Hematopetik Kök Hücre Transplantasyonu Yapılan Hastalarda Bağışıklığın Yeniden Yapılanması

Hematopoietic stem cell transplantation (HSCT) is widely used today in the treatment of many diseases. HSCT can completely cure malign diseases like leukemia as well as non-malign diseases like thalassemia. During allogeneic HSCT, complications such as graft versus host disease (GVHD) caused by immune interaction of patient and host cells, infections caused by suppression of the immune system, veno-occlusive disease (VOD), and graft failure may occur and these complications may lead to treatment failure. Delay in immune reconstitution after hematopoietic stem cell transplantation is thought to be associated with high morbidity due to infectious complications. In clinical trials, it has been shown that in patients receiving myeloablative regimens, neutrophil function returns to normal within weeks, natural killer (NK) cells function within one month, CD4(+) T cells function within years (1-5 years for memory cells, >5 years for T regulatory cells), CD8(+) T cells function within months (2-6 months for memory and effector cells), and B cells function within years and this duration is even longer for patients with GVHD. Complete functional recovery of these cells is variable and depends on the intensity and duration of immunosuppressive therapy, in the case of GVHD and also in the clinical course of some diseases. Other factors affecting immune reconstitution include underlying disease that require HSCT, history of chemotherapy or radiotherapy, nutritional condition, age of patient and donor, characteristics of conditioning regimens, total body radiation or use of anti-lymphocytic antibodies, stem cell source, procedures applied to the products, patient-donor HLA match, and infections after transplantation. In this retrospective study, lymphocyte subgroups were evaluated before transplantation and 1, 3, 6, 12, and 24 months after transplantation and whether there is an association between transplant related complications and immune reconstitution was investigated. xi Evaluation of absolute values of lymphocyte subgroups in 81 patients revealed that CD3(+) lymphocyte numbers returned to pre-HSCT levels at 3 months, CD4(+) T lymphocytes at 12 months, CD8(+) T lymphocytes at 3 months, CD19(+) B lymphocytes at 12 months and CD4/CD8 ratio at 24 months. Besides, CD3+4-8- double negative T lymphocytes returned to pre-HSCT levels at 6 months. CD16/56(+)CD3(+) NK-T and CD16/56(+)CD3(-) NK lymphocytes returned to pre-HSCT levels within a short time of 1 month. Association between lymphocyte subgroup and HSCT related complications were also investigated in our study. For this purpose, absolute values of activated T lymphocyte subgroups during GVHD and/or before the development of GVHD were evaluated using lymphocyte activation markers in patients with acute and chronic GVHD which are immunological complications of HSCT. When absolute levels of lymphocyte subgroups were compared in patients with and without acute GVHD, recovery of CD3(+) and CD4(+) lymphocytes were found to be delayed in patients with acute GVHD; CD3(+) lymphocyte counts returned to pre-HSCT levels at 6 months in patients with acute GVHD (3 months in those without acute GVHD) and CD4(+) lymphocyte counts returned to pre-HSCT levels at 24 months in patients with acute GVHD (12 months in those without acute GVHD). CD8(+) T lymphocytes returned to pre-HSCT levels at 3 months both in patients with and without acute GVHD. In patients with acute GVHD, CD8(+) T lymphocyte counts were found to be higher at 6, 12 and 24 months when compared to those of patients without acute GVHD (p≤0.05). Besides, CD19(+) B lymphocyte counts returned to pre-HSCT levels at 12 months in patients with acute GVHD and at 6 months in patients without acute GVHD. CD19(+) B lymphocyte count was also lower at 1,3, 6, 12 and 24 months in patients with acute GVHD when compared to those without acute GVHD (p≤0.05). CD4/8 ratio returned to pre-HSCT levels at 24 months in both groups. The absolute numbers of CD16/56(+)CD3(+) NK-T and CD16/56(+)CD3(+) NK lymphocytes returned to pre-HSCT levels within a short period of 1 month in both patients with and without acute GVHD. In order to evaluate the markers related to T lymphocyte activation in patients with acute GVHD, analysis of HLA-DR expression as a marker of CD3(+) T lymphocyte xii activation, CD8/57 for CD8(+) T lymphocyte activation, CD8/56 as a marker of NK cell activation, and CD4/25 and CD4/28 for CD4(+) T lymphocyte activation were performed. In patients with and without acute GVHD, the absolute values of activated CD3 (CD3/HLA-DR), activated CD8 (CD8/56) and activated NK (CD8/57) cells were found to be increased rapidly at an early stage after HSCT. This condition was thought to reflect lymphocyte activation; which occured after donor T lymphocytes, primarily cytotoxic T lymphocytes came across to the patient tissues at an early stage after HSCT. Besides, CD3/HLA-DR(+), CD8/56(+) and CD8/57(+) activated T lymphocytes were found to reach higher levels at 12 and 24 months in patients with acute GVHD when compared to those without acute GVHD (p≤0.05). CD3+4-8- ‘double negative’ T lymphocytes were also evaluated in our study. In patients with acute GVHD, CD3+4-8- ‘double negative’ T lymphocytes count was higher at 12 months than that of patients without acute GVHD (p≤0.05). First, CD4/25(+) activated T lymphocytes were found to be decreased after HSCT, but returned to pre-HSCT levels at 24 months in both patients groups with and without acute GVHD. Besides, in patients with acute GVHD, activated CD4/25(+) lymphocyte count was higher at 24 months (p≤0.05). CD4/28(+) activated T lymphocyte count decreased after HSCT in both groups; later, in patients without acute GVHD, their counts returned to pre-HSCT levels at 24 months while their counts still did not return to pre-HSCT levels at 24 months in patients with acute GVHD.When absolute levels of lymphocyte subgroups were compared in patients with and without chronic GVHD, CD3(+) lymphocyte count returned to pre-HSCT levels at 1 month in patients with chronic GVHD and at 6 months in patients without chronic GVHD. CD4(+) T lymphocyte count returned to pre-HSCT levels at 12 months both in patients with and without chronic GVHD. While CD8(+) T lymphocyte count returned to pre-HSCT levels as early as 1 month both in patients with and without chronic GVHD, CD8(+) T lymphocyte count was higher in patients with chronic GVHD at 1, 3, 6, 12, and 24 months when compared to those without chronic GVHD (p≤0.05). CD19(+) B lymphocyte count returned to pre-HSCT levels at 12 months both in patients with and without chronic GVHD, whereas CD19(+) B lymphocyte count was lower in patients with chronic GVHD at 3, 6, and 12 months (p≤0.05). CD4/8 ratio returned to pre-HSCT levels at 24 months in both groups. xiii CD16/56(+)CD3(+) NK-T and CD16/56(+)CD3(-) NK lymphocytes returned to pre-HSCT values within 1 month after HSCT in both groups. When specific subgroups reflecting lymphocyte activation were evaluated in patients with chronic GVHD, activated CD8/57(+) T lymphocyte count was higher at 1, 3, 6, 12, and 24 months, while activated CD8/56(+) NK lymphocyte count was higher at 12 and 24 months than those of patients without chronic GVHD (p≤0.05). Activated CD3/HLA-DR(+) T lymphocyte count was higher at 1, 6, 12, and 24 months in the chronic GVHD group. CD3+4-8- double negative T lymphocytes returned to pre-HSCT levels at 1 month in patients with chronic HSCT and at 6 months in patients without chronic GHVD. Activated CD4/25(+) T lymphocytes returned to pre-HSCT levels at 24 months in both groups, while CD4/28(+) activated T lymphocytes reached pre-HSCT values at 12 months in patients with chronic GVHD and at 24 months in patients without chronic GVHD. Besides, CD4/25(+) activated T lymphocyte count was higher at 1, 3, 6, and 24 months in patients with chronic GVHD. Higher counts of CD3(+) lymphocytes, CD8(+) T lymphocytes, CD4/25(+), CD8/56(+), CD8/57(+), CD3/DR(+) activated T lymphocytes in patients with chronic GVHD suggest that these lymphocyte subgroups play an important role in GVHD pathogenesis. If chronic GVHD does not take controlled, these lymphocytes were found to be at increased levels. In addition, low counts of CD19(+) B lymphocytes in patients with chronic GVHD at 3, 6, and 12 months suggests that development of chronic GVHD delays the reconstitution of B lymphocytes. Besides, high levels of CD3(+) lymphocytes, CD8(+) T lymphocytes, CD4/25(+),CD8/57(+), CD3/DR(+) activated lymphocytes at 1 month when chronic GVHD symptoms have not yet developed suggests that these lymphocyte subgroups may be used as a warning sign forchronic GVHD. Due to the association of delay in immune reconstitution and infectious complications after HSCT, lymphocyte subgroups were evaluated in patients with and without CMV reactivation. CD3(+) lymphocyte count returned to pre-HSCT levels at 6 months in patients with CMV reactivation and at 12 months in patients without CMV reactivation and CD3(+) lymphocyte count was higher at 3, 6, 12, and 24 months in patients with CMV reactivation (p≤0.05). CD4(+) T lymphocyte count xiv returned to pre-HSCT levels at 24 months both in patients with and without CMV reactivation. CD8(+) T lymphocytes reached pre-HSCT levels at 1 month in patients with CMV reactivation and at 3 months in those without CMV reactivation and CD8(+) lymphocyte counts were higher at 3, 6, 12, and 24 months in patients with CMV reactivation (p≤0.05). CD19(+) B lymphocyte count returned to pre-HSCT levels at 6 months in patients with CMV reactivation and at 12 months in those without CMV reactivation. CD4/8 ratio returned to pre-HSCT levels at 24 months in both groups. In addition, CD16/56(+)CD3(+) NK-T cells and CD16/56(+)CD3(-) NK lymphocytes returned to pre-HSCT levels within 1 month after HSCT in both groups. When specific subgroups reflecting lymphocyte activation were evaluated in patients with CMV reactivation, both CD8/57(+) activated T lymphocytes and CD3/HLA-DR(+) activated T lymphocytes counts were higher in patients with CMV reactivation at 6, 12, and 24 months than those without CMV reactivation (p≤0.05). CD8/56(+) activated NK lymphocyte profiles were similar both in patients with and without CMV reactivation. CD3+4-8- double negative T lymphocyte count was higher in patients with CMV reactivation at 12 months than those without CMV reactivation. CD4/28(+) activated T lymphocytes returned to pre-HSCT levels at 24 months both in patients with and without CMV reactivation and CD4/25(+) activated T lymphocytes returned to pre-HSCT levels at 24 months in patients without CMV reactivation while their counts still did not return to pre-HSCT levels at 24 months in patients with CMV reactivation. Higher CD3(+) and CD8(+) T lymphocyte counts at 3, 6, 12, and 24 months; CD8/57(+) and CD3/HLA-DR(+) activated T lymphocyte counts at 6, 12, and 24 months; CD4/25(+) activated T lymphocytes at 3 months; and CD3+4-8- double negative T lymphocyte counts at 12 months in patients with CMV reactivation when compared to those without CMV reactivation suggests that these lymphocyte subgroups may play an important role in CMV reactivation. In summary; return of CD3(+) lymphocyte count to pre-HSCT values at 3 months, CD4(+) T lymphocyte count at 12 months, CD8(+) T lymphocytes at 3 months, CD19(+) B lymphocytes at 12 months, CD4/CD8 cell ratio at 24 months, and xv CD16/56(+)CD3(+) NK-T and CD16/56(+)CD3(-) NK lymphocyte counts at 1 month after HSCT demonstrates that immune reconstitution may extend up to 2 years in patients underwent allogenic HSCT. Development of acute GVHD has been found to delay in immune reconstitution of especially CD3(+) lymphocytes, CD4(+) T lymphocytes, and CD19(+) B lymphocytes. Absolute numbers of activated CD3 (CD3/HLA-DR), activated CD8 (CD8/56) and activated NK (CD8/57) were found to be increased rapidly in early stages after HSCT both in patients with and without acute GVHD; this condition was thought to reflect lymphocyte activation; which occured after donor T lymphocytes, primarily cytotoxic T lymphocytes came across to the patient tissues at an early stage after HSCT. Since CD3(+) lymphocytes, CD8(+) T lymphocytes, CD4/25(+),CD8/57(+) and CD3/DR(+) activated T lymphocyte counts were found to be higher in patients with chronic GVHD as early as 1 month even when chronic GVHD symptoms were not evident, these lymphocyte subgroups may be used as a warning sign for the development of chronic GVHD.Hematopoetik kök hücre transplantasyonu (HKHT) günümüzde birçok hastalık tedavisinde yaygın olarak kullanılmaktadır. Hematopoetik kök hücre transplantasyonu lösemi gibi malign hastalıkların yanısıra talasemi gibi malign olmayan birçok hastalığın tam tedavisini sağlayabilmektedir. Allojenik HKHT sonrasında görülebilen hasta donör hücreleri arasındaki immun etkileşim nedeniyle gelişen graft versus host hastalığı (GVHH), immun sistem baskılanmasına bağlı olarak gelişen enfeksiyonlar, veno-okluziv hastalık (VOH), graft yetmezliği gibi komplikasyonlar HKHT’nun başarısızlığına neden olabilmektedir (1) . HKHT sonrasında bağışıklığın yeniden yapılanmasındaki (BYY) gecikmenin enfeksiyöz komplikasyonlara bağlı morbidite ile ilişkili olduğu düşünülmektedir. Klinik çalışmalarda miyeloablatif rejim alan hastalarda nötrofillerin haftalar içerisinde, naturel killer (NK) hücrelerin bir ay içinde, CD 4 (+) T lenfositlerin yıllar içerisinde (Memory hücreler 1-5 yıl, T regulatuar hücreler >5yıl), CD8 (+) T lenfositlerin aylar içerisinde (Memory ve efektör T lenfositler için 2-6 ay), B lenfositlerin yıllar içerisinde yeniden yapılandığı ve GVHH olan hastalarda bağışıklığın yeniden yapılanmasının daha geç olduğu gösterilmiştir. GVHH gibi yoğun ve uzun süre immun supresif kullanımı gereken durumlarda ve hastalıkların klinik seyirlerine göre bu hücre fonksiyonlarının tam olarak geri dönmesi değişkenlik göstermektedir. Ayrıca HKHT öncesi altta yatan hastalık, kemoterapi veya radyoterapi almak, beslenme durumu, hasta ve donör yaşı, hazırlık rejimi özellikleri, total vücud ışınlaması veya anti-lenfositik antikorların kullanımı, kök hücre kaynağı, ürüne uygulanan işlemler, hasta-donör HLA uyumu ve nakil sonrasındaki enfeksiyonlar HKHT başarısını ve BYY’nı etkileyen faktörler olarak sıralanabilir (1). v Çalışmamızda retrospektif olarak hastaların HKHT öncesi ve HKHT sonrası 1., 3., 6., 12., ve 24. aylardaki lenfosit alt grupları incelendi ve nakil ilişkili komplikasyonlar ile bağışıklığın yeniden yapılanması arasındaki ilişki araştırıldı. Bu amaçla 81 allojenik HKHT yapılan hastada lenfosit alt gruplarının absolü değerleri karşılaştırıldığında; HKHT sonrasında CD3 (+) lenfosit sayılarının 3. ayda, CD4 (+) T lenfositlerin 12. ayda, CD8 (+) T lenfositlerin 3. ayda, CD19 (+) B lenfositlerin 12. ayda ve CD4/CD8 hücre oranının 24. ayda HKHT öncesi değerlere ulaştığı saptandı. Ayrıca CD3+4-8- double negatif T lenfositlerin 6. ayda HKHT öncesi değerlere ulaştığı izlendi. CD16/56(+)CD3(+) NK-T ve CD16/56(+)CD3(-) NK lenfositlerin 1 ay gibi kısa bir süre içerisinde HKHT öncesi değerlere ulaştığı görüldü. Çalışmada lenfosit alt gruplarıyla HKHT ilişkili komplikasyonlar arasındaki ilişki de araştırıldı. Bu kapsamda HKHT’nun immunolojik komplikasyonu olan akut ve kronik GVHH gelişen hastalarda lenfosit aktivasyon belirteçleri de kullanılarak aktive T lenfosit alt gruplarının GVHH sürecinde ve/veya ortaya çıkmadan önce absolü değerleri incelendi. Akut GVHH gelişen ve gelişmeyen hastalarda lenfosit alt gruplarının absolü değerleri karşılaştırıldığında; HKHT sonrasında CD3 ve CD4 lenfosit yeniden yapılanmasının geciktiği; CD3 (+) lenfosit sayılarının akut GVHH gelişen grupta 6. ayda (gelişmeyenlerde 3. ay), CD4 (+) T lenfosit sayılarının ise 24. ayda (gelişmeyenlerde 12. ayda) HKHT öncesi değerlere ulaştığı izlendi. CD8 (+) T lenfositlerin ise akut GVHH gelişen ve gelişmeyen her iki grupta da 3. ayda HKHT öncesi değerlere ulaştığı gözlendi. CD8 (+) T lenfosit sayıları akut GVHH gelişen grupta 6.,12.,24.aylarda akut GVHH gelişmeyen gruba göre daha yüksek değerlerde seyretti (p≤0.05). Ayrıca CD19 (+) B lenfosit sayılarının akut GVHH gelişen grupta daha geç ve 12. ayda, akut GVHH gelişmeyen grupta ise 6. ayda HKHT öncesi değerlere ulaştığı görüldü. Ayrıca CD19(+) B lenfositlerin akut GVHH grubunda 1.,3.,6.,12.,24. aylarda akut GVHH olmayan gruba göre daha düşük olduğu görüldü (p≤0.05). CD4/8 oranının her iki grupta da ancak 24. ayda HKHT öncesi değerlere geri döndüğü izlendi. CD16/56(+)CD3(+) NK-T ve CD16/56(+)CD3(+) NK lenfosit vi absolü değerlerinin akut GVHH gelişen ve gelişmeyen her iki grupta da 1 ay gibi kısa bir süre içerisinde HKHT öncesi değerlere döndüğü gözlendi. Akut GVHH olan hastalarda T lenfosit aktivasyonuna ilişkin belirteçlerin değerlendirilmesi amacıyla; CD3(+) T lenfositlerin aktivasyon belirteci olarak HLA-DR ekspresyonunu, CD8 (+) T lenfositler için CD8/57, NK hücrelerinin aktivasyon belirteci olarak CD8/56, CD4(+) T lenfositler için CD4/25 ve CD4/28 ekspresyonları analiz edildi. Akut GVHH gelişen ve gelişmeyen her iki hasta grubunda HKHT sonrası erken dönemde aktive CD3 (CD3/HLA-DR), aktive CD8 (CD8/56) ve aktive NK (CD8/57) absolü değerlerinin hızla yükseldiği görüldü. Bu durumun HKHT sonrası erken dönemde başlıca sitotoksik T lenfositler olmak üzere donör T lenfositlerinin hasta dokularıyla karşılaşmasına paralel olarak lenfosit aktivasyonunu yansıttığı düşünüldü. Ayrıca CD3/HLA-DR(+), CD8/56(+) ve CD8/57(+) aktive T lenfositlerin 12. ve 24. ayda akut GVHH grubunda akut GVHH olmayan gruba göre daha yüksek değerlere ulaştığı gözlendi (p≤0.05). Çalışmada ayrıca CD3+4-8- ‘double negatif’ hücreler incelendi. Akut GVHH gelişen grupta CD3+4-8- ‘double negatif’ hücrelerin 12. ayda daha yüksek oranda olduğu saptandı (p≤0.05). CD4/25(+) aktive T lenfositlerin akut GVHH gelişen ve gelişmeyen her iki grupta HKHT sonrasında önce azalma gösterdiği, ancak 24. ayda HKHT öncesi değerlere ulaştığı izlendi. Ayrıca akut GVHH gelişen grupta CD4/25(+) aktive T lenfositlerin 24. Ayda daha yüksek değerlerde olduğu görüldü (p≤0.05). CD4/28(+) aktive T lenfositlerin her iki grupta HKHT sonrasında azalma gösterdiği; sonrasında akut GVHH gelişmeyen grupta 24. ayda HKHT öncesi değerlere ulaşıldığı; akut GVHH gelişen grupta ise 24. ayda halen HKHT öncesi değerlere ulaşılamadığı izlendi. Kronik GVHH gelişen ve gelişmeyen hastalarda lenfosit alt gruplarının absolü değerleri karşılaştırıldığında; HKHT sonrasında CD3 (+) lenfosit sayılarının kronik GVHH gelişen grupta 1.ayda, kronik GVHH gelişmeyen grupta ise 6. ayda HKHT öncesi değerlere ulaştığı görüldü. CD4 (+) T lenfosit sayılarının kronik GVHH gelişen ve gelişmeyen her iki grupta 12. ayda HKHT öncesi değerlere ulaştığı görüldü. CD8 (+) T lenfositlerin her iki grupta da 1 ay gibi kısa bir süre içerisinde HKHT öncesi değerlere ulaştığı ve kronik GVHH gelişen grupta CD8 (+) T lenfositlerin 1.,3,,6.,12.,24.aylarda tüm takiplerde daha yüksek seyrettiği görüldü vii (p≤0.05). CD19 (+) B lenfosit sayılarının her iki grupta 12. ayda HKHT öncesi değerlere ulaştığı, ancak kronik GVHH gelişen grupta CD19 (+) B lenfosit sayılarının 3.,6.,12. aylarda daha düşük seyrettiği görüldü (p≤0.05). CD4/8 oranının her iki grupta da ancak 24. ayda HKHT öncesi değerlere geri döndüğü izlendi. CD16/56(+)CD3(+) NK-T ve CD16/56(+)CD3(-) NK lenfositlerin HKHT sonrasında her iki grupta 1 ay içerisinde HKHT öncesi değerlere ulaştığı saptandı. Kronik GVHH olan hastalarda lenfosit aktivasyonunu yansıtan spesifik alt gruplar incelendiğinde; CD8/57(+) aktive T lenfositlerin kronik GVHH grubunda 1.,3,,6.,12.,24.aylarda tüm takiplerde daha yüksek seyrettiği; CD8/56(+) aktive NK lenfositlerin ise 12. ve 24. aylarda daha yüksek olduğu görüldü (p≤0.05). CD3/HLA-DR(+) aktive T lenfositlerin kronik GVHH grubunda 1.,6.,12.,24.aylardaki takiplerde daha yüksek seyrettiği izlendi. CD3+4-8- double negatif T lenfositlerin kronik GVHH gelişen grupta 1.ay ve kronik GVHH gelişmeyen grupta 6. ayda HKHT öncesi değerlere ulaştığı görüldü. CD4/25(+) aktive T lenfositlerin her iki grupta 24. ayda ve CD4/28(+) aktive T lenfositlerin kronik GVHH olan grupta 12. ay, kronik GVHH olmayan grupta 24. ayda HKHT öncesi değerlere ulaştığı saptandı. Ayrıca CD4/25(+) aktive T lenfositlerin kronik GVHH olan grupta 1.,3.,6.,24.aylarda daha yüksek seyrettiği izlendi. Kronik GVHH gelişen grupta CD3(+) lenfositler, CD8(+) T lenfositler, CD4/25(+), CD8/56(+), CD8/57(+), CD3/DR(+) aktive T lenfositlerin daha yüksek seyretmesi bu lenfosit alt gruplarının kronik GVHH patogenezinde rol alması ve kronik GVHH’nin henüz kontrol altına alınamaması ile ilişkili olduğunu düşündürmektedir. Bunun yanı sıra CD19 (+) B lenfosit sayılarının kronik GVHH gelişen grupta 3.,6.,12. aylarda daha düşük seyretmesi kronik GVHH gelişmesinin B lenfosit yeniden yapılanmasını olumsuz etkilediğini düşündürmüştür. Ayrıca CD3 (+) lenfositler, CD8(+) T lenfositler, CD4/25(+),CD8/57(+), CD3/DR(+) aktive T lenfositlerin 1.ay gibi erken bir dönemde henüz kronik GVHH bulguları başlamadan kronik GVHH grubunda daha yüksek saptanması, bu lenfosit alt gruplarının kronik GVHH için uyarıcı bir işaret olarak kullanılabileceğini düşündürmektedir. İmmun yeniden yapılanmanın gecikmesinin HKHT sonrasında enfeksiyöz komplikasyonlarla ilişkisi nedeniyle CMV reaktivasyonu gelişen ve gelişmeyen hastalarda lenfosit alt grupları incelendi. HKHT sonrasında CD3(+) lenfosit viii sayılarının CMV reaktivasyonu gelişen grupta 6.ayda, CMV reaktivasyonu gelişmeyen grupta ise 12. ayda HKHT öncesi değerlere ulaştığı ve CMV reaktivasyonu gelişen grupta CD3(+) lenfositlerin 3,,6.,12.,24.aylarda daha yüksek seyrettiği görüldü (p≤0.05). CD4(+) T lenfosit sayılarının CMV reaktivasyonu gelişen ve gelişmeyen her iki grupta 24.

COVID-19 associated multisystemic inflammatory syndrome in 614 children with and without overlap with Kawasaki disease-Turk MIS-C study group.

Multisystemic inflammatory syndrome (MIS-C) diagnosis remains difficult because the clinical features overlap with Kawasaki disease (KD). The study aims to highlight the clinical and laboratory features and outcomes of patients with MISC whose clinical manifestations overlap with or without KD. This study is a retrospective analysis of a case series designed for patients aged 1 month to 18 years in 28 hospitals between November 1, 2020, and June 9, 2021. Patient demographics, complaints, laboratory results, echocardiographic results, system involvement, and outcomes were recorded. A total of 614 patients were enrolled; the median age was 7.4 years (interquartile range (IQR) 3.9-12 years). A total of 277 (45.1%) patients with MIS-C had manifestations that overlapped with KD, including 92 (33.3%) patients with complete KD and 185 (66.7%) with incomplete KD. Lymphocyte and platelet counts were significantly lower in patients with MISC, overlapped with KD (lymphocyte count 1080 vs. 1280 cells x mu L, p = 0.028; platelet count 166 vs. 216 cells x 10(3)/mu L, p 12 years reduced the risk of overlap with KD by 66% (p < 0.001, 95% CI 0.217-0.550), lethargy increased the risk of overlap with KD by 2.6-fold (p = 0.011, 95% CI 1.244-5.439), and each unit more albumin (g/dl) reduced the risk of overlap with KD by 60% (p < 0.001, 95% CI 0.298-0.559)

A snapshot of pediatric inpatients and outpatients with COVID-19: a point prevalence study from Turkey

This multi-center point prevalence study evaluated children who were diagnosed as having coronavirus disease 2019 (COVID-19). On February 2nd, 2022, inpatients and outpatients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included in the study from 12 cities and 24 centers in Turkey. Of 8605 patients on February 2nd, 2022, in participating centers, 706 (8.2%) had COVID-19. The median age of the 706 patients was 92.50 months, 53.4% were female, and 76.7% were inpatients. The three most common symptoms of the patients with COVID-19 were fever (56.6%), cough (41.3%), and fatigue (27.5%). The three most common underlying chronic diseases (UCDs) were asthma (3.4%), neurologic disorders (3.3%), and obesity (2.6%). The SARS-CoV-2-related pneumoniae rate was 10.7%. The COVID-19 vaccination rate was 12.5% in all patients. Among patients aged over 12 years with access to the vaccine given by the Republic of Turkey Ministry of Health, the vaccination rate was 38.7%. Patients with UCDs presented with dyspnea and pneumoniae more frequently than those without UCDs (p < 0.001 for both). The rates of fever, diarrhea, and pneumoniae were higher in patients without COVID-19 vaccinations (p = 0.001, p = 0.012, and p = 0.027). Conclusion: To lessen the effects of the disease, all eligible children should receive the COVID-19 vaccine. The illness may specifically endanger children with UCDs. What is Known: • Children with COVID-19 mainly present with fever and cough, as in adults. • COVID-19 may specifically threaten children with underlying chronic diseases. What is New: • Children with obesity have a higher vaccination rate against COVID-19 than children without obesity. • Among unvaccinated children, fever and pneumoniae might be seen at a higher ratio than among vaccinated children

Mortality Risk Factors among Critically Ill Children with Acute COVID-19 in PICUs: A Multicenter Study from Turkish Pediatric Critical COVID-19 and MIS-C Study Group

© 2022 Lippincott Williams and Wilkins. All rights reserved.Background: During the coronavirus disease 2019 (COVID-19) pandemic, the world has a large number of reported COVID-19 cases and deaths. Information on characteristics and mortality rate of pediatric intensive care unit (PICU) cases with COVID-19 remains limited. This study aims to identify the risk factors for mortality related to COVID-19 in children admitted to PICU. Methods: A retrospective multicenter cohort study was conducted between March 2020 and April 2021 at 44 PICUs in Turkey. Children who were 1 month-18-year of age with confirmed COVID-19 admitted to PICU were included in the study. Children with multisystem inflammatory syndrome and asymptomatic for COVID-19 were excluded. Results: Of 335 patients with COVID-19, the median age was 6.8 years (IQR: 1.2-14) and 180 (53.7 %) were male, 215 (64.2 %) had at least one comorbidity. Age and gender were not related to mortality. Among 335 patients, 166 (49.5%) received mechanical ventilation, 17 (5.1%) received renal replacement therapy and 44 (13.1 %) died. Children with medical complexity, congenital heart disease, immunosuppression and malignancy had significantly higher mortality. On multivariable logistic regression analysis, organ failure index [odds ratio (OR): 2.1, 95 confidence interval (CI): 1.55-2.85], and having congenital heart disease (OR: 2.65, 95 CI: 1.03-6.80), were associated with mortality. Conclusions: This study presents detailed data on clinical characteristics and outcomes of patients with COVID-19 admitted to PICU in the first pandemic year in Turkey. Our study shows that having congenital heart disease is associated with mortality. In addition, the high organ failure score in follow-up predict mortality