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.

Clinical and subclinical acute kidney injury in children with mild-to-moderate COVID-19.

BACKGROUND: Our aim was to identify acute kidney injury (AKI) and subacute kidney injury using both KDIGO criteria and urinary biomarkers in children with mild/moderate COVID-19. METHODS: This cross-sectional study included 71 children who were hospitalized with a diagnosis of COVID-19 from 3 centers in Istanbul and 75 healthy children. We used a combination of functional (serum creatinine) and damage (NGAL, KIM-1, and IL-18) markers for the definition of AKI and subclinical AKI. Clinical and laboratory features were evaluated as predictors of AKI and subclinical AKI. RESULTS: Patients had significantly higher levels of urinary biomarkers and urine albumin-creatinine ratio than healthy controls (p < 0.001). Twelve patients (16.9%) developed AKI based on KDIGO criteria, and 22 patients (31%) had subclinical AKI. AKI group had significantly higher values of neutrophil count on admission than both subclinical AKI and non-AKI groups (p < 0.05 for all). Neutrophil count was independently associated with the presence of AKI (p = 0.014). CONCLUSIONS: This study reveals that even children with a mild or moderate disease course are at risk for AKI. Association between neutrophil count and AKI may point out the role of inflammation in the development of AKI. IMPACT: The key message of our article is that not only children with severe disease but also children with mild or moderate disease have an increased risk for kidney injury due to COVID-19. Urinary biomarkers enable the diagnosis of a significant number of patients with subclinical AKI in patients without elevation in serum creatinine. Our findings reveal that patients with high neutrophil count may be more prone to develop AKI and should be followed up carefully. We conclude that even children with mild or moderate COVID-19 disease courses should be evaluated for AKI and subclinical AKI, which may improve patient outcomes.

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.

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.

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.

SARS-CoV-2 seropositivity among pediatric health care personnel after the first peak of the pandemic: nationwide surveillance in Turkey.

BACKGROUND: Understanding SARS-CoV-2 seroprevalence among health care personnel is important to explore risk factors for transmission, develop elimination strategies and form a view on the necessity and frequency of surveillance in the future. METHODS: We enrolled 4927 health care personnel working in pediatric units at 32 hospitals from 7 different regions of Turkey in a study to determine SARS Co-V-2 seroprevalence after the first peak of the COVID-19 pandemic. A point of care serologic lateral flow rapid test kit for immunoglobulin (Ig)M/IgG was used. Seroprevalence and its association with demographic characteristics and possible risk factors were analyzed. RESULTS: SARS-CoV-2 seropositivity prevalence in health care personnel tested was 6.1%. Seropositivity was more common among those who did not universally wear protective masks (10.6% vs 6.1%). Having a COVID-19-positive co-worker increased the likelihood of infection. The least and the most experienced personnel were more likely to be infected. Most of the seropositive health care personnel (68.0%) did not suspect that they had previously had COVID-19. CONCLUSIONS: Health surveillance for health care personnel involving routine point-of-care nucleic acid testing and monitoring personal protective equipment adherence are suggested as important strategies to protect health care personnel from COVID-19 and reduce nosocomial SARS-CoV-2 transmission.

The First Newborn Case of Coronavirus Disease 2019 (COVID-19) in Turkey: Journal of Pediatric Infection

Herein, we report a case of a 17-day-old male newborn with neonatal COVID-19 disease confirmed using pharyngeal swab testing positive with real-time reverse transcription polymerase chain reaction (rRT-PCR) assay for SARS-CoV-2. Laboratory analysis results of the child were as follows: hemoglobin: 14.5 g/dl, white blood cell count: 7.88x109/L, lymphocyte count: 3.40x109/L, neutrophil count: 1.96x109/L, platelet count: 260x103/L, and C-reactive protein: 1.8 mg/L (0-5). [...]the fact that the baby was 17 days old when diagnosed suggests that he got the virus in the postnatal period. [...]we could not be clear about the terms of vertical transmission. First reports have shown newborns born to SARS-CoV-2-infected mothers and all samples, including amniotic fluid, breast milk, and cord blood were negative for nucleic acid test for SARS-CoV-2 (17,18).

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.

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.

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.

A case of a very large haemorrhagic pericardial effusion in an adolescent patient with COVID-19 infection.

An otherwise healthy 17-year-old adolescent boy presented with upper respiratory tract symptoms and was diagnosed with coronavirus disease 2019 infection. A haemorrhagic pericardial effusion was found in the transthoracic echocardiography. He was treated with pericardiocentesis, ibuprofen, and hydroxychloroquine. A large pericardial effusion may complicate COVID-19 in children and should be considered in acute decompensation.