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Title: The course of SARS-CoV-2 infection and its complications in children
Abstract:
On 11 March 2020, the World Health Organization (WHO) announced the COVID-19 pandemic. In the first three years, over 6.5 million deaths for COVID-19 were reported to WHO, mainly from Europe and North America. The real number of deaths in the world is assessed to be three times larger. From the beginning of the pandemic, children were reported all over the world to present with an asymptomatic or mild course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Children were reported to constitute 1–2% of COVID-19 patients and it was very rare that admission to hospital was required. Nevertheless, during the following years, the percentage of hospitalization among children has increased since the emergence of more contagious (SARS-CoV-2) variants and the achievement of a high vaccination rate in adults. The first pediatric deaths were reported. Such situation required thorough surveillance and ongoing update on COVID-19 management for children, and also risk group identification, testing criteria, and indications for hospitalization. 4.2. Research purpose, research problems The main aim of the study was to describe the COVID-19 characteristics of hospitalized children based on findings from over 1400 pediatric patients, especially in terms of clinical presentation, laboratory findings, trends in pandemic waves, and outc ; omes. Specifically, the following issues were analyzed: 1. What were the differences among the subsequent pandemic waves due to SARSCoV- 2 variants – because the clinical presentation of COVID-19 has been changing due to the following SARS-CoV-2 variants and raising herd immunity. 2. What was the relation between the course of pediatric COVID-19 and age – because from the beginning of the pandemic, age was reported as one of the most important risk factors for a severe course, hospitalization, and death due to COVID-19. 3. What were the characteristics of the patients with a severe course of the disease. Especially, I focused on the possibilities for prediction of the severity of COVID-19 on admission to the hospital. 4.3. Studied population Patients aged 0–18 years with laboratory-confirmed COVID-19, hospitalized in the Department of Infectious Diseases and Pediatrics, Zeromski Specialist Hospital in Krakow, and The Children University Hospital, Jagiellonian University Collegium Medicum, Krakow, Poland were included in the study. All patients were symptomatic. 4.4. Definitions SARS-CoV-2 infection was diagnosed using a positive reverse transcription and real-time polymerase chain reaction (RT-PCR) test. Since 30 October 2020, second-generation antigen tests from a nasopharyngeal swab were performed in certified laboratories. The severe cas ; e was diagnosed in patients with pneumonia, age 0–18 years, laboratoryconfirmed SARS-CoV-2 infection, and a new requirement for supplemental oxygen or increased requirement from baseline without new or increased need for ventilatory support (noninvasive or invasive). Patients diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C) were excluded. Criteria for hospital admission were similar to other pediatric infectious diseases, such as dyspnea, seizures, dehydration from fever, vomiting, and diarrhea. According to Polish Expert Group recommendations, hospital referrals were also required for children with congenital heart defects, neurologic diseases, genetic disorders, chronic renal diseases, mucoviscidosis, broncho-pulmonary dysplasia, immunodeficiency after organ transplantation, and diabetes mellitus. Included also were newborns, infants, and children with obesity, especially with a body mass index (BMI) >30 kg/m2 . Data were collected in all successively admitted patients, based on a standard protocol. On admission, after taking the medical history and performing a physical examination, a planned set of laboratory tests was taken in all patients, including complete blood count (CBC) parameters, C-reactive protein (CRP), alanine transaminase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), ferritin, procalcitonin (PCT). A ; ll children with severe course of COVID-19 had imaging tests taken (i.e., lung ultrasound (LU), chest X-ray, and highresolution computed tomography (HRCT)). All children were subject to careful medical observation and treatment in accordance with current guidelines. Data on the course of hospitalization was also recorded in a planned and strictly structured manner in a specially designed database (the length of hospitalization, the length of oxygen treatment, antiviral treatment, systemic steroid therapy, pediatric intensive care unit (PICU) admission, respiratory therapy, and deaths). 4.5. Patients and methods (applies to article No 1) This study comprised 1407 patients with COVID-19, hospitalized between March 2020 and April 2022 in the Department of Infectious Diseases and Pediatrics, Zeromski Specialist Hospital in Krakow: 112 (8%) from the first wave (1 March to 30 September 2020), 175 (12.4%) from the second (1 October 2020 to 31 January 2021), 195 (13.8%) from the third (1 February to 31 May 2021), 511 (36.3%) from the fourth (1 October 2021 to 15 January 2022), 414 (29.5%) from the fifth (16 January to 30 April 2022). Demographic characteristics, clinical presentation, laboratory findings, lung imaging, outcomes, and final diagnoses were compared between the subsequent pandemic waves caused by different SARS-CoV-2 variants. 4.6. Patie ; nts and methods (applies to article No 2) 1405 patients with COVID-19 hospitalized between March 2020 and April 2022 in the Department of Infectious Diseases and Pediatrics, Zeromski Specialist Hospital in Krakow were included in the study. To assess the COVID-19 characteristics depending on age, they were assigned to three study groups: 567 infants (0–12 months), 470 toddlers (1–5 years), and 368 children (5–18 years). Demographic characteristics, clinical presentation, laboratory findings, lung imaging, outcomes, and final diagnoses were compared between the age groups. 4.7. Patients and methods (applies to article No 3) 70 among 2338 children (3%) hospitalized in two centers between 23 March 2020 and 30 September 2022 met the criteria of COVID-19 severe course. In the first stage of the analysis, the population of children with severe COVID-19 was described in detail. Next, among children diagnosed with severe COVID-19, the following subgroups of patients were identified for further analysis: 1) children who did not require mechanical ventilation; 2) children requiring mechanical ventilation; 3) children who died due to severe COVID-19. In the final stage of the analysis, the data of children with severe COVID-19 was also compared with the data of children who were hospitalized due to COVID-19, but did not meet the criteria for severe ; COVID-19. 4.8. Statistical analysis The statistical analysis was performed using SPSS ver. 27 software (Armonk, NY, USA). Results were presented based on the parameters of descriptive statistics, including the mean values and standard deviations (SD) for the quantitative variables with a normal distribution or median values with the interquartile range for non-normally distributed data. Categorical variables were presented as numbers with percentages. Qualitative values were compared by the chi-square test. The Kruskal–Wallis test was used for the analysis of the continuous variables investigated in the study. In all cases of statistical significance, a pairwise comparison between the groups was performed using a post-hoc test. In all analyses, a p-value < 0.05 was considered statistically significant. 4.9. Ethics The study was performed in accordance with the ethical standards of the Declaration of Helsinki and its later amendments. It was approved by the Ethics Committee of the Regional Medical Chamber in Krakow No OIL/KBL/18/2020 on 10 March 2020. 4.10. Summary of the results 4.10.1. Article No 1 published in Journal of Clinical Medicine In the study, results of data analysis of the COVID-19 course in the first five waves of the pandemic, obtained from 1407 patients who met the inclusion criteria, were presented. The demographic characte ; ristics showed a slight prevalence of boys in all five waves. Significant differences in the age of patients were found between the following pandemic waves. The median age was the highest in the first wave (95.8 months) and significantly lower in others, decreasing in the following waves (it was 14.6 months in the fifth wave). Severe courses of the disease were rare, and there were no significant differences in severity between the five waves, although we did observe increased hospitalizations in the fourth and fifth waves. The comorbidities were similar. The basic differences in the clinical presentation were the frequency of respiratory symptoms (rhinitis, cough, dyspnea, auscultatory changes, and lower respiratory infection diagnosed by imaging), which increased from the second to the fourth waves. In contrast, gastrointestinal symptoms (vomiting and diarrhea) were the most common in the second wave. More neurological symptoms occurred in the fourth wave. Regarding the final diagnoses of the hospitalized COVID-19 pediatric patients, the number of children with upper respiratory or gastroenterological symptoms was the highest in the fifth wave, while that of lower respiratory infection was most common in the first wave. We observed more upper than lower respiratory infections and shorter lengths of stay in the hospital in the fifth wave. Sta ; tistically significant differences in the first five waves of the pandemic in terms of CRP, blood platelets, and lactate dehydrogenase were found. 4.10.2. Article No2 published in Journal of Clinical Medicine In this study, concerning the relation between the course of COVID-19 and the child’s age, 1405 patients met the inclusion criteria. The large predominance of the youngest children were observed. Patients in the first year of life constituted 40.35% of the sample, and children younger than five years accounted for 73.8% of the hospitalized patients with COVID-19. Comorbidities associated with the increased risk of severe disease mainly affected children older than five years (42.3%). The most frequent symptoms were fever, cough, and rhinitis, especially in infants and toddlers. In infants, cough and dyspnea were more common symptoms of upper respiratory tract infection, and the most common diagnosis was laryngitis. High fever, vomiting, and diarrhea were observed much more frequently in patients aged 0–5 years, but gastroenterocolitis in our cohort was diagnosed as most common in children older than five years. Neurologic symptoms were significantly more common in the group of children older than five years. Regarding to laboratory findings, we observed leucopenia, neutropenia, lymphocytosis, thrombocytopenia, and elevated CRP, CK, LDH, ; ALT, and D-dimers as typical in most pediatric patients with COVID-19, especially in patients 0–5 years old. The median length of hospitalization in our cohort was 3–4 days and was significantly longer in the group of infants. 4.10.3. Article No 3 published in Archives of Medical Science 70 among 2338 hospitalized pediatric patients met the severity criteria established for the study and were enrolled in the analysis. In the group of patients requiring invasive oxygen treatment the prevalence of those with underlying conditions was significant, and 100% of children who died because of COVID-19 had comorbidities. The most often were the same as in other studies – genetic conditions, neurologic conditions, metabolic conditions, cardiovascular disease, obesity, diabetes mellitus, chronic pulmonary diseases, immunosuppression. Children who required mechanical ventilation manifested cough and dehydration on admission more often. As regards laboratory results, higher markers of inflammation, lymphopenia, and thrombocytopenia with higher concentrations of ferritin and LDH were observed. In children who died because of COVID-19 inflammation markers, leucopenia, thrombocytopenia, LDH, and ferritin level were extremely high. The lack of BCG vaccination was found in 12% of children with severe COVID-19 and 3% in other hospitalized children. None of the ; children with severe course of COVID-19 were vaccinated against COVID-19. 4.11. Conclusions 1. The study confirmed that a life-threatening course of COVID-19 in children was relatively rare. However, children with pneumonia, dehydration from fever, gastrointestinal symptoms, and loss of smell and taste, as well as those with neurological symptoms, represented most of the patients requiring hospitalization. The absolute number of hospitalizations was significantly higher in the fourth and fifth waves than in the first three waves. The clinical course of the disease changed between March 2020 and April 2022 due to the predominance of different SARS-CoV-2 variants and raising herd immunity. 2. Many statistically significant differences in disease signs and symptoms were observed between age groups. Infants were the most often hospitalized patients in the first two years of the pandemic. The reasons for infant hospitalization were the necessity of intravenous rehydration because of dehydration in the course of high fever, vomiting and diarrhea, and appetite disorders. Severe courses requiring oxygen supplementation and antiviral therapy were more common in adolescents. 3. Risk factors for the severe course of COVID-19 were: young age, lack of COVID-19 and BCG vaccination, auscultation changes, and dyspnea on admission. The presence of comorbid ; ities, high CRP, LDH, and ferritin levels were the predictors of mechanical ventilation necessity and death. Among children mechanically ventilated teenagers were the patients with a prognosis of recovery, but infants with comorbidities were at the highest risk of death. My observations of the large group including over 1400 hospitalized children may be useful for defining the high-risk group for severe COVID-19 and could help to guide hospital admission and prevention of COVID-19 in pediatric patients.
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Rada Dyscypliny Nauki medyczne
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Jun 4, 2024
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