The rationality of drug treatment and clinical characteristics in children with SARS-CoV-2 infection: a retrospective analysis

Abstract

Background

With the ongoing global pandemic of coronavirus disease 2019 (COVID-19), the rational use of medications and clinical profiles in the afflicted children—a particularly susceptible group—warrant further investigation. This paper analyzed the rationality of medicinal treatments and clinical characteristics in children with COVID-19.

Methods

We retrospectively reviewed the clinical data of pediatric inpatients with COVID-19 admitted to the Fifth Hospital of Xiamen from January 2025 to December 2025. Clinical classifications, symptoms, outcomes, complications and the use of therapeutic drugs were statistically analyzed. The rationality of medication was assessed by indication consistency and administration routes.

Results

The clinical cure and improvement rate reached 99.22% in the 129 confirmed pediatric cases of COVID-19. They were categorized into a mild group (69 cases, 53.49%), a moderate group (59 cases, 45.74%), and a critical group (1 case, 0.77%). Clinical manifestations mainly included fever, cough, and runny nose. A significant difference was evident between the mild group and the moderate group in age, weight, outcomes, and clinical symptoms (e.g., coughing, runny nose, and nasal congestion) (P < 0.05 for all). Compared with the mild group, the moderate group reported a significantly higher reception of expectorants, nebulized inhalation medication, antihistamines, glucocorticoids, and antibiotics (P < 0.05 for all). In the mild and moderate groups, the irrational use of medications involved 3 types of drugs in 15 pediatric patients, including 2 cases (3.39%) of inhaled corticosteroid (ICS), 8 cases (13.11%) of antibacterial drugs, and 5 cases (5.43%) of interferon alpha 1b for injection. The irrationality of the first two types was attributed to inconsistent medication indications and that of the last type to mismatched administration routes. One rare complication, specifically multisystem inflammatory syndrome in children (MIS-C), was identified in the critical group.

Conclusion

The clinical manifestations of COVID-19 in children are predominantly mild and moderate, with an overall favorable prognosis. The moderate group presents more pronounced respiratory symptoms (cough, runny nose, nasal congestion). The risk of complications in children with mild to moderate symptoms is similar, emphasizing the importance of early screening and prevention of complications. In clinical care for children with COVID-19, medication irrationality, such as indication inconsistency and mismatched administration routes, still exist in the administration of antiviral drugs, glucocorticoids, and antibiotics in some children with mild to moderate symptoms. The findings indicate a need for further optimizing real-world clinical practice and provide some insights for rational drug use.

Introduction

The global pandemic of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), was declared by the World Health Organization on March 11, 2020 [1]. Since January 8, 2023, COVID-19 has been officially classified as a Class B infectious disease in China, which is monitored continually and managed as a statutory infectious disease, without the need of mandatory centralized quarantine [2]. Ever since, much progress has been made in China in terms of the pathogenesis, clinical features, and treatment of COVID-19, and the diagnosis and treatment for adults with COVID-19 have been increasingly improved [3], COVID-19 continues to circulate in China at this stage according to the information released by the Chinese Center for Disease Control and Prevention. Compared with adults, SARS-CoV-2 causes milder symptoms and fewer deaths in children and adolescents [4]. However, pediatric patients face a distinct challenge: a paucity of approved therapeutic measures. Newly authorized antiviral agents or prophylactics often lack the support of pediatric-specific clinical data and indications, leading to a widespread off-label use. This practice may introduce significant risks, ranging from dosing uncertainty, therapeutic inefficacy, to unknown adverse reactions. Consequently, it is of paramount clinical importance to conduct real-world studies on the rational use of drugs in children with COVID-19.

Currently, despite the availability of some domestic and international studies on pediatric COVID-19, which mainly focus on descriptive analysis of clinical characteristics in this particular patient population [4–8], there is a notable gap in the systematic analysis, from the perspective of clinical pharmacists, of the current status of real-world drug treatment schemes, medication indications, and potential irrationality in the drug administration. To address this gap, we, for the first time, adopted a clinical pharmacist-led approach to assess the rationality in the drug use, retrospectively analyzing clinical data from 129 children with COVID-19. The main objectives of this study came in three-fold: to systematically describe the clinical characteristics of children with COVID-19; to evaluate the rationality of drug treatment schemes based on current diagnostic and treatment guidelines and analyze the types and potential risks of irrational drug use; and to provide real-world medicinal evidence for optimizing individualized diagnosis and treatment of pediatric COVID-19, ultimately enhancing the safety and effectiveness of clinical drug use in treating pediatric patients with COVID-19.

Materials and methods

Study population

This study was a single-center retrospective study. A total of 129 pediatric inpatients with COVID-19 were admitted to our hospital from January 2025 to December 2025, who met the inclusion criteria for this study. The eligible patients (n = 129) met the following inclusion criteria: (1) an age of < 18 years; (2) a diagnosis based on a comprehensive analysis of epidemiological history, clinical manifestations, laboratory tests, etc.; (3) a positive report of SARS-CoV-2 nucleic acid or antigen test. Patients (n = 0) were excluded for either of the following conditions: (1) an absence of critical clinical data or (2) repeated hospitalizations.

The research was approved by Medical Ethics Committee of The Fifth Hospital of Xiamen (Ethics Approval Number: XMWY-LL-2026-022). As a retrospective study, the requirement for informed consent from patients and guardians was waived.

Diagnosis criteria and clinical classification

The diagnosis and clinical classification of COVID-19 in this study were based on a previous study [2]. As reported in the reference, the diagnostic criteria include: (1) the presence of relevant clinical manifestations of SARS-CoV-2 infection and (2) a positive result in SARS-CoV-2 nucleic acid or antigen testing.

Cases of pediatric COVID-19 are clinically classified as: (1) Asymptomatic infection; (2) Mild cases, mainly manifested as fever, cough, nasal congestion, etc., with no clinical and physical signs of lower respiratory tract involvement; (3) Moderate cases, with respiratory symptoms such as cough and shortness of breath, and chest imaging evidence of changes of viral pneumonia, which fall short of the criteria of severe pneumonia; (4) Severe cases, meeting any of the following criteria, including ① specific respiratory rates [≥ 60 times/min (< 2 months old), ≥ 50 times/min (2–12 months old), ≥ 40 times/min (1–5 years old), ≥ 30 times/min (> 5 years old) (after ruling out the effects of fever and crying)], ② finger oxygen saturation ≤ 93%, ③ dyspnea (assisted breathing, cyanosis, intermittent apnea), ④ disturbance of consciousness or convulsion, ⑤ food refusal or feeding difficulty, with signs of dehydration, ⑥ pulmonary high-resolution CT evidence of bilateral or multi-lobe infiltrates, and rapid progression of disease (> 50%) in a short period or with pleural effusion; (5) Critical cases, meeting any of the following criteria, including ① respiratory failure, ② shock, ③ complications of acute encephalopathy, acute necrotizing encephalopathy or severe dysfunction of other organs that require intensive care.

Data collection

The data were collected from the resident physician workstation system at our hospital, including gender, age, weight, medical history, length of hospital stay, diagnosis, symptoms, peak fever, duration of fever, complications, treatment medications, and microbiological test results.

Evaluation of rationality of medicinal treatment

The rationality of antiviral medication was evaluated by relevant treatment consensus [2, 9]; the clinical application of glucocorticoids was assessed according to relevant normative documents [2, 3, 10–12]; and the use of antibiotics was evaluated by the “National Antimicrobial Therapy Guidelines (3rd Edition)” [13]. The irrationality in medication administration was defined as deviations from the recommended indications, administration routes, or treatment regimens in the drug instructions, guidelines or evaluation documents.

Statistical methods

Statistical analysis was processed with SPSS 20.0 software. Categorical data were presented as frequencies and percentages (%) and intergroup differences were compared by the chi-square test or fisher’s exact tests. Continuous data with normal distribution were presented as mean ± standard deviation (mean ± SD), with intergroup differences analyzed by the independent-samples t-test. Non-normally distributed continuous data were reported as median (interquartile range) [P50 (P25, P75)] or median (range). A value of P < 0.05 was designated as statistically significant.

Results

Basic information and clinical manifestations

Of the 129 confirmed pediatric cases of COVID-19, there were 74 males (57.36%) and 55 females (42.64%), with a male-to-female ratio of (1.35:1). The age of onset ranged from 28 days to 13 years old, with the highest number of cases in infants (51 cases, 39.53%). The average length of hospital stay was 3 days (range: 1–9 days).

The enrolled 129 cases were categorized into a mild group (69 cases, 53.49%), a moderate group (59 cases, 45.74%), and a critical group (1 case, 0.77%). No severe or asymptomatic cases were reported. One case was classified as critical and received intensive care, who was diagnosed with: (1) Kawasaki Disease, (2) multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection, (3) SARS-CoV-2 pneumonia, and (4) adenovirus infection, and comorbid with diarrhea and abnormal coagulation function.

Out of 129 pediatric cases, 122 (94.57%) presented with fever, with an average fever duration of 2.53 ± 1.40 days. Common respiratory symptoms included cough (75 cases, 58.14%), runny nose (41 cases, 31.78%), nasal congestion (34 cases, 24.36%), hoarseness (12 cases, 9.30%), sore throat (9 cases, 6.98%), wheezing (2 cases, 1.55%), and foaming at the mouth (2 cases, 1.55%). Gastrointestinal symptoms included diarrhea (31 cases, 24.03%), vomiting (19 cases, 14.73%), and abdominal pain (4 cases, 3.10%). Other clinical manifestations comprised chills (7 cases, 5.43%), aversion to cold (6 cases, 4.65%), rash (3 cases, 2.33%), chest pain (2 cases, 1.55%), and complaint of itching, dizziness, headache, cracked and congested lips, and hard and swollen limbs (1 case each, 0.78%).

After standardized treatment, a combined clinical recovery and improvement rate of 99.22% was reported. The details of the outcomes of the pediatric patients were as follows: 39 cases of clinical recovery (30.23%), 89 cases of improvement upon discharge (68.99%), and 1 case of no improvement (0.78%), which was transferred for further treatment. There were no fatalities.

As there was only one critical case, it was not included in the analysis. Therefore, this study focused on the statistical analysis between the mild and moderate groups, while the clinical characteristics of the single critical case were presented descriptively.

Given the small sample size of adolescent patients (n = 4), they were not included in the group analysis. The analysis focused on major clinical symptoms with an incidence rate greater than 10%. Statistical significance was observed between the mild and moderate groups in terms of age, weight, outcome, cough, runny nose, and nasal congestion (P < 0.05). However, there was no statistical significance found in terms of gender, days of fever, fever peak, fever, diarrhea, and vomiting (P > 0.05), as shown in Table 1.

Table 1.

Basic information and clinical manifestations of pediatric patients

	Total (n = 129)	Mild (n = 69)	Moderate(n = 59)	Critical (n = 1)	Chi-square /t-test	P-value
Age					10.432	0.015
28 days∼<1 year	51(39.53%)	36(52.17%)	14(23.73%)	1(100.00%)
1∼<3years	44(34.11%)	22(31.88%)	22(37.29%)	0
3∼<6 years	10(7.75%)	4(5.80%)	6(10.17%)	0
6∼<12 years	20(15.50%)	7(10.14%)	13(22.03%)	0
12∼<18 years	4(3.10%)	0	4(6.78%)	0
Gender					0.592	0.442
male	74(57.36%)	42(60.87%)	31(52.54%)	1(100.00%)
female	55(42.64%)	27(39.13%)	28(47.46%)	0
Clinical symptoms
fever	122(94.57%)	68(98.55%)	53(89.83%)	1(100.00%)	3.144	0.076
cough	75(58.14%)	18(26.09%)	57(96.61%)	0	62.324	0.000
runny nose	41(31.78%)	10(14.49%)	31(52.54%)	0	19.438	0.000
nasal congestion	34(26.36%)	10(14.49%)	24(40.68%)	0	9.877	0.002
diarrhea	31(24.03%)	13(18.84%)	17(28.81%)	1(100.00%)	1.251	0.263
vomiting	19(14.73%)	12(17.39%)	7(11.86%)	0	0.394	0.530
Outcomes					25.621	0.000
improvement	89(68.99%)	35(50.72%)	53(89.83%)	1(100.00%)
clinical recovery	39(30.23%)	34(49.28%)	5(8.47%)	0
unchanged condition	1(0.78%)	0	1(1.69%)	0
Days of fever(d)	2.53 ± 1.40	2.55 ± 1.21	2.42 ± 1.45	-	0.540	0.590
Fever peak(℃)	39.11 ± 0.57	39.06 ± 0.55	39.16 ± 0.60	-	-0.918	0.361
Weight(kg)	14.63 ± 11.87	11.59 ± 7.62	18.31 ± 14.75	-	-3.158	0.002

Values are depicted as n/N (%) or mean ± SD. For continuous variables, P values are derived from independent-samples t-test. For categorical variables, P values are from the chi-square test. P < 0.05 was considered statistically significant

The underlying health conditions

Out of 129 pediatric cases, 11 cases had underlying medical conditions (8.53%). In the mild group, there were 1 case of acute lymphoblastic leukemia, 1 congenital heart disease, 2 febrile seizure, 2 favism, and 1 thalassemia. In the moderate group, there were 1 case of alpha-thalassemia and febrile seizure, 2 febrile seizure, and 1 chronic hepatitis B and chronic sinusitis.

Medication treatment status

A total of 10 major therapeutic drugs with a usage rate of over 10% were included for analysis. Antiviral drugs included human interferon alpha-1b for injection and ribavirin spray; antipyretic analgesics mainly consisted of dexibuprofen oral suspension, paracetamol for suspension and diclofenac sodium suppositories; vitamins mainly included vitamin C injection and vitamin B6 injection; expectorants comprised ambroxol hydrochloride injection, acetylcysteine solution for inhalation, and ambroxol hydrochloride and clenbuterol hydrochloride oral solution; nebulized inhalation medication mainly consisted of budesonide suspension for inhalation, terbutaline sulfate nebulizer solution, and ipratropium bromide solution for inhalation; antibacterial drugs mainly involved ceftriaxone sodium for injection and azithromycin for injection; glucocorticoids were mainly composed of budesonide suspension for inhalation, methylprednisolone sodium succinate for injection, and prednisone acetate tablets. The main gastrointestinal therapeutic drugs included Saccharomyces boulardii sachets, combined bacillus Subtilis and enterococcus faecium granules with multivitamines, montmorillonite powder, and cimetidine injection. Antihistamines mainly were desloratadine for suspension. Chinese patent drugs mainly included Lianhua Qingwen granules, Qinxuan Zhike granules, and Xia’er Re Suqing granules. Compared with the mild group, the moderate group received a significantly higher administration of expectorants, nebulized inhalation medication, antihistamines, glucocorticoids, and antibiotics (P < 0.05 for each). No significant difference was found for the other five categories of drugs (antiviral drugs, antipyretic analgesics, vitamins, gastrointestinal therapeutic drugs, and Chinese patent drug) (P > 0.05) (Table 2).

Table 2.

Comparison of main therapeutic drugs for pediatric patients

Drug Classification	Total (n = 129)	Mild (n = 69)	Moderate(n = 59)	Critical(n = 1)	Chi-square test	P-value
Antiviral drugs	105(81.40)	59(85.51)	45(76.27)	1(100.00)	1.226	0.268
Antipyretic analgesics	88(68.22)	49(71.01)	38(64.41)	1(100.00)	0.370	0.543
Vitamins	87(67.44)	48(69.57)	38(64.41)	1(100.00)	0.186	0.667
Expectorants	67(51.94)	13(18.84)	53(89.83)	1(100.00)	61.365	0.000
Nebulized inhalation medication	59(45.74)	7(10.14)	51(86.44)	1(100.00)	71.664	0.000
Antibacterial drugs	61(47.29)	25(36.23)	35(59.32)	1(100.00)	5.914	0.015
Glucocorticoids	59(45.74)	7(10.14)	51(86.44)	1(100.00)	71.664	0.000
Gastrointestinal therapeutic drugs	34(26.36)	17(24.64)	16(27.12)	1(100.00)	0.014	0.907
Antihistamines	33(25.58)	9(13.04)	23(38.98)	1(100.00)	10.072	0.002
Chinese patent drug	25(19.38)	11(15.94)	13(22.03)	1(100.00)	0.427	0.514

Both nebulized inhalation medication and glucocorticoids included inhaled corticosteroid (ICS). Values are depicted as n/N (%). P values are from Chi-square test. P < 0.05 was considered statistically significant

Analysis of reasons and types of irrationality in the use of clinical medication

Among the 129 pediatric patients, irrational medication prescription was evident with 3 types of drugs in 15 patients, including antibacterial drugs in 8 cases (13.11%), interferon alpha-1b for injection in 5 cases (5.43%), and ICS in 2 cases (3.39%). The main reasons for the irrationality were indication inconsistency and mismatched administration routes, as shown in Table 3.

Table 3.

Types of medication irrationality involved in clinical medication orders for pediatric patients

Drug	Types of medication irrationality	Case count/Total	Percentage(%)
Human interferon alpha 1b for injection	mismatched administration routes.	5/92	5.43
ICS	inconsistent medication indications	2/59	3.39
Antibacterial drugs	inconsistent medication indications	8/61	13.11

Complications

In the 3 groups of children, the most common complications were electrolyte disorders in 17 cases, elevated transaminases in 14 cases, and myocardial damage in 10 cases, except for one case of MIS-C in the critical group. The patient was a 6-month-old male infant who primarily presented with persistent fever for 8 days (peak temperature 39.3℃), rash, lips congested and chapped, cold and swollen extremities, diarrhea, and abnormal coagulation. These symptoms met the diagnostic criteria for COVID-19-related MIS-C [2]. The patient improved and was discharged after symptomatic treatments. Except for neutropenia, which occurred significantly more frequently in the moderate group than in the mild group (P < 0.05), there were no significant differences in the incidence of other complications between the mild and moderate groups (P > 0.05) (Table 4).

Table 4.

Complications in pediatric patients [Cases (%)]

Complications	Mild (n = 69)	Moderate (n = 59)	Critical (n = 1)	Chi-square test	P-value
Electrolyte imbalance	6(8.70%)	10(16.95%)	1(100%)	1.298	0.255
Elevated transaminases	7(10.14%)	7(11.86%)	0	0.001	0.979
Myocardial damage	6(8.70%)	4(6.78%)	0	-	0.752
Leukopenia	1(1.45%)	1(1.69%)	0	-	1.000
Neutropenia	0	4(6.78%)	0	-	0.043
Anemia	1(1.45%)	0	0	-	1.000
Platelet count increase or decrease	0	2(3.39%)	0	-	0.211
Metabolic acidosis	1(1.45%)	0	0	-	1.000
Acute otitis media	0	1(1.69%)	0	-	0.461
MIS-C	0	0	1(100%)	-	1.000
Total	17	28	2

Values are presented as n/N (%). The electrolyte imbalance and elevated transaminases were analyzed by Chi-square test and other complications by Fisher’s exact test. P < 0.05 was considered statistically significant

Pathogen examination and co-infection status

Out of the 129 cases, 113 cases (87.60%) underwent pathogen microbiological testing. A total of 41 cases (31.78%) reported concomitant infections with other pathogens. Of them, 16 cases were positive for viruses, including 5 cases of respiratory syncytial virus, 3 cases of rhinovirus, 3 cases of adenovirus, 1 case of parainfluenza virus type I, 1 case of influenza, 1 case of human metapneumovirus, 1 case of rotavirus, and 1 case of respiratory syncytial virus combined with adenovirus; 13 cases tested positive for pathogen microbial cultures, including 5 cases of Streptococcus pneumoniae, 1 case of Moraxella catarrhalis, 1 case of Streptococcus pneumoniae combined with Streptococcus pyogenes detected in throat swabs, 4 cases of Streptococcus pneumoniae, 1 case of Moraxella catarrhalis, and 1 case of Klebsiella pneumoniae detected in sputum cultures; one case was positive for fungal infection, with Candida albicans detected in a throat swab; 11 cases tested positive for atypical pathogen infections, including 9 cases of Mycoplasma pneumoniae antibodies, 1 case of Chlamydia pneumoniae antibodies, and 1 case of both Mycoplasma pneumoniae and Chlamydia pneumoniae antibodies.

Discussion

This study classified 129 pediatric COVID-19 cases clinically, most of which were mild and moderate cases. These findings are highly consistent with a regional study demonstrating typical mild to moderate severity in pediatric COVID-19 infections [4]. The mild group predominantly consisted of infants (28 days to < 1 year old) (36 cases, 52.17%), with most presenting with fever as the initial symptom. Among infant cases, 18 (50.00%) had fever as the sole symptom. Due to the heightened parental awareness of children’s health, early medical attention and standardized treatment were sought promptly upon symptom onset. Overall, a trend towards mild symptoms was evident in the pediatric COVID-19 cases, which was attributed not only to viral strain variations [14–16] and children’s unique immune responses [17] but also to timely interventions by caregivers in reducing severe and critical cases.

The clinical manifestations of COVID-19 in children are diverse. In the current study, the clinical classification criteria involved respiratory symptoms and imaging findings. It found that fever, respiratory symptoms (cough, runny nose, nasal congestion), and digestive symptoms (diarrhea, vomiting) were the main clinical features in children with COVID-19, consistent with other relevant studies [7, 18]. Compared with the mild group, respiratory symptoms were more prevalent in the moderate group (P < 0.05). The potential explanation may lie in the fact that during the entry of SARS-CoV-2 into host cells by binding to the angiotensin-converting enzyme 2 receptor through its surface spike protein, the respiratory system is most commonly affected, with the virus invasion causing the shedding of respiratory epithelial cells, congestion, edema, and increased mucus secretion, forming the pathological basis of respiratory symptoms [2]. Significant difference in the outcomes was found between the mild and moderate groups. The recovery rate was higher in the mild group than in the moderate group (49.28% vs. 8.47%), while the improvement rate was significantly higher in the moderate group than in the mild group (89.83% vs. 50.72%), with no deaths reported, indicating an overall favorable prognosis.

Some studies have shown that males are more prone to COVID-19 than women, regardless of age [15]. In this study, the male-to-female ratio was 1.35:1, indicating a higher proportion in males, though no statistical difference was found (P > 0.05). Due to the limited sample size of the current study, further investigations of larger samples are needed for clarification.

In this study, some pediatric patients experienced complications, with electrolyte imbalance (17 cases, 13.18%) being the most common, mainly characterized by decreased blood potassium, occasionally accompanied by decreased blood sodium, related to reduced food intake, fever-induced sweating, and gastrointestinal fluid loss due to the disease. Some patients showed elevated transaminases (14 cases, 10.85%), ranging from mild to moderate elevation, consistent with previous literature [19], and often self-recovering post-infection. No significant intergroup differences in complication rates were found between the mild and moderate groups, except for a higher incidence of neutropenia in the latter (P < 0.05), indicating a similar risk of complications in both groups, necessitating equal attention to the prevention and management of various complications in clinical practice. In the critical group, the single case of MIS-C was caused by SARS-CoV-2 and co-infected with adenovirus. MIS-C is essentially a cytokine storm-like disease resulting from an abnormal immune response triggered by a viral infection and is a rare post-infection complication of COVID-19 in children [9, 20]. The standard treatments of MIS-C and its core pathophysiological mechanisms remain to be clarified, underscoring an ongoing need for vigilance against such rare complications in clinical practice.

According to the clinical guidelines and expert consensus on pediatric COVID-19 published in China [2, 3, 9], children with mild or moderate severity are typically managed primarily with symptomatic and supportive care. Antipyretics may be administered for high fever, and cough suppressants and expectorants may be given for significant cough and sputum production. Antiviral or antibacterial therapy should be considered when necessary. For children with severe or critical conditions, treatments such as oxygen therapy, respiratory and circulatory support, glucocorticoids, and blood purification are administered along with symptomatic and supportive care. Based on these standardized treatment guidelines, the current study presented a detailed analysis of some of the drug treatments involved.

Currently, no approved specific antiviral drug for children with COVID-19 is available in China. Based on domestic and international studies on the use of interferon-alpha (IFN-α) to treat viral infectious diseases and SARS-CoV-2 infection, IFN-α can effectively reduce viral load and its early administration can help alleviate symptoms and shorten the course of the illness. Accordingly, an aerosolized administration of IFN-α is recommended for children with pneumonia and other lower respiratory tract infections [2]. Ribavirin is a broad-spectrum antiviral drug. In the current study, the results showed that 92 cases (71.32%) of pediatric patients received an antiviral therapy with human interferon alpha-1b injection. Among them, 5 children, who only presented with fever or concurrent symptoms like diarrhea and rash, received an aerosol administration of human interferon alpha-1b injection, which mainly deposits the drug in the lungs and may limit its effects on fever and other systemic infections. Although the aerosol administration of interferon alpha-1b injection for viral respiratory diseases has been filed for off-label use in our hospital, caution should be exercised in the administration route to avoid excessive aerosol administration without clear indications of lung involvement, preventing irrational drug use due to mismatched administration routes and treatment targets.

The use of glucocorticoids in pediatric COVID-19 patients should strictly adhere to indications. In some severe and critical cases, acute pharyngitis or laryngotracheitis, wheezing, and MIS-C, glucocorticoids can be used at the physician’s discretion [3]. A study has documented a 45.75% usage rate for nebulized inhalation medication and glucocorticoids. In the moderate group, the rate of ICS use was as high as 86.44%. Among them, only 14 cases (23.73%) had symptoms of acute pharyngitis or wheezing, while the remaining 45 cases (76.27%) were mainly diagnosed with acute bronchitis or pneumonia. The systemic use of glucocorticoids had clear indications, but the use of ICS for treating acute bronchitis or pneumonia remains controversial. The “Expert consensus on rational usage of nebulization treatment on childhood respiratory system diseases” emphasizes that ICS is not recommended as the first choice for common pneumonia [11]. However, the “Expert Consensus on the Rational Use for Inhaled Medicines Administrated by Nebulizers (2024 Edition)” points out that lung infections can lead to increased airway secretions, thick yellow purulent sputum, or noticeable respiratory symptoms like coughing and wheezing, in such cases, appropriate nebulized expectorants, ICS, or bronchodilators can be administered based on individual circumstances [12]. Nevertheless, this consensus still lacks a clear clinical guidance on the indications for using ICS in lung infections, with ambiguous delineation of specific clinical boundaries. Moreover, the potential adverse reactions of ICS, such as hoarseness, cough, throat discomfort, and oral candidiasis, should not be overlooked. Given the controversial evidence-based medicinal evidence for the use of ICS in the treatment of acute bronchitis or pneumonia in children, and the presence of two cases with inconsistent medication indications in this study, controversies surrounding the indications for the use of ICS remain in current clinical practice. Therefore, relevant treatment strategies require further verification through more high-quality research.

Chinese patent drugs are preparations developed under the theoretical guidance of traditional Chinese medicine, using raw herbal materials as ingredients. They are processed according to prescribed formulas and standards into dosage forms of specific specifications and can be used directly for the prevention and treatment of diseases [21]. In this study, some pediatric patients were treated with Chinese patent drugs such as Lianhua Qingwen Granules, Qingxuan Zhike Granules, and Xiao’er Resuqing Granules. Based on their herbal compositions, these formulations primarily consist of heat-clearing and detoxifying herbs (e.g., Forsythiae Fructus, Lonicerae Japonicae Flos) and lung-clearing herbs (e.g., Platycodonis Radix), targeting symptoms such as fever, cough, nasal congestion, and rhinorrhea. The instruction for Lianhua Qingwen Granules recommends its use for COVID-19-related fever, cough, and fatigue [22]. Clinical guidelines suggest that Qingxuan Zhike Granules may be used for prominent cough in pediatric COVID-19 patients [9], while Xiao’er Resuqing Granules are indicated for fever, nasal congestion, rhinorrhea, and cough [23]. As a distinctive feature of China’s healthcare system, Chinese patent drugs are characterized by diverse dosage forms and extensive clinical application [24], reflecting the principle of “differential diagnosis and specific treatment” in traditional Chinese medicine in the management of COVID-19 in children. The aforementioned medications are commonly used pediatric formulations with appropriate dosages and administration routes in this cohort. However, aside from a limited number of Chinese patent drugs with explicit COVID-19 indications, scarcity remains regarding high-quality evidence-based medical data supporting the efficacy and safety of most Chinese patent drugs for pediatric COVID-19 and further investigations are warranted.

Out of the 129 pediatric COVID-19 cases, 61 were treated with antibiotics, resulting in a rate of 47.29%, significantly decreased from the antibiotic utilization rate in pediatric inpatients of our hospital in 2021 (88.00%) [25]. An evaluation of the rationality of antibiotic use revealed that 8 cases (13.11%) were treated irrationally, as these children, though diagnosed with COVID-19, had normal or slightly elevated inflammatory markers and were unnecessarily prescribed antibiotics for infection control. The notable decrease in antibiotic usage among pediatric COVID-19 cases in this study may be attributed to several factors. Firstly, with the improvement in the COVID-19 epidemic prevention and control system and the accumulation of clinical expertise, the latest COVID-19 treatment guidelines have explicitly emphasized the avoidance of inappropriate antibiotic use, effectively curbing the unwarranted and prophylactic use of antibiotics [3]. Secondly, clinical pharmacists have contributed to an enhanced awareness of rational antibiotic use among pediatric physicians through prescription reviews, pharmaceutical ward rounds, and training on proper medication use, thereby further standardizing the clinical application of antibiotics.

A recent review on acute COVID-19 management in children and adolescents highlights the diverse global therapeutic strategies, encompassing antiviral therapies (e.g., Remdesivir, Nirmatrelvir/Ritonavir [Paxlovid]), immunomodulators (e.g., glucocorticoids, interleukin-6 (IL-6) inhibitors, and Janus kinase (JAK) inhibitors), and prophylactic anticoagulation [26]. However, significant heterogeneity exists in pediatric recommendations across national guidelines. For instance, the National Institutes of Health (NIH) guidelines endorse Remdesivir for high-risk infants weighing > 3 kg without age restriction, and approve Nirmatrelvir/Ritonavir for adolescents aged ≥ 12 years and weighing ≥ 40 kg [27]. In contrast, these specific antiviral agents for routine pediatric use (< 18 years) are yet to be approved in China. Instead, nebulized IFN-α is recommended for antiviral therapy. Regarding immunomodulation, Chinese guidelines emphasize the stringent and short-term use of glucocorticoids, restrict IL-6 inhibitors to severe/critical cases, and note the limited evidence for JAK inhibitors in pediatric populations [2, 9]. The pharmacotherapy administered in our cohort—primarily consisting of antivirals, antipyretics, expectorants, vitamins, and other supportive care—generally aligns with these domestic principles of rational drug use.

Study limitations

Some limitations remain in this study. Firstly, this is a single-center retrospective study, which may limit the generalizability of the research results due to the limited research context. Secondly, after its classification as a Class B infectious disease [2], the nucleic acid testing for COVID-19 is no longer required. This has resulted in a limited collection of pediatric COVID-19 cases, particularly few severe and critical cases. The limitations in sample size and case composition may affect the representativeness of the study conclusions, and the findings still require further validation through studies with larger sample sizes. Furthermore, the statistical analysis focused solely on the clinical characteristics and medication differences among children with mild and moderate severity. No in-depth clinical analysis or mechanistic exploration was conducted for the sole critical case, making it impossible to fully reflect the diagnostic and therapeutic features or prognostic patterns of severe pediatric COVID-19. Finally, this study focused solely on clinical symptoms, treatment, and short-term outcomes during the hospitalization. It did not conduct a follow-up on post-discharge outcomes or long-term prognosis. Due to the lack of a systematic evaluation of the long-term impact of the disease, long-term complications, and the long-term safety of therapeutic drugs, it is difficult to provide a comprehensive picture of the long-term clinical and therapeutic outcomes of pediatric COVID-19 and the potential risks associated with the medications.

Recommendations for future studies

Given the limitations of this study, future research should include multicenter, prospective clinical trials on pediatric COVID-19, focusing on the appropriate use, clinical efficacy, drug safety, and long-term prognosis of antiviral drugs, ICS, and antibiotics in children, thereby addressing the shortcomings of single-center, retrospective studies and insufficient sample sizes. At the same time, the involvement of clinical pharmacists throughout the entire process of pediatric COVID-19 diagnosis and treatment should be further strengthened. In-depth research on clinical pharmacists’ participation in the rational management of pediatric medication should be conducted to optimize treatment regimens, provide higher-quality evidence-based medical support for individualized pediatric COVID-19 treatment, and promote a standardized care for pediatric COVID-19.

Conclusion

Based on the available data, this study attempts to clarify the clinical characteristics, types of complications, and current status of drug treatment for pediatric COVID-19 cases. It identifies key issues of medicine irrationality in clinical drug use and proposes optimization suggestions to provide practical references for standardized clinical diagnosis and treatment of pediatric COVID-19, precise prevention of complications, and rational drug use. It is worth noting that there are few reports on drug practice research from the perspective of clinical pharmacists, highlighting its practical exploration value and real significance.

Abbreviations

COVID-19

Coronavirus disease 2019

SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2

MIS-C

Multisystem inflammatory syndrome in children

ICS

Inhaled corticosteroid

IFN-α

Interferon-alpha

IL-6

Interleukin-6

JAK

Janus kinase

NIH

National institutes of health

Authors’ contributions

Wenqiong He and Min Ren conceived and designed the study. Wenliu Qiu and Weimin Zhong collected samples data , Ling Su and Huoshu Chen performed data analysis and wrote the manuscript. All authors reviewed and approved the manuscript.

Funding

This study did not receive any funding in any form.

Data availability

The data are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki and was approved by Medical Ethics Committee of The Fifth Hospital of Xiamen (Ethics Approval Number: XMWY-LL-2026-022). As a retrospective study, the Medical Ethics Committee of The Fifth Hospital of Xiamen waived the necessity of informed consent from patients and their guardians.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.