MIS-C tanısı alan hastalarda c-reaktif protein (CRP)/albümin oranının prognostik değerinin belirlenmesi
Determination of the prognostic value of C-reaktive protein (CRP)/albumin ratio in patients diagnosed with MİS-C
Yazar: YASEMİN TİLKİ
Danışman: DOÇ. DR. SEHER ERDOĞAN
Sağlık Bilimleri Üniversitesi / İstanbul Ümraniye Eğitim ve Araştırma Hastanesi / Çocuk Sağlığı ve Hastalıkları Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2022
Konu: Çocuk Sağlığı ve Hastalıkları = Child Health and Diseases
Dizin: Albüminler = Albumins ; C reaktif protein = C reactive protein ; COVID 19 = COVID 19 ; Multisistem inflamatuar sendrom = Multisystem inflammatory syndrome ; SARS virüsü = SARS virus ; Çocuklar = Children ; İnflamasyon = Inflammation

Özet:
AMAÇ: Koronavirüs hastalığı 2019, çocuklarda erişkinlere kıyasla daha az
sıklıkla görülmekte ve daha hafif bulgularla seyretmektedir. Fakat Avrupa'da Nisan
2020'nin sonlarında SARS-CoV-2 enfeksiyonu geçiren bazı çocuklarda ateş, karın
ağrısı, şok, miyokardiyal yetmezlik ve yoğun bakımı ihtiyacı geliştiği görülmüş ve
bu yeni hastalığa Çoklu Sistemik İnflamatuvar Sendrom (MIS-C) adı verilmiştir.
Hastalığın patogenezi net değildir, immün sistemin kontrolsüz inflamasyonu
sonucunda çoklu organ tutulumuna ait bulgularla seyretmekte ve hatta ölüme neden
olmaktadır. Bu hastaların hızlı bir şekilde tanı almaları ve tedavilerine zaman
kaybedilmeden başlanması mortalite ve morbiditenin önlenmesi açısından büyük
önem taşımaktadır.
Çoklu sistemik inflamatuvar sendromunda inflamatuvar belirteçlerde aşırı bir
yanıt görülebilir. Serum C-reaktif protein (CRP), eritrosit sedimentasyon hızı (ESH),
fibrinojen, D-dimer, ferritin, laktat dehidrogenaz (LDH), interlökin 6 (IL-6), nötrofil
sayısında artış görülürken lenfopeni, trombositopeni, albümin ve kan sodyum
düşüklüğü saptanabilir. MIS-C yeni tanımlandığı ve uzun süreli hastaların izlemi
yapılmadığından prognozu halen belirsizdir. Pek çok çalışmada, kritik hastalarda
prognozu belirlemede biyobelirteçlerin rolü araştırılmıştır. Biz de bu çalışmada;
MIS-C hastalarının klinik, demografik ve laboratuvar verilerini değerlendirmeyi,
CRP/Albümin oranının hastalığın klinik seyrine olan etkisini ve çocuk yoğun bakım
ünitesi (ÇYBÜ) ihtiyacını tahmin etmedeki rolünü araştırmayı amaçladık.
GEREÇ ve YÖNTEM: Çalışmamızda Kasım 2020-Mart 2022 tarihleri
arasında Sağlık Bilimleri Üniversitesi Ümraniye Eğitim ve Araştırıma Hastanesi
Çocuk Sağlığı ve Hastalıkları servisi ve Çocuk Yoğun Bakım Ünitesi'nde (ÇYBÜ)
MIS-C tanısı alan 1 ay-l8 yaş arası hastaların izlem dosyalarından klinik bulguları,
demografik özellikleri, eşlik eden ek hastalık varlığı, servis ve ÇYBÜ yatış günleri,

Abstract:
OBJECTIVE: Coronavirus disease 2019 is seen less frequently in children
compared to adults and progresses with milder symptoms. However, in Europe in
late April 2020, some children who had SARS-CoV-2 infection developed fever,
abdominal pain, shock, myocardial failure and the need for intensive care, and this
new disease was named Multiple Systemic Inflammatory Syndrome (MIS-C). The
pathogenesis of the disease is not clear, it progresses with findings of multi-organ
involvement as a result of uncontrolled inflammation of the immune system and even
causes death. The rapid diagnosis of these patients and the initiation of their
treatment without delay are of great importance in terms of preventing mortality and
morbidity. An excessive response of inflammatory markers may be seen in multiple
systemic inflammatory syndrome. Serum C reactive protein (CRP), erythrocyte
sedimentation rate (ESH), fibrinogen, D-dimer, ferritin, lactate dehydrogenase
(LDH), interleukin 6 (IL-6), increased neutrophil count, lymphopenia,
thrombocytopenia, low albumin and blood sodium detectable. The prognosis is still
uncertain as MIS-C has been newly defined and long-term patients have not been
followed up. In many studies, the role of biomarkers in determining the prognosis of
critically ill patients has been investigated. In this study, we also; We aimed to
evaluate the clinical, demographic and laboratory data of MIS-C patients, to
investigate the effect of CRP/Albumin ratio on the clinical course of the disease and
its role in estimating the need for PICU.
MATERIALS and METHODS: In our study, the clinical findings and
demographic characteristics of the patients aged 1 month to 18 years who were
diagnosed with MIS-C in the Health Sciences University Ümraniye Training and
Research Hospital Pediatrics and Pediatric Intensive Care Unit (PICU) between
November 2020 and March 2022. , presence of comorbid disease, hospitalization
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days in the service and PICU, pediatric mortality risk score (PRISM score) within the
first 24 hours of hospitalization, need for mechanical ventilator and number of days,
need for inotropic drug infusion, need for CRRT and/or ECMO, and during
hospitalization. Other treatments applied and prognosis were examined.
RESULTS: A total of 147 patients were included in the study. The mean age
of the patients was 90.4±62.8 months, 57 of them were girls. 25 of the patients had
comorbidities, RT-PCR positivity rate was 10.2%, serology positivity was 86%.
Fever was found to be the most common complaint at admission. It was observed
that the gastrointestinal system was most frequently involved (57.8%), followed by
the mucocutaneous system (49%), the cardiovascular system (27.2%), the respiratory
system (12.2%) and the neurological system (9.5%). 45.6% of the patients were
lymphopenic, 19% were thrombocytopenic, and the CRP/Albumin ratio was 3.08.
Ferritin level >500 ng/mL in 51 (34.7%) patients, D-dimer≥1500 ng/mL in 104
(71.2%), CRP >5 mg/dL in 116 (78.9%) patients PCT was >0.05 ng/dL, 87.8%, and
hyponatremia was detected in 68 patients (46.3%). Respiratory support was given to
12.2% of the patients, IVIG treatment was applied to 125 patients, 101 (68.7%)
patients were given systemic glucocorticoid, 90 (61.2%) patients were given aspirin
as anticoagulant treatment, and 92 (62.6%) patients were given enoxaparin. 21
(14.1%) patients required vasopressor medication. Therapeutic plasma exchange was
applied to 19 (12.9%) patients, continuous renal replacement therapy to 4 patients,
and extracorporeal membrane oxygenation to 1 patient. While 99 of the patients were
followed in the pediatric service, 46 (31.3%) were hospitalized and treated in the
pediatric intensive care unit. Patients with Kawasaki-like disease had a lower mean
age, higher lymphocyte count and troponin level, and a higher rate of TPE, and a
shorter hospital stay. The neutrophil percentage of the patients hospitalized in the
PICU was higher (p<0.001), the lymphocyte count, hemoglobin level and platelet
count were lower than in the ward patients. The median NLR was 8.46 in PICU
admissions and 4.20 in ward patients (p=0.001). CRP, ferritin, D-dimer, troponin,
ALT, AST, urea and creatinine levels were higher in the PICU hospitalized patient
group. Similarly, the CRP/Albumin ratio was significantly higher in the PICU
hospitalized patient group, p<0.001). When the groups of patients who were
xii
hospitalized in the PICU for <5 days and ≥5 days were compared, it was found that
the triglyceride levels of the patients who were hospitalized for ≥5 days were lower
(p=0.04). The PRISM, PELOD and VIS scores of the patients who underwent TPE
were found to be significantly higher (p<0.001). While thrombocyte count,
sedimentation rate, albumin and fibrinogen levels were lower in patients who
underwent TPD; ferritin, troponin, proBNP and D-dimer, AST, ALT, urea,
creatinine, LDH levels were found to be higher (p values: <0.05). ROC curves were
created to predict CRP/Albumin ratio, PICU admission, TPD application, and
mechanical ventilation. ROC curve created for PICU admission was found to be
significant. Accordingly, the cut-off point was 4.55 and the sensitivity, specificity,
PPD and NPD were 63%, 77%, 56% and 82%, respectively. A positive and weak
linear correlation was found between the CRP/Albumin ratio and the PRISM score
and PELOD score (r:0.3, p<0.001). It was determined that high ferritin and D-dimer
increased the risk of PICU hospitalization by 1 fold (p=.014 and p=.001,
respectively), and high NLR ratio increased 1.069 times (p<.001).
CONCLUSION: The findings of our study supported that the CRP/Albumin
ratio could be a good indicator in determining the need for intensive care in patients
diagnosed with MISC. The CRP/Albumin ratio has the advantages of being a simple,
inexpensive and easily applicable method. It can be used as a good prognostic
marker in determining the severity of the disease in MISC patients. It should also be
considered that patients with high ferritin, D-dimer and NLR levels may need PICU,
and these laboratory parameters should be closely monitored.
KEYWORDS: MIS-C, covid-19, CRP, albumin