Discussion
This meta-analysis showed approximately one-quarter of children were
asymptomatic, which is very alarming as these children could be
asymptomatic spreaders. Studies reveal comparable or prolonged spread of
virus by asymptomatic carriers compared to symptomatic
patients11,12 ,however this theory is debatable in
recent literature13. It could be an important factor
to consider in public health policy-making regarding re-opening of
schools and play areas. The proportion of asymptomatic patients in China
and outside China were similar in our study, 28% and 21% respectively.
However, these numbers are likely an underestimation due to the small
number of data-rich studies published outside China and the sampling
bias towards hospitalized and more ill children.
Fever and cough were the most reported symptoms in this meta-analysis,
which is consistent with findings reported by two other
meta-analyses14. This study shows that children
present with more upper respiratory findings such as sore throat, nasal
congestion and rhinorrhea, whereas dyspnea is less frequently seen in
children compared to their adult counterparts15. An
array of gastrointestinal symptoms such as nausea, vomiting, abdominal
pain and diarrhea are reported in pediatric patients with COVID-19,
however, it is difficult to discern the proportion of these symptoms
attributable to the disease process or part of the side-effects of
therapeutic agents used for treatment or a combination of both. Our
study showed approximately one out of seven children had some associated
co-morbidity. This was unlike other meta-analyses in the literature
which under or infrequently reported comorbidities in pediatric
patients13,14. We further dissected the comorbidities
and found the most common being history of congenital heart disease and
obesity. The other co-morbidities associated with COVID-19 presentation
in children in our study included history of prematurity, neurological
diseases (epilepsy, febrile seizures), asthma, cancer and diabetes,
which is distinctive from what was found in most adult
studies16.
This meta-analysis’ findings revealed neutropenia, lymphocytosis and
leukopenia as the most common white cell abnormalities. Interestingly,
neutropenia was not analyzed in other meta-analyses and hence was not
reported14,17. This study also showed elevated CRP,
LFTs and Lactate Dehydrogenase (LDH) similar to the studies by Ding et
al and Zhang el al14,17. Our study also showed
elevated procalcitonin which was mirrored by Ding et al, but dissimilar
from Zhang et al. Co-infections were found in close to one-fourth of
patients, which is again a peculiar finding of pediatric COVID-19 and
the most common co-infections were due to Mycoplasma pneumoniaeand Influenza A/B. Ground glass opacities on CT-scan were the most
common radiological finding present in more than a third of patients,
resembling previous literature on pediatric
COVID-1914. Another interesting radiological finding
of this meta-analysis was the equal proportion of unilateral and
bilateral lesions in CT-scans in children with COVID-19. In contrast,
Mantovani et al reported a higher proportion of unilateral involvement
than bilateral, while most other meta-analyses have not described other
radio findings other than GGOs13,14,17. It is
important to note that this study’s confidence intervals were narrower
and hence more precise than other meta-analyses due to the higher sample
size from data-rich articles.
95.9% of patients were hospitalized and 93.9% of patients received
some form of treatment based on our findings. This observation could be
skewed, as most studies with sufficient data to synthesize the clinical
findings and outcomes would consist of more symptomatic, sick and
hospitalized patients. Anti-virals were the most used therapeutic
agents, apart from analgesics and herbal medicines, followed by
antibiotics. It is important to note that there was an expected
therapeutic variability due to different protocols across the world as
well as the changing trends of the pandemic. Intravenous immunoglobulin
(IVIG) and glucocorticoids were unique treatment options for pediatric
patients with SARS-CoV-2, especially with the emergence of
MIS-C18. This analysis did not show frequent use of
hydroxychloroquine treatment (5.7%) as expected and one of the reasons
for that could be the evolving therapeutic trends over the course of the
pandemic.
Of the hospitalized patients, a small proportion required intensive care
admission and even fewer required mechanical ventilation. These
important outcomes are under-reported in meta-analysis
literature13,14,17. Shock was one of the striking
complications of the disease course present in about 13% of patients,
as highlighted by our meta-analysis. 83.3% of patients were discharged
and this value could be confounded by the time span of the studies and
different protocols for patient discharge. Our meta-analysis reports
higher than expected death rate (4.2%) compared to surveillance
data19, but this may be due to sampling and reporting
bias within studies.
It is possible that our results were confounded by the lack of data
outside of China, heterogeneity of a few variables and potential bias
within the articles selected. In addition, the variations of diagnostic
and therapeutic protocols in different parts of the world and its
transformation with the evolving pandemic affects the outcomes reported.
Despite the lack of data-rich MIS-C literature published until early
July 2020, three MIS-C studies were included in our meta-analysis with
26 patients presenting with prolonged fever and a combination of signs
and symptoms such as gastrointestinal manifestations, rash,
conjunctivitis, shock with or without multiorgan
failure20-22. More data on MIS-C is needed to better
equip clinicians and epidemiologists in navigating the rough seas of
this global pandemic.