COVID–19 is a novel infection and has been known for only a few months. Thus, knowledge of the disease, especially in specific groups of patients, e.g., children, is scarce and limited. As the epidemic is ongoing, every reported observation on the epidemiological and clinical characteristics of the infection is essential for our understanding of the disease. To date, a large share of the scientific evidence has originated in China. It is possible that country-specific factors (e.g., nutrition, epidemiological influences, day care) in European children may differ from the Chinese population 14. To the best of our knowledge, we present one of the first reports on COVID–19 in the pediatric population outside of China.
In our group of 319 patients suspected for COVID–19, 4.7% were positive. In a study performed in Madrid by Tagarro et al., 41 of 365 (11.2%) pediatric patients had positive test results during the first two weeks of the epidemic in Spain 4. In early January 2020, in Wuhan, of 366 children screened for SARS-CoV–2 infection, 6 patients (1.6%) were positive 15. The median age of our patients was 10.5 years (range 10 months—14 years). In other studies, the mean age of affected children differed. In the study from Madrid, the median age was 3 years (range 0—15 years); in the US, among all 2572 COVID cases, the median age was 11 years (range 0—17)4,7. In the largest Chinese pediatric case series by Dong et al. that reported 2143 patients with COVID–19, the mean age was 7 years, similar to the study from Wuhan on 171 patients, in which the median age was 6.7 years (1 day—15 years)8,9. No significant predominance of sex was found in any pediatric report. In the study by Dong et al., there were 56.6% boys in the study group, which is similar to our 53.3% 9.
Available data suggest that the main source of infection in children is household exposure, as 56.0% - 90% of the diagnosed children had an infected family member 1,6. This trend was even more pronounced in our study, where family clustering occurred for all infected children. In addition, among our patients, there were two pairs of siblings. Our observations revealed that the highest risk of infection exists when the presence of clinical symptoms is accompanied by confirmed contact with an infected family member (62.5%).
On the basis of previously published data, COVID–19 symptoms seem to be less severe in children than in adults9,14. Approximately 10% of cases in children are asymptomatic 1. In the study by Dong et al., with the largest child case series so far, over 90% of the 2143 patients diagnosed with COVID–19 had either asymptomatic or mild-to-moderate disease9. In the remaining 5.2%, the course of the disease was severe, and in 0.6%, it was critical 9. In our group, 33.3% patients were asymptomatic, which may result from the fact that we tested asymptomatic children with confirmed contact with an infected relative. In the remaining patients, the course of the disease was mild-to- moderate, with no severe or critical cases. Several explanations for the milder presentation of COVID- 19 in children have been suggested 14,16. First, children might have a different immune response to SARS-CoV–2 than adults 16. Children, especially young children, tend to have repeated exposure to many viral infections, which may benefit their immune system when it responds to SARS-CoV–2 14.
Second, the presence of other viruses in the mucosa of the airways, which is common in children, may limit the growth of SARS-CoV–2 by direct virus-to-virus competition 16. Another possibility is that the S protein of SARS-CoV–2 binds to angiotensin-converting enzyme 2, which is less mature in young children, protecting them against the virus 14.
Observations from the US on 291 pediatric and 10,944 adult patients revealed that clinical symptoms of COVID–19 are observed less frequently in children than in adults 7. A previous report found that 73% of children and 93% of adult patients had symptoms of fever, cough, or shortness of breath 7. According to Chinese reports on pediatric COVID–19 patients, the most common symptoms were fever, which occurred in 44–50% of children, and cough, experienced by 38% of patients, followed by rhinitis, fatigue, headache, diarrhea, and dyspnea 1,17,18. This is similar to our observations that fever occurred in 46.7% and cough in 40% of the COVID–19 patients. Interestingly, both symptoms were significantly more frequent in patients negative for COVID–19 (70.3% and 71.3%, respectively). In addition, gastrointestinal symptoms were observed more commonly in the COVID- 19-positive patients: 20% experienced diarrhea and 13.3% experienced vomiting. In the US cohort, these symptoms were observed in 13% and 11% of children, respectively 7. In a study that included 171 children from Wuhan Children’s Hospital, diarrhea occurred in 8.8% of patients, and vomiting occurred in 6.4% of patients 8.
Eleven children in our group (73.3%) were hospitalized. This proportion is higher compared to other cohorts, e.g., the US, where 1.6%–2.5% of 123 patients required hospitalization 19. However, in 7 out of 11 cases, only a short 1-day hospitalization was necessary to perform clinical evaluation, laboratory testing and chest X-ray. In one patient, radiological features of pneumonia were observed. This patient received combined treatment with azithromycin and chloroquine as part of a clinical trial. The child recovered without severe complications. No severe or critical cases requiring hospitalization in the PICU were observed in our group, similar to observations of other authors from China6,18.
However, several individual cases of children requiring mechanical ventilation and PICU admission have been reported thus far 4,14.
A significant number of our patients were negative for COVID–19, and other diagnoses were established, including bacterial infections, that required proper treatment. This is an essential finding during a pandemic, when access to health services may be limited. In symptomatic children suspected of having COVID–19, other, more common infections are possible and should not be overlooked. To our knowledge, there are no published data that compare the clinical courses of COVID–19 and influenza in children. In our study, 10% of patients suspected of having COVID–19 were infected with influenza virus. This rate is similar to observations from Wuhan, where among 366 children, influenza A or B was detected in 43 (11.8%) patients 15. In one patient, coinfection with COVID–19 and influenza was diagnosed. Clinical presentation of both diseases differed significantly. First, all cases of influenza were symptomatic and had a higher frequency of fever, cough, and sore throat, whereas COVID–19 patients more frequently suffered from diarrhea. There was no difference between groups in the proportion of hospitalized patients; however, antibiotic treatment was more commonly implemented in the COVID–19 group.
This study was limited by a small number of children with a confirmed SARS-CoV–2 infection. We did not include asymptomatic patients with no epidemiological history, which might have influenced the final number of infected cases. However, considering that the pandemic is ongoing, the results presented here provide valuable data for understanding the epidemiological and clinical features of COVID–19 in the pediatric population.
On the basis of our experience, we conclude that the clinical course of COVID–19 in the pediatric population is usually mild or asymptomatic. In symptomatic children with suspected COVID–19 and those who have been screened for COVID–19, other infections are common and should not be overlooked. The main risk factor for SARS-CoV–2 infection in children is close household contact with an infected relative. Thus, children who have an infected family member should be tested for COVID–19, irrespective of their clinical presentation.