Aysun BENLİ, Yavuz Burak TOR, Serap ŞİMŞEK YAVUZ, Seniha BAŞARAN, Atahan ÇAĞATAY, Halit ÖZSÜT, Ahmet GÜL, Haluk ERAKSOY

SARS-COV-2’NİN GİZLİ TEHLİKESİ; ERİŞKİNLERDE MULTİSİSTEM İNFLAMATUAR SENDROM (MIS-A): TÜRKİYE’DE TEK MERKEZDEN İLK OLGU SERİSİ

Amaç: Multisistem İnflamatuar Sendrom (MIS), COVID-19 sonrası erken dönemde görülen ve bağışıklık yanıtının bozulmasıyla geliştiği düşünülen sıklıkla çocuklarda görülen bir durumdur. Erişkinlerde nadiren bildirilmiştir. Bu makalede Türkiye’de takip edilen ilk yetişkin MIS (MIS-A) olgu serisi sunulmaktadır. Gereç ve Yöntem: Centers for Disease Control and Prevention’in MIS-A tanı kriterlerini karşılayan altı hasta çalışmaya dahil edildi. Hastaların demografik, klinik, laboratuvar, radyolojik özellikleri ile tedavi uygulamaları ve sonuçları kaydedildi. Bulgular: Tüm olgular COVID-19’u hafif şiddette geçirmişti. Hastaların hepsi ateş, şiddetli yorgunluk ve hipotansiyon ile başvurdular. Beş hastada anormal ekokardiyografi bulguları saptandı. Sadece bir hastada çoklu mukokutanöz bulgular mevcuttu. Yaygın laboratuvar özellikleri arasında lenfopeni, C-Reaktif Protein, prokalsitonin, pro-brain natriüretik peptid (pro-BNP), D-dimer ve ferritin artışı vardı. Tüm hastaların SARS-CoV-2 antikoru pozitifti. Beş hastada kortikosteroid ve/veya anakinra, iki hastada intravenöz immunoglobulin tedavisi ve hepsinde düşük moleküler ağırlıklı heparin tedavisi kullanıldı. Ampirik olarak başlanan antibiyotik tedavileri alınan kültürler negatif sonuçlanınca kesildi. Antiinflamatuar tedavi sonrası hastaların hipotansiyonu düzeldi, hiçbirinde yoğun bakım takibi ihtiyacı olmadı ve olgularımızda mortalite görülmedi. Sonuç: MIS-A, çeşitli klinik tablolara neden olan ve sepsis ile karıştırılabilen ciddi ve ölümcül bir durumdur. Rekombinant IL-1 reseptör antagonisti olan anakinra, sitokin kaskadını erken aşamada bloke ettiği için MIS-A tedavisinde kullanılabilecek önemli bir ajandır. MIS-A’da erken teşhis ve antiinflamatuar tedavi ile olumlu sonuçlar alınacaktır. Pandeminin hız kestiği ancak henüz bitmediği bu dönemde klinisyenlerin ölümcül olabilen MIS-A hakkında farkındalığının artırılması gerekmektedir. Anahtar Kelimeler: SARS-CoV-2, COVID-19, multisystem inflamatuar sendrom, erişkin, anakinra, steroid tedavisi

Anahtar Kelimeler:

SARS-CoV-2, COVID-19, Multisistem inflamatuar sendrom, SARS-CoV-2, COVID-19

HIDDEN DANGER OF SARS-COV-2; MULTISYSTEM INFLAMMATORY SYNDROME IN ADULTS (MIS-A): FIRST CASE SERIES IN A SINGLE CENTER FROM TURKIYE

Objective: Multisystem Inflammatory Syndrome (MIS) is a condition seen in the early post-COVID-19 period and thought to develop with an impaired immune response. It has been usually reported in children but rarely in adults. Here we report the first adult MIS (MIS-A) case series from Turkiye. Material and Methods: Six patients who met the Centers for Disease Control and Prevention’s MIS-A diagnostic criteria were included in the study. The demographic, clinical, laboratory, radiological characteristics and therapy regimes and outcomes of the patients were recorded. Results: All of our cases had a history of mild COVID-19. They presented with fever, severe fatigue and hypotension. Abnormal echocardiography findings were detected in five patients. Only one patient had multiple mucocutaneous findings. Common laboratory features were lymphopenia, markedly increased C-Reaktive Protein, procalcitonin, pro-brain natriuretic peptide (pro-BNP), D-dimer, and ferritin. All patients had positive SARSCoV- 2 antibody result. Corticosteroids and/or anakinra were used in five, and intravenous immunoglobulin was used in two patients. Low-molecular-weight heparin (LMWH) was used for all cases. Empirically initiated antibiotic treatments were discontinued after cultures were negative. After anti-inflammatory treatment, the hypotension of the patients resolved, they did not need intensive care follow-up and no mortality was seen in our cases. Conclusions: MIS-A is a severe and mortal condition that causes various clinical pictures and can be confused with sepsis. Anakinra, a recombinant IL-1 receptor antagonist, is a significant agent that can be used in the treatment of MIS-A since it blocks the cytokine cascade at an early stage. The satisfactory responses will be obtained with early diagnosis and anti-inflammatory treatment. In this period when the pandemic is not over yet, it is necessary to increase the awareness of clinicians about MIS-A, which can be fatal.

Keywords:

SARS-CoV-2 COVID-19, multisystem inflammatory syndrome, adult, anakinra, steroid therapy,

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1. Iwasaki M, Saito J, Zhao H, Sakamoto A, Hirota K, Ma D. Inflammation triggered by SARS-CoV-2 and ACE2 augment drives multiple organ failure of severe COVID-19: Molecular mechanisms and implications. Inflammation 2021;44(1):13-34. [CrossRef] google scholar
2. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al. Multisystem inflammatory syndrome in US children and adolescents. N Engl J Med 2020;383:334-46. [CrossRef] google scholar
3. Sokolovsky S, Soni P, Hoffman T, Kahn P, Scheers-Masters J. COVID-19 associated Kawasaki-like multisystem inflammatory disease in an adult. Am J of Emerg Med 2021;39:253.e1-2. [CrossRef] google scholar
4. Morris SB, Schwartz NG, Patel P, Abbo L, Beauchamps L, Balan S, et al. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection-United Kingdom and United States, March-August 2020. MMWR Morb Mortal Wkly Rep 2020;69(40):1450-6. [CrossRef] google scholar
5. Centers for Disease Control and Prevention. Multisystem inflammatory syndrome in adults (MIS-A): case definition. Available at: https://www.cdc.gov/mis/ mis-a/hcp.html#:~:text=Case%20Definition%20for%20 MIS%2DA,following%20clinical%20and%20laboratory%20 criteria. Accessed 19 December 2021. google scholar
6. Weisberg SP, Connors T, Zhu Y, Baldwin M, Lin WH, Wontakal S, et al. Antibody responses to SARS-CoV2 are distinct in children with MIS-C compared to adults with COVID-19. medRxiv 2020. [CrossRef] google scholar
7. Cheng MH, Zhang S, Porritt RA, Rivas MN, Paschold L, Willscher E, et al. Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation. Proc Natl Acad Sci U S A 2020;117(41) :25254-62. [CrossRef] google scholar
8. Rowley AH. Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Nat Rev Immunol 2020;20(8):453-454. [CrossRef] google scholar
9. Jiang L, Tang K, Levin M, Irfan O, Morris SK, Wilson K, et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis 2020;20(11):e276-88. [CrossRef] google scholar
10. Belhadjer Z, Meot M, Bajolle F, Khraiche D, Legendre A, Abakka S, et al. Acute heart failure in multisystem inflammatory syndrome in children in the context of global SARS-CoV-2 pandemic. Circulation 2020;142(5):429-36. [CrossRef] google scholar
11. Lamers MM, Beumer J, Vaart J, Knoops K, Puschhof J, Breugem TI, et al. SARS-CoV-2 productively infects human gut enterocytes. Science 2020;369(6499):50-4. [CrossRef] google scholar
12. Consiglio CR, Cotugno N, Sardh, F, Pou C, Amodio, D, Rodriguez L, et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell 2020;183(4):968-81. [CrossRef] google scholar
13. Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, et al. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA 2020;324(3):259-69. [CrossRef] google scholar
14. Davies P, Evans C, Kanthimathinathan HK, Lillie J, Brierley J, Waters G, et al. Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study. Lancet Child Adolesc Health 2020;4(9):669-77. [CrossRef] google scholar
15. Sperotto F, Friedman KG, Son MBF, VanderPluym CJ, Newburger JW, Dionne A. Cardiac manifestations in SARS-CoV-2-associated multisystem inflammatory syndrome in children: a comprehensive review and proposed clinical approach. Eur J Pediatr 2021;180(2):307-22. [CrossRef] google scholar
16. Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383(4):347-58. [CrossRef] google scholar
17. Chousterman BG, Swirski FK, Weber GF. Cytokine storm and sepsis disease pathogenesis. In Seminars in immunopathology. Semin Immunopathol 2017;39(5):517-28. [CrossRef] google scholar
18. Netea MG, van der Meer JWM. Trained immunity: an ancient way of remembering. Cell Host Microbe 2017;21(3):297-300. [CrossRef] google scholar
19. Mera S, Tatulescu D, Cismaru C, Bondor C, Slavcovici A, Zanc V, et al. Multiplex cytokine profiling in patients with sepsis. APMIS 2011;119(2):155-63. [CrossRef] google scholar