Comparison of general pediatric ward admissions between the COVID-19 pandemic and pre-pandemic period.

BACKGROUND: The COVID-19 pandemic has affected many aspects of life as well as hospital admissions. We hypothesized that many infectious diseases and hospitalizations in the pediatric age group might have decreased during the pandemic period. OBJECTIVE: Evaluate patients admitted to the general pediatric wards during the pandemic in comparison with the pre-pandemic period. DESIGN: Retrospective cross-sectional SETTING: General pediatrics wards of a tertiary hospital in Istanbul PATIENTS AND METHODS: The study included patients aged 0-18 years who were followed up while hospitalized in the general pediatrics wards between 11 March 2019 and 11 March 2021. The hospitalizations were grouped as pre-pandemic and pandemic based on the date when COVID-19 was declared a pandemic (11 March 2020). MAIN OUTCOME MEASURES: Hospital admissions, length of stay, diagnoses, gender, age. SAMPLE SIZE AND CHARACTERISTICS: 4343 hospitalizations. RESULTS: Of the total 4343 hospitalizations meeting the inclusion criteria, 2786 (64.1%) occurred before the pandemic and 1557 (35.9%) during the pandemic, a 44% decrease. The distribution of all hospitalization diagnoses during the two years was as follows: respiratory tract diseases, 1768 (40.7%); neurological diseases, 946 (21.8%); gastrointestinal diseases, 550 (12.7%); hematological and oncological diseases, 514 (11.8%); genitourinary system and nephrological diseases, 504 (11.6%); and soft tissue infections, 255 (5.9%). During two years, there were 1418 (32.7%) patients with lower respiratory tract infections, 316 (7.3%) with gastroenteritis, and 440 (10.1%) with urinary system infections. The median hospital stay was 6 days before the pandemic and 4 days during the pandemic (P<.0001). During the pandemic, the rate of respiratory diseases decreased from 48.7 to 26.5%, and that of lower respiratory tract infections decreased from 40.5 to 18.6% (P<.0001). CONCLUSION: Both previous studies and our results indicate that many infectious diseases in the pediatric age group significantly decreased, especially in the first months of the COVID-19 pandemic. LIMITATIONS: Single-center study. CONFLICT OF INTEREST: None.

The characteristics of patients with COVID-19-associated pediatric vasculitis: an international, multicenter study.

OBJECTIVE: COVID-19 associated pediatric vasculitis other than Kawasaki disease (KD)-like vasculitis in multisystem inflammatory syndrome in children (MIS-C) is very rare. We aimed to analyze the characteristics, treatment and outcome in COVID-19-associated pediatric vasculitis (excluding KD-like vasculitis in MIS-C). METHODS: The inclusion criteria were as follows: 1) <18 years at vasculitis onset; 2) evidence of vasculitis; 3) evidence of SARS-CoV-2 exposure; 4) ≤3 months between SARS-CoV-2 exposure and vasculitis onset. Patients with MIS-C were excluded. RESULTS: Forty-one patients (median age 8.3 years; M/F=1.3) were included from 14 centers and six countries. The most frequent vasculitis subtype was IgA vasculitis/Henoch Schönlein purpura (IgAV/HSP) (n=30). The median duration between SARS-CoV-2 exposure and vasculitis onset was 13 days. Skin (92.7%) and gastrointestinal (61%) involvements were the most common manifestations of vasculitis. Most patients (68.3%) received corticosteroids; while 14.6% used additional immunosuppressive drugs. Remission was achieved in all. All IgAV/HSP patients had skin manifestations while 18 (60%) and 13 (43.3%) had gastrointestinal system and renal involvement, respectively. When we compared the features of these patients with those of a pre-pandemic pediatric IgAV/HSP cohort (n=159), fever (30% vs. 5%; p<0.001) and renal involvement (43.3% vs. 17.6%; p=0.002) were more common, while recovery without treatment (10% vs. 39%; p=0.002) and complete recovery (86.7% vs. 99.4%; p=0.002) were less frequent among COVID-19-associated IgAV/HSP patients. CONCLUSION: This is the largest cohort of children with COVID-19 associated vasculitis (excluding MIS-C). Our findings suggest a more severe disease course in COVID-19-associated pediatric IgAV/HSP patients compared to pre-pandemic patients. This article is protected by copyright. All rights reserved.

Anakinra treatment in multisystemic inflammatory syndrome in children (MIS-C) associated with COVID-19.

Objective: The study aimed to report the efficacy and safety of anakinra treatment in patients with the refractory multisystemic inflammatory syndrome in children (MIS-C). Methods: This is a cross-sectional retrospective study consisting of pediatric patients diagnosed with MIS-C who were treated with anakinra. Results: Among the 378 patients diagnosed with MIS-C, 82 patients (21.6%) who were treated with anakinra were included in the study. The median age of patients was 115 (6-214) months. The median duration of hospitalization was 15 (6-42) days. Sixty patients (73.1%) were admitted to the pediatric intensive care unit. Patients were treated with a median dose of 2.7 mg/kg/day anakinra concomitant with IVIG and steroids. Intravenous anakinra was applied to 12 patients while 70 patients received it subcutaneously. Twenty-eight patients required high dose (4-10 mg/kg/day) anakinra. The median day of anakinra initiation was 2 (1-14) days and the median duration of anakinra use was 7 (1-41) days. No injection site reactions were observed while elevated transaminase levels were detected in 13 patients. Seventy-three patients (89.1%) were discharged without any sequela or morbidity. Seven patients (1.8%) died. Abnormal echocardiographic findings continued in two patients (2.4%) (coronary artery dilatation in one, low ejection fraction in one) at discharge and became normal on the 2nd month. Conclusion: Based on the results of the study, anakinra was associated with clinical improvements and was safe for most patients with refractory MIS-C.

Radiological findings of multisystem inflammatory syndrome in children associated with COVID-19.

OBJECTIVE: To retrospectively evaluate the imaging and clinical findings of patients diagnosed with multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. METHODS: The clinical, laboratory and radiological data of 110 patients (74 male and 36 female) diagnosed with COVID-19-related MIS-C between June 2020 and November 2021 were evaluated retrospectively. Cases with a diagnosis of MIS-C based on a positive real time polymerase chain reaction (RT-PCR) test or serology results according to the WHO criteria were included in the study. All the radiological data were evaluated by a pediatric radiologist with 14 years of radiology experience. RESULTS: Peribronchial thickening and hyperinflation were the most common findings on chest X-ray, while atelectasis and pleural effusion were often present in thoracic CT. Cardiac involvement was detected in 30% of the patients, mainly with valve insufficiency and systolic dysfunction, and 7.2% of these patients had sequalae findings. The most common abdominal findings were hepatosplenomegaly, mesenteric inflammation, lymphadenomegaly, thickening of the intestinal walls and free fluid. 23 of the patients had comorbidities. Neurological radiological findings observed in a total of six patients were reversible splenial lesion syndrome, posterior reversible encephalopathy syndrome, meningitis, and cerebral edema. 37 patients were followed up in the intensive care unit and 2 of them died. CONCLUSION: Radiological findings seen in MIS-C vary according to the affected system. There is no specific radiologic finding for this disease, but radiological findings can assist in the evaluation of affected systems and guide treatment. ADVANCES IN KNOWLEDGE: Since there are few studies with a limited number of patients in the literature, data on this subject are limited. We aimed to contribute to the literature with our large patient data.

The Multifaceted Presentation of the Multisystem Inflammatory Syndrome in Children: Data from a Cluster Analysis.

BACKGROUND: The aim of this study was to evaluate the outcomes of patients with the multisystem inflammatory syndrome in children (MIS-C) according to phenotypes of disease and define the prognostic factors for the severe course. METHODS: This cross-sectional study included 293 patients with MIS-C from seven pediatric rheumatology centers. A two-step cluster analysis was performed to define the spectrum of disease and their outcomes were compared between each group. RESULTS: Four subgroups were identified as follows: cluster I, predominantly Kawasaki-like features (n = 100); cluster II, predominantly MAS-like features (n = 34); cluster III, predominantly LV dysfunction (n = 47); cluster IV, other presentations (n = 112). The duration of fever was longer in cluster II and the length of hospitalization was longer in both clusters II and III. Laboratory findings revealed lower lymphocyte and platelet counts and higher acute phase reactants (APRs) in cluster II, while patients in cluster IV showed less inflammation with lower APRs. The resolution of abnormal laboratory findings was longer in clusters II and III, while it was shortest in cluster IV. Seven patients died. Among them, four belonged to cluster II, while three were labeled as cluster III. Patients with severe course had higher levels of neutrophil-lymphocyte ratio, mean platelet volume, procalcitonin, ferritin, interleukin-6, fibrinogen, D-Dimer, BNP, and troponin-I, and lower levels of lymphocyte and platelet counts. CONCLUSION: As shown, MIS-C is not a single disease presenting with various clinical features and outcomes. Understanding the disease spectrum will provide individualized management.

The clinical course and short-term health outcomes of multisystem inflammatory syndrome in children in the single pediatric rheumatology center.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition resulting in excessive response of the immune system after SARS-CoV-2 infection. We report a single-center cohort of children with MIS-C, describing the spectrum of presentation, therapies, clinical course, and short-term outcomes. METHODS: This is a prospective observational study from to a tertiary pediatric rheumatology center including patients (aged 1 month to 21 years) diagnosed with MIS-C between April 2020-April 2021. Demographic, clinical, laboratory results and follow-up data were collected through the electronic patient record system and analyzed. RESULTS: A total of 67 patients with MIS-C were included in the study. Fever was detected in all patients; gastrointestinal system symptoms were found in 67.2% of the patients, rash in 38.8%, conjunctivitis in 31.3%, hypotension in 26.9% myocarditis, and/or pericarditis in 22.4%, respectively. Respiratory symptoms were only in five patients (7.5%). Kawasaki Disease like presentation was found 37.3% of the patients. The mean duration of hospitalization was 11.8 7.07 days. Fifty-seven patients (85%) received intravenous immunoglobulin (IVIG), 45 (67%) received corticosteroids, 17 (25.3%) received anakinra, and one (1.5%) received tocilizumab. Seven of the patients (10.4%) underwent therapeutic plasma exchange (TPE). In 21 (31.3%) patients, a pediatric intensive care unit (PICU) was required in a median of 2 days. The first finding to improve was fever, while the first parameter to decrease was ferritin (median 6.5 days (IQR, 4-11.2 days)). Sixty-five patients were discharged home with a median duration of hospital stay of 10 days (IQR, 7-15 days). CONCLUSION: Patients with MIS-C may have severe cardiac findings and intensive care requirements in admission and hospital follow-up. The vast majority of these findings improve with effective treatment without any sequelae until discharge and in a short time in follow-up. Although the pathogenesis and treatment plan of the disease are partially elucidated, follow-up studies are needed in terms of long-term prognosis and relapse probabilities.

The clinical course of SARS-CoV-2 infection among children with rheumatic disease under biologic therapy: a retrospective and multicenter study.

The effects of biological disease-modifying antirheumatic drugs (bDMARDs) in the clinical course of COVID-19 on children with underlying rheumatologic diseases have not been fully demonstrated. To evaluate the course of COVID-19 infection in patients with rheumatic disease receiving bDMARD treatment. This was a retrospective, multicenter study conducted in pediatric patients infected by SARS-CoV-2 and under bDMARDs therapy. The study population consisted of 113 patients (72 female/41 male). The mean age of the patients was 12.87 ± 4.69 years. The primary diagnosis of the cohort was as follows: 63 juvenile idiopathic arthritis, 35 systemic autoinflammatory diseases, 10 vasculitides, and five cases of connective tissue diseases. The mean duration of the primary disease was 4.62 ± 3.65 years. A total of 19 patients had additional comorbid diseases. Thirty-five patients were treated with canakinumab, 25 with adalimumab, 18 with etanercept, 10 with infliximab, nine with tocilizumab, six with rituximab, four with anakinra, three with tofacitinib, and one with abatacept. The median exposure time of the biological drug was 13.5 months. Seventy-one patients had symptomatic COVID-19, while 42 were asymptomatic. Twenty-four patients required hospitalization. Five patients presented with MIS-C. The hospitalized patients were younger and had a shorter duration of rheumatic disease compared to ambulatory patients, although the difference was not statistically significant. Steroid usage, presence of fever, and dyspnea were more common among the hospitalized patients. A worsening in the course of both COVID-19 and current disease was not noticed under bDMARDs, however, to end with a strong conclusion multicentric international studies are required.

Evaluation of radiological findings in pediatric patients with COVID-19 in Turkey.

OBJECTIVE: The objective of the study was to describe the findings of pediatric patients diagnosed with COVID-19 in computed tomography (CT) and chest X-ray (CXR) images. Therefore, the aim of this study is to show protecting the children from radiation as much as possible while guiding the diagnosis. METHODS: Between March and June 2020, 148 pediatric patients examined who underwent CT due to suspicion of COVID-19. Fifty patients of 148 with normal thorax CT and negative reverse transcription polymerase chain reaction (RT-PCR) were excluded from the study. Of the remaining 98 patients were evaluated retrospectively by two pediatric radiologists with 15 years of experience. RESULTS: The demographic, clinical, and laboratory data were evaluated for 52 RT-PCR-positive patients. CT finding of 23 RT-PCR positive and 12 negative patients was classified. According to our study, unilateral (61-67%), multifocal (50-52%), and peripheral (83-91%) involvement were higher in all groups. Lower lobe involvement was frequently detected (58-65%). The most frequently detected parenchymal lesion was ground-glass opacity followed by consolidated areas accompanying ground-grass opacities. Halo sign and vascular enlargement signs were the common signs of lung lesions (35%). In addition, some rare findings not previously described in this disease in children were mentioned in this study. The clinical course of all our patients was mild and control radiological imaging checked by CXR. CONCLUSION: Most pediatric patients have a mild course. Hence, a balance between the risk of radiation and necessity for chest CT is very important. Low-dose CT scan is more suitable for pediatric patients but still it should be used cautiously.

Differences and similarities of multisystem inflammatory syndrome in children, Kawasaki disease and macrophage activating syndrome due to systemic juvenile idiopathic arthritis: a comparative study.

To compare the clinical and laboratory findings of multisystem inflammatory syndrome in children (MIS-C), patients with Kawasaki disease (KD) and with macrophage activating syndrome due to systemic juvenile idiopathic arthritis (sJIA-MAS) on real-life data. Patients diagnosed with MIS-C, KD, and sJIA-MAS from 12 different centers in Turkey who were followed for at least 6 months were included in the study. Demographic, clinical, and laboratory findings of all patients were analyzed. A total of 154 MIS-C, 59 KD, and 31 sJIA-MAS patients were included. The median age of patients with MIS-C were higher than those with KD while lower than those with sJIA-MAS (8.2, 3, 12 years, respectively). Myalgia (39.6%), cardiac (50.6%), gastrointestinal (72.7%), and neurological (22.1%) involvements were more common in patients with MIS-C compared to others. MIS-C patients had lower levels of lymphocyte (950 vs 1700 cells/µl) and thrombocyte (173,000 vs 355,000 cells/µl) counts and higher pro-BNP (1108 vs 55 pg/ml) levels than KD. Ferritin levels were higher in patients with MIS-C compared to patients with KD while they were lower than patients with sJIA-MAS (440, 170, 10,442 ng/ml, respectively). Patients with MIS-C had a shorter duration of hospitalization than sJIA-MAS (p = 0.02) while they required intensive care unit admission more frequently (55 vs 8 patients, p < 0.001). The median MAS/sJIA score of MIS-C patients was - 1.64 (- 5.23 to 9.68) and the median MAS/sJIA score of sJIA-MAS patients was -2.81 ([- 3.79] to [- 1.27]). MIS-C patients displayed certain differences in clinical and laboratory features when compared to KD and sJIA-MAS. Definition of the differences and similarities between MIS-C and the other intense inflammatory syndromes of childhood such as KD and MAS will help the clinicians while making timely diagnosis.

SARS-CoV-2 infection in children with rheumatic disease: Experience of a tertiary referral center.

OBJECTIVES: In this study, we present our clinical severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) experience in patients with childhood rheumatic disease during novel coronavirus-2019 (COVID-19) pandemic. PATIENTS AND METHODS: A total of 87 patients (50 males, 37 females; median age: 12 years; range, 6.6 to 16 years) suspected of having COVID-19 at our pediatric rheumatology clinic between March 11th and October 15th 2020 were retrospectively analyzed. Demographic and clinical features, treatments, laboratory results, imaging findings, and clinical outcomes of the patients diagnosed with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) were retrieved from the medical records. The diagnosis of SARS-CoV-2 infection was made based on the reverse transcriptase-polymerase chain reaction test. RESULTS: The most common rheumatic diseases were juvenile idiopathic arthritis and familial Mediterranean fever (35.6% and 34.5%, respectively). Twenty-six of these patients were treated with biological disease-modifying anti-rheumatic drugs. SARS-CoV-2 infection was tested as positive in 84 (96.5%) patients. Also, 51 (58.6%) patients had an epidemiological contact to a person with COVID-19. Eighteen patients met the clinical criteria and diagnosed with MIS-C. The COVID-19 outbreak also caused exacerbation of systemic disease in 56 children due to medication cessation, postponed drug switch, or recurrent viral infection. CONCLUSION: Children with rheumatic disease do not appear to present a higher risk of severe COVID-19. The immunosuppressive treatments can be adjusted in case of infection; otherwise, it is not recommended to interrupt the treatments. Physicians should be cautious about the hyperinflammatory syndrome associated with COVID-19 in rheumatic children, which may be severe in this group of patients and may be confused with primary diseases.

The Role of Therapeutic Plasma Exchange (TPE) in Multisystem Inflammatory Syndrome in Children (MIS-C).

Multisystemic inflammatory syndrome in children (MIS-C) is a new potentially life-threatening disease that is related to coronavirus disease 2019 (COVID-19). The aim of this study is to reveal the clinical and laboratory results of MIS-C and the role of therapeutic plasma exchange (TPE) in its treatment. Clinical, laboratory and radiological characteristics of the patients who were admitted to the pediatric ward and pediatric intensive care unit (PICU) of a tertiary hospital with a diagnosis of MIS-C between April 2020 and March 2021 were included in the study. Forty-one patients were admitted to our hospital with a diagnosis of MIS-C. Twenty-one (51.2%) patients were admitted to the PICU. Six patients needed invasive mechanical ventilation (14.6%), 10 patients (24.4%) TPE and 3 patients (7.3%) needed extracorporeal membrane oxygenation (ECMO). The patients were grouped according to need for PICU admission (Group 1: no need for PICU, Group 2: need for PICU admission). Group 2 had significantly higher levels of C-reactive protein (CRP), alanine aminotransferase (ALT), ferritin, D-dimer, pro-B type natriuretic peptide (pro BNP) and lactate (p < 0.05). Hyponatremia found to be an independent risk factor for inpatient MIS-C in the PICU. We think that dynamic laboratory trending is beneficial in determining the need for PICU admission and TPE may be effective in critically ill patients.