Discussion
According to data reported by our hospital,5 RP
patients have clinical characteristics of younger age and milder
symptoms, and according to the 39 pediatric patients we observed in
previous follow-up, most of them are mild symptoms, and there is no
severe patient. Our study found that children have a higher incidence of
RP compared with adults. However, there was no statistically significant
difference between the RP group and the control group in terms of age,
gender distribution, clinical symptoms, CT positive findings, and
incidence of co-infection. Children with RP have a higher proportion of
family cluster infections.9-10 According to our
observation, other patients in the family are generally cured first and
close contacts were also without RP during followed-up, which can
basically rule out the possibility of infecting children from other
family members. However, it is still unknown whether children with RP
are still infectious, because the children have to be isolated at home
for 2 weeks after discharge and almost have no contact with the outside
world.This also indicates us that SARS-CoV-2 is extremely
resilient.11It seems to coexist peacefully with
humans. In any case, disinfection of household environment and hand
hygiene must be the top priority for disease prevention and
control.12
The underlying risk factors of high incidence of RP and the viral
clearance mechanism in children are still not completely
understood.13 T lymphocyte and phagocyte function may
play an important role.T lymphocytes help clear viruses and regulate
innate immune system responses.Chu et al demonstrated that MERS-CoV
infection can induce T cells apoptosis through the activation of
external and intrinsic apoptotic
pathways.14Coleman et al found that the depletion of
CD4+ T cells,
CD8+T cells or macrophages had no
effect on the replication of MERS-CoV in infected lungs of
mice.15 Earlier
studies have revealed that SARS-CoV,which share the same cell entry
receptors with SARS-CoV-2,could
infect immune cells,including T lymphocytes, monocytes,and
macrophages.The CD4+ and CD8+ T
cells counts decreased at the onset of
illness.16-17These studies indicated that the reduction of T cells is likely to
contribute to the continuous replication and RP of SARS-CoV-2. However,
our investigation did not observe this similar change and no significant
difference between the two groups. After analysis,there may be the
following reasons. First, the sampling time point may be in the early
stage of the disease, the children’s immune system is imperfect, and the
response is relatively slow and lagging. This may also explain why
children are asymptomatic or mild, but the incidence of RP is
high.3,5 Second, the sample size is small, and there
are many missing values in the control group, which may be different
from the true level.These also suggest that CD4+ and
CD8+ T cells count may not be suitable to be
predictors of RP.
The average WBC level of pediatric patients in our investigation is
totally within the normal reference range, which is consistent with
related
reports,18 but
WBC in the RP group is significantly higher than the control group.As
far as we know, there is still no accurate answer to why the WBC in the
RP group is higher than the control group. However, PCT, hs-CRP, IL-6
are within the normal range and there is no difference between the two
groups.Obviously,the impact of co-infection is negligible.We speculate
that this may be related to the weak response of the innate immune
system and the reduction of WBC depletion of the RP group.
The coagulation cascade is
activated during viral infections. This response may be part of the host
defense system to limit spread of the pathogen.19 A
good balance between host coagulation and viral infection can improve
pathological disease outcomes.20 However, excessive
activation of the coagulation cascade can be deleterious. Tissue factor
(TF) appears to be the major activator of the coagulation cascade during
viral infection.19 Tang et al found that non-survivors
of COVID-19 showed significantly higher levels of D-dimer, longer PT and
APTT.We also observed a similar change. Compared with the control group,
the PT and APTT of the RP group were prolonged, but there was no
significant difference in FIB, ATIII, and D-dimer. This suggests that
the activation of the exogenous coagulation pathway with TF as the
starting point may be involved in the process of immune clearance of
SARS-CoV-2,and it is milder in
children. At present, there is still too much unknown, and the specific
role and mechanism of the activation of coagulation cascade in
SARS-CoV-2 clearance need to be further explored.
There are several limitations in our retrospective cohort study. First,
due to the small sample size of the single-center research hospital,
logistic regression analysis cannot be used to control confounding
factors. Second, the children may be in different stages of
COVID-19 when they are admitted to
the hospital. Third,some children’s humoral immune function and
lymphocyte subclassification data by flow cytometry are missing, which
may not reflect the true difference between the two
groups.Therefore,these results should be carefully interpreted owing to
potential selection bias and
residual confounding. Larger cohort studies from other cities in China
and other countries may also be needed to provide further data support.