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\begin{document}

\title{Comparative analysis of hematology parameters after Human
cytomegalovirus infection in children of different ages}



\author[1]{Yingying Wang}%
\author[2]{Zhou Zheng}%
\author[2]{Lijuan Kan}%
\author[2]{Dan Xiong}%
\author[1]{Xiuming Zhang}%
\affil[1]{Xinxiang Medical University}%
\affil[2]{Affiliated Hospital of Shenzhen University}%


\vspace{-1em}



  
  \date{June 08, 2024}


\begingroup
\let\center\flushleft
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\selectlanguage{english}
\begin{abstract}
\textbf{Background:} Children vulnerable to Human cytomegalovirus ( HCMV
) infection, most of them are recessive infection, easy to lead to
missed diagnosis. However, missing early diagnosis and treatment may
have adverse consequences for the child. Therefore, the purpose of this
study was to evaluate the hematological parameters in HCMV-infected
infants or children less than 6 years. \textbf{Method:}A retrospective
analysis of 223 children aged 0-6 years who had accepted urine HCMV-DNA
testing in Luohu People's Hospital. The children were divided into 0
day-21 days, 22 days-6 months, 7 months-11 months, 12 months-23 months,
and 2 years-6 years groups according to their age when they were tested,
and total white blood cell count (WBC), lymphocyte percentage (L\%),
lymphocyte count (LYM), alanine transaminsase (ALT), aspartate
transaminase (AST), \selectlanguage{greek}γ-\selectlanguage{english}glutamy1 transferase (GGT), urea nitrogen (UREA),
and creatinine (CREA) of different age groups were compared.
\textbf{Results:} The L\% and LYM of HCMV-infected children aged 0d-6y
were significantly higher than those of the control group (
\emph{P}\textless{}0.05); The ALT and GGT of HCMV-infected children aged
0-12m and AST of HCMV-infected children aged 0d-2y were significantly
higher than control group ( \emph{P}\textless{}0.05), but this
difference did not show up among older children (
\emph{P}\textless{}0.05); Compared with control group, there was no
significant difference in UREA and CREA of HCMV-infected children aged
0d-6y ( \emph{P}\textgreater{}0.05). In addition, we found that GGT was
highest in HCMV-infected children aged 0-21d and decreased with the
increase of age. \textbf{Conclusion:}HCMV infection can increase
lymphocytes in the peripheral blood of children from 0 to 6 years old,
and cause more serious hepatobiliary injury to younger children.
However, renal damage caused by HCMV is rare in childhood.%
\end{abstract}%



\sloppy


\textbf{1. Introduction}

Human cytomegalovirus (HCMV) is a double-stranded DNA virus belonging to
the \selectlanguage{greek}β-\selectlanguage{english}herpesviridae family \textsuperscript{1}. HCMV infection is common
globally, with approximately 60\% of people in developed countries
having HCMV specific IgG antibodies, while in many developing countries
this proportion exceeds 90\% \textsuperscript{2}. This high prevalence
rate of HCMV infection is mainly due to the fact that can be efected at
any age through body fluids (i.e., urine, saliva, and human breast milk)
from-infected individuals \textsuperscript{3}, and HCMV persists for the
lifetime of the host after primary infection \textsuperscript{4}. HCMV
infection in adults with normal immune function will not cause obvious
clinical symptoms,however, primary infection usually occur in early
childhood. A survey of HCMV infection found that HCMV seroprevalence
reached 75\% in children less than 6 years \textsuperscript{5}.

Due to the immature development of immune function of young
children\textsuperscript{6}, HCMV infection may cause diseases of liver,
blood, digestive tract, kidney, lung and other organs
\textsuperscript{7-12}, and young children have no specific clinical
symptoms in the early stage of HCMV infection. Therefore, we need to
investigate the hematology parameters (i.e., WBC, L\%, LYM, ALT, AST,
GGT, UREA, and CREA) of young children of different ages to provide a
reference basis for diagnosis and treatment of infants infected with
HCMV.

\textbf{2. Materials and methods}

\textbf{2.1 Study population}

This retrospective study collected data from the children (aged 0-6
years) who underwent examine HCMV-DNA at the Department of Medical
Laboratory, Luohu People's Hospital, Shenzhen, China, from July 2019 to
April 2023. This study was approved by the Reproductive Medicine Ethics
Committee of Shenzhen Luohu People's Hospital (2023-LHQRMYY-KYLL-028).

A total of 223 children were included in the study, including 132
HCMV-infected children and 91 non-HCMV-infected children. According to
reference intervals of blood cell analysis for children in People's
Republic of China (PRC) health industry standard WS/T
779-2021\textsuperscript{13}, Children were divided into five subgroups
(i.e., children at 0 to 21 days (0d-21d, children at 22 days to 6 months
(22d-6m, only children younger than 6 months were recruited in this
group ), children at 7 months to 11 months (7m-11m, only children
younger than 1 year were recruited in this group), children at 12 months
to 23 months (12m-23m, only children younger than 2 years were recruited
in this group), and children at 2 years to 6 years (2y-6y, only children
younger than 6 years were recruited in this group) based on the age at
which HCMV-DNA was detected. The newborn with HCMV-DNA positive detected
in saliva and/or urine of infants aged 0d-21d can be considered as
congenital HCMV infection \textsuperscript{14}.

\textbf{Inclusion and exclusion criteria are as follows:}

\textbf{Inclusion criteria:} (1) HCMV-infected group:HCMV-DNA [?] 4.0 \selectlanguage{ngerman}×
10\textsuperscript{2} copies/ml in the urine of child, and the child has
not received antiviral treatment; (2) Control group
(no-HCMV-infected)\selectlanguage{english}:HCMV-DNA \textless{} 4.0 x
10\textsuperscript{2}copies/ml in the urine of children and diagnosed as
HCMV-infected.

\textbf{Exclusion criteria:} All subjects in this experiment should meet
the following exclusion criteria: (1) active or known chronic infection
(such as autoimmune disease, diabetes, and cardiovascular disease); (2)
infectious diseases (hepatitis virus, herpes virus, rubella virus,
rubella virus, mycoplasma, chlamydia, AIDS, syphilis, toxoplasma gondii,
and other infections); (3) serious blood disease; (4) history of
malignancy.

\textbf{2.2 Detection of urine HCMV-DNA}

This technique is based on TaqMan PCR- Fluorescence probe technology,
1ml of urine specimen was centrifuged at 12000 rpm for 5 min. Urine
supernatant was discarded, and the pellet was collected and mixed with
50 \selectlanguage{greek}μ\selectlanguage{english}l of DNA extraction solution. Putting the10 \selectlanguage{greek}μ\selectlanguage{english}l of the above mixture,
10 \selectlanguage{greek}μ\selectlanguage{english}l of the treated negative-positive control,and 10 \selectlanguage{greek}μ\selectlanguage{english}l \selectlanguage{ngerman}× 4 of the
quantitative reference substance were respectively added into each
individual tube with the 40\selectlanguage{greek}μ\selectlanguage{english}l PCR mixture (Quantitative Diagnostic Kit
for HCMV-DNA, Hunan, China) and centrifuged for 10s, PCR was performed
using the 7500 real-time PCR system (Applied Biosystem, CA, USA ) Under
the following conditions: one cycle of 5for 2 min and 94 for 5 min;
followed by 45 cycles of 94 for 15 s and 57 for 31 s; one cycle of 25
for 10 s. The fluorescence signal emitted by fluorescein-labeled probe
is collected by PCR instrument, and the amplification curve and Ct value
are judged. HCMV DNA [?] 4.0 for 10\textsuperscript{2} copies/ml of
specimen was regarded as positive.

\textbf{2.3 Detection of hematological parameters}

2.3.1 Detection of White blood cells

2 ml of venous blood of the subjects was drawn into a vacuum blood
collection tube containing EDTA-K2 anticoagulant. Blood cells were
automatically absorbed, diluted, stained, and measured by routine
analyzer (XN-1000, SYSMEX) to obtain the information of blood cells, and
then the WBC, L\%, and LYM were recorded.

2.3.2 Detection of Liver and kidney function

The venous blood was drawn in a vacuum blood collection tube without
anticoagulant. After standing at room temperature for 30 min, the blood
was centrifuged at 3500 rpm for 5 min to obtain serum. If the specimen
can't be detected in time, refrigerate the centrifuged specimen in a
refrigerator at 2-8. The liver and renal function were detected in
Automatic biochemical analyzer (COBASC 701, Roche), and then ALT, AST,
GGT, UREA, and CREA were recorded.

\textbf{2.4 Statistical analyses}

Statistical analysis was performed using the SPSS ver. 26.0 software
(SPSS, Inc., Chicago, IL, USA). Quantitative data (such as WBC, L\%,
LYM, ALT, AST, GGT, UREA, CREA) with normal distribution or approximate
normal distribution were expressed as mean \selectlanguage{ngerman}± standard deviation. T test
or Mann-Whitney test was used to compare the data between the two
groups. Comparing the data among multiple groups, the analysis of
variance or Kruskal Wallis test is adopted. A \emph{P} -value
\textless{} 0.05 was considered to be statistically significant.

\textbf{3. Results}

\textbf{3.1 Patient characteristics}

A total of 223 children were enrolled the investigation (Table 1). Out
of these, 42 children aged 0d-21d (HCMV infection group (n=20) and
control group (n=22)), 98 children aged 22d-6m (HCMV infection group
(n=74) and control group (n=24)), 35 children aged 7m-11m (HCMV
infection group (n=17) and control group (n=18)), 17 children aged
12m-23m (HCMV infection group (n=6) and control group (n=11)), 31
children aged 2y-6y (HCMV infection group (n=15) and control group
(n=16)). The characteristics of all children are shown in Table 1.

\textbf{3.2 White blood cells related parameters characteristics after
HCMV infection in children of different age}

To analyze the effect of HCMV infection on white blood cells, we
compared the changes of the WBC, L\% and LYM in HCMV-infected children
and corresponding control group (Table 2). Compared with the
corresponding control group the L\% and LYM of HCMV-infected children
increased significantly in 0d-21d, 22d-6m, 7m-11m, 12m-23m, and 2y-6y
groups (\emph{P} \textless{}0.05) (Table 2). The change of WBC is
complicated, in the age groups of 22d-6m, 7m-11m and 2y-6y, the WBC of
children infected with HCMV is higher than that of their control groups
(Table 2). However, there was no significant increase in WBC in groups
0d-21d and 12m-23m compared with the control groups (\emph{P}
\textless{}0.05) (Table 2). The results showed that HCMV infection can
cause increase lymphocytes in children's peripheral blood, but not all
WBC of HCMV-infected children aged 0d-6y were elevated.

\textbf{3.3 Liver function related parameters characteristics after HCMV
infection in children of different ages}

To further ascertain the effect of HCMV-infection on Liver function, we
compared the changes of the ALT, AST and GGT in HCMV-infected children
and control group (Table 3). The ALT of HCMV-infected children within 6
months were significantly higher than their control groups (\emph{P}
\textless{}0.05)\selectlanguage{english},but there was no significant difference in ALT between
HCMV-infected children aged 7m-6y and their control groups (\emph{P}
\textgreater{}0.05) (Table 3). The AST of HCMV-infected children within
2 years was significantly higher than that of their corresponding
control groups (\emph{P} \textless{}0.05)\selectlanguage{english},but there was no significant
difference in AST between HCMV-infected children aged 2y-6y and their
control groups (\emph{P} \textgreater{}0.05) (Table 3). The GGT of
HCMV-infected children within 1 years were significantly higher than
their corresponding control groups (\emph{P} \textless{}0.05)\selectlanguage{english},but there
was no significant difference in GGT between HCMV-infected children aged
12m-6y and their corresponding control groups (\emph{P}
\textgreater{}0.05) (Table 3). Therefore, we speculate that HCMV
infection has more damage to the liver of younger children than older
children.

\textbf{3.4 Renal function related parameters characteristics after HCMV
infection in children of different ages}

In order to investigate the effect of HCMV infection on renal function,
the changes of CREA and UREA were investigated (Table 4). We found that
there was no significant difference in CREA and UREA between
HCMV-infected groups aged from 0 to 6y and their control groups
(\emph{P} \textgreater{}0.05) (Table 4). However, CREA levels were
significantly higher than normal in three HCMV-infected children aged
0d-21d (Table 4). Therefore, we speculate that HCMV infection has little
influence on children aged 0d-6y, or the probability that HCMV infection
has influence on CREA or UREA is rare.

\textbf{3.5 Hematological parameters of infants and children with HCMV
infection in different age groups}

There is no significant difference in white blood cells among different
age groups except that L\% and LYM in group 0-21d are slightly lower
than those in group 22d-6m (\emph{P} \textless{}0.05) (Table 5). In
addition, HCMV infection in children of different ages can have
different effects on liver function, among which the results of ALT in
children aged 0d-21d are the lowest, however, infants of 22d-6m are the
highest, and then decrease with the increase of children's age (Table
5). AST of 22d-6m and 7m-11m groups was significantly higher than that
in 0d-21d, 12m-23m, and 2y-6y groups (\emph{P} \textless{}0.05) (Table
5). The GGT of HCMV-infected children aged 0d-21d was the highest, and
then decreased with age (Table 5), which means that CMV may cause less
hepatobiliary damage in older children in the 22d-6y age group. And
children with 0-21d are special. Because the ALT of Infants aged 0d-21d
is lower than other age groups, but GGT is significantly higher than
other age groups, which suggests that the injuries of children aged
0d-21d may mainly come from gallbladder and bile duct. As for the effect
of HCMV on renal function, UREA had no significant difference among
different age groups, but CREA of 0d-21d group was significantly higher
than that in other age groups(\emph{P} \textless{}0.05) (Table 5). which
indicating that children of 0d-21d age group may have a higher risk of
kidney disease after being infected with HCMV.

\textbf{4. Discussion}

Infants or children infected with HCMV are prone to missed diagnosis
because the vast majority of infants and children are mainly
characterized by occult infection. However, CMV can cause some infants
with corresponding complications such as low cellular immune function,
deafness and mental retardation.

In the process of HCMV infection, the number, distribution and
proportion of WBC in peripheral blood may change. In a retrospective
study, it was found that WBC and L\% in pneumonia children with HCMV
infection within 6 years were higher than those respiratory infection
caused by other viruses but no bacterial infection \textsuperscript{15}.
Moreover, in HCMV-infected children within 3 months\selectlanguage{english},their WBC and LYM
were higher than those in normal group (\emph{P}
\textless{}0.01)\textsuperscript{16}. In this study, we found that the
LYM and L\% of HCMV-infected children aged 0d-6y were higher than
control group, but not all WBC of HCMV-infected children aged 0d-6y were
higher than control group. We speculate that the reason may be related
to the occurrence of autoimmune neutropenia after HCMV infection or
neutropenia caused by ganciclovir treatment \textsuperscript{17, 18}.
Further studies have found that HCMV can induce specific changes in
lymphocyte subsets, which mainly show that HCMV-positive people have
more lymphocytes, CD8+T cells and CD28+T cells, and the ratio of CD4+/
CD8+ cells decrease \textsuperscript{19}. Moreover, some scholars
believe that CD4+ and CD8+T lymphocyte reaction is related to HCMV
infection rate and mortality \textsuperscript{20}, so lymphocyte
response plays an important role in controlling HCMV infection.

CMV has a wide tropism to cells, and the liver and gallbladder are also
the prone organs of CMV infection. The main manifestations of HCMV liver
injury in children are jaundice, hepatomegaly and cholestasis. A
significant association between HCMV antibodies and liver enzymes (ALT,
AST, and GGT) was found in a HCMV-screening of 455 patients with liver
dysfunction \textsuperscript{21}. In 49 children with HCMV between 7
days and 32 months of age, Alt and AST were elevated in all patients and
26.5\% suffered from cholestasis \textsuperscript{22}. Goel et al. found
that 52\% newborns with cholestasis had HCMV in their
liver\textsuperscript{23}, and a report showed that HCMV can also cause
acute cholecystitis in adults with normal immunity \textsuperscript{24}.
These results suggest that HCMV infection may cause liver and biliary
system damage in children. In our study, HCMV-infected childrens' GGT,
ALT, and AST were significantly higher than their corresponding control
group. But not all children infected with HCMV showed abnormal liver
function. About 50\% of infants who have been exposed to cervical and
vaginal secretions containing HCMV during perinatal period and 50\%-60\%
of infants who have eaten breast milk containing HCMV after birth will
develop HCMV infection \textsuperscript{25}. In addition, our data
showed that the damage of HCMV to gallbladder and bile duct in children
aged 0-21d is greater than that to liver, and the damage of HCMV to
liver and gallbladder will be weakened with the growth of infant age. we
speculate the reason may be related to the maturation of the infant
immune system.

HCMV can replicate in the renal tubules of congenital HCMV-infected
children and excrete in urine, which suggests that kidney is the target
organ of HCMV \textsuperscript{26}. Infants and children are generally
susceptible to CMV, but there are few reports about kidney damage caused
by CMV infection in infants and children \textsuperscript{27}. It is now
known that HCMV infection is part of major infection complications
following kidney transplantation \textsuperscript{28}. In addition, it
has been found that HCMV reactivation can lead to an increase in UREA
and CREA in patients with sepsis, and these variables are correlated
with viral load, but infection with the virus may not be associated with
an increased risk of renal malformation \textsuperscript{29}. Our data
showed that the renal function was no statistical difference between
HCMV-infected childrens' and their control groups. Therefore, it can be
considered that renal dysfunction caused by HCMV infection is a rare
event. In addition, it can also be considered that the degree of renal
damage caused by HCMV infection is relatively light, and some more
sensitive indicators are needed to monitor.

In addition, the CREA of HCMV-infected children aged 0d-21d was
significantly higher than other age groups, but it was no significant
difference compared with control group. The reason may be that the CREA
of the newborn reflects the state of the mother's renal function, and
within 1-2 weeks after the baby is born, CREA will gradually decrease
and turn into the real creatinine of the baby \textsuperscript{30}\begin{CJK}{UTF8}{gbsn}。

\end{CJK}\selectlanguage{english}\textbf{5. Conclusions}

In conclusion, the current analysis reveals that HCMV infection can
cause the increase of lymphocytes in children aged 0-6y. The damage of
HCMV to liver and gallbladder gradually decreases with age. HCMV
infection may have little effect on renal function or be rare cases.
Serum creatinine cannot be used to evaluate neonatal renal function
because it is affected by maternal renal function. And we anticipate to
provide diagnostic value for children infected with HCMV in different
age groups through these common hematology parameters.

\textbf{Acknowledgments}

We thank the study staff and all the infants and children who
participated in this study.

Financial Support: Shenzhen Key Medical Discipline Construction Fund
(grant number SZXK054).

\textbf{Potential Conflict of interest}

There are no relevant financial or non-financial competing interests to
report.

\textbf{Author Contributions}

Y.Y.W and Z.Z conceived and designed the study; X.M.Z acquired funding;
Y.Y.W and Z.Z performed the analysis; D.X contributed analytic tools;
D.X and L.J.K supervised the work; Y.Y.W and Z.Z wrote the original
draft, reviewed and edited the paper. All authors have read and agreed
to the published version of the manuscript.

\textbf{ORCID}

Yingying wang ID https://orcid.org/0009-0008-0429-5818

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10.14309/01.ajg.0000787408.62364.22.

25 Kadambari S, Whittaker E, Lyall H. Postnatally acquired
cytomegalovirus infection in extremely premature infants: how best to
manage?. Arch Dis Child Fetal Neonatal Ed. 2020;105(3):334-339.
doi:10.1136/archdischild-2019-317650.

26 R\selectlanguage{ngerman}íos-Barnés M, Fortuny C, Alarcón A, Noguera-Julian A. Renal
Involvement in Congenital Cytomegalovirus Infection: A Systematic
Review. Microorganisms. 2021;9(6):1304. Published 2021 Jun 15.
doi:10.3390/microorganisms9061304.

27 Murugananth S, Padmaraj R, Gopalakrishnan N, et al. Isolated renal
involvement of cytomegalovirus inclusion disease in an infant. Saudi J
Kidney Dis Transpl. 2018;29(1):198-201. doi:10.4103/1319-2442.225176.

28 Ruan Y, Guo W, Liang S, Xu Z, Niu T. Diagnostic performance of
cytomegalovirus (CMV) immune monitoring with ELISPOT and QuantiFERON-CMV
assay in kidney transplantation: A PRISMA-compliant article. Medicine
(Baltimore). 2019;98(16):e15228. doi:10.1097/MD.0000000000015228.

29 Ríos-Barnés M, Fortuny C, Alarcón A, Noguera-Julian A. Renal
Involvement in Congenital Cytomegalovirus Infection: A Systematic
Review. Microorganisms. 2021;9(6):1304. Published 2021 Jun 15.
doi:10.3390/microorganisms9061304.

30 Mohr Lytsen R, Taageby Nielsen S, Kongsgaard Hansen M, et al. Markers
of Kidney Function in Early Childhood and Association With Maternal
Comorbidity. JAMA Netw Open. 2022;5(11):e2243146. Published 2022 Nov 1.
doi:10.1001/jamanetworkopen.2022.43146.

\textbf{Table 1. The baseline characteristics of 223 children}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\textbf{Factors} & \textbf{N} \textbf{(\%)} & \textbf{HCMV-infected} &
\textbf{Control groups}\tabularnewline
\midrule
\endhead
\textbf{Gender} & & &\tabularnewline
Male & 125(56.05\%) & &\tabularnewline
Female & 98(43.95\%) & &\tabularnewline
\textbf{Age} & & &\tabularnewline
0d-21d & 42(18.83\%) & 20 & 22\tabularnewline
22d-6m & 98(43.95\%) & 74 & 24\tabularnewline
7m-11m & 35(15.70\%) & 17 & 18\tabularnewline
12m-23m & 17(7.62\%) & 6 & 11\tabularnewline
2y-6y & 31(13.90\%) & 15 & 16\tabularnewline
Total & 223 & 132 & 91\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 2. Comparison of white blood cell parameters after HCMV
infection in children of different ages}\selectlanguage{english}
\begin{longtable}[]{@{}llllllllll@{}}
\toprule
& \textbf{WBC} & \textbf{WBC} & \textbf{WBC} & \textbf{L\%} &
\textbf{L\%} & \textbf{L\%} & \textbf{LYM} & \textbf{LYM} &
\textbf{LYM}\tabularnewline
\textbf{group} & HCMV & Control & \emph{P value} & HCMV & Control &
\emph{P value} & HCMV & Control & \emph{P value}\tabularnewline
0d-21d & 11.86\selectlanguage{ngerman}±3.65 & 12.91\selectlanguage{ngerman}±3.18 & ns & 54.61\selectlanguage{ngerman}±15.84 & 28.15\selectlanguage{ngerman}±7.72 &
\textless{}0.01 & 5.96\selectlanguage{ngerman}±1.85 & 3.4\selectlanguage{ngerman}±1.00 & \textless{}0.01\tabularnewline
22d-6m & 10.65\selectlanguage{ngerman}±3.89 & 8.26\selectlanguage{ngerman}±1.77 & \textless{}0.01 & 67.62\selectlanguage{ngerman}±10.45 &
53.55\selectlanguage{ngerman}±12.5 & \textless{}0.01 & 7.21\selectlanguage{ngerman}±3.04 & 4.22\selectlanguage{ngerman}±1.24 &
\textless{}0.01\tabularnewline
7m-11m & 10.23\selectlanguage{ngerman}±2.64 & 8.48\selectlanguage{ngerman}±1.30 & \textless{}0.05 & 64.84\selectlanguage{ngerman}±11.68 &
51.81\selectlanguage{ngerman}±16.04 & \textless{}0.05 & 6.59\selectlanguage{ngerman}±1.57 & 4.31\selectlanguage{ngerman}±1.29 &
\textless{}0.01\tabularnewline
12m-23m & 9.98\selectlanguage{ngerman}±3.67 & 7.42\selectlanguage{ngerman}±1.49 & ns & 64.25\selectlanguage{ngerman}±9.34 & 43.48\selectlanguage{ngerman}±9.00 &
\textless{}0.01 & 6.24\selectlanguage{ngerman}±1.83 & 3.12\selectlanguage{ngerman}±0.86 & \textless{}0.01\tabularnewline
2y-6y & 10.82\selectlanguage{ngerman}±3.23 & 8.37\selectlanguage{ngerman}±1.14 & \textless{}0.05 & 61.55\selectlanguage{ngerman}±11.73 &
42.13\selectlanguage{ngerman}±7.03 & \textless{}0.01 & 6.24\selectlanguage{ngerman}±2.39 & 3.43\selectlanguage{ngerman}±0.55 &
\textless{}0.01\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 3. Comparison of hepatobiliary injury-related parameters
after HCMV infection in children of different ages}\selectlanguage{english}
\begin{longtable}[]{@{}llllllllll@{}}
\toprule
& \textbf{ALT} & \textbf{ALT} & \textbf{ALT} & \textbf{AST} &
\textbf{AST} & \textbf{AST} & \textbf{GGT} & \textbf{GGT} &
\textbf{GGT}\tabularnewline
\textbf{group} & HCMV & Control & \emph{P value} & HCMV & Control &
\emph{P value} & HCMV & Control & \emph{P value}\tabularnewline
0d-21d & 13.48\selectlanguage{ngerman}±9.28 & 8.75\selectlanguage{ngerman}±3.15 & \textless{}0.05 & 50.81\selectlanguage{ngerman}±23.11 &
33.85\selectlanguage{ngerman}±11.81 & \textless{}0.01 & 274.64\selectlanguage{ngerman}±130.81 & 107.14\selectlanguage{ngerman}±44.75 &
\textless{}0.01\tabularnewline
22d-6m & 43.33\selectlanguage{ngerman}±33.08 & 17.18\selectlanguage{ngerman}±8.54 & \textless{}0.01 & 57.00.\selectlanguage{ngerman}±29.8 &
30.78\selectlanguage{ngerman}±14.88 & \textless{}0.01 & 62.61\selectlanguage{ngerman}±52.2 & 36.8\selectlanguage{ngerman}±25.45 &
\textless{}0.01\tabularnewline
7m-11m & 38.22\selectlanguage{ngerman}±33.27 & 22.16\selectlanguage{ngerman}±5.01 & ns & 57.54\selectlanguage{ngerman}±26.9 & 31.95\selectlanguage{ngerman}±7.39 &
\textless{}0.01 & 24.93\selectlanguage{ngerman}±19.23 & 10.83\selectlanguage{ngerman}±3.68 &
\textless{}0.05\tabularnewline
12m-23m & 28.83\selectlanguage{ngerman}±24.24 & 16.68\selectlanguage{ngerman}±5.00 & ns & 43.3\selectlanguage{ngerman}±10.59 & 29.07\selectlanguage{ngerman}±8.25 &
\textless{}0.01 & 8.25\selectlanguage{ngerman}±3.77 & 12.03\selectlanguage{ngerman}±3.07 & ns\tabularnewline
2y-6y & 20.5\selectlanguage{ngerman}±16.58 & 13.66\selectlanguage{ngerman}±5.36 & ns & 33.23\selectlanguage{ngerman}±8.51 & 28.11\selectlanguage{ngerman}±5.86 & ns &
16.81\selectlanguage{ngerman}±15.42 & 12.07\selectlanguage{ngerman}±2.98 & ns\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 4. Comparison of kidney injury-related parameters after
HCMV infection in children of different ages}\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& \textbf{UREA} & \textbf{UREA} & \textbf{UREA} & \textbf{CREA} &
\textbf{CREA} & \textbf{CREA}\tabularnewline
\textbf{group} & HCMV & Control & \emph{P value} & HCMV & Control &
\emph{P value}\tabularnewline
0d-21d & 3.25\selectlanguage{ngerman}±1.51 & 2.59\selectlanguage{ngerman}±1.69 & ns & 49.31\selectlanguage{ngerman}±18.19 & 41.85\selectlanguage{ngerman}±12.07 &
ns\tabularnewline
22d-6m & 2.26\selectlanguage{ngerman}±0.99 & 2.45\selectlanguage{ngerman}±1.05 & ns & 25.47\selectlanguage{ngerman}±10.60 & 23.04\selectlanguage{ngerman}±6.39 &
ns\tabularnewline
7m-11m & 2.47\selectlanguage{ngerman}±1.25 & 3.05\selectlanguage{ngerman}±0.94 & ns & 28.14\selectlanguage{ngerman}±5.44 & 30.64\selectlanguage{ngerman}±7.71 &
ns\tabularnewline
12m-23m & 4.28\selectlanguage{ngerman}±0.75 & 4.2\selectlanguage{ngerman}±1.06 & ns & 27.88\selectlanguage{ngerman}±7.18 & 26.39\selectlanguage{ngerman}±8.43 &
ns\tabularnewline
2y-6y & 3.94\selectlanguage{ngerman}±1.26 & 3.97\selectlanguage{ngerman}±0.83 & ns & 32.47\selectlanguage{ngerman}±3.95 & 32.6\selectlanguage{ngerman}±8.88 &
ns\tabularnewline
\bottomrule
\end{longtable}

Table 5. Hematological parameters of children with HCMV infection in
different age groups\selectlanguage{english}
\begin{longtable}[]{@{}llllllllll@{}}
\toprule
& \textbf{WBC} & \textbf{L\%} & \textbf{LYM} & \textbf{ALT} &
\textbf{AST} & \textbf{GGT} & \textbf{GGT} & \textbf{UREA} &
\textbf{CREA}\tabularnewline
0d-21d & 11.86\selectlanguage{ngerman}±3.65\textsuperscript{a} & 54.61\selectlanguage{ngerman}±15.84\textsuperscript{a}
& 5.96\selectlanguage{ngerman}±1.85\textsuperscript{a} & 13.48\selectlanguage{ngerman}±9.28\textsuperscript{a} &
50.81\selectlanguage{ngerman}±23.11\textsuperscript{a} & 274.64\selectlanguage{ngerman}±130.81\textsuperscript{d} &
3.23\selectlanguage{ngerman}±1.58\textsuperscript{ab} & 3.23\selectlanguage{ngerman}±1.58\textsuperscript{ab} &
49.26\selectlanguage{ngerman}±18.85\textsuperscript{c}\tabularnewline
22d-6m & 10.65\selectlanguage{ngerman}±3.89\textsuperscript{a} & 67.62\selectlanguage{ngerman}±10.45\textsuperscript{b}
& 7.21\selectlanguage{ngerman}±3.04\textsuperscript{a} & 43.33\selectlanguage{ngerman}±33.08\textsuperscript{d} &
57.00\selectlanguage{ngerman}±29.8\textsuperscript{b} & 62.61\selectlanguage{ngerman}±52.2\textsuperscript{c} &
2.45\selectlanguage{ngerman}±1.01\textsuperscript{a} & 2.45\selectlanguage{ngerman}±1.01\textsuperscript{a} &
25.47\selectlanguage{ngerman}±10.60\textsuperscript{a}\tabularnewline
7m-11m & 10.23\selectlanguage{ngerman}±2.64\textsuperscript{a} & 64.84\selectlanguage{ngerman}±11.68\textsuperscript{a}
& 6.59\selectlanguage{ngerman}±1.57\textsuperscript{a} & 38.22\selectlanguage{ngerman}±33.27\textsuperscript{c} &
57.54\selectlanguage{ngerman}±26.9\textsuperscript{b} & 24.93\selectlanguage{ngerman}±19.23\textsuperscript{b} &
2.47\selectlanguage{ngerman}±1.25\textsuperscript{a} & 2.47\selectlanguage{ngerman}±1.25\textsuperscript{a} &
28.14\selectlanguage{ngerman}±5.44\textsuperscript{b}\tabularnewline
12m-23m & 9.98\selectlanguage{ngerman}±3.67\textsuperscript{a} & 64.25\selectlanguage{ngerman}±9.34\textsuperscript{a} &
6.24\selectlanguage{ngerman}±1.83\textsuperscript{a} & 28.83\selectlanguage{ngerman}±24.24\textsuperscript{b} &
43.3\selectlanguage{ngerman}±10.59\textsuperscript{a} & 8.25\selectlanguage{ngerman}±3.77\textsuperscript{a} &
4.28\selectlanguage{ngerman}±0.75\textsuperscript{b} & 4.28\selectlanguage{ngerman}±0.75\textsuperscript{b} &
27.88\selectlanguage{ngerman}±7.18\textsuperscript{b}\tabularnewline
2y-6y & 10.82\selectlanguage{ngerman}±3.23\textsuperscript{a} & 61.55\selectlanguage{ngerman}±11.73\textsuperscript{a} &
6.24\selectlanguage{ngerman}±2.39\textsuperscript{a} & 20.50\selectlanguage{ngerman}±16.58\textsuperscript{a} &
33.23\selectlanguage{ngerman}±8.51\textsuperscript{a} & 16.81\selectlanguage{ngerman}±15.42\textsuperscript{ab} &
3.94\selectlanguage{ngerman}±1.26\textsuperscript{b} & 3.94\selectlanguage{ngerman}±1.26\textsuperscript{b} &
32.47\selectlanguage{ngerman}±3.95\textsuperscript{b}\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{ngerman}

\selectlanguage{english}
\FloatBarrier
\end{document}

