Features of the course of COVID-19 infection in children

Ilona K. Nakhusheva, Darya O. Yurchenko, Milena M. Sviridova, Nikita K. Dzhgarkava, Mark V. Yarosh, Yulia E. Emets. Features of the course of Covid-19 infection in children. Cardiometry; Issue No. 27; May 2023; p. 86-95; DOI: 10.18137/cardiome-try.2023.27.8695; Available from: issues/no27-may-2023/features-course-covid-19

Coronaviruses can cause a number of diseases in humans and animals. Four types of common coronaviruses, namely, HCoV2-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 provoke upper respiratory infections in humans. In 2002-2003 a new coronavirus SARS-CoV appeared, the reservoir of which was originally bats, and in humans the infection was manifested by severe acute respiratory syndrome (Severe Acute Respiratoty Syndrome, SARS). In 2012, a new reassortant coronavirus, called MERS, causing Middle East Respiratory Syndrome was recorded. SARS-CoV and MERS were characterized by high mortality rates, however, the latter was quickly localized [1, 2].

The 2019 new coronavirus disease (COVID-19) is the fifth pandemic since the 1918 influenza pandemic [3]. For the first time, patients with unusual symptoms began to appear in December 2019 in the Chinese city of Wuhan, Hubei Province. By January 2, 2020, the 2019-nCoV virus infection was detected in 41 hospitalized patients using PCR. The majority of hospitalized patients (73%) were men, and the average age of patients was 49 years. Of the 41 patients, 27 had visited the Huanan Seafood Market, leading to the initial suggestion of an epidemiological link to the disease. In addition, a familial incidence cluster was found. Usually, at the onset of the disease, fever (98%), cough (76%), shortness of breath (55%), myalgia and fatigue (44%), sputum production (28%), headache (8%), hemoptysis (5%), diarrhea (3%) and lymphopenia (63%). were noted. Changes were found on CT scans. Among the complications, distress syndrome (29%), RNA anemia (15%), heart damage (12%), and secondary infection (10%) were noted. In patients admitted to the ICU, elevated levels of IL-2, IL-7, IL-10, GSCF, TNFα, etc. were observed, which indicated the role of the immune system in the pathogenesis of the disease [4].

Initially, due to the symptoms, the disease was called Wuhan pneumonia. The complete genome sequencing conducted has shown that this is a new coronavirus, which has become the seventh member of the Coronaviridae family, capable of infecting humans. The phylogenetic analysis of the entire viral genome (29,903 nucleotides) has demonstrated that the virus is most closely related (nucleotide similarity 89.1%) to a group of SARS-like coronaviruses (genus Betacoro- navirus, subgenus Sarbecovirus), which had been previously found in bats in China [5]. The Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, which is responsible for virus classification and taxonomy nomenclature, has proposed using the names SARS-CoV-2/host/location/isolate/ date for isolates [6]. Since the first recorded detection, various variants of SARS-CoV-2 have been identified. The last highly mutated variant was the Omicron species, which was of concern due to its increased transmissibility, a possible decrease in the effectiveness of treatment, and a number of other factors [7].

With the onset of the COVID-19 pandemic, it has become clear that children infected with SARS-CoV-2 are predominantly asymptomatic carriers or those with few symptoms thereof. In children, unlike adults, anosmia and ageusia, as well as life-threatening complications, are rare. However, the so-called multisystem inflammatory syndrome and neurological complications have been described in children with COVID-19 [8]. This makes it relevant to analyze the specifics of the clinical manifestations of the infectious disease caused by SARS-CoV-2 in children.

The aim of this research work is to study the features of the clinical course of COVID-19 infection in pediatric patients.

Spread and pathogenesis of COVID-19 infection

The 2019 coronavirus disease caused more than 6 million deaths worldwide, triggering a global health crisis [9]. The mortality rate from the disease varies from 0% to more than 20% in different countries [10]. As of March 6, 2023, the number of the recorded cases worldwide reached 680,721,138 people, of which 653,592,180 individuals recovered [11].

At the early stages of the COVID-19 pandemic, children accounted for no more than 2% of all laboratory-confirmed cases of SARS-CoV-2 [12, 13, 14]. In Ontario, from January 2020 to June 30, 2021, children accounted for 12.9% of the total number of confirmed cases of COVID-19, although the proportion of children in the population was 18.7%. The highest incidence was recorded in children aged 14-17 years [15]. In a Chinese study analyzing data from 72,314 case records, the majority of the patients (87%) were aged 30–79 years, 1% of them were aged under 9 years, 1% were aged 10–19 years, and 3% were patients aged 80 years and over[14]. The WHO data suggest that children account for 8.5% of all reported cases, usually with a mild form of the disease [8]. Thus, the initial data on the incidence of COVID-19 in children have been adjusted upwards.

The main role in the initial pathogenesis of COVID-19 is played by angiotensin-converting enzyme-2 (ACE-2), which plays the role of a receptor for the entry of the SARS-CoV-2 virus [16]. There are two forms of ACE-2. The full-length form of mACE2 is located on cell membranes and consists of a transmembrane anchor and an extracellular domain. mACE2 is the receptor site for the spike protein (S) of the SARS-CoV-2 virus. The S1 subunit of the S protein causes virus infection of the host cell. The soluble form of sACE2 is released into the bloodstream, where it freely circulates. ACE-2 may become a therapeutic target: it has been proposed to use the human recombinant ACE-2 protein (hrACE2) to saturate the viral S-pro-tein and thus prevent SARS-Cov-2 from entering cells. ACE-2 is expressed in the lungs, the small intestine, the testis, the kidneys, the heart muscle, the colon, and the thyroid gland [17]. The lower expression of ACE2 in children may explain the lower infection rate of SARS-CoV-2 as compared with adults [18].

After the penetration of the SARS-CoV-2 virus into the body, the so-called cytokine storm plays an important role in pathogenesis, which is associated with the development of acute respiratory distress syndrome, multiple organ failure, and exacerbation of the disease. At the early stages of infection with SARS-CoV-2, there is a delayed release of cytokines in respiratory epithelial cells, macrophages, and dendritic cells. Later, these cells produce low levels of interferons and high levels of pro-inflammatory cytokines (IL-1, IL-6, TNF) and chemokines. The delayed release of interferons hinders the antiviral defense by the body [19].

Clinical manifestations of COVID-19

Children are typically oligosymptomatic or asymptomatic for COVID-19 infection. The prevalence of asymptomatic course in children is estimated to be at 15.8-35.9% [20, 21, 22]. Asymptomatic children with COVID-19 can play an important epidemiological role, contributing to the spread of infection among people, and at the same time, contributing to the development of herd immunity [20]. There is an opinion that the cumulative incidence is higher than the number of reported cases of COVID-19, and it is likely that a share of the pediatric patients do not report their symptoms [23]. The wide variety of clinical manifestations of COVID-19 in children can make it difficult to diagnose the disease. For example, one study showed that testing for SARS-CoV-2 based on symptoms alone failed to make a correct diagnosis in 45% of the hospitalized children [24]. In the same publication, the mean age of children (n=438) was recorded to be 6.5 years. COVID-19 was suspected based on symptoms in 41.6% of the patients only. The most informative symptoms in children were fever (occurred in 69.8% of the examined), diarrhea or vomiting (45.6%), abdominal pain (33%), symptoms of an upper respiratory tract infection (28.6%), shortness of breath (14.8%), and skin lesions (11%). The ratio between the infected boys and girls approaches 1.15 [25].

The most frequently detectable and the most often occurring symptom in COVID-19 is fever (in more than 60% of the children) that is accompanied by cough, sore throat, and rhinorrhea [21, 25-28]. Many children have symptoms like headache, diarrhea, vomiting, fatigue, myalgia, tachypnea, tachycardia, and rash [13, 22, 25, 26, 27, 29-31]. One publication indicates that 6% of the children have only gastrointestinal symptoms [28]. Some key characteristics of pediatric New England patients with COVID-19 are presented below herein (see Table 1 herein).

Unlike adults, anosmia and ageusia are rarely diagnosed in children with COVID-19 that makes diagnosis difficult, since other symptoms are not specific [29, 32].

No correlation was found between viral load on the one hand and parameters such as gender, age, fever, hospitalization, type of SARS-CoV-2 on the other hand [29]. The most common comorbidity in children infected with SARS-CoV-2 is obesity (6%) [28]. According to other data, the most common comorbidities are asthma (10%), diabetes (8%), and obesity (5%) [30]. A multicenter retrospective cohort study showed that children with clinical manifestations of COVID-19 and comorbidities were more likely to require intensive care (70% vs 37%, p=0.008). In many patients, an increased risk of intensive care was associated with obesity (63% vs 28%, p=0.02). Children with asthma were more likely to receive respiratory support (28% vs 8%, p=0.02). Patients admitted to the ICU had higher rates of renal dysfunction (43% vs 10%, p=0.002) [33].

In general, the share of severe forms of the disease in children is less than in adults. Y. Dong et al. in a pa-

Table 1

Epidemiological characteristics, clinical manifestations and radiological signs in children (n=171) with SARS-CoV-2 infection [22]

Parameter, feature Value Average age 6,7 лет Age <1 18,1% Age 1-5 years 23,4% Age 6-10 years 33,9% Age 11-15 years 24,6% Boys / girls 60,8% / 39,2% Diagnosis Asymptomatic infection 15,8% Upper respiratory infection 19,3% Pneumonia 64,9% Epidemiological information: Familial cluster 90,1% Unindentifed infection source 8,8% Contact with other suspicious sources Symptoms: Cough 48,5% Pharyngeal erythema 46,2% Fever 41,5% Averaged duration of fever, days 3 (1-16) Т <37,5ºC 58,5% T 37,5-38,0ºC 9,4% T 38,1-39,0ºC 22,8% T >39,0ºC 9,4% Diarrhea 8,8% Fatigue, weakness 7,6% Rhinorrhea 7,6% Vomiting 6,4% Nasal congestion 5,3% Tachypnea at hospital admission 28,7% Tachycardia at hospital admission 42,1% Oxygen saturation <92% at hospital admission 2,3% Breast CT data deviation from normal parameters: Ground-glass opacity 32,7% Local lung shadow spots 18,7% Two-side shadow spots 12,3% Interstitial abnormalities 1,2% per demonstrated that more than 90% of the children (n=2135) infected with SARS-CoV-2 had asymptomatic, mild or moderate forms of the disease. The average age of patients was 7 years (2-14 years), 56.6% of the cases were recorded in boys, and the average time from the onset to diagnosis was 2 days. The severity of the disease was distributed as follows: asymptomatic course covered 4.4%; mild form was recorded in 51% of the cases; moderate severity accounted for 38.7%; severe course was reported in 5.2% of the cases, and the critical condition was reported in 0.6% of the disease cases. Moreover, the number of severe and critical forms in children was distributed on the age-related basis as follows : <1 year – 8.8% and 1.9%, respectively; 1-5 years – 6.9% and 0.4%, respectively; 6-10 years – 4.2% and 0%, respectively; 11-15 years old – 3.4% and 0.7%, respectively; >15 years – 2.7% and 0.3%, respectively [34]. In contrast, another publication reported that none of the 14 infants was diagnosed with a severe form of the disease [28]. The classification of patients according to severity, taking into account the damage to the respiratory tract, is presented below herein (see Table 2 given herein).

Table 2

Classification of patients with COVID-19 infection according to the severity of the disease [35]

Form of disease	Characteristics
Asymptomatic	SARS-CoV-2 DNA positive test, no clinical or radiological signs of disease
Mild	Symptoms of acute upper respiratory infection (fever, fatigue, myalgia, cough, sore throat, rhinitis, sneezing) or gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea)
Moderate	Pneumonia (frequent fever, cough) without pronounced hypoxemia, breast CT scans with foci
Severe	Pneumonia with hypoxemia (SpO2<92%)
Critical condition	Acute respiratory distress syndrome can be accompanied by shock, encephalopathy, heart failure, blood coagulation abnormality, acute renal damage

Although COVID-19 infection in children is generally milder than in adults, since the spring of 2020, there have been some reports by medical institutions in Europe and the United States on children with Kawasaki disease (KD) and toxic shock syndrome (TSS), which has received the name of childhood multisystem inflammatory syndrome (CMIS), which has been found to be in apparent association with the COVID-19 infection. The main signs of CMIS were rash, signs of myocardial dysfunction, damage to the heart and coronary vessels, a disorder in the blood coagulation system, acute gastrointestinal symptoms, arterial hypotension, and sometimes a state of shock. IgM and/or IgG antibodies to SARS-CoV-2 were detected in most children with KD, and in some cases the PCR reaction from nasopharyngeal swabs was also positive. Leukopenia, thrombocytopenia, lymphopenia, signs of macrophage activation syndrome (MAS) were observed in blood, that was a consequence of the cytokine storm described earlier in adults. Moreover, KD developed in 7% of the patients with COVID-19. Sometimes infected children are diagnosed with Takatsubo syndrome with a decrease in the left ventricular (LV) ejection fraction below 30% [36].

Children with SARS-CoV-2 infection may experience neurological complications. Patients with a neurological complication are more likely to have concomitant neurological pathology compared with patients without it (22% vs 8%) [37]. The reference literature describes a case of acute transverse myelitis in an 11-year-old girl with COVID-19, who was admitted with complaints of initial paresis of the lower extremities, urinary and fecal retention, epigastric pain and fever for 3 days. The patient was administered with pulse therapy with methylprednisolone, intravenous immunoglobulin, several sessions of plasmapheresis, and supporting therapy: all this only slightly improved her condition [38]. Another publication presented a clinical case of a 17-month-old girl with COVID-19 and acute disseminated encephalomyelitis that developed against that background. The girl had irritability, weakness in the upper limbs, and a gait abnormality. Her brain MRI with contrast showed diffuse T2 hyperintensity without contrast enhancement. Treatment with high doses of methylprednisolone and intravenous immunoglobulin resulted in clinical improvement [39]. There has also been a report on fulminant myocarditis with complete heart block, elevated troponin I levels, and a sharp decrease in systolic function under the COVID-19 infection [40]. The infectious disease under consideration can also be complicated by shock, heart failure, acute respiratory distress syndrome (ARDS), rhabdomyolysis, renal damage, acute renal failure, eye diseases (congestive conjunctivitis, conjunctival discharge etc.) [35, 41-43].

Clinical manifestations of COVID-19 in Russian children

Among children hospitalized with symptoms of acute respiratory viral infections in the Children’s hospital named after. St. Olga (St. Petersburg) in 20202021 SARS-CoV-2 was found only in a third of patients, in 4.3% of the cases together with CoV-OC43/ CoV-229E coronaviruses, and in 11.6% in combination with other viral infections (metapneumoviruses, parainfluenza, rhinoviruses). Mostly the children became infected by their family members. Among the leading symptoms in children, fever, catarrhal phenomena, gastrointestinal disorders and anosmia prevailed. In children under one year old, predominantly intoxication, fever, and colitis were observed, rarely hemocolitis; monocytosis was determined in their blood. In the group older than 7 years, blood showed an increase in ESR and leukopenia, and in the biochemical analysis recorded was an increase in CRP. The severity of the disease and the clinical manifestations strongly depended on the age of the child. Children in the first month of life suffered from the disease in a mild form, and among patients aged 7–18 years, severe forms of the disease were more often diagnosed [44].

According to the SHHI “Children’s Municipal Clinical Hospital named after Z.A. Bashlyaeva DZM” (Moscow) for the observation period since March 2020 till June 2021, the most frequent clinical manifestations of COVID-19 infection in children in the 2nd and 3rd waves of the epidemic were reported symptoms of nasopharyngitis – 50.5% and 48.5%; pneumonia without respiratory failure (RF) – 22.5% and 26.1%; pneumonia with RF – 5.9% and 8.7%; pathological symptoms of the central nervous system (anosmia, cerebroasthe-nia) – 2.3% and 2.0%; mucocutaneous manifestations (conjunctivitis, rashes) – 2.1% and 2.5%; heart damage – 0.4% and 0.3%, respectively. The multisystem inflammatory syndrome, which was manifested by fever, rhinopharyngitis, polyform rash, conjunctivitis/ scleritis, swelling of the extremities with an increase in the level of acute inflammation indicators (D-dimer, C-reactive protein, ferritin, IL-6), was diagnosed in 2.9% of the hospitalized children in 2020 and 0.3% in 2021 [45]. In hospitalized children, a moderate form of the disease was mainly observed (96.7 and 96.9%), while a severe condition was noted in 3.3 and 3.1% of the children. The 3rd wave of COVID-19, compared with the 2nd wave of the disease in children, was characterized by a longer shedding of the virus, an almost 90 | Cardiometry | Issue 27. May 2023

10-fold decrease in the occurrence of the multisystem inflammatory syndrome, and the predominance of signs of ARVI and viral pneumonia in the clinical picture. Such changes could be due to the spread of a new mutant SARSCoV-2 Delta coronavirus species (VO-C21APR-02, B.1.617.2) in Russia. The respective CT data on the occurrence rate and volume of the affected lung were comparable for the periods of the 2nd and 3rd waves of the infection [45].

In Omsk and the Omsk region, the number of children with coronavirus infection was 3.78% of the total number of the infected pediatric patients, and in 61.8% of them the infection processes was recorded to be mild. The epidemiological picture was dominated by intrafa-milial transmission of the infection. Diarrheal (loose stools, abdominal pain), intoxication (hyperthermia, loss of appetite, nausea) and catarrhal (cough, nasal congestion, rhinorrhea) syndromes were revealed. The disease manifested itself in several clinical forms: pharyngitis (52.9%), rhinopharyngitis (13.2%), rhi-nopharyngotracheitis (8.8%), tracheitis (3.1%), bronchitis (5.8%), and pneumonia (16.2%). Anosmia was observed only in children older than 10 years. In pneumonia, the area of lung injury (MSCT data) did not exceed 25%. In 67.7% of the children, the temperature was increased mainly to subfebrile values. In laboratory tests, lymphocytosis (42.6%), leukopenia (36.8%), sometimes leukocytosis (4.4%) were noted [46].

Similar data were obtained on the incidence of COVID-19 in children in Karaganda, where 67.6% of the children had a mild form of the disease, 31.2% had a moderate form, and 1.2% of children had a severe form thereof. 60% of the cases were reported in children older than 7 years. In half of the cases, subfebrile and febrile hyperthermia (51.1%), cough (51.2%) were noted, while symptoms of intoxication (35.9%) and diarrhea (2.4%) were less common. Their CT examination revealed bronchitis and pneumonia in 7.8% and 20.3% of the cases. In one case, CMIS (Kawasaki-like) was diagnosed. In mild forms of coronavirus infection, RF (respiratory failure) was not observed in children and SpO2 exceeded 95%. In the moderate variant, RF1 was diagnosed in 8% of the children, SpO2≥93%, lung damage on CT was less than 25% in 78% of the examined patients. Severe forms were characterized by RF2, SpO2<93%, lung involvement on CT was 25-50% in 22% of the examined children [47].

Compared with adults in the city of Orenburg, children with COVID-19 had a blurred clinical pic- ture. An increase in the body temperature was observed in 91.5% of the children, but the values rarely exceeded 38.5ºС. In a third of the pediatric patients, symptoms of intoxication (weakness, headache, muscle pain, loss of appetite) were determined. 82% of the children had catarrhal signs, and their cough was dry and unproductive. Anosmia was not found. Rhinor-rhea was more often observed with a negative PCR test for COVID-19. RF was extremely rare. 18% of the children were worried about unexpressed diarrhea and abdominal pain. For comparison, in the clinical picture of adults with COVID-19, cough was observed in 74% of the cases, fever – in 70% of the recorded cases, anosmia – in 31%, headache and weakness – in 18% of the cases. Rarely observed were diarrhea, rash, and chills. Rhinorrhea was also more common with a negative PCR test. In the children, PCR tests were not informative, and they were associated with the severity and duration of the disease [48].

Thus, the main manifestations of the COVID-19 infection are consistent with data reported for pediatric populations in other countries. Attention is drawn to the decrease in the severity of the manifestations of the disease with an increase in the duration of the period of virus shedding.

Treatment of COVID-19 infection

Despite the lack of evidence-based therapy demonstrating efficacy in the treatment of COVID-19 infection, children are given at least one course of treatment aimed at modulating the course of the infection. The most commonly used medication offers hydroxychlorin solely or in combination with some other agents, including azithromycin, the antiviral remdisivir, and to-cilizumab (anti-IL-6 receptor antibodies). The Infectious Diseases Society of America has recommended that any proposed treatments for COVID-19 infection be limited to official clinical trials due to the lack of proven efficacy of the drugs and due to possible side effects [49].

Interferon therapy is an etiotropic treatment for viral infection, and it is advisable to prescribe it to children with COVID-19 both as monotherapy and in combination with some antiviral drugs. In the experiment, treatment of cell cultures with interferon types I and III led to a threefold decrease in RNA titer and suppression of viral replication by 90% [50]. The addition of interferon-alpha 2b to the lopinavir+ritonavir regimen in patients with the COVID-19 infection resulted in a reduction in mortality [51].

The Karaganda hospital did not provide antiviral therapy to children with COVID-19 due to lack of evidence of effectiveness. Anti-inflammatory drugs were mainly administered in those cases as follows: paracetamol 10-15 mg/kg, ibuprofen 5-10 mg/kg. If a bacterial infection was available, antibiotics were prescribed, and in case of diarrhea, rehydration was performed [47].

In a severe COVID-19 infection case complicated by KD and toxic shock, the patient is prescribed empirical antibiotic therapy: in toxic shock – vancomycin, clindamycin, cefepime; with damage to the gastrointestinal tract – ceftriaxone with metronidazole. Remsedivir is also administered; prescribed are immunoglobulin, aspirin intravenously, according to indications glucocorticoids; in case of abnormalities in the cardiac performance administered is pulse therapy with methylprednisolone, enoxaparin [36].

The existing expert opinion regarding the use of lopinavir-ritonavir is controversial, considering the results of a recently published study by B. Cao et al. The data obtained showed that treatment with lopinavir-ritonavir in the COVID-19 infection did not improve treatment outcomes compared with standard therapy (supplemental oxygen when needed, non-invasive and invasive ventilation, antibiotic therapy, vasopressor support, renal replacement therapy, and extracorporeal membrane oxygenation). In particular, there was no difference in times since hospitalization till clinical improvement. Mortality on day 28 was almost the same in the lopinavir-ritona-vir group and in the standard therapy group (19% vs 25%). Detection of viral RNA at different time intervals was comparable in both groups. Gastrointestinal complications were more common in the lopinavir– ritonavir group, although other adverse events were more common in the standard therapy group [52]. Thus, the most justified at present is symptomatic and supportive therapy, which demonstrates obvious effectiveness. Attempts to modulate the infectious process with antiviral drugs need multicenter clinical evidence.

Results

The data reviewed in the article show that the course of COVID-19 infection in children has its own characteristics, and in the Russian pediatric population there are no fundamental differences from children in other countries in relation to the patterns ob-

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served in the disease in question. It is noteworthy that due to improved diagnostics, the estimated prevalence of the SARS-CoV-2 virus in children has increased from less than 2% to 8.5%. And considering the frequent asymptomatic course thereof, the actual infection rates are likely even higher.

The oligosymptomatic course and nonspecific symptoms may make it difficult to diagnose the COVID-19 infection in children. In addition, as noted above, anosmia is observed quite rarely and mainly in older children. Thus, the probability of making a correct diagnosis is high only during periods of total PCR screening and alertness regarding SARS-CoV-2 as the most likely etiological factor in the midst of an epidemic.

As it was the case with adults, the presence of comorbidity influenced the course of the COVID-19 disease. Most often, severe forms of the coronavirus infection were associated with diabetes, asthma, obesity that increased the need for resuscitation and respiratory support. The presence of previous neurological pathology was accompanied by a significant increase in the occurrence of neurological complications. Another serious complication often seen in children with COVID-19 was the multisystem inflammatory syndrome, often manifesting as a Kawasaki-like syndrome. A feature of the clinical manifestation of the COVID-19 infection in children can be considered a high occurrence rate of gastrointestinal manifestations, and sometimes the disease is limited only to them.

Paradoxically, the viral load did not affect the presentation of fever and the rate of hospitalization of the pediatric patients. Moreover, the children of the first year of life suffered from the disease in a mild form that might be due to the immaturity of the ACE2 receptors, which served as a “key” for the penetration of the SARS-CoV-2 virus into a cell.

Russian pediatricians drew their attention to a decrease in the severity of the course of COVID-19 infection in the 3rd wave compared with the 2nd one, a 10-fold drop in the occurrence of the multisystem inflammatory syndrome, as well as an increase in the period of viral shedding by children. This is likely due to mutations in viral strains that contribute to the spread of the virus in the human population. Thus, the reverse side of reducing the severity and mortality is an increase in the spread of the virus among people and the formation of herd immunity.

Conclusions:

• 1.    The pediatric population is featured by predominantly oligosymptomatic or asymptomatic course of the COVID-19 infection.

• 2.    Among the children with COVID-19, there is recorded a slight predominance of boys.

• 3.    Children are more likely than adults to be diagnosed with gastrointestinal symptoms of COVID-19.

• 4.    Cases of the SARSCoV-2 carriage reported by laboratory methods in children vary in the range of 8.5-12.7% of all infected pediatric patients, but however, considering the frequent oligosymptomatic or asymptomatic course of the infection in pediatric patients, it can be assumed that these values may be actually higher.

• 5.    The course of the COVID-19 infection in children is milder and leads to fewer complications compared with adult patients.

• 6.    Considering the dangerous complications of COVID-19 infection in children, the greatest risks are associated with their multisystem inflammatory syndrome and neurological complications.