The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread to over 192 countries and territories, causing an enormous loss of lives and economic devastation.
The clinical presentation of this disease varies hugely between individuals, causing asymptomatic or mild infection in most cases but leading to life-threatening disease in about 15% of infections. Only about 0.4% of cases have been diagnosed in children below 10 years of age.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
A new study, released on the medRxiv* preprint server, deals with the clinical presentation, tests and complications in children and adolescents with COVID-19.
Study details
The researchers carried out a systematic review and meta-analysis of studies on children and adolescents with COVID-19. This included 50 papers, describing retrospective studies, covering a variety of ages. The meta-analysis included 49 studies, with over 1,600 participants.
Boys accounted for over 50% of cases, as in earlier studies.
Symptoms among children and adolescents
The researchers found that about 56% of children and adolescents with COVID-19 had fever, 45% had cough, while flu-like symptoms were reported in less than 15%. These include sneezing, vomiting, diarrhea, headache, tiredness and shortness of breath, in less than 20%.
Muscle pain and a higher sputum volume, as well as abdominal pain, were found in less than 10% of children each.
The presence of a sore throat, headache, diarrhea and vomiting, and shortness of breath, in children with COVID-19, was associated with a higher likelihood of reporting. This publication bias was not present with the other symptoms.
This study shows that children and adolescents most frequently have fever and cough on presentation with COVID-19, the other symptoms being less common though still significant. This agrees with the earlier finding that the typical features of COVID-19 in adults include fever, cough and tiredness.
Earlier research has shown that nasal stuffiness, a runny nose and diarrhea were not as common in children as in adults. Children are also less likely to be infected, and symptoms may be milder. This implies that children may have hidden infections more often.
Among critically ill children, almost 40% required mechanical ventilation.
Laboratory findings
Of the 13 most common laboratory findings, 40% had high procalcitonin, 30% had elevated lactate dehydrogenase (LDH), almost the same for a high lymphocyte count, creatine kinase and C-reactive protein.
Other common laboratory findings included a high AST, a low white cell count, high D-dimer levels, all in about a fifth of the children. Lymphopenia, high white cell count and high ALT was found in 15% each except for the last, which was found in 7%.
Again, publication bias was found for a low white cell count, high AST and high D-dimer, but not the other laboratory tests.
The positive findings here indicate viral infection. Earlier studies have shown that the most common laboratory abnormalities in adults are high CRP and lymphopenia, which are relatively non-specific.
The current markers are also non-specific in children and adolescents. Earlier research has shown that mortality, the presence of acute respiratory distress syndrome (ARDS), headache, increased leukocyte count, and elevated LDH, are higher in older patients.
As such, these findings cannot serve as reliable markers to rule out or confirm a diagnosis of COVID-19 in doubtful pediatric cases.
The origin of these markers may be in the cytokine storm associated with severe COVID-19. Also, this infection may affect primarily CD4 T cells and thus account for the lymphopenia.
In the current study, about 30% of children had a raised lymphocyte count, which is almost double the percentage with lymphopenia. This may indicate the difference in immune landscape, as the child’s immune system is growing and developing.
The increased frequency of elevated AST, in a quarter of cases, relative to ALT, may indicate varying grades of liver damage. However, renal damage appears to be very rare among children.
CT chest findings
On computed tomography (CT) chest scans, positive chest scans were found in two-thirds of children. Most common were lower lobe abnormalities in over half the patients. A third had ground-glass opacities, patches or bilateral pneumonia, or upper lobe involvement. About a quarter had pneumonia in one lung, and less than 15% showed tubercles. Pleural effusion was present in 3%.
Only pneumonia of both lungs was associated with publication bias.
Chest CT has been established to be a high-quality marker for COVID-19 pneumonia and other lung lesions. This is especially so because most patients have mild symptomatic illness but have more obvious chest lesions.
Thus, it could be used to pick up lesions with a low rate of missed diagnosis. However, while 84% of adult patients had a positive CT scan, the figure in children and adolescents was 67%.
The CT scan findings in children are non-specific, mainly ground-glass opacities and patchy shadows, as with other viral pneumonias. The most common location is the lower lobe, at 56%, with the upper lobe in 30%.
Bilateral pneumonia was found in a third of the pediatric cases but in almost three-quarters of adults with COVID-19.
Mortality was under-reported as only three studies of critical COVID-19 in children reported the number of deaths. Of the 1,600 patients in the 49 studies, there were only 7 deaths, indicating low COVID-19 mortality in this age group.
What are the implications?
The latest and most comprehensive study for clinical characteristics of COVID-19 in children and adolescents, from the first report of COVID-19 to July 10, 2020, including clinical features, laboratory outcomes, and chest CT findings.”
The findings show the greater challenge involved in diagnosing and containing SARS-CoV-2 infection in children and adolescents compared to adults, with more asymptomatic and mild cases. More cases may therefore escape detection, which may allow the viral spread to continue.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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