DISCUSSION
There are data from Europe, Asia and America confirming that the proportion of children infected with COVİD-19 in the community is low (varying from 1% in young children to 6% in older children) (4). Among children, the incidence of COVID-19 disease was reported 12.3% (171 of 1391 children) in a study in China and 11.2% (41 of 365 children) in a study in Spain (6,7). In our study, RT-PCR test was done in 835 children with suspected COVID-19 infection and the test was positive in 178 (21.3%) children. The incidence of COVID-19 disease in children in the community is 1-5%, while the incidence of COVID-19 disease in children is approximately 10-20% in suspected pediatric cases.
Of the studies with reported that patients’ mean age varied across studies from 6.2 to 11 years (8). In our study the mean age of patients who was confirmed diagnosis COVID-19 was 10.5 year. As can be seen, the incidence of COVID-19 is higher in older children. This situation can be explain that usually, younger children take part in fewer daily social activities than teenagers, and their contact opportunities with carriers or patients should thus be lower, resulting in a lower risk of getting the COVID-19 illness, as stated in a review (9).
In our study, a total of 28 COVID-19 patients were identified in approximately 3 months from the beginning to June 30, while 150 COVID-19 patients were identified in the next 2.5 months. This is may be due to the normalization and social life in our country starting from June. In addition, the increase in our cases during the summer season indicates that there is no seasonal difference in the pandemic outbreak.
It has been reported that, the presenting clinical symptoms of pediatric COVID-19 patients were fever and cough (10,11). In our study, while fever was the most common symptom with 67%, headache (41%) was the more common symptom than cough (37%). Other common symptoms were sore throat (26%), fatigue (23%), myalgia (23%) and diarrhea (21%). The reason for the excessive headache, fatigue and myalgia in our study may be due to the large number of older children who could express their symptoms. In our knowledge, our study is the first study conducted according to the number of symptoms, and it is seen that pediatric COVID-19 patients presents with an average of four symptoms.
In a systematic review of the literature, it was reported that there were no studies reported data about pediatric loss of smell or taste (8). In our study, 13% of the patients had loss of smell, and 9% of patients had loss of taste. There have been case reports of neurological complications in adults with COVID-19 including peripheral nervous disorders, but there has not been a clear indication that neurological complications predominate in children infected with COVID-19 (4,12). In our study, a 17-year-old male patient had a left leg paralysis lasting for 12 days. In addition, five patients had atypical symptoms. These were hoarseness in one patient, backache in two patients, conjunctivitis in one patient, and painful swelling in the eyes in one patient. It is seen that especially adolescent children can present with very different symptoms.
The World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) and several other government health agencies emphasize fever and respiratory symptoms in the criteria for suspected cases (13,14,15), however, we detected in our study that children can have a wide range of symptoms. While 40% of the patients have gastrointestinal symptoms with fever or respiratory symptoms, 15% of the patients have only gastrointestinal symptoms without fever or respiratory symptoms.
In our study, Fifteen (8.6%) of the patients were hospitalized, three (1.7%) of them were required intensive care unit and one patient who had neurological comorbid disease was died from SARS-CoV-2 infection. Our study was similar to previous pediatric COVID-19 studies in terms of hospitalization, intensive care, and death (16,17,18). Compared to adults, COVID-19 infection is seen to be milder and cause less hospitalizations and patient deaths in children (11,16,19). The reason for this is remain elusive, some hypotheses have been proposed. First, children and adults have different immune systems. Children’s weaker immune responses may prevent pulmonary destruction caused by virus-induced immune responses. Children are vulnerable to having many viral infections, and they can establish innate immune responses. In addition, various viruses simultaneously invading the airways and mucosa of the lungs may competitively inhibit SARS-CoV-2. Some researchers also suggested that children’s innate immune responses are more active, and their respiratory tracts are healthier because of their low exposure to cigarette smoke and air pollution (10). Second, Ageing is associated with a progressive decline in the normal functioning of the immune system, which leads to weaker immune responses and impairs a person’s ability to respond to new stimulants. This process involves the natural involution of the thymus, starting during or soon after the first year of birth. It then shows an accelerated decline after puberty, and the thymic microenvironment cells continue to reduce by 3% to 5% a year. After the fourth and fifth decade of life, the involution of the thymus leads to a significant decline in naїve T cell output. This affects the composition of the peripheral CD4 and CD8 T-cell pool and has a negative influence on the adaptive immunity that is considered to be the leading cause of morbidity and mortality in the elderly. It has been reported that, the number of T cells was significantly decreased in patients affected by COVID-19 disease, suggesting that dysregulation of the immune response involving T lymphocytes was present in this pathological infection (20). Third, SARS-CoV-2 enters respiratory epithelial cells by attaching to angiotensin converting enzyme-2 (ACE-2) via S-protein. After entering pneumocytes, SARS-CoV-2 downregulates ACE-2 expression, decreasing angiotensin-2 metabolism. Elevated angiotensin-2 increases pulmonary vascular permeability and inflammation, hence worsening of lung injury. Angiotensin-2 levels have been found to be increased in COVID-19 patients compared to healthy adults. ACE-2 levels decrease in old age and co-morbidities like hypertension and diabetes, possibly explaining worse lung injury and prognosis of SARS-CoV-2 in them. High levels of ACE-2 activity in children could be protective in children with COVID-19, leading to less severe disease in this age group compared to elderly (21).
Twenty (11.4%) of our patients had asthma. Only two of the patients with asthma were hospitalized and didn’t require intensive care unit. Our study supports an international study that states that children with asthma do not appear to be disproportionately affected by COVID-19 (22).
Sixty one percent of the patients were infected by close contact with family members diagnosed with COVID-19, 20% of the patients were infected via close contact with non- family members diagnosed with COVID-19, 6% of the patients had a history of exposure in an epidemic area, including wedding hall, condolence house and shopping center and 13% of the patients with unknown source of infection, however, most of them had a history of using public transport. Therefore, we consider that especially crowded indoor environments are the main centers of the spread of the outbreak.
According to studies, it is reported that children are unlikely to be index cases and most of them acquire COVID-19 infection from adults and especially family members (4,10,23,24,25). In our study, in half of the 68 patients whose source of infection was outside of family members, nobody had COVID-19 at home after them, but at least one person at home was infected with COVID-19 in the other half, however, most of them at the same time with the child had a history of close contact with non- family members diagnosed with COVID-19. In addition, at least one family member was hospitalized in 31 patients whose source of infection was family members and at least one family member was hospitalized in only one patients whose source of infection was outside of family members. Therefore, our study supports the systematic review concludes that children are unlikely to be the main drivers of the pandemic (26).
The mean age and mean symptoms of patients whose source of infection was outside of family members was more than whose source of infection was family members. It may be due to older children having more outside social activities and being able to express themselves better and be aware of their symptoms.
lymphocytopenia is reported to be associated with severe COVID-19 infection in adults (10). Guan et al studied 1099 adult patients and found the rate of lymphocytopenia was 83.2% (27). In a study conducted in Italy, lymphocytopenia was found in 15.7% of pediatric COVID-19 patients and increases in aspartate aminotransferase and alanine aminotransferase were reported in 18.3% and 11.8%, respectively (28). In our study, lymphocytopenia was detected in 19.7% of the patients, however, liver enzymes were increased in very few patients.
In a study lung findings were detected in 27 (46%) of the patients who underwent chest X- ray imaging. It was unilateral in 15 and bilateral in 12 patients. Localized increase in density was observed in 27 patients while a diffuse increase in density was observed in cases who were admitted to the intensive care unit (29). In our study, 52 patients were underwent chest X-ray. Lung findings were detected in 19 (36.5%) patients. It was unilateral localized increase in density in seven patients on the right lower zone, bilateral localized increase in density in six, unilateral mild bronchial thickening in five patients on the right zone and bilateral diffuse increase in density in one patient.