SARS-COV-2 infections in children: The role of fibrinogen in predicting diagnosis and severity: A retrospective cohort study.

BACKGROUND: Evaluating predictors of coronavirus disease 2019 (COVID-19) and severity among children may help clinicians manage the high rate of hospital admissions for suspected cases. OBJECTIVES: This study aimed to evaluate the demographic, clinical and laboratory characteristics of children during the pandemic, and determine the predictors of COVID-19 and moderate-to-severe disease. MATERIAL AND METHODS: This retrospective cohort study included all consecutive COVID-19 cases in patients aged <18 years who presented to the Pediatric Emergency Department at Haseki Training and Research Hospital (Istanbul, Turkey) between March 15 and May 1, 2020, and underwent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) analysis of oro-nasopharyngeal swabs (n = 1137). RESULTS: The frequency of SARS-CoV-2 PCR positivity was 28.6%. The COVID-19 (+) group presented with sore throat, headache and myalgia significantly more frequently than the COVID-19 (-) group. Multivariate logistic regression models showed independent predictors of SARS-CoV-2 positivity as follows: age, contact history, lymphocyte count <1500/mm3, and neutrophil count <4000/mm3. In addition, higher age, neutrophil count and fibrinogen levels were independent predictors of severity. The diagnostic cutoff value for fibrinogen (370.5 mg/dL) had a sensitivity of 53.12, specificity of 83.95, positive predictive value (PPV) of 39.53, and negative predictive value (NPV) of 90.07 for predicting severity. CONCLUSIONS: Symptomatology, whether alone or in combination with other approaches, may be an appropriate strategy to guide the diagnosis and management of COVID-19.

Kidney Involvement in Pediatric COVID-19 Cases: A Single-Center Experience.

OBJECTIVE: The kidney is the second most commonly affected organ by severe acute respiratory syndrome coronavirus-2, characterized by hematuria, proteinuria, and acute kidney injury. There are few studies describing renal involvement in pediatric cases. MATERIALS AND METHODS: This retrospective study evaluated the prevalence of hematuria, proteinuria, and acute kidney injury in severe acute respiratory syndrome coronavirus-2-positive pediatric cases (1-18 years old) who visited emergency department between March and November 2020. Patients with urinary tract infections were excluded. An age-specific upper limit of reference interval was used to define "elevated serum creatinine" (greater than upper limit of reference interval) and acute kidney injury (>1.5 times upper limit of reference interval). RESULTS: A total of 228 patients were evaluated, median age was 12.7 years (interquartile range: 7.5; 16.1), and 51.3% were male. The prevalence of asymptomatic, mild, and moderate-to-severe disease was 12.7% (29/228), 77.2% (176/228), and 10.1% (23/228), respectively. The prevalence of hematuria, proteinuria, and elevated serum creatinine was 15.8% (36/228), 6% (14/228), and 3% (7/228), respectively. Kidney involvement (i.e., at least 1 of these findings) was 23.2% (53/228) and significantly higher in the moderate-to-severe disease (43.5%). None of the patients met the acute kidney injury criterion. In logistic regression analysis, female sex (odds ratio: 1.97, 95 CI%: 1.03; 3.70, P = .040) and fever (odds ratio: 2.28, 95% CI: 1.19; 4.36, P = .012) were independent predictors of kidney involvement. Three patients demonstrated a kidney presentation (macroscopic hematuria) on admission, and another patient was diagnosed with C3 glomerulonephritis during hospitalization. CONCLUSION: Kidney involvement was found about in 1 quarter of children with coronavirus disease 2019. Awareness and recognition of kidney involvement and follow-up are important in the management.

Diagnostic and Prognostic Biomarkers of Coronavirus Disease 2019 in Children.

Predictors of early diagnosis and severe infection in children with coronavirus disease 2019 (COVID-19), which has killed more than 4 million people worldwide, have not been identified. However, some biomarkers, including cytokines and chemokines, are associated with the diagnosis, pathogenesis and severity of COVID-19 in adults. We examined whether such biomarkers can be used to predict the diagnosis and prognosis of COVID-19 in pediatric patients. Eighty-nine children were included in the study, comprising three patient groups of 69 patients (6 severe, 36 moderate and 27 mild) diagnosed with COVID-19 by real-time polymerase chain reaction observed for 2-216 months and clinical findings and 20 healthy children in the same age group. Hemogram, coagulation, inflammatory parameters and serum levels of 16 cytokines and chemokines were measured in blood samples and were analyzed and compared with clinical data. Interleukin 1-beta (IL-1ß), interleukin-12 (IL-12) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in the COVID-19 patients (p = 0.035, p = 0.006 and p < 0.001). Additionally, D-dimer and IP-10 levels were higher in the severe group (p = 0.043 for D-dimer, area under the curve = 0.743, p = 0.027 for IP-10). Lymphocytes, C-reactive protein and procalcitonin levels were not diagnostic or prognostic factors in pediatric patients (p = 0.304, p = 0.144 and p = 0.67). Increased IL-1ß, IL-12 and IP-10 levels in children with COVID-19 are indicators for early diagnosis, and D-dimer and IP-10 levels are predictive of disease severity. In children with COVID-19, these biomarkers can provide information on prognosis and enable early treatment.

Demographic and Clinical Characteristics of COVID-19 in Children and the Effect of Household Tobacco Smoke Exposure on COVID-19.

OBJECTIVE: Environmental tobacco smoke (ETS) exposure is associated with many diseases, including lower respiratory tract infections, in pediatric age groups. In this study, we aimed to assess the effect of household ETS exposure on symptom frequency and clinical severity in children and adolescents with COVID-19. MATERIALS AND METHODS: This retrospective study included pediatric cases (<18 years old) with a positive SARS-CoV-2 test, who were admitted to our hospital between 20.03.2020 and 01.05.2020. Patients with respiratory diseases and active smokers were excluded. Demographic characteristics, symptoms, and clinical severity of COVID-19 were obtained from parents and children using a questionnaire and from patients' files. Household ETS exposure was assessed by questionnaire. RESULTS: A total of 167 patients (median age 145 months, 50.7 % male) were included in the study. The frequency of household ETS exposure was 50.9%, and the frequency of cough was significantly higher in exposed children than non-exposed children (71.4% vs 50.8% respectively, p=0.02). The frequency of both fever and cough was significantly higher ETS-exposed in the subgroup of cases with a mild clinical course (69.5% vs 48.1% respectively, p= 0.02 for fever and 67.8% vs 44.4% respectively, p=0.01 for cough). There was no relationship between clinical severity and household ETS exposure. CONCLUSION: Household ETS exposure may impact COVID-19 pediatric cases as demonstrated by the increased frequency of cough and fever in ETS-exposed children. As new lockdown measures are implemented, increasing public awareness about the effect of household ETS exposure on COVID-19as well as encouraging a decrease in ETS exposure are essential.

Authors' reply: the biologic importance of the vitamin D binding protein polymorphism in pediatric COVID-19 patients.

What is Known? • Vitamin D has multiple roles in the immune system that can modulate the body reaction to an infection • Vitamin D binding protein (DBP) is the key transport protein which, along with albumin, binds over 99% of the circulating vitamin D metabolites What is New? • Lower 25 OH vitamin D levels were associated with higher inflammation markers, suggesting an important role of vitamin D in the clinical course of COVID-19 in children and adolescents probably by regulating the systemic inflammatory response • Further studies are warranted to investigate the possible causal association of DBP levels and polymorphism with vitamin D status (total and bioavailable vitamin D) in COVID-19 patients.

The association between vitamin D levels and the clinical severity and inflammation markers in pediatric COVID-19 patients: single-center experience from a pandemic hospital.

Vitamin D has an immunomodulating property that regulates the inflammatory response. In this study, the aim was to evaluate the relationship between vitamin D levels and clinical severity and inflammation markers in children and adolescents with COVID-19. The clinical and laboratory records of 103 pediatric cases with COVID-19, whose vitamin D levels had been measured, were retrospectively reviewed. The cases were divided into groups according to their clinical severity (asymptomatic, mild, and moderate-to-severe) and vitamin D levels. The moderate-to-severe clinical group had significantly higher inflammation markers (CRP, procalcitonin, fibrinogen, D-dimer) and a lower lymphocyte count compared to both the mild and asymptomatic groups. The 25 OH vitamin D levels were also significantly lower (p < 0.001), and the ratio of vitamin D deficiency was 70.6% in the moderate-to-severe group. The vitamin D-deficient group had a significantly higher age and fibrinogen levels while also having a lower lymphocyte count compared to the insufficient and normal groups. The 25 OH vitamin D level was correlated positively with the lymphocyte count (r = 0.375, p = <0.001), and negatively with age (r = -0.496, p = <0.001), CRP (r = -0.309, p = 0.002) and fibrinogen levels (r = -0.381, p = <0.001). In a logistic regression analysis, vitamin D deficiency, D-dimer, and fibrinogen levels on admission were independent predictors of severe clinical course.Conclusion: This study revealed an association between vitamin D deficiency and clinical severity, in addition to inflammation markers in pediatric COVID-19 cases. Prophylactic vitamin D supplementation may be considered, especially in the adolescent age group. What is Known: • • The pathology of COVID-19 involves a complex interaction between the SARS-CoV-2 and the immune system. Hyperinflammation/cytokine storm is held responsible for the severity of the disease. • Vitamin D has multiple roles in the immune system that can modulate the body reaction to an infection. What is New: • • Clinically more severe group had significantly lower vit D levels and significantly higher inflammation markers. • Lower 25 OH vit D levels were associated with higher inflammation markers, suggesting an important role of vitamin D in the clinical course of COVID-19 in children and adolescents probably by regulating the systemic inflammatory response.