Evaluation of Clinical, Biochemical, and Demographic Characteristics of Paediatric COVID-19 Patients Admitted to Dicle University Hospital

Introduction and aim: In this study, we aim to determine how laboratory parameters were related to the clinical courses of patients admitted to the Dicle University Faculty of Medicine Department of Paediatrics and Paediatric Intensive Care Unit with COVID-19 diagnoses from March 2020 to November 2021. Materials and method: Clinical, biochemical and demographic characteristics of 220 patients between 0 and 16 years old with COVID-19 diagnoses at admission were analysed retrospectively. Results: We found that 57.3% of patients were male and 42.7% female, with a mean age of 107.8 ± 65.5 (range 1-192) months. Of the cases, 48.6% (n = 107) were asymptomatic, 35.5% (n = 78) were mild, 11.8% (n = 26) were moderately severe and 3.6% (n = 8) were severe. The patients’ site of admission, mortality rates, C reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and fibrinogen levels differed significantly (p < 0.001). Conclusion: It is important to learn about the clinical course of the disease by accurately interpreting the results of blood parameters and appropriate imaging studies.


Introduction
years old, and being treated and monitored as an inpatient.
Exclusion criteria were having a COVID-19 diagnosis unconfirmed by a PCR test, being older than 16 years, or having clinical information and biochemical results missing in the hospital information management system.
Demographic (sex, age), clinical (disease severity, admission complaint, admission unit and length of hospitalisation) and laboratory parameters of patients diagnosed and admitted to the hospital during the pandemic were examined retrospectively. Patient records were used to access the clinical and biochemical results. To this end, the patients' blood count, biochemistry and coagulation parameters were compared.
Combined oropharyngeal/nasopharyngeal swab samples were obtained from all participants for COVID-19. They were studied at the laboratory using the Light Cyler 96 (ROCHE®, Basel, Switzerland) device and the DIAGNOVITAL® DIAGNO5plex NS SARS-CoV-2 Real Time PCR (İstanbul, Turkey) detection kits in line with the instructions of the manufacturer, resulting in positive or negative labelling according to manufacturers' instructions.

Statistical analysis
Statistical Package for Social Sciences (SPSS) version 24 (IBM Corp., Armonk, NY, USA) software was used to conduct all statistical analyses. Percentage values were calculated for discrete variables. Two groups were compared with Student's t-test or Mann-Whitney U test in the case of numerical variables, while categorical variables were compared with the help of the chi-square test. Student's t-test was used to check the significance levels of correlation coefficients, and the two-sided level of significance was accepted as α < 0.05.

Results
The analysis of the patients regarding sex distribution showed that 57.3% were male and 42.7% female, with a mean age of 107.8 ± 65.5 (range 1-192) months. The mean length of hospitalisation was 3.7 ± 3.1 (range 1-20) days.
Five (2.3%) patients died at the end of the treatment period. Two hundred and three (92.7%) patients were hospitalised at the department of paediatrics and 16 (7.3%) in the COVID-19 paediatric intensive care unit.
The classification of the patients by disease severity demonstrated that 48.6% (n = 107) had an asymptomatic disease, 35.5% (n = 78) mild disease, 11.8% (n = 26) moderately severe disease and 3.6% (n = 8) severe disease. One patient who presented to the paediatric emergency department died.
The analysis of the laboratory results by the status of hospital discharge showed that the discharged patients had a mean C reactive protein (CRP) level of 1.28 ± 3.73, and the deceased patients had a mean CRP level of 8.78 ± 8.14. The discharged patients had a mean lactate dehydrogenase (LDH) level of 276.82 ± 120.32, and the deceased patients had a mean LDH level of 654.00 ± 279.22. The mean ferritin level of the discharged patients was 146.80 ± 448.47, and that of the deceased patients was 1269.03 ± 412.55. The mean fibrinogen levels of the discharged and deceased patients were 250.81 ± 113.05 and 427.33 ± 259.18, respectively. A significant difference was observed between the CRP, LDH, ferritin and fibrinogen levels of the discharged and deceased patients (p < 0.001) (

Discussion
Coronavirus is one of the major microbiological disease agents in animals and humans. At the end of December 2019, a novel type of coronavirus was defined in a pneumonia epidemic in China's Wuhan city of the Hubei province, spreading rapidly since then and resulting in a worldwide pandemic [6]. In January 2020, the World Health Organization defined the agent in patients presenting with fever, cough, respiratory difficulty, nausea and diarrhoea as a novel coronavirus (2019-nCoV), which was not detected in humans before. The disease was later denominated as COVID-19. As a result of its close genetic resemblance to SARS-CoV, the virus was named SARS-CoV-2. Although the disease was initially limited to the Wuhan South China sea products market workers, it rapidly spread worldwide, compelling the World Health Organization to declare COVID-19 a pandemic as of 11 March 2020 [7].
Studies and data published on COVID-19 mainly focus on adults due to a greater prevalence and increased severity in that population segment because the paediatric population was reportedly rarely examined and tested in the early phases of the pandemic, limiting the data on the number of paediatric cases [8].
According to a study in Italy in 2020, 13.3% of patients treated for COVID-19 were hospitalised, and only 3.5% required intensive care [9]. In a 2019 study from Spain analysing the data of 365 paediatric COVID-19 patients, 66.7% were hospitalised for treatment, and only 9.1% of these patients were transferred to the intensive care unit [10]. In our study, a large majority of patients (92.7%) were admitted to the COVID-19 paediatric clinic, and a lesser percentage (7.3%) was admitted to the COVID-19 paediatric intensive care unit.
CRP is a highly sensitive protein with an increased plasma concentration during myocardial infarction, stress, trauma, infection, inflammation, surgery and neoplastic proliferation. The inflammation-based increase occurs within six to 12 hours and reaches its maximum by the 48th hour. It increases and decreases before other acute phase reactants. It does not indicate the cause of inflammation and is used during the course of inflammation. CRP increased particularly in 75-93% of severe COVID-19 patients [11]. We found that the CRP levels showed a significant difference in mortality (p < 0.001), with the deceased patients presenting significantly higher CRP levels.
Studies have shown that LDH levels increased in COVID-19 patients. LDH catalyses the last step of aerobic glycolysis (i.e., the reversible conversion of pyruvate to lactate) [12]. LDH reference ranges are initially high in children but gradually decrease during childhood. LDH increases in myocardial infarction, haemolytic anaemia, megaloblastic anaemia, hepatic disorders and progressive muscular dystrophy, and it is also used for the follow-up of non-Hodgkin lymphoma and leukaemia. In a study conducted on 140 COVID-19 patients from China in 2019, LDH appeared to be one of the most important predictors of intensive care unit admission [13]. LDH increases are prevalent in cases of COVID-19 treated in the intensive care unit, showing a poor prognosis. We observed statistically significant LDH levels were 16 times higher in our patients admitted to the COVID-19 intensive care unit compared to patients admitted to the ward. Moreover, analysing according to the LDH levels, we found significantly different mortality rates. Our study also demonstrated that the discharged patients had significantly lower LDH levels than those who died.
A study of 43 patient series reported that patients with severe COVID-19 disease had significantly higher fibrinogen levels. COVID-19 is associated with a rise in the inflammatory markers like D-dimer, fibrinogen and pro-inflammatory cytokines [14,15]. The fibrinogen levels were approximately two times higher in the deceased patients than in the discharged ones in our study.

Conclusions
It is important to identify in terms of protection that may deteriorate in COVİD-19 patients. Early detection of these patients will reduce mortality. Patients with higher CRP, LDH, ferritin and fibrinogen levels had a higher risk of being admitted to the intensive care unit and dying, which makes it vital to foresee the course of COVID-19. A rapid and accurate treatment will save lives in these patient groups.