Search

Background: Few studies highlight the stratification of COVID-19 vaccine effectiveness on MIS-C according to vaccine status, types and SARS-COV-2 variants., Methods: A web-based analysis was conducted through searches of PubMed, Web of Science and Medline databases from January 1, 2020, to May 16, 2023. The search terms used were (multisystem inflammatory syndrome in children OR MIS-C OR PIMS OR PIMS-TS) AND (COVID-19 OR SARS-CoV-2) AND (vaccine OR vaccination) AND (children OR adolescents OR pediatric)., Results: 6701 children from 13 studies met the MIS-C definition. 92.1 % (1332/1446) of MIS-C cases were unvaccinated, whereas partial vaccination and full vaccination were 3.7 % (54/1446) and 4.2 % (60/1446)respectively. In the two studies encompassing 41 vaccinated MIS-C cases, 34 (82.9 %) received BNT162b2, 2 (4.9 %) received mRNA-1273, 4 (9.8 %) received Sinovac vaccine, and only one received a heterologous primary-boost regimen. Among 838 vaccinated MIS-C cases with different SARS-COV-2 variants, 23（2.8 %） were infected by the Wild-type, 80（9.5 %） by the Alpha variant, 521（62.2 %） by the Delta variant, and 214（25.5 %） by the Omicron variant. A significant difference was observed in vaccination rates among MIS-C cases across different variant pandemics (χ 2  = 37.79, P < 0.001). The highest vaccination rate (26.3 %) occurred in the Alpha predominant period, thereafter dropped to 5.0 % in the Delta predominant period, and then increased to 12.6 % in the Omicron predominant period., Conclusions: Heterologous vaccination might provide a slightly more protective effect than homologous manner for MIS-C. As the virus mutates over time, its pathogenicity to MIS-C degrades among vaccinated individuals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Microglial phenotype alternation is a potential novel pathogenic mechanism for cerebral ischemia. Cerebral ischemia induced autophagy aggravates inflammation and neural injury. However, the effect of autophagy in the modulation of microglial phenotype is still unknown. In this study, we investigated the role of autophagic flux in the alternation of microglial phenotype following oxygen glucose deprivation/reperfusion (OGD/R) in BV-2 cells. Inhibition of autophagic flux by NH4Cl exposure significantly increased the level of microtubule-associated protein 1 light chain 3 (LC3)-II and p62 in control and OGD/R (12h, 24h and 48h) groups, but did not change their expression in OGD/R 72h group, indicating that autophagic flux was inhibited at OGD/R 72h. Once autophagic flux was inhibited at OGD/R 72h or at OGD/R 24h (with NH4Cl), BV-2 cells mainly showed M1 phenotype with increased tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and decreased M2 markers including interleukin-10 (IL-10), Arginase 1 (Arg-1), and brain derived neurotrophic factor (BDNF). Further study indicated that inhibition of autophagic flux activated NF-κB pathway and decreased the activity of cAMP-response element binding protein (CREB), which contributed to the alternation of microglial phenotype. Therefore, inhibition of autophagic flux regulated the alternation of microglial phenotype by modulating the balance between NF-κB and CREB., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Resident microglia are the major immune cells in the brain, acting as the first defense of the central nervous system. Following cerebral ischemia, microglia respond to this injury at first and transform from surveying microglia to active state. The activated microglia play a dual role in the ischemic injury, due to distinct microglia phenotypes, including deleterious M1 and neuroprotective M2. However, microglia show transient M2 phenotype followed by a shift to M1. The high ratio of M1 to M2 is significantly related to ischemic injury. Many signal pathways participate in the alternation of microglial phenotype, presenting potential therapeutic targets for selectively modulating M2 polarization of microglia. In this review, we discuss how the M2 phenotype mediates neuroprotective effects and summarize the alternation of signaling cascades that control microglial phenotype after ischemic stroke., (Copyright © 2015. Published by Elsevier B.V.)