[Long COVID in Children: A Pediatric Center Experience]. / COVID-19 Nedeniyle Hastanede Yatan Çocuk Hastalarda Uzun Dönem Etkilerin ve Uzamis COVID Sikliginin Degerlendirilmesi.

Although COVID-19 (Coronavirus disease-2019) is observed to be milder in children, it has been observed that the symptoms continue for a long time in many people after the acute period of the disease, especially the multisystemic inflammatory syndrome (MISC) that developed after COVID-19 with the progression of the pandemic. Although it was first defined by different names such as long COVID and post COVID in adults, it has been observed in studies that similar complaints such as cough, fatigue and difficulty in concentrating continue for a long time in children, just as in adults. In our study, we aimed to evaluate the status of long COVID in childhood. Our study included patients aged from one month to 18 years with moderate and severe symptoms who were hospitalized and discharged for SARS-CoV-2 infection in Istanbul University Faculty of Medicine between November 1, 2020 and November 1, 2021. A questionnaire form was created to learn about the complaints of the patients and their ongoing complaints. The patients/parents were called by phone and their complaints were recorded in the questionnaire. The patients were classified according to the definitions in the guidelines published by NICE, RCGP and SIGN. In total, 116 patients were included; 57.8% (n= 64) male, 42.5% (n= 49) female; 53.4% (n= 62) 0-9, 46.6% (n= 54) 10-18 years old. Comorbid conditions were found in 64 (55.2%) patients. The mean follow-up period was 5.90 ± 3.61 [min-max (1-12)] months; longest symptom durations: decrease in effort loss/fatigue 19.25 ± 74.56 (0-365) days, concentration difficulties 11.12 ± 49.75 (0-365) days, fatigue 9.61 ± 34.96 (0-365) days and cough were 8.34 ± 35.37 (0-365) days. The percentage of the patients who met the definition of subacute/ongoing symptomatic COVID-19 was 37.9% (n= 44). The most common symptoms were the decrease of effort capacity/fatigue 12.1% (n= 14) and the concentration difficulties 10.3% (n= 12) in subacute symptomatic patients. The percentage of patients matching the definition of chronic/post COVID-19 was 11.2% (n= 13). In the first year of the disease, ongoing complaints such as fatigue and concentration difficulties were observed in eight patients. The rate of concentration difficulties in the 10-18 age group was statistically significantly higher than the 0-9 age group (p= 0.037). In terms of other symptoms, no significant difference was found according to age, gender and concomitant disease status. Out of these, one patient was diagnosed with Type 2 diabetes mellitus during the acute illness, and two patients were diagnosed with allergic rhinitis after COVID-19. A statistically significant difference was found in the rates of concentration disorders according to age groups with subacute/ongoing symptoms. Although only the hospitalized patients were included, fatigue and difficulty in concentration were among the most common ongoing symptoms in our study, similar to the literature, and they were seen to be more common in older children. It is important both for early diagnosis and awareness to follow up children with COVID-19 in terms of symptoms, not only in terms of prolonged symptoms but also in terms of new diseases.

Humoral response and safety of BNT162b2 mRNA vaccine in children with rheumatic diseases.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) vaccine represents a cornerstone in tackling the pandemic and with the approval of the BNT162b2 mRNA vaccine in December 2020, it has become a beacon of hope for people around the world, including children. This study aimed to present the data on the humoral response and safety of vaccine in a cohort of patients with paediatric rheumatic diseases receiving immunomodulatory treatments. METHODS: Forty-one children with paediatric rheumatic diseases were included and were vaccinated with the BNT162b2 mRNA vaccine (two doses of 30 µg administered 3-4 weeks apart). To assess the humoral response, IgG antibodies developed against the S1/Receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein at baseline and 3-4 weeks after the second dose were measured. The possible local and systemic side effects and disease activity scores were evaluated during the study period. RESULTS: After the second dose of vaccine, markedly elevated anti-RBD IgG titres were observed in all patients with a median titre of 20 474 AU/ml [interquartile range (IQR) 6534-36 151] with a good safety profile. The median disease duration was 4.3 (IQR 3.5-5.6) years. In the cohort, 14 (34.1%) received conventional DMARDs (cDMARDs), 16 (39%) received biologic DMARDs (bDMARDs) and 11 (26.8%) received a combined therapy (cDMARDs and bDMARDs). Patients treated with combined therapy [median 4695 (IQR 2764-26 491)] had significantly lower median titres of anti-RBD IgG than those receiving only cDMARDs. CONCLUSION: Paediatric rheumatic diseases patients receiving immunomodulatory treatments were able to mount an effective humoral response after two dose regimens of BNT162b2 mRNA vaccine safely without interrupting their current treatments.

Evaluation of vaccination status of health care workers for recommended vaccines and their acceptance of SARS-CoV-2 vaccines.

INTRODUCTION: Health care workers (HCWs) are disproportionately exposed to infectious diseases and play a role in nosocomial transmission, making them a key demographic for vaccination. HCW vaccination rates are not optimal in many countries; hence, compulsory vaccination policies have been implemented in some countries. Although these policies are effective and necessary under certain conditions, resolving HCWs' hesitancies and misconceptions about vaccines is crucial. HCWs have the advantage of direct contact with patients; hence, they can respond to safety concerns, explain the benefits of vaccination, and counter antivaccine campaigns that escalate during pandemics, as has been observed with COVID-19. METHOD: A short survey was carried out in May-June 2020 on the vaccination status of HCWs working with pediatric patients with COVID-19. The survey inquired about their vaccination status (mumps/measles/rubella [MMR], varicella, influenza, and diphtheria/tetanus [dT]) and willingness to receive hypothetical future COVID-19 vaccines. The respondents were grouped according to gender, age, occupation, and region. RESULTS: In total, 4927 HCWs responded to the survey. Most were young, healthy adults. The overall vaccination rates were 57.8% for dT in the past 10 years, 44.5% for MMR, 33.2% for varicella, and 13.5% for influenza. Vaccination rates were the highest among physicians. The majority of HCWs (81%) stated that they would be willing to receive COVID-19 vaccines. CONCLUSION: Although vaccination rates for well-established vaccines were low, a majority of HCWs were willing to receive COVID-19 vaccines when available. Education and administrative trust should be enhanced to increase vaccination rates among HCWs.

Multisystem inflammatory syndrome in children

As the COVID-19 pandemic continues, children can be infected with the virus that causes COVID-19. Clinical symptoms of children with COVID from China, where the disease was first reported, generally were less severe than adults. However, at the end of April 2020 in Europe, it was observed that some children with SARS-CoV-2 infection developed fever, abdominal pain, shock, myocardial insufficiency and they needed to be taken care of in intensive care unit. This new disease has been called multisystem inflammatory syndrome in children (MIS-C). Although the pathogenesis of MIS-C is unclear, it progresses with signs of multiorgan involvement as a result of uncontrolled inflammation of the immune system and even causes death. Therefore, the diagnosis and treatment of patients with MIS-C should be managed quickly. In this review, the pathophysiology, clinical and laboratory findings, diagnostic methods, and treatment regimens of MIS-C were discussed.

Multisystem inflammatory syndrome in children associated with COVID-19 in 101 cases from Turkey (Turk-MISC study).

AIM: Multisystem inflammatory syndrome in children (MIS-C) may cause shock and even death in children. The aim of this study is to describe the clinical features, laboratory characteristics and outcome of children diagnosed with MIS-C in 25 different hospitals in Turkey. METHODS: The retrospective study was conducted between 8 April and 28 October 2020 in 25 different hospitals from 17 cities. Data were collected from patients' medical records using a standardised form. Clinical and laboratory characteristics and outcomes according to different age groups, gender and body mass index percentiles were compared using multivariate logistic regression analysis. RESULTS: The study comprised 101 patients, median age 7 years (interquartile range (IQR) 4.6-9.3); 51 (50.5%) were boys. Reverse-transcriptase polymerase chain reaction (PCR) assay was positive in 21/100 (21%) patients; 62/83 (74.6%) patients had positive serology for SARS-CoV-2. The predominant complaints were fever (100%), fatigue (n = 90, 89.1%), and gastrointestinal symptoms (n = 81, 80.2%). Serum C-reactive protein (in 101 patients, median 165 mg/L; range 112-228), erythrocyte sedimentation rate (73/84, median 53 mm/s; IQR 30-84) and procalcitonin levels (86/89, median 5 µg/L; IQR 0.58-20.2) were elevated. Thirty-eight patients (37.6%) required admission to intensive care. Kawasaki disease (KD) was diagnosed in 70 (69.3%) patients, 40 of whom had classical KD. Most patients were treated with intravenous immunoglobulin (n = 92, 91%) and glucocorticoids (n = 59, 58.4%). Seven patients (6.9%) died. CONCLUSION: The clinical spectrum of MIS-C is broad, but clinicians should consider MIS-C in the differential diagnosis when persistent fever, fatigue and gastrointestinal symptoms are prominent. Most patients diagnosed with MIS-C were previously healthy. Immunomodulatory treatment and supportive intensive care are important in the management of cases with MIS-C. Glucocorticoids and intravenous immunoglobulins are the most common immunomodulatory treatment options for MIS-C. Prompt diagnosis and prompt treatment are essential for optimal management.

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 × µL, p = 0.028; platelet count 166 vs. 216 cells × 103/µL, p < 0.001). The median serum procalcitonin levels were statistically higher in patients overlapped with KD (3.18 vs. 1.68 µg/L, p = 0.001). Coronary artery dilatation was statistically significant in patients with overlap with KD (13.4% vs. 6.8%, p = 0.007), while myocarditis was significantly more common in patients without overlap with KD features (2.6% vs 7.4%, p = 0.009). The association between clinical and laboratory findings and overlap with KD was investigated. Age > 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). CONCLUSION: Almost half of the patients with MISC had clinical features that overlapped with KD; in particular, incomplete KD was present. The median age was lower in patients with KD-like features. Lymphocyte and platelet counts were lower, and ferritin and procalcitonin levels were significantly higher in patients with overlap with KD. WHAT IS KNOWN: • In some cases of MIS-C, the clinical symptoms overlap with Kawasaki disease. • Compared to Kawasaki disease, lymphopenia was an independent predictor of MIS-C. WHAT IS NEW: • Half of the patients had clinical features that overlapped with Kawasaki disease. • In patients whose clinical features overlapped with KD, procalcitonin levels were almost 15 times higher than normal. • Lethargy increased the risk of overlap with KD by 2.6-fold in MIS-C patients. • Transient bradycardia was noted in approximately 10% of our patients after initiation of treatment.

Correlation of laboratory parameters and Chest CT findings in young adults with COVID-19 and comparison of imaging findings with children.

PURPOSE: We aimed to compare COVID-19 imaging findings of young adults (19-35 years of age) with those of children (0-18 years) and to correlate imaging findings of young adults with their laboratory tests. MATERIALS AND METHODS: This retrospective study included Real Time-Polymerase Chain Reaction (RT-PCR) confirmed 130 young adults (mean age: 28.39 ± 4.77; 65 male, 65 female) and 36 children (mean age: 12.41 ± 4.51; 17 male, 19 female), between March and June 2020. COVID-19 related imaging findings on chest CT were examined in young adults and compared with children by the Mann-Whitney U, and Chi-square or Fisher's exact test. Laboratory examinations of young adults were assessed in terms of correlation with radiological findings by the Spearman's correlation analysis. RESULTS: Bilateral multiple distributions (p = 0.014), subpleural involvement, and pleural thickening (p = 0.004), GGOs with internal consolidations were more frequent in adults (p = 0.009). Infiltrations were significantly larger than 20 mm in young adults (p = 0.011). The rates of feeding vessel sign, vascular enlargement, and halo sign were significantly higher in young adults (p < 0.003). Highly significant positive correlations were found between radiological and biochemical parameters. CONCLUSION: Distribution, size, and pattern of COVID-19 related imaging findings differed in children and young adults. Radiological findings were correlated with biochemical parameters but not with blood count results of young adults.

Epidemiological, Clinical, and Laboratory Features of Children With COVID-19 in Turkey.

Objectives: The aim of this study is to identify the epidemiological, clinical, and laboratory features of coronavirus disease 2019 (COVID-19) in children. Methods: A retrospective study was conducted by pediatric infectious disease specialists from 32 different hospitals from all over Turkey by case record forms. Pediatric cases who were diagnosed as COVID-19 between March 16, 2020, and June 15, 2020 were included. Case characteristics including age, sex, dates of disease onset and diagnosis, family, and contact information were recorded. Clinical data, including the duration and severity of symptoms, were also collected. Laboratory parameters like biochemical tests and complete blood count, chest X-ray, and chest computed tomography (CT) were determined. Results: There were 1,156 confirmed pediatric COVID-19 cases. In total, male cases constituted 50.3% (n = 582) and females constituted 49.7% (n = 574). The median age of the confirmed cases was 10.75 years (4.5-14.6). Of the total cases, 90 were younger than 1 year of age (7.8%), 108 were 1-3 years of age (9.3%), 148 were 3-6 years of age (12.8%), 298 were 6-12 years of age (25.8%), 233 were 12-15 years of age (20.2%), and 268 cases were older than 15 years of age (23.2%). The most common symptom of the patients at the first visit was fever (50.4%) (n = 583) for a median of 2 days (IQR: 1-3 days). Fever was median at 38.4°C (38.0-38.7°C). The second most common symptom was cough (n = 543, 46.9%). The other common symptoms were sore throat (n = 143, 12.4%), myalgia (n = 141, 12.2%), dyspnea (n = 118, 10.2%), diarrhea (n = 112, 9.7%), stomachache (n = 71, 6.1%), and nasal discharge (n = 63, 5.4%). When patients were classified according to disease severity, 263 (22.7%) patients were asymptomatic, 668 (57.7%) patients had mild disease, 209 (18.1%) had moderate disease, and 16 (1.5%) cases had severe disease. One hundred and forty-nine (12.9%) cases had underlying diseases among the total cases; 56% of the patients who had severe disease had an underlying condition (p < 0.01). The need for hospitalization did not differ between patients who had an underlying condition and those who do not have (p = 0.38), but the need for intensive care was higher in patients who had an underlying condition (p < 0.01). Forty-seven (31.5%) of the cases having underlying conditions had asthma or lung disease (38 of them had asthma). Conclusions: To the best of our knowledge, this is one of the largest pediatric data about confirmed COVID-19 cases. Children from all ages appear to be susceptible to COVID-19, and there is a significant difference in symptomatology and laboratory findings by means of age distribution.

Plasma D-dimer : a promising indicator of COVID-19 infection severity or only an acute phase reactant.

OBJECTIVE: Serum D-dimer levels, as well as other biomarkers related to coagulation, are significantly elevated during severe community acquired pneumonia. The aim of this study is to investigate the utility of plasma D-dimer levels determining the severity of inflammation and prognosis in pediatric patients with COVID-19 infection. METHODS: We retrospectively chart reviewed medical records of pediatric patients (< 18 years of age) admitted to Istanbul Fcaulty of Medicine, Department of Pediatrics Infectious Disease Service between March 11, and June 30, 2020. We collected demographic, clinical, biochemical and radiographic data. RESULTS: A hundred and seventy-one pediatric patients (1 - 216 months of age) admitted to pediatric infecitous disease service included in this study. Patients were classified into 4 categories; 1) COVID-19 infection confirmed by PCR, 2) Suspected COVID-19 infection due to close exposure history and radiographic findings, 3) Lower respiratory tract infection other than COVID-19 confirmed with multiplex respiratory viral panel, and 4) Systemic infections other than lower respiratory tract infection. Lymphopenia was observed significantly higher in patients with COVID-19 infection compared to patients with other respiratory viral infections (p=0.06). In patients with radiographic findings concerning for COVID-19 infection, elevated serum D-dimer levels were detected significantly higher than lymphopenia (p=0.07). CONCLUSIONS: Elevated serum D-dimer levels at baseline are associated with inflammation especially in patients with COVID-19 infection with radipgraphic findings. Monitoring serum D-dimer levels may be used for early identification of severe cases in children.

Imaging Features of Pediatric COVID-19 on Chest Radiography and Chest CT: A Retrospective, Single-Center Study.

RATIONALE AND OBJECTIVES: This study aims to reveal the imaging features of Coronavirus Disease 2019 (COVID-19) in children. MATERIALS AND METHODS: Sixty-nine chest radiographs and 37 chest CT examinations of 74 children (36 male; median (interquartile range) age:11 (6.25-15) years, 38 female; median (interquartile range) age: 12 (5.75-16) years) with positive real-time reverse transcription-polymerase chain reaction results between March 10 and May 31, 2020, were evaluated in this retrospective study. Differences in 0-<6, 6-<12, and 12-18 years of age groups were assessed with the Fisher's exact test or Kruskal-Wallis tests. RESULTS: Right-sided (3/69, 4.3%) or bilateral (3/69, 4.3%) ground-glass opacities without significant difference in age groups were depicted as radiographic findings related to COVID-19 in children. Opacities were either single (7/37, 18.9%) or bilateral (7/37, 18.9%) around the distal third of the bronchovascular bundle on CT. There was no significant difference in the median size of the largest opacities, total numbers of opacities and involved lobes, and the distance of the closest opacity to the pleura among age groups (p > 0.05). The rate of ground-glass opacities with or without consolidation (17/37, 45.94%) was higher than consolidation alone (6/37, 16.2%). Feeding vessel sign (16/37, 43.2%), halo sign (9/37, 24.3%), pleural thickening (6/37, 16.2%), interlobular interstitial thickening (5/37, 13.5%), and lymphadenopathy (3/37, 8.1%) were other imaging findings. CONCLUSION: Unilateral or bilateral distributed ground-glass opacities often associated with feeding vessel sign, halo sign, and pleural thickening on chest CT without significant differences between age groups were findings of COVID-19 in children.