Evaluation of Tubular Dysfunction Using Urine Biomarkers in Children with COVID-19.

OBJECTIVE: The coronavirus disease pandemic is a major problem that the world has been facing since December 2019. It mainly affects the respiratory system; however, the disease can affect the kidneys to different degrees. This study aimed to determine the changes in tubular dysfunction and inflammation parameters in children with coronavirus disease using urine biomarkers. MATERIALS AND METHODS: We included 36 children who tested positive for severe acute respiratory syndrome coronavirus 2 on real-time reverse transcriptase-polymerase chain reaction using respiratory specimens. Coronavirus disease-positive and -negative period parameters were evaluated. For measurement of interleukin-1ß, interleukin-6, and urine ß2 microglobulin levels, patients' urine samples were collected at diagnosis and 1 month after discharge. Additionally, routine urine and hematological parameters were evaluated concurrently. RESULTS: For all patients, the median urine ß2 microglobulin, serum urea, and lactate dehydrogenase levels were significantly higher in the coronavirus disease-positive period than in the coronavirus disease-negative period (P < .05). Further, serum platelet count was significantly lower in the coronavirus disease-positive period than in the coronavirus disease-negative period (P < .05). However, there was no difference in serum creatinine, interleukin-6, or interleukin-1ß levels between the 2 periods (P > .05). CONCLUSION: Our results suggest kidney involvement and tubular dysfunction in patients with asymptomatic, mild, and moderate infections. Furthermore, interleukin-1ß and interleukin-6 levels were high in the urine, even in non-critically ill patients. We believe that these findings contribute to the accumulation of evidence on continued inflammation in the kidney.

Does aeroallergen sensitivity and allergic rhinitis in children cause milder COVID-19 infection?

Background: There are conflicting data with regard to the impact of respiratory and allergic comorbidities on the course of novel coronavirus disease 2019 (COVID-19) in children. Objective: This study aimed to investigate the relationship between allergic diseases and COVID-19 severity in pediatric patients. Methods: Seventy-five pediatric patients with COVID-19 were classified according to clinical severity and evaluated in the allergy/immunology and pulmonology departments 1 to 3 months after the infection resolved. Blood was collected from the patients for a complete blood cell count and assessment of immunoglobulin and total immunoglobulin E (IgE) levels, and skin-prick tests and spirometry tests were performed. Results: A total of 75 patients ages 5-18 years were evaluated. COVID-19 was asymptomatic/mild in 44 patients and moderate/severe/critical in 31 patients. Based on allergy evaluation, allergic rhinitis was diagnosed in 19 patients (25.3%), asthma in 10 patients (13%), and atopic dermatitis in 3 patients (4%). Aeroallergen sensitivity was detected in 26 patients (34.7%). COVID-19 infection was asymptomatic/mild in 15 patients with allergic rhinitis (78.9%) and in 21 with aeroallergen sensitivity (80.8%) (p = 0.038 and p = 0.005, respectively). There was no difference in severity between the patients with and without asthma (p = 0.550). The median (interquartile range) total IgE level was significantly higher in the asymptomatic/mild group (71.8 [30.7-211.2]) (p = 0.015). There were no differences in terms of spirometry parameters. Conclusion: Aeroallergen sensitization and allergic rhinitis in children may be associated with a milder course of COVID-19. The knowledge that atopy is associated with less-severe COVID-19 outcomes in children may guide clinical risk classification.

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.

The association of viral load and disease severity in children with COVID-19.

It is still not fully understood how to predict the future prognosis of patients at the diagnosis coronavirus disease 2019 (COVID-19) due to the wide clinical range of the disease. We aimed to evaluate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load could predict the clinical course of pediatric patients. This study was conducted retrospectively with medical records of pediatric patients who were tested for SARS-CoV2 between April 12 and October 25, 2020 in the University of Health Sciences, Ankara Educating and Training Hospital and Hacettepe University Faculty of Medicine. We evaluated 518 pediatric patients diagnosed with COVID-19 and classified according to severity as asymptomatic (16.2%), mild (59.6%), moderate (20.2%), and critical/severe (3.9%) cases. We analyzed patients in four groups in terms of ages: <4, 5-9, 10-14, and 15-17 years. There was no statistically significant difference in terms of ∆Ct value among age groups, different gender and the existence of underlying diseases in each disease course. The ∆Ct values were relatively lower in the first 2 days of symptoms than after days in all groups. Our study has indicated that children with COVID-19 have similar amount of viral load in all disease courses irrespective of the age and underlying disease. It should be taken into account that, regardless of the severity of the disease, pediatric patients may have a role in the transmission chain.

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.

Pneumococcal carriage in children with COVID-19.

Background: SARS-CoV-2 is the new virus, and Streptococcus pneumoniae is one of the most important pathogens affecting humans. However, we do not yet know whether these microorganisms interact. Thus, we aimed to evaluate the relationship between Streptococcus pneumoniae and SARS-CoV-2 in pediatric patients.Methods: This study was conducted retrospectively by means of medical records of pediatric patients who were tested for SARS-CoV-2 between March 11 and June 04, 2020, in the University of Health Sciences, Ankara Educating and Training Hospital and Hacettepe University Faculty of Medicine.Results: We evaluated 829 pediatric patients for S. pneumoniae and SARS-CoV-2 from their nasopharyngeal specimen. Of 115 children positive for SARS-CoV-2, 32.2% had a positive S. pneumoniae test, whereas of 714 children negative for SARS-CoV-2, 14.1% had a positive S. pneumoniae test (p < .01). We compared patients with positive vs. negative SARS-CoV-2 tests according to S. pneumoniae positivity There were no statistically significant differences in terms of gender, underlying disease, fever, cough, leukocytosis, lymphopenia, increased CRP, increased procalcitonin, findings of chest x-ray, severity of disease, and treatment.Conclusion: The nasopharyngeal S. pneumoniae carriage rate in patients with COVID-19 was higher than in non-infected children, while S. pneumoniae carriage did not affect the course of COVID-19 disease. Pneumococcal vaccination is significant, such that we do not know the outcomes of increased pneumococcal carriage for the upcoming months of pandemic.

Characteristics and Management of Children with COVID-19 in Turkey

Aims: Limited data about disease management strategies are available for pediatric patients with coronavirus disease-2019, particularly in Turkey. This study aimed to share the data on patients aged under 18 years in our country to be beneficial for understanding the disease course in children. Methods: A retrospective review of the medical records of pediatric patients aged under 18 years who were confirmed as coronavirus disease-2019 between March 11, and June 23, 2020, and were admitted to our hospitals was conducted. Results: A total of 220 pediatric patients with coronavirus disease-2019 were evaluated, of which 48.2% were boys, with a median age of 10 years, and 9.5% had underlying diseases. Patients were classified according to severity, with the percentages of asymptomatic, mild, moderate, and critical/severe cases determined to be 25.5%, 45%, 26.8%, and 2.7%, respectively. Extracorporeal membrane oxygenation was required in two patients (0.9%) and mechanical ventilation in three (1.4%). Targeted therapies were used in six patients (2.7%), with hydroxychloroquine being the most commonly used agent either alone (one patient) or in combination with favipiravir (five patients). Two patients (0.9%) died, and nine (4.1%) were still hospitalized during the study period. Conclusion: Although the disease course of coronavirus disease-2019 seems to be mild in children, critical illness is significant, and the treatment strategy primarily should consist of supportive care according to our preliminary observations.