儿童感染新冠病毒后,肠屏障受损可能导致多系统炎症综合征
创作:aluba 审核:aluba 06月08日
  • 纳入19名MIS-C患儿、26名急性COVID-19患儿及55名对照;
  • 在MIS-C患儿中,新冠病毒在胃肠道的长期存在导致连蛋白释放(肠道通透性增加的生物标志物),伴随着新冠病毒抗原从肠道进入血液,从而造成过度的炎症应答;
  • 使用拉瑞唑来(一种连蛋白拮抗剂)治疗可降低MIS-C患儿血浆中的新冠病毒Spike抗原及炎症标志物的水平,并改善发热、胃肠道症状及通气状态。
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aluba
部分儿童感染新冠病毒后,可能发展出多系统炎症综合征(MIS-C),但发病机制尚未明确。Journal of Clinical Investigation上发表的一项最新研究发现,新冠病毒感染后,肠道上皮细胞释放的连蛋白造成肠道通透性增加,以促进新冠病毒抗原从肠道进入血液,从而导致了过度的炎症应答。利用连蛋白拮抗剂(拉瑞唑来,larazotide)治疗,可降低MIS-C患儿血浆中的新冠病毒Spike抗原水平,缓解炎症应答并有效缓解症状。
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Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier

连蛋白依赖性肠道粘膜屏障受损驱动儿童多系统炎症综合征

10.1172/JCI149633

05-25, Article

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BACKGROUND: Weeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called Multisystem Inflammatory Syndrome in Children (MIS-C). Gastrointestinal symptoms are common in MIS-C patients and severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not previously been identified.
METHODS: Here, we analyzed biospecimens from 100 children: 19 children with MIS-C, 26 with acute COVID-19, and 55 controls. Stool was assessed for SARS-CoV-2 by RT-PCR and plasma was assessed for markers of breakdown of mucosal barrier integrity, including zonulin. Ultrasensitive antigen detection was used to probe for SARS-CoV-2 antigenemia in plasma, and immune responses were characterized. As proof of concept, we treated a MIS-C patient with larazotide, a zonulin antagonist, and monitored impact on antigenemia and clinical response.
RESULTS: We showed that in MIS-C, prolonged presence of SARS-CoV-2 in the GI tract leads to release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. The MIS-C patient treated with larazotide displayed a coinciding decrease in plasma SARS-CoV-2 Spike antigen levels, inflammatory markers, and a resultant clinical improvement above that achieved with currently available treatments.
CONCLUSION: These mechanistic data of MIS-C pathogenesis provide insight into targets for diagnosing, treating, and preventing MIS-C, which are urgently needed for this increasingly common severe COVID-19-related disease in children.

First Authors:
Lael M Yonker,Tal Gilboa,Alana F Ogata

Correspondence Authors:
David R Walt,Alessio Fasano

All Authors:
Lael M Yonker,Tal Gilboa,Alana F Ogata,Yasmeen Senussi,Roey Lazarovits,Brittany P Boribong,Yannic C Bartsch,Maggie Loiselle,Magali Noval Rivas,Rebecca A Porritt,Rosiane Lima,Jameson P Davis,Eva J Farkas,Madeleine D Burns,Nicola Young,Vinay S Mahajan,Soroush Hajizadeh,Xcanda I Herrera Lopez,Johannes Kreuzer,Robert Morris,Enid E Martinez,Isaac Han,Kettner Griswold,Nicholas C Barry,David B Thompson,George Church,Andrea G Edlow,Wilhelm Haas,Shiv Pillai,Moshe Arditi,Galit Alter,David R Walt,Alessio Fasano

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