JOURNAL OF HEPATO-GASTROENTEROLOGY RESEARCH | ЖУРНАЛ ГЕПАТО-ГАСТРОЭНТЕРОЛОГИЧЕСКИХ ИССЛЕДОВАНИЙ
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Belyх N. A,
MD, PhD, Dr Med Sci, Associate Professor, Head of the Department of Faculty and Polyclinic Pediatrics with
the Course of Pediatric of Postgraduate Education, Ryazan State Medical University, Ryazan, Russian Federation.
Nataliya A. Anikeeva,
MD, PhD, Assistant Professor of the Department of Faculty and Polyclinic Pediatrics with the Course of
Pediatric of Postgraduate Education, Ryazan State Medical University, Ryazan, Russian Federation.
Anastasia Yu. Panferuhina,
student of Ryazan State Medical University, Ryazan, Russian Federation
Tatyana Ye. Filatova,
MD, PhD, Assistant Professor of the Department
of Polyclinic Therapy, Prophylaxis Medicine and Genera,
Ryazan State Medical University, Ryazan, Russian Federation.
Inna V. Piznyur
Assistant Professor of the Department of Faculty and Polyclinic Pediatrics with the Course of Pediatric of
Postgraduate Education, Ryazan State Medical University
Ryazan, Russian Federation.
CLINICAL AND EPIDEMIOLOGICAL FEATURES IN PEDIATRIC PATIENTS IN WITH SARS-COV-2
INFECTION IN THE RYAZAN REGION
ANNOTATION
To study the clinical and laboratory features of the course of SARS-CoV-2 infection (COVID-19) in children
of the Ryazan region. A retrospective study carried out with the participation of 55 children hospitalized at the City
Clinical Hospital No. 11 (Ryazan) from April 2020 to March 2021 with a diagnosis of new coronavirus infection
COVID-19. Among those hospitalized, there was a predominance of children over the age of 12 years (61.8%). Almost
one third of patients had comorbid pathology. The most common comorbidities were obesity, CVS and CNS pathology.
More than half of the hospitalized children (58.2%) had intrafamilial contact with laboratory-confirmed cases of
COVID-19. The main clinical manifestations in the observed children were: symptoms of intoxication, respiratory tract
lesions and gastrointestinal symptoms. In the dominant number of cases (63.6%), lung damage corresponded to mild
(CT-1) severity. More than half of the children (63.6%) had a concomitant bacterial infection. IgM antibodies to
Mycoplasma pneumoniae were detected by ELISA in 15 patients (27.3%). A direct correlation was found between the
degree of lung damage and the level of CRP (r = 0.31, p = 0.019), ALT (r = 0.30, p = 0.05) and LDH (r=0.27, p = 0.05),
as well as the presence of concomitant diseases (r = 0.41, p = 0.002). Against the background of the therapy, positive
dynamics was noted in the condition of all patients. Lethal outcomes not recorded in the studied sample of patients.
Almost half of the patients (40%) had a comorbid pathology. The presence of concomitant bacterial infection
was detected in 63.6% of children. Most patients are diagnosed with respiratory mycoplasmosis. A significant positive
correlation was established between the degree of damage to the lung tissue and the presence of concomitant diseases,
as well as deviations from the norm of a number of laboratory parameters (CRP, ALT, LDH). With timely treatment,
most patients with viral lung disease caused by the new coronavirus infection COVID-19 had a favorable outcome of
the disease.
Key words
: new coronavirus infection, viral lung disease, community-acquired pneumonia, children
Белых Н.А,
Доктор медицинских наук, доцент, заведующий кафедрой факультетской и поликлинической педиатрии
с курсом педиатрии последипломного образования Рязанского государственного медицинского университета,
Рязань, Российская Федерация.
Наталия Александровна Аникеева,
Доктор медицинских наук, доцент кафедры факультетской и поликлинической педиатрии с курсом
педиатрии последипломного образования Рязанского государственного медицинского университета, Рязань,
Российская Федерация.
Анастасия Ю. Панферухина,
студентка Рязанского государственного медицинского университета, Рязань, Российская Федерация
JOURNAL OF HEPATO-GASTROENTEROLOGY RESEARCH | ЖУРНАЛ ГЕПАТО-ГАСТРОЭНТЕРОЛОГИЧЕСКИХ ИССЛЕДОВАНИЙ
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Татьяна Е. Филатова,
Доктор медицинских наук, доцент кафедры поликлинической терапии, медицинской и общей
профилактики Рязанского государственного медицинского университета, Рязань, Российская Федерация.
Инна Васильевна Пизнюр
Доцент кафедры факультетской и поликлинической педиатрии с курсом педиатрии последипломного
образования Рязанского государственного медицинского университета
Рязань, Российская Федерация.
КЛИНИКО-ЭПИДЕМИОЛОГИЧЕСКИЕ ОСОБЕННОСТИ У ПЕДИАТРИЧЕСКИХ БОЛЬНЫХ
ИНФЕКЦИЕЙ SARS-COV-2 В РЯЗАНСКОЙ ОБЛАСТИ
АННОТАЦИЯ
Изучить клинико-лабораторные особенности течения инфекции SARS-CoV-2 (COVID-19) у детей
Рязанской области. Проведено ретроспективное исследование с участием 55 детей, госпитализированных в
Городскую клиническую больницу № 11 (Рязань) с апреля 2020 года по март 2021 года с диагнозом новой
коронавирусной инфекции COVID-19. Среди госпитализированных преобладали дети старше 12 лет (61,8%).
Почти у трети пациентов наблюдалась коморбидная патология. Наиболее частыми сопутствующими
заболеваниями были ожирение, патология ССС и ЦНС. Более половины госпитализированных детей (58,2%)
имели внутрисемейный контакт с лабораторно подтвержденными случаями COVID-19. Основными
клиническими проявлениями у наблюдаемых детей были: симптомы интоксикации, поражения дыхательных
путей и желудочно-кишечные симптомы. В преобладающем числе случаев (63,6%) поражение легких
соответствовало легкой (КТ-1) степени тяжести. Более половины детей (63,6%) имели сопутствующую
бактериальную инфекцию. Антитела IgM к Mycoplasma pneumoniae с помощью ИФА выявлены у 15 пациентов
(27,3%). Была обнаружена прямая корреляция между степенью поражения легких и уровнем CRP (r = 0,31, p =
0,019), АЛТ (r = 0,30, p = 0,05) и ЛДГ (r = 0,27, p = 0,05), а также как наличие сопутствующих заболеваний (r =
0,41, p = 0,002). На фоне проведенной терапии отмечена положительная динамика в состоянии всех пациентов.
Летальных исходов у исследуемой выборки пациентов не зафиксировано.
Почти половина пациентов (40%) имели сопутствующую патологию. Наличие сопутствующей
бактериальной инфекции выявлено у 63,6% детей. У большинства пациентов диагностируется респираторный
микоплазмоз. Установлена достоверная положительная корреляция между степенью поражения легочной ткани
и наличием сопутствующих заболеваний, а также отклонениями от нормы ряда лабораторных показателей
(СРБ, АЛТ, ЛДГ). При своевременном лечении у большинства пациентов с вирусным заболеванием легких,
вызванным новой коронавирусной инфекцией COVID-19, исход болезни был благоприятным.
Ключевые слова:
новая коронавирусная инфекция, вирусное заболевание легких, внебольничная
пневмония, дети.
Background.
COVID-19 is an acute infectious
disease, caused by a member of the
Coronaviridae
family
-
SARS-CoV-2
, which characterized by its ability to cause
severe damage to the lung tissue in humans. The first case
of COVID-19 infection was registered at the end of
December 2019 in China (Hubei province, Wuhan city)
[1]. The virus has spread at a rapid pace almost across the
globe. By March 2020, the number of countries, with
confirmed cases of COVID-19, reached 114, in
connection with which the WHO declared a pandemic
[2].
According to world statistics, at the time of this
writing (September 2021), there were 222,969,174
confirmed cases of COVID-19 in 214 countries of the
world, of which 197,776,410 were recovered, and the
number of deaths reached 4,604,072 [3]. At the same
time, the number of cases of COVID-19 among children
and adolescents in the structure of morbidity in different
countries is not large and does not exceed 16%. So, on
the territory of the Russian Federation, patients aged 0-18
years with a confirmed diagnosis of COVID-19 make up
7.6% of the total [4]. In the United States, according to
the American Academy of Pediatrics, children account for
15.1% of the total number of patients diagnosed with
SARS-CoV-2 infection [5], and in China people under 19
years old account for 2.2% of COVID-19 cases [6].
The spectrum of clinical manifestations of
COVID-19 is very diverse. Currently, many scenarios of
the course of this disease have been described: from
asymptomatic carriage to extremely severe forms
characterized by the involvement of various organs and
systems in the pathological process, the development of
multiple organ failure and a high frequency of deaths
[1,6]. At the same time, in children and adolescents the
new coronavirus infection, in general, is proceeding
relatively favorably. In contrast to the adult population, in
the pediatric population asymptomatic and mild forms of
the disease are mainly found [4,6,7]. The severity of
clinical manifestations is most often due to the defeat of
the terminal sections of the respiratory tract and the
development of pneumonia [7,8,9].
According to a Russian study in 218 sick
children, the development of COVID-19-associated
pneumonia observed in 11.5% of cases, and the
frequency of lung damage was significantly higher
among infants and adolescents [7]. The authors noted,
that in children of the first year of life an atypical course
of the disease was mainly recorded, while for patients of
JOURNAL OF HEPATO-GASTROENTEROLOGY RESEARCH | ЖУРНАЛ ГЕПАТО-ГАСТРОЭНТЕРОЛОГИЧЕСКИХ ИССЛЕДОВАНИЙ
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puberty age the manifest course of COVID-19 was more
typical. In an American study W.R. Otto et al. report, that
of 424 children, who tested positive for SARS-CoV-2,
pneumonia was found in 77 (18.2%) patients, 24 children
of which required respiratory support [8]. M. Jahangir
and M. Nawaz indicate, that in patients (n=224) of
pediatric wards with confirmed SARS-CoV-2 infection in
147 (65.6%) cases, radiographic changes were found,
indicating the development of pneumonia, as a rule, of
mild severity [9].
Some authors pay attention to the presence of
comorbidity as the main risk factor for the development
of COVID-19 pneumonia in children [9,10]. However, in
a systematic review and meta-analysis by C.R. Jutzeler et
al. [11] reported, that in a study involving 1,056 children
and newborns with COVID-19, when performing
computed tomography, changes in lung tissue indicating
pneumonia were detected in 65% of patients, and the
presence of concomitant pathology was detected in only 2
children. Insufficiency and inconsistency of data, as well
as a limited number of works, devoted to the problem of
lung damage in children with a new coronavirus
infection, determine the relevance of this study.
Aim
: to study the clinical and laboratory
features of the course of SARS-CoV-2 infection
(COVID-19) in children of the Ryazan region.
Materials and research methods
. A single-
center pilot observational study carried out with the
participation of 55 children (30 boys, 25 girls),
hospitalized at the City Clinical Hospital No. 11 (Ryazan)
from April 2020 to March 2021 with a diagnosis of new
coronavirus infection COVID-19. The diagnosis verified
according to modern clinical and laboratory criteria for
etiological diagnostics, including the detection of
ribonucleic acid (RNA) of SARS-CoV-2 in the material
of a smear from the oropharynx and nasopharynx by
polymerase chain reaction (PCR), as well as taking into
account modern clinical and radiological criteria for viral
lung damage using specialized methods of radiation
diagnostics.
The inclusion criteria for the study were: age
from 1 month up to 17 years; the diagnosis verified by
the detection of SARS-CoV-2 RNA by the PCR method:
new coronavirus infection COVID-19; the presence of
signs of damage to the lung tissue, typical for pneumonia
of viral etiology, according to the X-ray computed
tomography (X-ray CT) of the chest. C-reactive protein
(CRP), alanine aminotransferase (ALT), aspartate
aminotransferase (AST), lactate dehydrogenase (LDH),
creatinine phosphokinase-MB (CPK-MB), serum ferritin
determined in all patients. Statistical processing
performed using the Pandas, SciPy libraries and the
Python programming language. Given the limited number
of observations, the absence of a normal distribution, the
methods of nonparametric statistics were used. For
quantitative variables, the median and quartiles were
calculated, the data are presented as Me [P25; P75], for
qualitative variables the determination of absolute values
and their shares (in %) was carried out. For the
correlation analysis, the Spearman rank correlation
coefficient (r) was calculated with an estimate of the
significance level (p). Differences were considered
statistically significant at p<0.05.
Results.
All patients with COVID-19 admitted
to an infectious diseases hospital for emergency
indications. Most of them were delivered by the transport
of the territorial center of disaster medicine from the
regional hospitals of the region (22 patients, 40.0%),
1
/
3
of children (17 patients, 30.9%) were admitted by the
referral of the district pediatrician, ambulance teams were
delivered from home 14 children (25.5%), 2 children
(3.6%) were hospitalized on self-referral without a
referral from medical organizations.Twenty children
(36.4%) were admitted to the hospital in the first 3 days
from the onset of the disease, 19 (34.6%) children – on 4-
6 days, 12 (21.8%) – on 7-10 days, 2 (3.6%) – on the 11-
14 days and 2 (3.6%) – after 14 days from the moment
the first clinical symptoms appeared.During the analysis
of the gender-age structure of the studied group of
patients (table 1), there were no significant differences in
the incidence of COVID-19 depending on gender. The
youngest patient was 1 month old, the oldest - 17 years
11 months old. Among those hospitalized, there was a
predominance of children over the age of 12 years (34
patients, 61.8%).
Table 1
Distribution of patients with COVID-19 by age and sex
Age groups
Gender
Total
Boys
Girls
0-12 months
4 (7.3%) 4
1 (1.8%)
5 (9.1%)
1-5 years
5 (9.1%)
1 (1.8%)
6 (10.9%)
5-12 years
2 (3.6%)
8 (14.6%)
10 (18.2%)
12-18 years
19 (34.5%)
15 (27.3%)
34 (61.8%)
Total:
30 (54.5%)
25 (45.5%)
55 (100%)
Various comorbidities had 17 (30.9%) patients,
the structure of which is shown in table 2. Moreover, a
combination of obesity with pathology of the
cardiovascular system had 5 children (9.1%).
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Table 2
The structure of comorbid pathology in the observed patients
Nosology
Quantity
n
%
Bronchial asthma
2
3,6%
Bronchopulmonary dysplasia in history
1
1,8%
Obesity
9
16,4%
Pathology of Central Nervous System
3
5,5%
Arterial hypertension
4
7,3%
Congenital heart defects
3
5,5%
More than half of the hospitalized (32 children,
58.2%) had intrafamilial contact with laboratory-
confirmed cases of COVID-19 in relatives, in 23 (41.8%)
patients the source of infection could not be identified
(fig. 1).
Figure 1. Data on contacts with laboratory-confirmed cases of COVID-19 in patients' relatives
At the time of admission, the condition of the
majority of patients was assessed as moderate (53
patients, 96.4%), 2 (3.6%) children were in a serious
condition. The severity was due to the presence of
respiratory disorders and the severity of the intoxication
syndrome. The main clinical symptoms, observed in
children with COVID-19 associated pneumonia, are
presented in table 3.
Table 3
The clinical symptoms in the observed patients
Clinical symptoms
Number
n
%
Intoxication symptoms
Fever
48
87,3%
Weakness/lethargy
31
56,4%
Decreased appetite
26
47,3%
Headache
28
50,9%
Myalgia
3
5,5%
Tachycardia
37
67,3%
Respiratory tract symptoms
Cough
53
96,4%
Sore throat
8
14,5%
Difficulty in nasal breathing
27
49,1%
Auscultators changes in the lungs (dry/wet rales)
11
20,0%
Shortness of breath
26
47,3%
Tachypnea
19
34,5%
Gastrointestinal symptoms
Nausea
4
7,3%
Vomiting
5
9,1%
Abdominal pain
2
3,6%
Diarrhea
3
5,5%
Other
Disturbances of taste and / or smell
17
30,9%
Skin rashes
1
1,8%
Among the clinical symptoms of infectious
toxicosis, fever of varying severity was most often
recorded, which was observed in 48 (87.3%) patients. In
most cases, the div temperature reached subfebrile
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values (22 patients, 40.0%), febrile fever observed in 20
(36.4%) patients, and fever increase of more than 39.1°C
(high febrile fever) at the time of admission was noted in
six children (10.9%). In 7 (12.7%) patients thermometry
indices corresponded to the norm. The median div
temperature was 37.9°C [37.4; 38.5]. Other intoxication
symptoms were rate: weakness/lethargy (31 patients,
56.4%), decreased appetite (26 patients, 47.3%),
headache (28 patients, 50.9%), myalgia (3 patients,
5.5%).
A common symptom of respiratory tract damage
was dry or unproductive cough (53 patients, 96.4%).
Dyspnea was present in 26 (47.3%) patients. In 9 (16.3%)
patients, there were symptoms of respiratory failure of 1-
2 degrees.
Blood oxygen saturation indices, as a rule,
corresponded to normal values (Me=98 [96; 99]),
decrease in saturation <95% had 5 patients (9%) (fig. 2)
Figure 2. Indicators of blood oxygen saturation in patients with COVID-19
In an objective study, 11 (20%) patients showed
auscultatory changes in the lungs in the form of dry or
wet rales. An increase in the respiratory rate (tachypnea)
in 19 patients (34.5%) revealed, tachycardia – in 37
patients (67.3%). In an objective study, 11 (20%) patients
showed auscultatory changes in the lungs in the form of
dry or wet rales.
Catarrhal inflammation of upper respiratory tract
had 28 (50.9%) children. At the same time, difficulty in
nasal breathing was noted in 27 (49.1%) patients, 8
(14.5%) patients actively complained of sore throat.
Disturbances of taste and smell registered mainly among
children of the older age group (17 patients, 30.9%).
Significantly less frequently, gastrointestinal symptoms
were detected: nausea - 4 patient (7.3%), single vomiting
– 5 (9.1%), diarrhea – 3 (5.5%), diffuse abdominal pain –
2 (3.6%). One patient has an urticarial-type skin rash
(1.8%).
The presence of lung tissue lesions typical for
pneumonia of viral etiology was established on the basis
of computed tomography data of the chest organs. In the
dominant number of cases (35 patients, 63.6%), lung
damage corresponded to mild (CT-1) severity.
Changes in laboratory parameters in patients
with COVID-19 associated pneumonia presented in table
4.
Hematological abnormalities in most patients
were represented by leukopenia (33 patients, 60.0%),
absolute lymphopenia (28 patients, 50.9%) and
neutropenia (22 patients, 40.0%). A change in the number
of
platelets
was
observed
in
18
patients,
thrombocytopenia occurred in 15 (27.3%) of them,
thrombocytosis was observed in 3 (5.5%) cases. ESR
acceleration was registered in 23 (41.8%) hospitalized
children. An increase of CRP had 19 (34.6%) patients,
ALT (alanine aminotransferase) and LDH (lactate
dehydrogenase) - in 11 (20.0%), AST (aspartate
aminotransferase) - in 14 (25.5%), CPK-MB (creatine
phosphokinase-MB) - in 24 (34.6%). The serum ferritin
in the overwhelming majority of patients was in the range
of normal values, hyperferritinaemia observed in 15
(27.3%) patients.
Pathological changes in the coagulogram
recorded in 8 (14.5%) cases, 5 (9.1%) children had an
increase in the D-dimer level ≥ 500 ng/L, 2 of them also
had a decrease in the level of fibrinogen in the blood,
isolated hypofibrinogenemia occurred in 1 (1.8%) patient,
hyperfibrinogenemia - in 2 (3.6%).
Figure 3. Grades of lung involvement on chest CT
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Table 4
The Laboratory Test Results of patients with COVID-19
Deviation of indicators
n
%
Me [P
25
; P
75
]
C
o
m
p
lete
b
lo
o
d
c
o
u
n
t
Leukopenia (10
9
/L)
33
60,0%
5,7 [4,7; 6,8]
Leukocytosis (10
9
/L)
7
12,7%
Abs.neutropenia (10
9
/L)
22
40,0%
2,9 [2,1;4,5]
Abs.neutrophilia (10
9
/L)
10
18,2%
Abs. lymphopenia (10
9
/L)
28
50,9%
1,9 [1,5; 3,0]
Abs. lymphocytosis(10
9
/L)
6
10,9%
Thrombocytopenia (10
9
/L)
15
27,3%
184 [248; 146]
Thrombocytosis (10
9
/L)
3
5,5%
ESR acceleration
(mm/h)
23
41,8%
12 [7; 18]
B
lo
o
d
b
io
ch
em
is
tr
y
ALT
>
40
U/L
11
20,0%
22 [16; 35]
AST
>
40
U/L
14
25,5%
29 [21; 42]
LDH
>
576
U/L
11
20,0%
462 [365; 532]
CPK-MV
>
24
U/L
24
43,6%
24 [20,2; 33,8]
CRP ≥
6
mg/L
19
34,6%
24[12; 48]
↑
Ferritin (ng/ml)
15
27,3%
75 [34; 175]
C
o
ag
u
lo
g
ra
m
Fibrinogen
>
4 g/L
2
3,6%
3,2 [2,61; 3,5]
Fibrinogen <2 g/L
3
5,5%
In 35 (63.6%) children, the presence of
concomitant bacterial infection revealed. The main
pathogens detected by throat swab culture are shown in
figure 4
Figure 4. Results of bacteriological examination of throat swab
IgM antibodies to
M. pneumoniae
detected by
ELISA in 15 patients (27.3%), 6 child have a
combination
of
mycoplasma
and
pneumococcal
infections (10.9%).
Treatment
of
patients
with
COVID-19
associated pneumonia carried out in accordance with
current clinical guidelines and included antiviral drugs,
non-steroidal
anti-inflammatory
drugs,
mucolytic,
anticoagulants and glucocorticosteroids. Three patients
needed to oxygen therapy. In the presence of concomitant
infection, antibacterial drugs were prescribed according
to the sensitivity of the isolated pathogen. Against the
background of the therapy, positive dynamics noted in
the all patients. Temperature normalization noted on the
7-10th day of inpatient treatment. Among other clinical
manifestations, ageusia, anosmia and cough persisted the
longest. By the time of discharge, the symptoms of
coughing had been stopped in all patients, however, sense
of smell and taste recovered only in 3 of 17 children. The
average length of stay in the hospital was 15±5 bed-days.
Complete regression of laboratory changes
achieved in 19 patients (34.5%). Most of the children (53
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patients, 96.4%) were discharged in satisfactory condition
under the further supervision of a local pediatrician at the
place of residence. To search for significant relationships
between the degree of lung tissue damage (according to
chest CT data) and laboratory parameters, the Spearman
rank correlations were assessed. A direct correlation was
found between the degree of lung damage and the level of
CRP (r = 0.31, p = 0.019). A similar relationship was
observed for ALT (r = 0.30, p = 0.05) and LDH (r = 0.27,
p = 0.05). A statistically significant positive correlation
was also established between the degree of lung tissue
damage and the presence of concomitant diseases (r =
0.41, p = 0.002).
Conclusions
: Among hospitalized patients with
community-acquired pneumonia associated with the new
coronavirus
infection
COVID-19,
there
was
a
predominance of children over the age of 12 years
(61.8%). Almost half of the patients (40%) had
concomitant diseases, among which the most common
were obesity, cardiovascular diseases, and pathology of
central nervous system. The presence of concomitant
bacterial infection detected in 63.6% of children. Most
patients diagnosed with respiratory mycoplasmosis. A
significant positive correlation was established between
the degree of lung damage and the presence of
concomitant diseases, as well as deviations from the
norm of a number of laboratory parameters (CRP, ALT,
LDH). With timely treatment, most patients with viral
lung disease caused by the new coronavirus infection
COVID-19 have a favorable outcome of the disease
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