Changing Disease Course of Crimean-Congo Hemorrhagic Fever in Children, Turkey.

Crimean-Congo hemorrhagic fever (CCHF), endemic in certain regions of the world, is listed as a priority disease with pandemic potential. Since CCHF was first identified in Turkey, children have been known to experience milder disease than adults. However, during the COVID-19 pandemic, we observed an unusually severe disease course, including hemophagocytic lymphohistiocytosis (HLH). We examined cytokine/chemokine profiles of 9/12 case-patients compared with healthy controls at 3 time intervals. Interferon pathway-related cytokines/chemokines, including interleukin (IL) 18, macrophage inflammatory protein 3α, and IL-33, were elevated, but tumor necrosis factor-α, IL-6, CXCL8 (formerly IL-8), and cytokines acting through C-C chemokine receptor 2 and CCR5 were lower among case-patients than controls. Interferon pathway activation and cytokines/chemokines acting through CCR2 and CCR5 improved health results among children with severe CCHF. Children can experience severe CCHF, including HLH, and HLH secondary to CCHF can be successfully treated with intravenous immunoglobulin and steroid therapy.

The difference of the inflammatory milieu in MIS-C and severe COVID-19.

BACKGROUND: Coronavirus disease 19 (COVID-19) may have a severe course in children. Multisystem inflammatory syndrome in children (MIS-C) is the post-COVID complication characterized by an exaggerated inflammation, observed in children. However, data on the underlying pathophysiology are sparse. We therefore aimed to assess the cytokine and chemokine profiles of children with MIS-C and compare these to life-threatening severe SARS-CoV-2 and healthy controls (HCs) to shed light on disease pathophysiology. METHODS: Samples of 31 children with MIS-C, 10 with severe/critical COVID-19 and 11 HCs were included. Cytokine and chemokine profiles were studied and compared in between groups. RESULTS: Most cytokines and chemokines related to IL-1 family and IFN-γ pathway (including IL-18 and MIG/CXCL9) and IL-17A were significantly higher in the MIS-C group when compared to the severe/critical COVID-19 group and HCs. IP-10/CXCL10 and IL-10 were higher in both MIS-C patients and severe/critical COVID-19 compared to HCs. CONCLUSION: Our results suggest that IL-1 and IFN-γ pathways play an important role in the pathophysiology of MIS-C. IMPACT: This study defines a pattern of distinctive immune responses in children with MIS-C and in patients with severe/critical COVID-19. As the COVID-19 pandemic continues, biomarkers to identify MIS-C risk are needed to guide our management that study results may shed light on it.

Chest imaging for COVID-19: a single-center comparative results in pediatric patients.

BACKGROUND: Chest computed tomography (CT) appears to be an important radiological modality for the diagnosis of COVID-19 in adults. Studies comparing the findings of such children with those of other viral infections have not been reported either. The aim of this study was to present comparative imaging findings of 75 pediatric COVID-19 patients and four patients with other viral upper respiratory tract infections. We also aimed to demonstrate the possible association between the radiological and laboratory findings in the COVID group. METHODS: From 11 March 2020 to 20 June 2020, 79 children (aged < 18 years) were enrolled. COVID-19 was detected by RT-PCR or antibody testing. A plain chest X-ray was obtained from all subjects. Non-contrast chest CT was performed for symptomatic patients. RESULTS: Seventy-five patients had COVID-19 and 4 were infected with other pathogens i.e. adenovirus, rhinovirus, parainfluenza virus B, respiratory syncytial virus. The ages of the patients (36 M, 43 F) ranged from 7 months to 17 years old. The sensitivity of chest X-ray (as compared to RT-PCR) was 10.67% (95 CI%: 4.72 - 19.94%). From 23 chest CT`s five of them were normal and nine of them had only nodules ( < 5mm). The sensitivity of CT was 78.26% (95CI%: 54.30 - 92.54%), false-negative rate was 21.7%. CONCLUSIONS: The sensitivity of chest CT was found to be low and any significant correlations could have not been depicted, between the radiological parameters and the presence of lymphopenia. Clinical follow-up combined with corresponding pathogen detection, and chest CT of the symptomatic COVID-19 patients might be a feasible/prompt protocol in children.

AI-Based Quantitative CT Analysis of Temporal Changes According to Disease Severity in COVID-19 Pneumonia.

OBJECTIVE: To quantitatively evaluate computed tomography (CT) parameters of coronavirus disease 2019 (COVID-19) pneumonia an artificial intelligence (AI)-based software in different clinical severity groups during the disease course. METHODS: From March 11 to April 15, 2020, 51 patients (age, 18-84 years; 28 men) diagnosed and hospitalized with COVID-19 pneumonia with a total of 116 CT scans were enrolled in the study. Patients were divided into mild (n = 12), moderate (n = 31), and severe (n = 8) groups based on clinical severity. An AI-based quantitative CT analysis, including lung volume, opacity score, opacity volume, percentage of opacity, and mean lung density, was performed in initial and follow-up CTs obtained at different time points. Receiver operating characteristic analysis was performed to find the diagnostic ability of quantitative CT parameters for discriminating severe from nonsevere pneumonia. RESULTS: In baseline assessment, the severe group had significantly higher opacity score, opacity volume, higher percentage of opacity, and higher mean lung density than the moderate group (all P ≤ 0.001). Through consecutive time points, the severe group had a significant decrease in lung volume (P = 0.006), a significant increase in total opacity score (P = 0.003), and percentage of opacity (P = 0.007). A significant increase in total opacity score was also observed for the mild group (P = 0.011). Residual opacities were observed in all groups. The involvement of more than 4 lobes (sensitivity, 100%; specificity, 65.26%), total opacity score greater than 4 (sensitivity, 100%; specificity, 64.21), total opacity volume greater than 337.4 mL (sensitivity, 80.95%; specificity, 84.21%), percentage of opacity greater than 11% (sensitivity, 80.95%; specificity, 88.42%), total high opacity volume greater than 10.5 mL (sensitivity, 95.24%; specificity, 66.32%), percentage of high opacity greater than 0.8% (sensitivity, 85.71%; specificity, 80.00%) and mean lung density HU greater than -705 HU (sensitivity, 57.14%; specificity, 90.53%) were related to severe pneumonia. CONCLUSIONS: An AI-based quantitative CT analysis is an objective tool in demonstrating disease severity and can also assist the clinician in follow-up by providing information about the disease course and prognosis according to different clinical severity groups.

Longitudinal Follow-up of Antibody Responses in Pediatric Patients With COVID-19 up to 9 Months After Infection.

INTRODUCTION: Antibody response developed within 2-3 weeks after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to decrease over time; however, there is limited data about antibody levels at 6 months or later postinfection, particularly in children. MATERIALS AND METHOD: A prospective multicenter study was performed using 315 samples of 74 confirmed and 10 probable coronavirus disease 2019 pediatric cases. About 20% of these cases were classified as asymptomatic, 74% as mild/moderate and 6% as severe/critical. Patients were included if at least 2 samples were available. The antibody response was classified as either early-period or late-period (14 days-3 months and after 6 months, respectively) for IgG response whereas IgA response was tested on various time intervals, including as early as 4 days up to 3 months. Euroimmun Anti-SARS-CoV-2 IgG and IgA and Genscript SARS-CoV-2 Surrogate Virus Neutralization Kits were used for antibody detection. RESULTS: There was no difference between the early-period and late-period IgG positivity (P = 0.1). However, the median IgG levels were 11.98 in the early periods and 4.05 in the late periods, with a significance of P < 0.001. Although the decrease in IgG levels was significant in asymptomatic and mild/moderate cases (P < 0.008 and P < 0.001, respectively), the decrease in severe/critical cases was moderate (P = 0.285). The sensitivity of the IgG after 15 days was higher than 94%, and the sensitivity of IgA was 88% on days 8-15. CONCLUSION: SARS-CoV-2 IgG antibody levels decreased after 6 months. The decrease was moderate in severe/critical cases. Overall, 95.8% of the patients remained positive up to 9 months after infection. Although the IgA response may be useful early on, the IgG response is useful after 14 days.

Predictive value of cytokine/chemokine responses for the disease severity and management in children and adult cases with COVID-19.

The disease course of children with coronavirus disease 2019 (COVID-19) seems milder as compared with adults, however, actual reason of the pathogenesis still remains unclear. There is a growing interest on possible relationship between pathogenicity or disease severity and biomarkers including cytokines or chemokines. We wondered whether these biomarkers could be used for the prediction of the prognosis of COVID-19 and improving our understanding on the variations between pediatric and adult cases with COVID-19. The acute phase serum levels of 25 cytokines and chemokines in the serum samples from 60 COVID-19 pediatric (n = 30) and adult cases (n = 30) including 20 severe or critically ill, 25 moderate and 15 mild patients and 30 healthy pediatric (n = 15) and adult (n = 15) volunteers were measured using commercially available fluorescent bead immunoassay and analyzed in combination with clinical data. Interferon gamma-induced protein 10 (IP-10) and macrophage inflammatory protein (MIP)-3ß levels were significantly higher in patient cohort including pediatric and adult cases with COVID-19 when compared with all healthy volunteers (p ≤ .001 in each) and whereas IP-10 levels were significantly higher in both pediatric and adult cases with severe disease course, MIP-3ß were significantly lower in healthy controls. Additionally, IP-10 is an independent predictor for disease severity, particularly in children and interleukin-6 seems a relatively good predictor for disease severity in adults. IP-10 and MIP-3ß seem good research candidates to understand severity of COVID-19 in both pediatric and adult population and to investigate possible pathophysiological mechanism of COVID-19.

Multisystem inflammatory syndrome in children during the COVID-19 pandemic in Turkey: first report from the Eastern Mediterranean.

OBJECTIVE: We aimed to describe the typical clinical and laboratory features and treatment of children diagnosed with multisystem inflammatory syndrome in children (MIS-C) and to understand the differences as compared to severe/critical pediatric cases with COVID-19 in an eastern Mediterranean country. METHODS: Children (aged <18 years) who diagnosed with MIS-C and severe/critical pediatric cases with COVID-19 and were admitted to hospital between March 26 and November 3, 2020 were enrolled in the study. RESULTS: A total of 52 patients, 22 patients diagnosed with COVID-19 with severe/critical disease course and 30 patients diagnosed with MIS-C, were included in the study. Although severe COVID-19 cases and cases with MIS-C share many clinical and laboratory features, MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe cases (p<0.001 for each). Of all, 53.3% of MIS-C cases had the evidence of myocardial involvement as compared to severe cases (27.2%). Additionally, C-reactive protein (CRP) and white blood cell (WBC) are the independent predictors for the diagnosis of MIS-C, particularly in the existence of conjunctival injection and rash. Corticosteroids, intravenous immunoglobulin (IVIG), and biologic immunomodulatory treatments were mainly used in MIS-C cases rather than cases with severe disease course. There were only three deaths among 52 patients, one of whom had Burkitt lymphoma and the two cases with severe COVID-19 of late referral. CONCLUSION: Differences between clinical presentations, acute phase responses, organ involvements, and management strategies indicate that MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19. Conjunctival injection and higher CRP and low WBC count are reliable diagnostic parameters for MIS-C cases. Key Points • MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe/critical pediatric cases with COVID-19. • Higher CRP and low total WBC count are the independent predictors for the diagnosis of MIS-C. • MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19.

Diagnostic value of lung ultrasonography in children with COVID-19.

BACKGROUND: Lung ultrasound (LUS) has been successfully used in the diagnosis of different pulmonary diseases. Present study design to determine the diagnostic value of LUS in the evaluation of children with novel coronavirus disease 2019 (COVID-19). METHODS AND OBJECTIVES: Prospective multicenter study, 40 children with confirmed COVID-19 were included. LUS was performed to all patients at admission. The chest X-ray and computed tomography (CT) were performed according to the decision of the primary physicians. LUS results were compared with chest X-ray and CT findings and diagnostic performance was determined. RESULTS: Of the 40 children median (range) was 10.5 (0.4-17.8) years. Chest X-ray and LUS were performed on all and chest CT was performed on 28 (70%) patients at the time of diagnosis. Sixteen (40%) patients had no apparent chest CT abnormalities suggestive of COVID-19, whereas 12 (30%) had abnormalities. LUS confirmed the diagnosis of pulmonary involvement in 10 of 12 patients with positive CT findings. LUS demonstrated normal lung patterns among 15 of 16 patients who had normal CT features. The sensitivity and the area under the receiver operating characteristics (ROC) curve (area under the ROC curve) identified by the chest X-ray and LUS tests were compared and statistically significantly different (McNemar's test: p = .016 and p = .001 respectively) detected. Chest X-ray displayed false-negative results for pulmonary involvement in 75% whereas for LUS it was 16.7%. CONCLUSIONS: LUS might be a useful tool in the diagnostic steps of children with COVID-19. A reduction in chest CT assessments may be possible when LUS is used in the initial diagnostic steps for these children.