Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Monocytic cell lines and primary myeloid cells with OAS1 , OAS2 , or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV-2 stimulation. Exogenous 2-5A suppresses cytokine production in OAS1- but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by MAVS deficiency. Recessive OAS–RNase L deficiencies in these patients unleash the production of SARS-CoV-2–triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.

Cardiac involvement is a common and serious problem in multisystem inflammatory syndrome in children (MIS-C). Echocardiographic evaluation of systolic and diastolic function by traditional, tissue Doppler and three-dimensional (3D) echocardiography was performed in consecutive 50 MIS-C patients during hospitalization and age-matched 40 healthy controls. On the day of worst left ventricular (LV) systolic function (echo-1), all left and right ventricular systolic function parameters were significantly lower ( p < 0.001), E/A ratio was significantly lower, and averaged E/e′ ratio was significantly higher (median 1.5 vs. 1.8, p < 0.05; 8.9 vs. 6.3, p < 0.001 respectively) in patients compared to control. Patients were divided into 2 groups according to 3D LV ejection fraction (LVEF) on the echo-1: Group 1; LVEF < 55%, 26 patients, and group 2; LVEF ≥ 55%, 24 patients. E/e′ ratio was significantly higher in group 1 than group 2 and control at discharge (median 7.4 vs. 6.9, p = 0.005; 7.4 vs. 6.3, p < 0.001 respectively). Coronary ectasia was detected in 2 patients (z score: 2.53, 2.6 in the right coronary artery), and resolved at discharge. Compared with group 2, group 1 had significantly higher troponin-I (median 658 vs. 65 ng/L; p < 0.001), NT-pro BNP (median 14,233 vs. 1824 ng/L; p = 0.001), procalcitonin (median 10.9 vs. 2.1 µg/L; p = 0.009), ferritin (median 1234 vs. 308 µg/L; p = 0.003). The most common findings were ventricular systolic dysfunction recovering during hospitalization, and persisting LV diastolic dysfunction in the reduced LVEF group at discharge. Coronary artery involvement was rare in the acute phase of the disease. Also, in MIS-C patients, the correlation between LV systolic dysfunction and markers of inflammation and cardiac biomarkers should be considered. Supplementary Information The online version contains supplementary material available at 10.1007/s00246-021-02738-3.

No abstract

Objectives:The aims of this study were to evaluate the role of biological agents in the treatment of severe multisystem inflammatory syndrome in children (MIS-C) and to assess the current application, outcomes, and adverse effects in patients who are followed up in a pediatric intensive care unit (PICU).Patients and Methods: This observational, descriptive, medical records review study was performed on patients with MIS-C admitted to the PICU between September 1 and November 1, 2020. Through medical records review, we confirmed that patients were positive for current or recent SARS-CoV-2 infection or for COVID-19 exposure history within the 4 weeks before the onset of symptoms.Results: A total of 33 patients with severe MIS-C were included (21 male) with a median age of 9 years. The most common signs and symptoms during disease course were fever (100%) and abdominal pain (75.5%). Clinical features of 63.6% patients were consistent with Kawasaki disease/Kawasaki disease shock syndrome, and 36.4% were consistent with secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Myocardial dysfunction and/or coronary artery abnormalities were detected in 18 patients during the PICU stay. Intravenous immunoglobulin and corticosteroids were given to 33 patients. Anakinra was administered to 23 patients (69.6%). There was a significant increase in lymphocyte and platelet counts and a significant decrease in ferritin, B-type natriuretic peptide, and troponin levels at the end of the first week of treatment in patients who were given biological therapy. Two patients were switched to tocilizumab because of an insufficient response to anakinra. The mortality rate of MIS-C patients admitted in PICU was 6.0%.Conclusions: Management of systemic inflammation and shock is important to decrease mortality and the development of persistent cardiac dysfunction in MIS-C. The aggressive treatment approach, including biological agents, may be required in patients with severe symptoms and cardiac dysfunction.

Background and aim: Creating potential clinical markers for risk assessment in patients with COVID-19 continues to be an area of interest. In this study, we aimed to evaluate whether serum albumin level and thrombocyte/lymphocyte ratio are related to the severity of the disease. Materials and methods:The patients were divided into two groups according to the severity of disease. Demographic data, serum albumin value, lymphocyte count, TLO-1 values (thrombocyte/lymphocyte ratio-1), the highest thrombocyte count during hospitalization, TLO-2 (thrombocyte/lymphocyte ratio-2) values formed by the highest thrombocyte count, were recorded.Results: There was no statistically significant differences (P > 0.05) in terms of sex, thrombocyte count at the time of admission, and highest thrombocyte count during hospital follow-up. There were statistically significant differences in terms of age, comorbidity, lymphocyte value at the time of hospitalization, lymphocyte count during hospital follow-up, TLO 1, TLO 2, and serum albumin values between the groups. The ICU group were found to be older, had higher rates of comorbidity, lower lymphocyte values, higher TLO 1-2, and lower serum albumin levels (P < 0.05). Conclusion:TLO-2 ratio above 260 and lymphocyte level below 1 103 cells/µL, would be a predictor of further intensive care unit need.

Background Heterozygous relatives of ataxia‐telangiectasia (AT) patients are at an increased risk for certain AT‐related manifestations. We also show that there is an increase of infection frequency in parents of AT patients. Thus, we hypothesized that the parents might exhibit immune alterations similar to their affected children. Methods Lymphocyte phenotyping to enumerate T‐ and B‐cell subsets was performed. Functional analyses included in vitro quantified γ‐H2AX, poly (ADP‐ribose) polymerase (PARP) and caspase‐9 proteins. Chromosomal instability was determined by comet assay. Results We analyzed 20 AT patients (14F/6M), 31 parents (16F/15M), and 35 age‐matched healthy controls. The AT patients’ parents exhibited low frequency of naive CD4+ T‐ (n = 14, 45%) and recent thymic emigrants (n = 11, 35%) in comparison with the age‐matched healthy donors. Interestingly, parents with low naive T cells also demonstrated high rate of recurrent infections (9/14, 64%). In comparison with age‐matched controls, parents who had recurrent infections and low naive T cells showed significantly higher baseline γ‐H2AX levels and H2O2‐induced DNA damage as well as increased cleaved caspase‐9 and PARP proteins. Conclusion Parents of AT patients could present with recurrent infections and display cellular defects that mimic AT patients. The observed immunological changes could be associated with increased DNA double‐strand breaks.

Giriş: Optik sinir kılıfı çapı (OSKÇ) kafa içi basınç artışı (KİBA) tanısının koyulması için ölçülür. Bilgisayarlı Tomografi (BT) ve Manyetik Rezonans görüntüleme (MRI) KİBA tespiti için sık kullanılır. Son zamanlarda ultrasonografik (US) yaklaşımla yapılan OSKÇ ölçümleri yatak başında kolayca yapılabilmesi ve sık tekrarlanabilir olması nedeniyle seçenek bir yöntem olarak öne çıkmaktadır. Çalışmamızda US ile yatak başında yapılan OSKÇ ölçümlerinin BT ve MRI ile yapılan ölçümlerle uyumu araştırıldı. Yöntemler: Araştırmamız tek merkezli, ileriye yönelik bir çalışmadır. Herhangi bir sebeple beyin BT/MRI'sı çekilmiş olup US uygulanabilen tüm 1 ay-18 yaş entübe hastalar, aile onamı alınarak çalışmaya dahil edildi. Tek bir nöroradyolog tarafından ölçülen BT/MRI OSKÇ değerleri ile tek bir araştırmacı tarafından saptanan US değerleri karşılaştırıldı. Bulgular: Çalışmamızda toplam 94 ölçüm yapıldı. US ile sağ gözde ortalama OSKÇ 4,56±0,66 cm, sol gözde ise 4,52±0,63 cm idi. BT/ MRI ölçümleri ise sağda 4,65±0,72 cm, solda 4,46±0,67 cm idi. Sağ ve sol taraflı US ve BT/MRI ortalama ölçümleri arasında anlamlı fark yoktu (p=0,4). Sağ OSKÇ için BT ve US ölçümleri arasındaki korelasyon kat sayısı r=0,448 (p=0,002), sol OSKÇ için ise r=0,448 (p=0,001) olup, BT ve US ölçümlerinde korelasyon her iki göz OSKÇ için lineer artış göstermekte ve aralarında orta derecede korelasyon bulunmaktaydı. Santral görüntüleme ile US arasında geçen sürenin 5 saatin altında olduğu 8 olguda BT/MRI ve US ile yapılan OSKÇ ölçümleri arasındaki korelasyonun arttığı (sağ r=0,774, p=0,024: sol r=0,811, p=0,014) görüldü. Introduction: Optic nerve sheath diameter (ONSD) measurements aid in diagnosis of increased intracranial pressure (ICP). Computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used modalities for detecting ICP. Lately, ONSD measurements via ultrasound (US) are getting popular as an alternative method due to the ease of performance at the bedside and repeatability. Our study objective was to investigate whether US measurements correlated with CT/MRI counterparts. Methods: This was a single-center, prospective study. All intubated patients aged 1 month-18 years with a cranial CT/MRI for any indications, who could be scanned ultrasonographically, were included after parental consent. Optic nerve US was performed by a single investigator. CT/MRI ONSDs were measured by a neuro-radiologist. Data obtained from US and CT/MRI scans were compared. Results: A total of 94 different measurements were obtained. The mean ONSD in US and CT was 4.56±0.66 cm and 4.65±0.72cm on the right side, whereas the mean left ONSD was 4.52±0.63 cm and 4.46±0.67 cm, respectively (p=0.4). Correlation coefficient for right ONSD was r=0.448 (p=0.002) while it was r=0.448 (p=0.001) for left ONSD. Both CT and US measurements showed a linear increase, and the correlation between them was moderate. A subgroup of 8 patients who had less than 5 hours between their central imaging and US scan showed strong correlation between measurements for both right and lef...

Aim: Coronavirus disease 2019 (COVID-19) is a pandemic with potential life-threatening outcomes. The current study aims to demonstrate the effect of tocilizumab in COVID-19 related cytokine storm. Material and Method: This retrospective cross-sectional study evaluated the patients who received tocilizumab for COVID-19 related cytokine storm between March and August 2020. Demographic, clinical, and laboratory findings were recorded. Computerized tomography (CT) scans, which were performed before tocilizumab infusion were scored. The characteristics of the patients who survived versus those who did not survive were assessed. Results: There was a total of 137 patients, 99 (72.3%) male and 38 (27.7%) female, with a median age of 62 years. Eighty-six (62.7%) patients had severe; 51 (37.2%) patients had critical disease course. The mortality rate was 24.1%. Higher mortality rates were present among patients older than 65 years, females, and with comorbid diseases (p=0.02, p=0.031, and p=0.01, respectively). The non-survived group had higher rates of mechanical ventilation (MV) support (85.2%) and admission to the intensive care unit (58.8%) (p