–16 years) during the BA.5 Omicron predominance period in the Athens metropolitan area. Serum samples were tested for SARS-CoV-2 nucleocapsid antibodies (Abs-N), representing natural infection during three periods of BA.5 predominance: 1 May 2022–31 August 2022 (period A), 1 September 2022–31 December 2022 (period B), and July 2023 (period C). Εpidemiological data were also collected. Additionally, in period C, Abs-N-seronegative samples were tested for SARS-CoV-2 spike antibodies (Abs-S). A total of 878 children were tested (males: 52.6%), with a median age (IQR) of 96 (36–156) months; the number of cases of seropositivity during the three periods were as follows: A: 292/417 (70%), B: 288/356 (80.9%), and C: 89/105 (84.8%), with p < 0.001. SARS-CoV-2 seropositivity increased from period A to C for children 0–1 year (p = 0.044), >1–4 years (p = 0.028), and >6–12 years (p = 0.003). Children > 6–12 years had the highest seropositivity rates in all periods (A: 77.3%, B: 91.4%, and C: 95.8%). A significant correlation of monthly median Abs-N titers with monthly seropositivity rates was detected (rs: 0.812, p = 0.008). During period C, 12/105 (11.4%) Abs-S-seropositive and Abs-N-seronegative samples were detected and total seropositivity was estimated at 96.2% (101/105). The findings of this study indicate a high SARS-CoV-2 exposure rate of children during the BA.5 predominance period and suggest that in future seroepidemiological studies, both antibodies should be tested in Abs-N-seronegative populations.

To prospectively study the kinetics of immune responses after immunization with the BNT162b2 mRNA COVID-19 vaccine and their association with epidemiological parameters and breakthrough infection (BI), we measured total (TAbs-WT) and neutralizing antibodies against wild-type (NAbs-WT) and Omicron (NAbs-O) SARS-CoV-2 spike proteins in healthcare workers (HCWs) after the second (4 and 8 months) and third dose (1 and 8 months). Vaccinated HCWs (n = 486), with a median age (IQR) of 49 years (38–56), were included in this prospective cohort study. BI was observed 4 and 8 months after the second dose in 8/486 (1.6%) and 15/486 (3.1%) HCWs, respectively, and 1 and 8 months after the third dose in 17/486 (3.5%) and 152/486 (31.3%) HCWs, respectively. A comparison of immune responses 1 month after the third dose in vaccinated HCWs without a BI or with a BI in the next 7 months did not detect any statistically significant differences in the TAbs-WT (median (IQR): 16,611.0 (13,011.0) U/mL vs. 17,572.5 (14,501.0) U/mL, p = 0.529) and NAbs-WT (median (IQR): 96.5% (1.7) vs. 96.7% (1.9), p = 0.555). After infection, HCWs with a BI had significantly increased TAbs-WT levels at all time points compared to healthy HCWs. The findings of the present study indicate that antibody levels after three doses of the BNT162b2 vaccine are not directly associated with the possibility of a BI.