{"id":13496,"date":"2025-03-07T15:00:12","date_gmt":"2025-03-07T15:00:12","guid":{"rendered":"https:\/\/www.drfz.de\/?p=13496"},"modified":"2025-03-13T14:23:29","modified_gmt":"2025-03-13T14:23:29","slug":"ebv-reactivation-as-a-key-mechanism-of-mis-c-after-sars-cov-2-infection","status":"publish","type":"post","link":"https:\/\/www.drfz.de\/en\/neuigkeiten\/ebv-reactivation-as-a-key-mechanism-of-mis-c-after-sars-cov-2-infection\/","title":{"rendered":"EBV reactivation as a key mechanism of MIS-C after SARS-CoV-2 infection"},"content":{"rendered":"\n

Why children become seriously ill weeks after a Covid-19 infection and how they can be cured<\/h3>\n\n\n\n

Researchers from Dr. Mir-Farzin Mashreghi\u2019s group from the German Rheumatology Research Center Berlin (DRFZ), a Leibniz Institute, and Prof. Dr. Tilmann Kallinich\u2019s group from Charit\u00e9 – Universit\u00e4tsmedizin Berlin and Liaison-Group leader at DRFZ, have gained important insights into multisystemic inflammatory syndrome in children (MIS-C). This rare but severe disease occurs 4 to 8 weeks after a SARS-CoV-2 infection and is caused by impaired reactivity of memory T cells. The cytokine TGF-\u03b2 plays a central role here: it impairs the function of T cells, triggers reactivation of the Epstein-Barr virus (EBV) and amplifies the systemic inflammatory reaction. A targeted blockade of TGF-\u03b2 was able to effectively interrupt these mechanisms in the study. The results were published in the high-ranking journal Nature<\/em>.<\/p>\n\n\n\n

The joint DRFZ and Charit\u00e9 study shows that acute MIS-C is characterised by a significant restriction of the reactivation of virus-reactive memory T cells. This dysfunction is caused by elevated serum TGF-\u03b2 levels, as observed in severe COVID-19 cases in adults. \u201cAs a result, T cell-mediated surveillance and elimination of latent viruses, especially EBV, is severely impaired\u201d, the first author, Dr. Carl Christoph Goetzke emphasizes.<\/p>\n\n\n\n

The researchers found that in MIS-C patients, a specific T cell expansion of EBV-reactive cells occurred, which were unable to eliminate infected cells due to the increased TGF-\u03b2 levels. At the same time, the high TGF-\u03b2 levels led to reactivation of EBV in B lymphocytes. This uncontrolled multiplication of the virus contributed decisively to the severe systemic inflammatory reaction. By blocking TGF-\u03b2, the functionality of the T cells was restored and EBV reactivation in infected B lymphocytes was prevented.<\/p>\n\n\n\n

The impairment of T cell reactivity caused by TGF-\u03b2 clearly correlates with an increased EBV concentration in activated B lymphocytes from the blood. Children who developed MIS-C after a SARS-CoV-2 infection were more likely to have antibodies against EBV in their blood than control groups of the same age who had also undergone a SARS-CoV-2 infection but did not develop MIS-C. A key finding from this observation is that children with latent EBV have an increased risk of developing MIS-C after a SARS-CoV-2 infection.<\/p>\n\n\n\n

The results of the study highlight the complex relationships between SARS-CoV-2 infections and secondary diseases, especially in children. They also provide valuable information for the development of targeted therapies for the treatment of MIS-C and other post-COVID-19 diseases that may be associated with EBV reactivation.<\/p>\n\n\n\n

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Press release by Charit\u00e9<\/a><\/div>\n<\/div>\n\n\n\n
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\n \n Original publication<\/a>\n\n Goetzke, C.C., Massoud, M., Frischbutter, S. et al. TGF\u03b2 links EBV to multisystem inflammatory syndrome in children. Nature (2025). https:\/\/doi.org\/10.1038\/s41586-025-08697-6<\/span>\n \n \n <\/span>\n <\/a>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/section>\n\n\n\n\n
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\n \n Related publication<\/a>\n\n Ferreira-Gomes M, Kruglov A, Durek P, Heinrich F, Tizian C, Heinz GA, Pascual-Reguant A, Du W, Mothes R, Fan C, Frischbutter S, Habenicht K, Budzinski L, Ninnemann J, Jani PK, Guerra GM, Lehmann K, Matz M, Ostendorf L, Heiberger L, Chang HD, Bauherr S, Maurer M, Sch\u00f6nrich G, Raftery M, Kallinich T, Mall MA, Angermair S, Treskatsch S, D\u00f6rner T, Corman VM, Diefenbach A, Volk HD, Elezkurtaj S, Winkler TH, Dong J, Hauser AE, Radbruch H, Witkowski M, Melchers F, Radbruch A, Mashreghi MF. SARS-CoV-2 in severe COVID-19 induces a TGF-\u03b2-dominated chronic immune response that does not target itself. Nat Commun. 2021 Mar 30;12(1):1961. doi: 10.1038\/s41467-021-22210-3. PMID: 33785765; PMCID: PMC8010106.<\/span>\n \n \n <\/span>\n <\/a>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/section>\n\n\n\n\n
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\n \n Related publication<\/a>\n\n Witkowski M, Tizian C, Ferreira-Gomes M, Niemeyer D, Jones TC, Heinrich F, Frischbutter S, Angermair S, Hohnstein T, Mattiola I, Nawrath P, McEwen S, Zocche S, Viviano E, Heinz GA, Maurer M, K\u00f6lsch U, Chua RL, Aschman T, Meisel C, Radke J, Sawitzki B, Roehmel J, Allers K, Moos V, Schneider T, Hanitsch L, Mall MA, Conrad C, Radbruch H, Duerr CU, Trapani JA, Marcenaro E, Kallinich T, Corman VM, Kurth F, Sander LE, Drosten C, Treskatsch S, Durek P, Kruglov A, Radbruch A, Mashreghi MF, Diefenbach A. Untimely TGF\u03b2 responses in COVID-19 limit antiviral functions of NK cells. Nature. 2021 Dec;600(7888):295-301. doi: 10.1038\/s41586-021-04142-6. Epub 2021 Oct 25. PMID: 34695836. <\/span>\n \n \n <\/span>\n <\/a>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/section>\n\n\n\n\n
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\n \n Related publication<\/a>\n\n Ferreira-Gomes M, Chen Y, Durek P, Rincon-Arevalo H, Heinrich F, Bauer L, Szelinski F, Guerra GM, Stefanski AL, Niedobitek A, Wiedemann A, Bondareva M, Ritter J, Lehmann K, Hardt S, Hipfl C, Hein S, Hildt E, Matz M, Mei HE, Cheng Q, Dang VD, Witkowski M, Lino AC, Kruglov A, Melchers F, Perka C, Schrezenmeier EV, Hutloff A, Radbruch A, D\u00f6rner T, Mashreghi MF. Recruitment of plasma cells from IL-21-dependent and IL-21-independent immune reactions to the bone marrow. Nat Commun. 2024 May 17;15(1):4182. doi: 10.1038\/s41467-024-48570-0. PMID: 38755157; PMCID: PMC11099182.<\/span>\n \n \n <\/span>\n <\/a>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/section>\n\n\n\n\n
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\n \n Related publication<\/a>\n\n Frischbutter S, Durek P, Witkowski M, Angermair S, Treskatsch S, Maurer M, Radbruch A, Mashreghi MF. Serum TGF\u03b2 as a predictive biomarker for severe disease and fatality of COVID-19. Eur J Immunol. 2023 Jun 30:e2350433. doi: 10.1002\/eji.202350433. Epub ahead of print. PMID: 37386908.<\/span>\n \n \n <\/span>\n <\/a>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/section>\n\n\n\n\n
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Group leaders involved<\/h2>\n \n <\/div>\n \n
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\n \"\" <\/div>\n
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Dr. Mir-Farzin Mashreghi<\/h2>\n
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\n Leader: Programme Area 3, PA 3 \u2013 Systems Rheumatology <\/p>\n

\n Group leader: Therapeutic Gene Regulation <\/p>\n <\/div>\n <\/div>\n\n

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mashreghi@drfz.de<\/a><\/p>\n <\/div>\n Dr. Mir-Farzin Mashreghi<\/span><\/a>\n<\/article>\n\n

\n \"\" <\/div>\n
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Prof. Dr. med. Tilmann Kallinich<\/h2>\n
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\n Programme Area 3, PA 3 \u2013 Systems Rheumatology <\/p>\n

\n Group leader: Chronic inflammation in childhood <\/p>\n Liaison working group with Charit\u00e9 – Dep. of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine<\/p>\n <\/div>\n <\/div>\n\n

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tilmann.kallinich@charite.de<\/a><\/p>\n <\/div>\n Prof. Dr. med. Tilmann Kallinich<\/span><\/a>\n<\/article> <\/div>\n <\/div>\n <\/section>\n\n\n\n

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Reactions from the media & press<\/h2>\n \n \n
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\n \n Spiegel\/Wissenschaft<\/a>\n\n \n \n <\/span>\n <\/a>\n <\/div>\n
\n \n Tagesspiegel<\/a>\n\n \n \n <\/span>\n <\/a>\n <\/div>\n
\n \n Tagesschau.de<\/a>\n\n \n \n <\/span>\n <\/a>\n <\/div>\n
\n \n Zeit<\/a>\n\n \n \n <\/span>\n <\/a>\n <\/div>\n
\n \n Frankfurter Allgemeine<\/a>\n\n \n \n <\/span>\n <\/a>\n <\/div>\n
\n \n Stern<\/a>\n\n \n \n <\/span>\n <\/a>\n <\/div>\n
\n \n Welt.de<\/a>\n\n \n \n <\/span>\n <\/a>\n <\/div>\n
\n \n Bild<\/a>\n\n \n \n <\/span>\n <\/a>\n <\/div>\n
\n \n Geo<\/a>\n\n \n \n <\/span>\n <\/a>\n <\/div>\n
\n \n Deutschlandfunk<\/a>\n\n \n \n <\/span>\n <\/a>\n <\/div>\n
\n \n rbb24<\/a>\n\n \n \n <\/span>\n <\/a>\n <\/div>\n
\n \n Blick<\/a>\n\n \n \n <\/span>\n <\/a>\n <\/div>\n
\n \n Swiss Info<\/a>\n\n \n \n <\/span>\n <\/a>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/section>\n\n","protected":false},"excerpt":{"rendered":"

Why children become seriously ill weeks after a Covid-19 infection and how they can be cured Researchers from Dr. Mir-Farzin Mashreghi\u2019s group from the German\u2026<\/p>\n","protected":false},"author":4,"featured_media":13936,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[288,291],"tags":[421,468,475,496,426],"programme-area-tax":[181],"working-group-tax":[244,258],"class_list":["post-13496","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-for-patients","category-publications","tag-chronic-inflammatory-diseases-of-childhood-adolescence","tag-kallinich","tag-mashreghi-en","tag-program-area-3","tag-therapeutic-gene-regulation","programme-area-tax-programme-area-3","working-group-tax-chronic-inflammation-in-childhood","working-group-tax-therapeutic-gene-regulation"],"acf":[],"yoast_head":"\nEBV reactivation as a key mechanism of 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