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Article

Effect of COVID-19 Disease on Serum Vitamin D Status in Children with Asthma—A Retrospective Study

by
Jaqueline Abdul-Razzak
1,2,†,
Mihaela Ionescu
3,*,
Radu Diaconu
2,*,
Alexandru Dan Popescu
4,
Elena Carmen Niculescu
2,
Ileana Octavia Petrescu
2,
Cristina Elena Singer
2,
Lucrețiu Radu
5,
Liliana Anghelina
2 and
Cristian Gheonea
2,†
1
Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
2
Department of Pediatrics “Mother and Child”, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
3
Department of Medical Informatics, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
4
Department of Endodontics, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
5
Department of Hygiene, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2025, 14(13), 4525; https://doi.org/10.3390/jcm14134525
Submission received: 3 June 2025 / Revised: 23 June 2025 / Accepted: 24 June 2025 / Published: 26 June 2025
(This article belongs to the Section Clinical Pediatrics)

Abstract

Background/Objectives: Vitamin D is known to decrease the risk of contracting respiratory infections and developing exacerbations for children with asthma. This research evaluates the alterations in serum vitamin D concentrations and examines lung function in children with asthma, as indicated by clinical symptoms and paraclinical results, after experiencing SARS-CoV-2 infection or other acute respiratory infections. Material and Method: This retrospective study included 145 children with asthma. For each patient, the following variables were acquired: demographic data, serum vitamin D levels, GINA asthma control levels, the fraction of exhaled nitric oxide (FeNO), pulmonary function tests parameters, data related to allergies, and the presence of exacerbations. Children were divided into two groups, according to the presence or absence of SARS-CoV-2 infection or other acute respiratory infections. Variables were statistically processed in SPSS. Results: In total, 93 children with asthma with SARS-CoV-2 infection or other acute respiratory infections and 52 children with asthma without SARS-CoV-2 infection or other acute respiratory infections were included in the study. Median serum vitamin D values were statistically significantly lower in children with a variable airflow limitation, compared to children with normal values (p = 0.004), as well as for children with partially controlled asthma, relative to children with well controlled asthma (p < 0.0005). Similarly, children with acute respiratory infections/COVID-19 disease had lower median values of serum vitamin D, compared to children without acute respiratory infections/COVID-19 disease (p < 0.0005). A decrease in serum vitamin D value was statistically significantly associated with an increase in FeNO value for children with asthma with COVID-19 disease (p = 0.027), as well as for the entire study group (p < 0.0005). Conclusions: Children with asthma who had acute respiratory infections, including COVID-19 disease, showed considerably reduced serum vitamin D levels and were linked to more significant airflow limitation, reduced asthma control and elevated airway inflammation, suggesting its potential role in influencing asthma severity and infection response.

1. Introduction

The prevalence of asthma in pediatric age is continuously increasing in recent years and in order to achieve a good control of this pathology it is necessary to have a correct diagnosis, an appropriate placement within the treatment step and a good understanding of the disease by children and parents [1,2]. There are a variety of factors that may cause exacerbations, including acute respiratory infections, aeroallergens, cigarette smoke or exercise [3].
The pathophysiologic process in asthma is the inflammation of the airways with the reduction of their diameter, leading to the activation of dendritic cells, eosinophils, neutrophils, mast cells, lymphocytes and various cytokines, which are responsible for the development of asthma features such as increased mucus secretion and bronchial hyperreactivity. Therefore, the treatment of asthma is to relieve the associated symptoms by reducing inflammation, which would limit the risk of exacerbations [4,5].
Vitamin D is known for its anti-inflammatory property, its serum concentrations playing an important role in shaping innate or acquired immunity. A vitamin D value > 30 ng/mL will result in a significant decrease in inflammatory cytokines; lower values (<15 ng/mL) do not have the ability to inhibit the inflammatory process [6,7]. Children with asthma who receive a dose of 400–1000 IU/day of vitamin D have a lower risk of contracting respiratory infections and developing exacerbations [8,9]. Vitamin D is a metabolite accessible to the general population, with numerous benefits for the body, being considered a secosteroid, having a similar structure to estrogen, testosterone, mineralocorticoids and glucocorticoids, thus potentiating its anti-inflammatory value [8,9,10,11,12,13,14,15].
The SARS-CoV-2 virus primarily affects the airways of the respiratory tract causing symptoms such as dry cough, dyspnea and other general signs such as fever, wheezing, dizziness, taste disorders or digestive manifestations. Children with chronic conditions such as heart or lung disease are vulnerable to contracting COVID-19 disease and are also at risk of developing multisystem inflammatory syndrome (MIS) 3–4 weeks after SARS-CoV-2 infection [16,17,18,19,20]. Additionally, patients who were infected with SARS-CoV-2 showed low vitamin D values, suggesting the benefit of vitamin D administration to provide a better prognosis, not only in COVID-19 disease but also in other respiratory infections [21].
SARS-CoV-2 infection can have negative consequences on patients with chronic diseases, in the case of asthma, an insufficient level of vitamin D can cause an increase in the frequency of exacerbations, as well as changes in lung function. As vitamin D has cytokine cascade inhibitory properties, it is essential to maintain an optimal serum level and even to supplement it in special epidemiologic conditions, such as COVID-19 pandemic, thus helping patients at risk [22,23,24,25,26].
The literature includes data on how vitamin D levels affected adult patients who had COVID-19 disease and who also had other associated chronic diseases. However, given the small number of SARS-CoV-2 infections in the pediatric population and the mild to moderate symptoms they have presented, few studies have been conducted to show the consequences of SARS-CoV-2 infection, especially in children with asthma. The novelty of this study is the correlation of serum vitamin D values with pulmonary function parameters and with nitric oxide in the exhaled air of children with asthma with COVID-19 disease or other acute respiratory infections. The hypothesis of this study is that there is an association between serum vitamin D levels and FeNO values along with pulmonary function parameters, for this category of patients.
The aim of this study is to assess changes in serum vitamin D levels and to evaluate lung function in children with asthma expressed through clinical symptoms and paraclinical findings following SARS-CoV-2 infection or other acute respiratory infections.

2. Materials and Methods

2.1. Study Design and Participants’ Selection

In this retrospective study, it was analyzed the level of serum vitamin D in a group of children who were previously diagnosed with asthma and who were infected with the SARS-CoV-2 virus or had other acute respiratory infections.
For this study, the following data were collected from each subject: demographic data, data related to allergies and asthma phenotype, data regarding the presence of exacerbations, treatment steps, as well as the GINA asthma control levels [27]. It also included values regarding the fraction of exhaled nitric oxide (FeNO) and the pulmonary function tests parameters. The SARS-CoV-2 infections and other acute respiratory infections were evaluated in terms of the level of serum vitamin D and how its values interfered with the outcome of children with asthma over time.
The level of serum vitamin D was measured for each child with asthma included in the study 3–4 weeks after COVID-19 disease or after an acute respiratory infection. Serum vitamin D levels were measured using the Alinity i 25-hydroxyvitamin D (25-OH Vitamin D) Immunoassay Reagent Kit (Abbott, Longford, Ireland) using the CMIA (chemiluminescent microparticle immunoassay) method. The range values of serum vitamin D for pediatric population are as follows: sufficiency ≥ 30 ng/mL, insufficiency between 20 and 29 ng/mL, and deficiency < 20 ng/mL.
To determine the lung function of children with asthma, the following parameters such as FVC (forced vital capacity), FEV1 (forced expiratory volume in the first second), PEF (peak expiratory flow) and FEF25–75 (forced mid expiratory flow) were recorded. It was also documented the airflow limitation using FEV1/FVC ratio (normal range values for FEV1/FVC ratio for pediatric population is >0.9 according to GINA guideline) [27]. The diagnostic device used to measure these pulmonary function tests parameters was the Vitalograph Pneumotrac 6800 spirometer (Vitalograph, Hamburg, Germany).
To measure FeNO values, the Aerocrine Niox Vero 12-1000 analyzer (NIOX Group plc, Uppsala, Sweden) was used, the results of this test being expressed in ppb (parts per billion).
SARS-CoV-2 infection was confirmed using a PCR test or a rapid antigen test. Other acute respiratory infections included in the study were Influenza A, Influenza B and Respiratory Syncytial Virus, confirmed by rapid antigen tests.
The study included children diagnosed with asthma in whom serum vitamin D levels were collected and who benefited from periodic follow-ups within the pediatric department of a regional tertiary hospital (Filantropia Clinical Municipal Hospital Craiova, Romania) during the COVID-19 pandemic and in the post-pandemic period (March 2020–July 2024).
The inclusion criteria were as follows:
(a)
Children with asthma who are less than 18 years old whose parents or legal tutors agreed to their participation in this study;
(b)
Children with known asthma under treatment;
(c)
Children with asthma who have measured serum vitamin D levels.
Exclusion criteria were as follows:
(a)
Children with asthma who present other chronic pathologies that may intervene in the results of the present study;
(b)
Children with asthma who did not have measured serum vitamin D levels.
To ensure sufficient generalizability and power for this study, the minimum number of participants was determined to be 134, value computed using the software application G*Power version 3.1.9.7, Heinrich Heine University Düsseldorf, Germany, based on a significance level α of 0.05, a power 1 − β equal to 0.8, and an effect size value of 0.5.
The study was approved by the Ethics Committee of the University of Medicine and Pharmacy of Craiova, no. 167/14.09.2023 and respected the Declaration of Helsinki. All subjects’ parents or legal tutors signed an informed consent form on behalf of pediatric patients.

2.2. Statistical Analysis

Study data were analyzed using SPSS (Statistical Package for Social Sciences) software, version 26 (SPSS Inc., Armonk, NY, USA). The Shapiro–Wilk test was used to evaluate the normality of continuous data series. Thus, based on the results, continuous variables were described as median values. Comparisons between various groups were performed using the Mann–Whitney U test and Kruskal–Wallis H test followed by pairwise comparisons based on Dunn’s procedure, in association with a Bonferroni correction recommended for multiple comparisons and Spearman’s rank-order correlation. Nominal and ordinal variables were defined as frequencies and percentages and were tested using the Chi-square test. The threshold of statistical significance was set to a p-value less than 0.05.

3. Results

Following the inclusion/exclusion criteria, a number of 145 children (90 boys) were finally enrolled in this study (study group A and study group B) (Figure 1).

3.1. Vitamin D Analysis

The study group included 145 children diagnosed with asthma, with ages less than 18 years old, and with the following gender distribution: 55 girls (37.90%) and 90 boys (62.10%). Relative to the residence area, the children from the study group mostly had an urban residence (104, 71.72%), and only less than a quarter were from rural areas (41, 28.28%). A Mann–Whitney U test was performed to identify if there were differences in serum vitamin D by gender or residence. Distributions of serum vitamin D for children within those categories were similar, as assessed by visual inspection. Median serum vitamin D value was not statistically significantly different between girls and boys, or between children from urban and rural areas, p > 0.05 (Table 1).
Half of the children included in the study group were diagnosed with asthma at ages between 6 and 11 years old (74 children, 51.03%). A significant percentage was dedicated to children who were diagnosed at ages less than 6 years old (44.14%), and only 4.83% (7 children) were diagnosed at ages above 12 years old. Children diagnosed at 6–11 years old had the highest serum vitamin D median value (28.50 ng/mL), followed closely by children diagnosed at early ages (27 ng/mL), while those diagnosed as teenagers exhibited the lowest median value (23 ng/mL). The result of the Mann–Whitney test regarding the presence of statistically significant differences in the serum vitamin D levels between children with various ages at diagnosis, yielded a value close to the statistical threshold, p = 0.074, potentially emphasizing the idea that higher ages at diagnosis could be associated with smaller values of serum vitamin D, still with caution relatively to the small number of children within the last age group (Table 1).
Serum vitamin D values were not statistically significantly different between children with and without the following allergies or allergic and atopic diseases: allergic rhinitis, atopic dermatitis, allergies regarding food, pollen, house dust, animal hair, mold or tobacco (p > 0.05; Table 1).
Table 2 presents the clinical context of the children included in the study lot. An analysis of serum vitamin D values by treatment step revealed that children within step 4 of treatment had a median value of 45 ng/mL, while all other children in various steps of the treatment had a median value smaller than or equal to 28 ng/mL. Still, there were no statistically significant differences in the serum vitamin D levels between these groups, p > 0.05. In relation to the asthma phenotype and parents with predisposition to atopy, there were no statistically significant differences between children from these groups, p > 0.05.
A Mann–Whitney U test was run to determine the differences in serum vitamin D values between children with a normal FEV1/FVC ratio or variable airflow limitation. Distributions of serum vitamin D for children within both categories of FEV1/FVC ratio were similar, as assessed by visual inspection. Median serum vitamin D value was statistically significantly lower in children with a variable airflow limitation (26 ng/mL) than in children with a normal value of FEV1/FVC ratio (36 ng/mL), p = 0.004. Children with partially controlled asthma have statistically significantly lower median serum vitamin D values (24 ng/mL), compared to children with well-controlled asthma (37 ng/mL), p < 0.0005. Similarly, children with acute respiratory infections/COVID-19 disease have lower median values of serum vitamin D (23 ng/mL), compared to children without acute respiratory infections/COVID-19 disease (46.50 ng/mL), and the differences between groups are statistically significant, p < 0.0005 (Table 2).
A Kruskal–Wallis test was performed to determine the differences in serum vitamin D levels between groups that differed in number of exacerbations per year: children with no exacerbation (n = 51), children with 1 exacerbation (n = 56), children with 2 exacerbations (n = 30) and children with 3 exacerbations (n = 8). Distributions of serum vitamin D values were similar for all groups, as assessed by visual inspection of a boxplot. Children with asthma with no exacerbations per year had a high median value of serum vitamin D, compared to children with at least one exacerbation per year; in fact, the median values of serum vitamin D decrease as the number of exacerbations per year increases. Median serum vitamin D values were statistically significantly different between children with different numbers of exacerbations, χ2(3) = 34.844, p < 0.0005. Subsequently, pairwise comparisons were completed using Dunn’s procedure. A Bonferroni correction for multiple comparisons was applied, with the statistical significance accepted for p < 0.0083. The post hoc analysis revealed statistically significant differences in serum vitamin D values between children with two exacerbations (21 ng/mL) and children with one exacerbation (26 ng/mL) (p = 0.005), and children with three exacerbations (13.50 ng/mL) (p < 0.0005) and children with no exacerbation (46 ng/mL) (p < 0.0005), but not between any other group combination (Table 2).
A Spearman’s rank-order correlation was performed to assess the potential association between serum vitamin D and FeNO, both for children with COVID-19 disease, and the entire study lot. The preliminary analysis determined the relationship to be monotonic, as assessed by visual inspection of a scatterplot. There was a statistically significant, moderate negative correlation between these variables, a decrease in serum vitamin D value being associated with an increase in the FeNO value, rs(77) = −0.249, p = 0.027 for children with COVID-19 disease, and rs(143) = −0.476, p < 0.0005 for the entire study group. Similar correlations were analyzed for pulmonary function tests parameters, FVC, FEV1, PEF, FEF25–75 and FEV1/FVC ratio, but no statistically significant associations were identified, p > 0.05 (Table 3).

3.2. Acute Respiratory Infections Analysis

Almost two thirds of children included in the study group presented acute respiratory infections (93 children, 64.14%). As described in Table 4, there are no statistically significant associations between acute respiratory infections and gender, residence and age at asthma diagnosis.
According to Table 5, the presence of acute respiratory infections is similarly distributed among children with asthma with various numbers of exacerbations per year, no association could be identified between these parameters, p > 0.05. Similar results are obtained regarding the presence of an atopic disease for at least one of the parents, p > 0.05.
Statistically significant associations were identified for acute respiratory infections and the FEV1/FVC ratio, GINA asthma control levels, and asthma phenotype. Around 80% of children with a variable airflow limitation have acute respiratory infections, compared to 35.42% children with a normal FEV1/FVC ratio. Similarly, 63.44% of children with partially controlled asthma have acute respiratory infections, compared to only 36.56% of children with well-controlled asthma. Asthma phenotype is also associated with acute respiratory infections, as 75% of children with a non-allergic phenotype have acute respiratory infections, compared to only 57.30% of children with an allergic phenotype (Table 5).

3.3. COVID-19 Analysis

A previous infection with SARS-CoV-2 virus was recorded for more than half of children included in the study group (79 children, 54.48% group). A Mann–Whitney U test was run to determine if there were differences in serum vitamin D between children with and without COVID-19 disease. Distributions of serum vitamin D for children within both categories were similar, as assessed by visual inspection. Median serum vitamin D value was statistically significantly lower in children with a previous SARS-CoV-2 infection (24 ng/mL) than in children without a previous infection (44 ng/mL), p < 0.0005 (Table 6).

4. Discussion

The COVID-19 pandemic caused changes in people’s daily routines, with the pediatric population suffering from chronic pathologies, being a category that required additional attention during this period [28]. The SARS-CoV-2 virus has shown a rather high level of contagiousness, ranging from mild symptoms to complications such as acute respiratory distress syndrome (ARDS), affecting both children and adults. Asthma, with an increasing number of cases among pediatric patients, has been a cause of concern for physicians worldwide [29,30,31].
In the present study, differences in serum vitamin D values were noted, which influenced the clinical and paraclinical outcomes of children with asthma during the COVID-19 pandemic and post-pandemic period following contract with SARS-CoV-2 infection or other acute respiratory infections compared to children with asthma who did not contract COVID-19 disease or other acute respiratory infections.
Recent studies have observed a significant decrease in airway inflammation and bronchial hyperresponsiveness leading to a decrease in the number of exacerbations, especially those induced by acute respiratory infections, with a standard dose of vitamin D given daily for 6 months producing these benefits [32,33,34,35]. In a study by Fedora et al., it was found that patients who had a lower incidence of exacerbations were those who were adherent to corticosteroids and vitamin D, thus proving the synergistic effects that vitamin D has with asthma treatment, especially in children [36].
Vitamin D acts through the vitamin D receptor (VDR) being expressed in approximately all immune cells in the body such as dendritic cells and macrophages, playing a role in improving the antimicrobial properties of these cells and therefore reducing viral replication and the production of anti-inflammatory cytokines [37,38,39,40].
Infection with SARS-CoV-2 virus causes an amplification of inflammatory cytokines (IL-6 and IFN-γ being expressed in children), which are in fact immune cells that are directed to the site of infection affecting the lungs through tissue destruction [41,42,43]. Recent studies have shown that a low level of vitamin D in children is a risk factor for COVID-19 disease and therefore an unfavorable prognosis of this infection, also being a predictor of an eventual MIS-C (Multisystemic inflammatory Syndrome in Children) [44,45,46,47].
In the current study, the number of exacerbations in children with asthma was inversely related to the serum vitamin D value, so that the lower the serum vitamin D value, the higher the number of exacerbations. Likewise, low serum vitamin D values were observed in children with asthma who had acute respiratory infections including SARS-CoV-2 infection.
Pro-inflammatory cells, such as Il-7 and Il-3, are involved in the pathogenesis of asthma, along with the increase in Th-17 cells, causing an imbalance between Th1 and Th2 cells. A low level of vitamin D affects the composition of the intestinal microbiome and therefore causes a low production of short-chain fatty acids (SCFAs), with a reduction in the maturation of dendritic cells and an increase in Th-17 activity. A decrease in SCFAs has consequences for the cells of the lung epithelium affected by asthma, with children with asthma being more susceptible to contract acute respiratory infections [9,48,49,50,51]. The influence of the SARS-CoV-2 virus on intestinal microbiota has also been proven, along with its effects on lung function [52,53].
The pulmonary function of children with asthma should be constantly monitored, especially under special epidemiological conditions. Studies have shown a correlation between vitamin D levels and lung function in children with asthma, so that vitamin D deficiency caused a decrease in spirometric values such as FEV1, FVC, and FEV1/FVC ratio, leading to impaired lung function. During infection with SARS-CoV-2, children with asthma show lung tissue damage, so that low values of FVC and FEV1 have been observed [54,55,56,57,58,59,60,61,62]. In the present study, children with asthma with COVID-19 disease or other acute respiratory infections had low serum vitamin D values and were more susceptible to pulmonary function changes and thus to variable airflow limitation.
Another parameter that was altered is nitric oxide in exhaled air. Children with asthma with low vitamin D levels showed elevated FeNO values, indicating airway inflammation compared to pediatric populations with asthma whose normal vitamin D values did not influence lung function [63,64]. The current research reported a statistically significant correlation between low serum vitamin D levels and elevated FeNO values.
Regarding the level of asthma control, studies have highlighted the importance of vitamin D in children with asthma and how this fat-soluble vitamin influences the course of chronic lung disease. Low serum vitamin D levels have been observed in patients with partially controlled and uncontrolled asthma, which may increase the risk of exacerbations [65,66]. This was also emphasized in the present study, children with asthma who had low serum vitamin D values were more likely to develop a more difficult disease course with exacerbations, which was observed in patients with partially controlled asthma (24 ng/mL) compared to patients with asthma whose normal serum vitamin D values had well controlled asthma (37 ng/mL).
Vitamin D has numerous benefits on the organism not only in preventing rickets but also in preventing contact with various respiratory infections, being also a predictor of acute respiratory infections in patients with asthma, avoiding exacerbations and determining a better control of lung function, thus improving the quality of life of pediatric patients [67,68,69]. The administration of a daily maintenance dose of vitamin D offers superior benefits compared to bolus administration of vitamin D weekly or every 1–3 months, thus keeping serum vitamin D levels within normal parameters and preventing the risk of acute respiratory infections, including SARS-CoV-2 infection [9,70,71,72,73].
Other micronutrients, such as B-complex vitamins, are also known to be critical for an effective immune response to viral pathogens, including SARS-CoV-2 infection. Recent studies have indicated that B vitamins are linked to better prognosis in COVID-19 outcomes. Thus, a holistic nutritional strategy, ensuring sufficiency of both vitamin D and other key immunomodulatory nutrients, may be the most effective approach for supporting respiratory health [53,74].
In this research, it can be observed that children with asthma with COVID-19 disease had low serum vitamin D values causing inflammatory changes in the airways observed both clinically and paraclinically. However, children with asthma who had other acute respiratory infections or who had not contracted SARS-CoV-2 infection had higher serum vitamin D values compared to those who had contracted COVID-19 disease, suggesting the importance of vitamin D in children with asthma, an optimal serum level being beneficial in special epidemiologic conditions, avoiding an unfavorable course of the disease.

4.1. Limitations of the Study

Due to the fact that the study period coincided with the COVID-19 pandemic period, children with asthma did not present for routine check-ups unless absolutely necessary, i.e., in case of medical emergencies, making it difficult to collect medical data and to assess the evolution of the disease over time. Another limitation of the study is that the number of children with asthma for whom the measured serum vitamin D was reduced because parents/legal guardians wanted to avoid the risk of contracting acute respiratory infections and thus SARS-CoV-2 infection during the COVID-19 pandemic. Additionally, due to the lock-down, access to routine medical services was limited, with major medical emergencies being prioritized and low vitamin D levels could be a consequence of limited outdoor activity and reduced sun exposure in children with asthma.

4.2. Recommendations for Further Research

This study provides valuable information on the effects that COVID-19 disease has on serum vitamin D levels in children with asthma. To consolidate the results of this study and better understand the impact of acute respiratory infections on children with asthma, additional research is needed to monitor the evolution of lung function, FeNO and serum vitamin D status. Additionally, including vitamin D dosing in the monitoring of children with asthma and evaluating FeNO as a potential predictive marker of airway inflammation could contribute to an individualized treatment. Further research is required to involve a wider population of children with asthma and time monitoring of serum vitamin D values to highlight the impact that SARS-CoV-2 infection had on children with asthma.

5. Conclusions

Children with asthma and acute respiratory infections, including COVID-19 disease, had significantly lower serum vitamin D levels, require a personalized therapeutic approach, especially in specific epidemiological conditions such as the COVID-19 pandemic. Lower serum vitamin D levels were associated with worse airflow limitation, poorer asthma control, and increased airway inflammation, highlighting its potential role in asthma severity and infection response.
A key finding is the significant negative correlation between serum vitamin D levels and FeNO values, a marker of airway inflammation, after COVID-19 disease. This retrospective study highlights certain aspects regarding the quality of asthma management in children such as serum vitamin D dosing along with supplementation, when necessary, implementation and compliance with an individualized therapeutic plan and constant medical follow-ups. All of these could be considered essential strategies for better and lasting control of the disease.

Author Contributions

Conceptualization, J.A.-R., M.I. and C.G.; methodology, R.D. and E.C.N.; software, M.I. and A.D.P.; validation, C.G., R.D. and L.A.; formal analysis, M.I., I.O.P. and C.E.S.; investigation, J.A.-R., C.G. and R.D.; resources, L.A., I.O.P. and E.C.N.; data curation, J.A.-R., M.I. and C.G.; writing—original draft preparation, J.A.-R., R.D. and M.I.; writing—review and editing, C.G., L.R. and E.C.N.; visualization, A.D.P., L.R. and C.E.S.; supervision, A.D.P. and L.A.; project administration, J.A.-R. and L.R. All authors have read and agreed to the published version of the manuscript.

Funding

The Article Processing Charges were funded by the University of Medicine and Pharmacy of Craiova, Romania.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by Ethics Committee of the University of Medicine and Pharmacy of Craiova (no. 167/14.09.2023).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study. All subjects’ parents or legal tutors signed an informed consent form.

Data Availability Statement

The authors declare that the data of this research are available from the corresponding authors upon reasonable request.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
FeNOFraction of Exhaled Nitric Oxide
FVCForced Vital Capacity
FEV1Forced Expiratory Volume in the First Second
PEFPeak Expiratory Flow
FEF25–75Forced Mid Expiratory Flow

References

  1. Szefler, S.J.; Fitzgerald, D.A.; Adachi, Y.; Doull, I.J.; Fischer, G.B.; Fletcher, M.; Hong, J.; García-Marcos, L.; Pedersen, S.; Østrem, A.; et al. A worldwide charter for all children with asthma. Pediatr. Pulmonol. 2020, 55, 1282–1292. [Google Scholar] [CrossRef] [PubMed]
  2. Asher, M.I.; García-Marcos, L.; Pearce, N.E.; Strachan, D.P. Trends in worldwide asthma prevalence. Eur. Respir. J. 2020, 56, 2002094. [Google Scholar] [CrossRef] [PubMed]
  3. van Meel, E.R.; Mensink-Bout, S.M.; den Dekker, H.T.; Ahluwalia, T.S.; Annesi-Maesano, I.; Arshad, S.H.; Baïz, N.; Barros, H.; von Berg, A.; Bisgaard, H.; et al. Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: A meta-analysis of 150 000 European children. Eur. Respir. J. 2022, 60, 2102395. [Google Scholar] [CrossRef]
  4. Hammad, H.; Lambrecht, B.N. The basic immunology of asthma. Cell 2021, 184, 1468–1485. [Google Scholar] [CrossRef]
  5. Bush, A. Pathophysiological mechanisms of asthma. Front. Pediatr. 2019, 7, 68. [Google Scholar] [CrossRef]
  6. Bouillon, R.; Marcocci, C.; Carmeliet, G.; Bikle, D.; White, J.H.; Dawson-Hughes, B.; Lips, P.; Munns, C.F.; Lazaretti-Castro, M.; Giustina, A.; et al. Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions. Endocr. Rev. 2019, 40, 1109–1151. [Google Scholar] [CrossRef] [PubMed]
  7. Zhang, Y.; Leung, D.Y.; Richers, B.N.; Liu, Y.; Remigio, L.K.; Riches, D.W.; Goleva, E. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J. Immunol. 2012, 188, 2127–2135. [Google Scholar] [CrossRef]
  8. Jolliffe, D.A.; Greenberg, L.; Hooper, R.L.; Griffiths, C.J.; Camargo, C.A., Jr.; Kerley, C.P.; Jensen, M.E.; Mauger, D.; Stelmach, I.; Urashima, M.; et al. Vitamin D supplementation to prevent asthma exacerbations: A systematic review and meta-analysis of individual participant data. Lancet Respir. Med. 2017, 5, 881–890. [Google Scholar] [CrossRef]
  9. Jolliffe, D.A.; Camargo, C.A., Jr.; Sluyter, J.D.; Aglipay, M.; Aloia, J.F.; Ganmaa, D.; Bergman, P.; Bischoff-Ferrari, P.H.A.; Borzutzky, A.; Damsgaard, C.T.; et al. Vitamin D supplementation to prevent acute respiratory infections: A systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 2021, 9, 276–292. [Google Scholar] [CrossRef]
  10. Martineau, A.R.; Jolliffe, D.A.; Hooper, R.L.; Greenberg, L.; Aloia, J.F.; Bergman, P.; Dubnov-Raz, G.; Esposito, S.; Ganmaa, D.; Ginde, A.A.; et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ 2017, 356, i6583. [Google Scholar] [CrossRef]
  11. Martineau, A.R.; Jolliffe, D.A.; Greenberg, L.; Aloia, J.F.; Bergman, P.; Dubnov-Raz, G.; Esposito, S.; Ganmaa, D.; Ginde, A.A.; Goodall, E.C.; et al. Vitamin D supplementation to prevent acute respiratory infections: Individual participant data meta-analysis. Health Technol. Assess. 2019, 23, 1–44. [Google Scholar] [CrossRef] [PubMed]
  12. Demer, L.L.; Hsu, J.J.; Tintut, Y. Steroid Hormone Vitamin D: Implications for Cardiovascular Disease. Circ. Res. 2018, 122, 1576–1585. [Google Scholar] [CrossRef] [PubMed]
  13. Bae, J.H.; Choe, H.J.; Holick, M.F.; Lim, S. Association of vitamin D status with COVID-19 and its severity: Vitamin D and COVID-19: A narrative review. Rev. Endocr. Metab. Disord. 2022, 23, 579–599. [Google Scholar] [CrossRef] [PubMed]
  14. Diaconu, I.D.; Gheorman, V.; Grigorie, G.A.; Gheonea, C.; Tenea-Cojan, T.-S.; Mahler, B.; Voropanov, I.A.; Firoiu, M.C.; Pîrvu, A.S.; Popescu, A.B.; et al. A Comprehensive Look at the Development of Asthma in Children. Children 2024, 11, 581. [Google Scholar] [CrossRef]
  15. Adam-Bonci, T.-I.; Cherecheș-Panța, P.; Bonci, E.-A.; Man, S.C.; Cutaș-Benedec, A.; Drugan, T.; Pop, R.M.; Irimie, A. Suboptimal Serum 25-Hydroxy-Vitamin D Is Associated with a History of Recent Disease Exacerbation in Pediatric Patients with Bronchial Asthma or Asthma-Suggestive Recurrent Wheezing. Int. J. Environ. Res. Public Health 2020, 17, 6545. [Google Scholar] [CrossRef]
  16. Wu, Z.; McGoogan, J.M. Characteristics of and important lessons from the coronavirus disease 2019 outbreak in China. JAMA 2020, 323, 1239–1242. [Google Scholar] [CrossRef]
  17. Cheung, K.S.; Hung, I.F.; Chan, P.P.; Lung, K.C.; Tso, E.; Liu, R. Gastrointestinal manifestations of SARS-CoV-2 infection and virus load in fecal samples from the HongKong cohert and systematic review and metanalysis. Gastroeneterology 2020, 1, 81–95. [Google Scholar] [CrossRef]
  18. Diorio, C.; Henrickson, S.E.; Vella, L.A.; McNerney, K.O.; Chase, J.; Burudpakdee, C.; Lee, J.H.; Jasen, C.; Balamuth, F.; Barrett, D.M.; et al. Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2. J. Clin. Investig. 2020, 11, 5967–5975. [Google Scholar] [CrossRef]
  19. Kouris, E.C.; Mirea, S.I.; Covaci, S.; Luminos, M.L.; Miron, V.D. Unraveling Dysgeusia in SARS-CoV-2 Infection: Clinical and Laboratory Insights from Hospitalized COVID-19 Patients in Romania. Pathogens 2025, 14, 300. [Google Scholar] [CrossRef]
  20. Miron, V.D.; Raianu, R.-O.; Filimon, C.; Craiu, M. Clinical Differences between SARS-CoV-2 and RSV Infections in Infants: Findings from a Case–Control Study. Viruses 2024, 16, 63. [Google Scholar] [CrossRef]
  21. Petrelli, F.; Luciani, A.; Perego, G.; Dognini, G.; Colombelli, P.L.; Ghidini, A. Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies. J Steroid Biochem Mol Biol. 2021, 211, 105883. [Google Scholar] [CrossRef] [PubMed]
  22. Guan, W.J.; Liang, W.H.; Zhao, Y.; Liang, H.R.; Chen, Z.S.; Li, Y.M.; Liu, X.Q.; Chen, R.C.; Tang, C.L.; Wang, T.; et al. Comorbidity and its impact on 1590 patients with COVID-19 in China: A nationwide analysis. Eur. Respir. J. 2020, 55, 2000547. [Google Scholar] [CrossRef] [PubMed]
  23. Chhiba, K.D.; Patel, G.B.; Vu, T.H.T.; Chen, M.M.; Guo, A.; Kudlaty, E.; Mai, Q.; Yeh, C.; Muhammad, L.N.; Harris, K.E.; et al. Prevalence and characterization of asthma in hospitalized and nonhospitalized patients with COVID-19. J. Allergy Clin. Immunol. 2020, 146, 307–314.e4. [Google Scholar] [CrossRef]
  24. Radujkovic, A.; Hippchen, T.; Tiwari-Heckler, S.; Dreher, S.; Boxberger, M.; Merle, U. Vitamin D Deficiency and Outcome of COVID-19 Patients. Nutrients 2020, 12, 2757. [Google Scholar] [CrossRef] [PubMed]
  25. Alvi, S.; Syed, J.G.; Nusrat, B.; Abbas Razvi, S.K.; Shah, Z.Z.; Shafaat Khan, Y.; Danish Khan, M.; Ali Khan, M. Frequency of Vitamin D Deficiency in Patients of Asthma. Cureus 2021, 13, e14828. [Google Scholar] [CrossRef]
  26. Islam, M.B.; Chowdhury, U.N.; Nashiry, M.A.; Moni, M.A. Severity of COVID-19 patients with coexistence of asthma and vitamin D deficiency. Inform. Med. Unlocked 2022, 34, 101116. [Google Scholar] [CrossRef]
  27. Global Strategy for Asthma Management and Prevention GINA. 2023. Available online: https://ginasthma.org/2023-gina-main-report/ (accessed on 1 November 2024).
  28. Enciu, B.G.; Tănase, A.A.; Drăgănescu, A.C.; Aramă, V.; Pițigoi, D.; Crăciun, M.-D. The COVID-19 Pandemic in Romania: A Comparative Description with Its Border Countries. Healthcare 2022, 10, 1223. [Google Scholar] [CrossRef]
  29. Barsoum, Z. Pediatric Asthma & Coronavirus (COVID-19)-Clinical Presentation in an Asthmatic Child—Case Report. SN Compr. Clin. Med. 2020, 2, 700–702. [Google Scholar]
  30. Kara, A.A.; Böncüoğlu, E.; Kıymet, E.; Arıkan, K.Ö.; Şahinkaya, Ş.; Düzgöl, M.; Cem, E.; Çelebi, M.; Ağın, H.; Bayram, S.N.; et al. Evaluation of predictors of severe-moderate COVID-19 infections at children: A review of 292 children. J. Med. Virol. 2021, 93, 6634–6640. [Google Scholar] [CrossRef]
  31. Bailey, L.C.; Razzaghi, H.; Burrows, E.K.; Bunnell, H.T.; Camacho, P.E.F.; Christakis, D.A.; Eckrich, D.; Kitzmiller, M.; Lin, S.M.; Magnusen, B.C.; et al. Assessment of 135 794 Pediatric Patients Tested for Severe Acute Respiratory Syndrome Coronavirus 2 across the United States. JAMA Pediatr. 2021, 175, 176–184. [Google Scholar] [CrossRef]
  32. Forno, E.; Bacharier, L.B.; Phipatanakul, W.; Guilbert, T.W.; Cabana, M.D.; Ross, K.; Covar, R.; E Gern, J.; Rosser, F.J.; Blatter, J.; et al. Effect of vitamin D3 supplementation on severe asthma exacerbations in children with asthma and low vitamin D levels: The VDKA randomized clinical trial. JAMA 2020, 324, 752–760. [Google Scholar] [CrossRef]
  33. Thakur, C.; Kumar, J.; Kumar, P.; Goyal, J.P.; Singh, K.; Gupta, A. Vitamin-D supplementation as an adjunct to standard treatment of asthma in children: A randomized controlled trial (ViDASTA Trial). Pediatr. Pulmonol. 2021, 56, 1427–1433. [Google Scholar] [CrossRef] [PubMed]
  34. Li, J.; Ye, L.; She, J.; Song, Y.; Melani, A.S. Clinical differences between early-and late-oset asthma: A population-bases cross-sectional study. Can. Respor. J. 2021, 2021, 8886520. [Google Scholar]
  35. Liu, Q.H.; Kan, X.; Wang, Y.B.; Liu, K.-X.; Zeng, D.; Domagala-Kulawik, J. Differences in the clinical characteristics of early- and late-onset asthma in elderly patients. BioMed Res. Int. 2020, 2020, 2940296. [Google Scholar] [CrossRef]
  36. Fedora, K.; Setyoningrum, R.A.; Aina, Q.; Rosyidah, L.N.; Ni’mah, N.L.; Titiharja, F.F. Vitamin D supplementation decrease asthma exacerbations in children: A systematic review and meta-analysis of randomized controlled trials. Ann. Med. 2024, 56, 2400313. [Google Scholar] [CrossRef] [PubMed]
  37. Durá-Travé, T.; Gallinas-Victoriano, F. COVID-19 in Children and Vitamin D. Int. J. Mol. Sci. 2024, 25, 12205. [Google Scholar] [CrossRef] [PubMed]
  38. Koivisto, O.; Hanel, A.; Carlberg, C. Key vitamin D target genes with function s in the mmune system. Nutrients 2020, 12, 1140. [Google Scholar] [CrossRef]
  39. Bilezikian, J.P.; Bikle, D.; Hewison, M.; Lazaretti-Castro, M.; Formenti, A.M.; Gupta, A.; Madhavan, M.V.; Nair, N.; Babalyan, V.; Hutchings, N.; et al. Mechanisms in endocrinology: Vitamn D and COVID-19. Eur. J. Endocrinol. 2020, 183, R133–R147. [Google Scholar] [CrossRef]
  40. Radu, I.A.; Ognean, M.L.; Ștef, L.; Giurgiu, D.I.; Cucerea, M.; Gheonea, C. Vitamin D: What We Know and What We Still Do Not Know About Vitamin D in Preterm Infants—A Literature Review. Children 2025, 12, 392. [Google Scholar] [CrossRef]
  41. Rhodes, J.M.; Subramanian, S.; Laird, E.; Griffin, G.; Kenny, R.A. Perspective: Vitamin D deficiency and COVID-19 severity—Plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis. J. Intern. Med. 2021, 289, 97–115. [Google Scholar] [CrossRef]
  42. Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506. [Google Scholar] [CrossRef]
  43. Sun, D.; Li, H.; Lu, X.-X.; Xiao, H.; Ren, J.; Zhang, F.-R.; Liu, Z.-S. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: A single center’s observational study. World J. Pediatr. 2020, 16, 251–259. [Google Scholar] [CrossRef] [PubMed]
  44. Kalia, V.; Studzinski, G.P.; Sarkar, S. Role of vitamin D in regulating COVID-19 severity—An immunological perspective. J. Leukoc. Biol. 2021, 110, 809–819. [Google Scholar] [CrossRef]
  45. Feketea, G.; Vlacha, V.; Bocsan, I.C.; Vassilopoulou, E.; Stanciu, L.A.; Zdrenghea, M. Vitamin D in Corona Virus Disease 2019 (COVID-19) Related Multisystem Inflammatory Syndrome in Children (MIS-C). Front. Immunol. 2021, 12, 648546. [Google Scholar] [CrossRef] [PubMed]
  46. Yılmaz, K.; Şen, V. Is Vitamin D Deficiency a Risk Factor for COVID-19 in Children? Pediatr. Pulmonol. 2020, 55, 3595–3601. [Google Scholar] [CrossRef]
  47. Miraglia del Giudice, M.; Indolfi, C.; Dinardo, G.; Decimo, F.; Decimo, A.; Klain, A. Vitamin D status can affect COVID-19 outcomes also in pediatric population. PharmaNutrition 2022, 22, 100319. [Google Scholar] [CrossRef]
  48. Kourosh, A.; Luna, R.A.; Balderas, M.; Nance, C.; Anagnostou, A.; Devaraj, S.; Davis, C.M. Fecal Microbiome Signatures Are Different in Food-Allergic Children Compared to Siblings and Healthy Children. Pediatr. Allergy Immunol. 2018, 29, 545–554. [Google Scholar] [CrossRef] [PubMed]
  49. Tabassum, A.; Ali, A.; Zahedi, F.D.; Ismail, N.A.S. Immunomodulatory Role of Vitamin D on Gut Microbiome in Children. Biomedicines 2023, 11, 1441. [Google Scholar] [CrossRef]
  50. Huang, J.; Zhou, X.; Dong, B.; Tan, H.; Li, Q.; Zhang, J.; Su, H.; Sun, X. Obesity-related asthma and its relationship with microbiota. Front. Cell Infect. Microbiol. 2024, 13, 1303899. [Google Scholar] [CrossRef]
  51. Krasowski, R.; Kamińska, K.; Głodek, K.; Ostrowska, J.; Zajda, K.; Pawliczak, R.; Kleniewska, P. The therapeutic potential of vitamin D supplementation in asthma. Pharmacol. Rep. 2025. [Google Scholar] [CrossRef]
  52. Chen, Y.; Gu, S.; Chen, Y.; Lu, H.; Shi, D.; Guo, J.; Wu, W.R.; Yang, Y.; Li, Y.; Xu, K.J.; et al. Six-month follow-up of gut microbiota richness in patients with COVID-19. Gut 2022, 71, 222–225. [Google Scholar] [CrossRef] [PubMed]
  53. Lin, R.; Xiao, M.; Cao, S.; Sun, Y.; Zhao, L.; Mao, X.; Chen, P.; Tong, X.; Ou, Z.; Zhu, H.; et al. Distinct gut microbiota and health outcomes in asymptomatic infection, viral nucleic acid test re-positive, and convalescent COVID-19 cases. mLife 2022, 1, 183–197. [Google Scholar] [CrossRef] [PubMed]
  54. Nasiri Kalmarzi, R.; Zamani, A.; Fathallahpour, A.; Ghaderi, E.; Rahehagh, R.; Kooti, W. The relationship between serum levels of vitamin D with asthma and its symptom severity: A case-control study. Allergol. Immunopathol. 2016, 44, 547–555. [Google Scholar] [CrossRef] [PubMed]
  55. Alyasin, S.; Momen, T.; Kashef, S.; Alipour, A.; Amin, R. The relationship between serum 25 hydroxy vitamin D levels and asthma in children. Allergy Asthma Immunol. Res. 2011, 3, 251–255. [Google Scholar] [CrossRef]
  56. Wang, M.; Liu, M.; Wang, C.; Xiao, Y.; An, T.; Zou, M.; Cheng, G. Association between vitamin D status and asthma control: A meta-analysis of randomized trials. Respir. Med. 2019, 150, 85–94. [Google Scholar] [CrossRef]
  57. Ehlayel, M.; Bener, A.; Sabbah, A. Is high prevalence of vitamin D deficiency evidence for asthma and allergy risks? Eur. Ann. Allergy Clin. Immunol. 2011, 43, 81–88. [Google Scholar]
  58. El Aaty, H.E.A.; El Aziz, A.A.A.; El Habashy, M.M.; Saafan, M.A.; El Hamed, S.A.A. Assessment of serum vitamin D in patients with bronchial asthma. Egypt. J. Chest Dis. Tuberc. 2015, 64, 1–5. [Google Scholar] [CrossRef]
  59. Jung, J.Y.; Kim, Y.S.; Kim, S.K.; Kim, H.Y.; Oh, Y.M.; Lee, S.M.; Seo, J.B.; KOLD Study. Relationship of vitamin D status with lung function and exercise capacity in COPD. Respirology 2015, 20, 782–789. [Google Scholar] [CrossRef]
  60. Sansone, F.; Di Filippo, P.; Russo, D.; Sgrazzutti, L.; Di Pillo, S.; Chiarelli, F.; Attanasi, M. Lung functionassessment in children with Long-Covid syndrome. Pediatr. Pulmonol. 2024, 59, 472–481. [Google Scholar] [CrossRef]
  61. Barreto, M.; Evangelisti, M.; Montesano, M.; Martella, S.; Villa, M.P. Pulmonary Function Testing in Asthmatic Children. Tests to Assess Outpatients During the COVID-19 Pandemic. Front. Pediatr. 2020, 8, 571112. [Google Scholar] [CrossRef]
  62. Torres-Castro, R.; Vasconcello-Castillo, L.; Alsina-Restoy, X.; Solis-Navarro, L.; Burgos, F.; Puppo, H.; Vilaró, J. Respiratory function in patients post-infection by COVID-19: A systematic review and meta-analysis. Pulmonology 2021, 27, 328–337. [Google Scholar] [CrossRef] [PubMed]
  63. Samaha, H.M.S.; Elsaid, A.R.; NasrEldin, E. Vitamin D and markers of airway inflammation in asthma. Egypt. J. Chest Dis. Tuberc. 2015, 64, 779–783. [Google Scholar] [CrossRef]
  64. Sung, M.; Jee, H.M.; Kim, J.H.; Ha, E.K.; Shin, Y.H.; Kim, J.H.; Lim, D.H.; Han, M.Y. Serum vitamin D level mitigates fractional exhaled nitric oxide linked to bisphenol-A in school-aged children. Eur. Rev. Med. Pharmacol. Sci. 2022, 26, 1640–1647. [Google Scholar]
  65. Kaur, N.; Kumar, V.; Singh, J.; Jain, H.; Paras, P.; Kaur, N.; Sareen, A.K. Assessment of the Relation Between Asthma Severity and Serum Vitamin D Levels: A Cross-Sectional Study. Cureus 2023, 15, e46826. [Google Scholar] [CrossRef] [PubMed]
  66. Khan, A.M.; Khan, S.; Saleem, D.M.; Khan, F.; Abbas, U.; Siraj, S. Serum vitamin D status in children of bronchial asthma. Rawal Med. J. 2020, 45, 607–610. [Google Scholar]
  67. Sharif, A.; Haddad Kashani, H.; Sharif, M.R. Association of 25-hydroxy vitamin D with asthma and its severity in children: A case-control study. Clin. Mol. Allergy 2020, 18, 7. [Google Scholar] [CrossRef]
  68. Aziz, D.A.; Abbas, A.; Viquar, W.; Munawar Hussain, A. Association of vitamin D levels and asthma exacerbations in children and adolescents: Experience from a tertiary care center. Monaldi Arch. Chest. Dis. 2023, 93, 2230. [Google Scholar] [CrossRef]
  69. Raju, A.; Luthra, G.; Shahbaz, M.; Almatooq, H.; Foucambert, P.; Esbrand, F.D.; Zafar, S.; Panthangi, V.; Kurupp, A.R.C.; Khan, S. Role of Vitamin D Deficiency in Increased Susceptibility to Respiratory Infections Among Children: A Systematic Review. Cureus 2022, 14, e29205. [Google Scholar] [CrossRef] [PubMed]
  70. Crowe, F.L.; Mughal, M.Z.; Maroof, Z.; Berry, J.; Kaleem, M.; Abburu, S.; Walraven, G.; Masher, M.I.; Chandramohan, D.; Manaseki-Holland, S. Vitamin D for growth and rickets in stunted children: A randomized trial. Pediatrics 2021, 147, e20200815. [Google Scholar] [CrossRef]
  71. Griffin, G.; Hewison, M.; Hopkin, J.; Kenny, R.A.; Quinton, R.; Rhodes, J.; Subramanian, S.; Thickett, D. Preventing vitamin D deficiency during the COVID-19 pandemic: UK definitions of vitamin D sufficiency and recommended supplement dose are set too low. Clin. Med. 2021, 21, e48–e51. [Google Scholar] [CrossRef]
  72. Griffin, G.; Hewison, M.; Hopkin, J.; Kenny, R.; Quinton, R.; Rhodes, J.; Subramanian, S.; Thickett, D. Vitamin D and COVID-19: Evidence and recommendations for supplementation. R. Soc. Open Sci. 2020, 7, 201912. [Google Scholar] [CrossRef] [PubMed]
  73. Griffin, G.; Hewison, M.; Hopkin, J.; Kenny, R.A.; Quinton, R.; Rhodes, J.; Subramanian, S.; Thickett, D. Perspective: Vitamin D supplementation prevents rickets and acute respiratory infections when given as daily maintenance but not as intermittent bolus: Implications for COVID-19. Clin. Med. 2021, 21, e144–e149. [Google Scholar] [CrossRef] [PubMed]
  74. Batista, K.S.; Cintra, V.M.; Lucena, P.A.F.; Manhães-De-Castro, R.; E Toscano, A.; Costa, L.P.; Queiroz, M.E.B.S.; de Andrade, S.M.; Guzman-Quevedo, O.; de S Aquino, J. The role of vitamin B12 in viral infections: A comprehensive review of its relationship with the muscle-gut-brain axis and implications for SARS-CoV-2 infection. Nutr. Rev. 2022, 80, 561–578. [Google Scholar] [CrossRef] [PubMed]
Figure 1. The structure of the study group.
Figure 1. The structure of the study group.
Jcm 14 04525 g001
Table 1. Distribution of the study group according to demographic data, allergic and atopic diseases.
Table 1. Distribution of the study group according to demographic data, allergic and atopic diseases.
ParameterCategory145 ChildrenVitamin Dp *
Median Value (ng/mL)
GenderFemales55 (37.90%)270.217
Males90 (62.10%)28
EnvironmentUrban104 (71.72%)270.855
Rural41 (28.28%)28
Age at asthma diagnosis<6 years old64 (44.14%)270.074
6–11 years old74 (51.03%)28.50
12–17 years old7 (4.83%)23
Allergic
rhinitis
Present90 (62.07%)280.626
Absent55 (37.93%)27
Atopic
dermatitis
Present23 (16.08%)270.697
Absent120 (83.92%)28
Allergies regarding foodPresent13 (8.97%)290.898
Absent132 (91.03%)27
PollenPresent27 (18.62%)280.865
Absent118 (81.38%)27
House dustPresent32 (22.07%)240.101
Absent113 (77.93%)28
Animal hairPresent20 (13.79%)25.500.372
Absent125 (86.21%)28
MoldPresent23 (15.86%)240.105
Absent122 (84.14%)28
TobaccoPresent3 (2.07%)250.257
Absent142 (97.93%)27.50
* Mann–Whitney test.
Table 2. Distribution of the study group according to serum vitamin D and different variables.
Table 2. Distribution of the study group according to serum vitamin D and different variables.
ParameterCategory145 ChildrenVitamin Dp
Median Value (ng/mL)
Treatment stepStep 15 (3.45%)280.415 *
Step 288 (60.69%)28
Step 346 (31.72%)25.50
Step 45 (3.45%)45
Step 51 (0.69%)8
FEV1/FVC ratioNormal48 (33.10%)360.004 **
Variable airflow limitation97 (66.90%)26
Exacerbations0/year51 (35.17%)46<0.0005 *,#
1/year56 (38.62%)26
2/year30 (20.69%)21
3/year8 (5.52%)13.50
GINA asthma control levelsWell controlled71 (48.97%)37<0.0005 **,#
Partially controlled74 (51.03%)24
Asthma
Phenotype
Allergic89 (61.38%)280.572 **
Non-allergic56 (38.62%)27
Parents with predisposition to atopyYes34 (23.45%)28.500.437 **
No111 (76.55%)27
Acute respiratory infections/COVID-19 diseaseYes93 (64.14%)23<0.0005 **,#
No52 (35.86%)46.50
* Kruskal–Wallis test. ** Mann–Whitney test. # Statistically significant. FEV1—Forced Expiratory Volume in the First Second. FVC—Forced Vital Capacity.
Table 3. Associations between pulmonary function tests parameters and serum vitamin D for the study group.
Table 3. Associations between pulmonary function tests parameters and serum vitamin D for the study group.
ParameterVitamin D
COVID-19 (n = 79)Study Group (n = 145)
Correlation Coefficientp *Correlation Coefficientp *
FeNO−0.2490.027−0.476<0.0005 #
FVC0.0460.6900.0320.701
FEV1−0.0070.9480.1130.176
PEF0.0270.811−0.0430.610
FEF25–750.0360.7550.0530.523
FEV1/FVC ratio−0.1900.0940.1050.210
* Spearman’s rank-order correlation. # Statistically significant. FeNO—Fraction of Exhaled Nitric Oxide. FVC—Forced Vital Capacity. FEV1—Forced Expiratory Volume in the First Second. PEF—Peak Expiratory Flow. FEF25–75—Forced Mid Expiratory Flow.
Table 4. Distribution of the study group by the presence of acute respiratory infections and demographic data.
Table 4. Distribution of the study group by the presence of acute respiratory infections and demographic data.
ParameterCategoryAcute Respiratory Infectionsp *
YesNoTotal
93 (64.14%)52 (35.86%)145 (100%)
GenderFemales37 (67.27%)18 (32.73%)55 (100%)0.538
39.78%34.62%
Males56 (62.22%)34 (37.78%)90 (100%)
60.22%65.38%
EnvironmentUrban66 (63.46%)38 (36.54%)104 (100%)0.787
70.97%73.08%
Rural27 (65.85%)14 (34.15%)41 (100%)
29.03%26.92%
Age at asthma
diagnosis
<638 (56.72%)29 (43.28%)67 (100%)0.844
46.91%42.65%
6–1139 (52%)36 (48%)75 (100%)
48.15%52.94%
12–174 (57.14%)3 (42.86%)7 (100%)
4.94%4.41%
* Chi-square test. The values in grey are summed by columns.
Table 5. Distribution of the study group according to acute respiratory infections and different variables.
Table 5. Distribution of the study group according to acute respiratory infections and different variables.
ParameterCategoryAcute Respiratory Infectionsp *
YesNoTotal
93 (64.14%)52 (35.86%)145 (100%)
Exacerbations0/year16 (31.37%)35 (68.63%)51 (100%)0.110
17.2%67.31%
1/year47 (83.93%)9 (16.07%)56 (100%)
50.54%17.31%
2/year23 (76.67%)7 (23.33%)30 (100%)
24.73%13.46%
3/year7 (87.5%)1 (12.5%)8 (100%)
7.53%1.92%
FEV1/FVC ratioNormal17 (35.42%)31 (64.58%)48 (100%)<0.0005 #
18.28%59.62%
Variable airflow
limitation
76 (78.35%)21 (21.65%)97 (100%)
81.72%40.38%
GINA asthma
control levels
Well controlled34 (47.89%)37 (52.11%)71 (100%)<0.0005 #
36.56%71.15%
Partially controlled59 (79.73%)15 (20.27%)74 (100%)
63.44%28.85%
Asthma
phenotype
Allergic51 (57.30%)38 (42.70%)89 (100%)0.031 #
54.84%73.08%
Non-allergic42 (75%)14 (25%)56 (100%)
45.16%26.92%
Parents with predisposition to atopyYes20 (58.82%)14 (41.18%)34 (100%)0.460
21.51%26.92%
No73 (65.77%)38 (34.23%)111 (100%)
78.49%73.08%
* Chi-square test. # Statistically significant. The values in grey are summed by columns. FEV1—Forced Expiratory Volume in the First Second. FVC—Forced Vital Capacity.
Table 6. Serum vitamin D values distribution based on COVID-19 disease presence and the presence of acute respiratory infections.
Table 6. Serum vitamin D values distribution based on COVID-19 disease presence and the presence of acute respiratory infections.
ParameterCategoryCOVID-19p *
YesNoTotal
79 (54.48%)66 (45.52%)145 (100%)
Vitamin DMedian values (ng/mL)2444-<0.0005 *,#
Acute
respiratory
infections
Yes79 (84.95%)14 (15.05%)93 (100%)<0.0005 **,#
100%21.21%
No0 (0%)52 (100%)52 (100%)
0%78.79%
* Mann–Whitney test. ** Chi-square test. # Statistically significant. The values in grey are summed by columns.
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Abdul-Razzak, J.; Ionescu, M.; Diaconu, R.; Popescu, A.D.; Niculescu, E.C.; Petrescu, I.O.; Singer, C.E.; Radu, L.; Anghelina, L.; Gheonea, C. Effect of COVID-19 Disease on Serum Vitamin D Status in Children with Asthma—A Retrospective Study. J. Clin. Med. 2025, 14, 4525. https://doi.org/10.3390/jcm14134525

AMA Style

Abdul-Razzak J, Ionescu M, Diaconu R, Popescu AD, Niculescu EC, Petrescu IO, Singer CE, Radu L, Anghelina L, Gheonea C. Effect of COVID-19 Disease on Serum Vitamin D Status in Children with Asthma—A Retrospective Study. Journal of Clinical Medicine. 2025; 14(13):4525. https://doi.org/10.3390/jcm14134525

Chicago/Turabian Style

Abdul-Razzak, Jaqueline, Mihaela Ionescu, Radu Diaconu, Alexandru Dan Popescu, Elena Carmen Niculescu, Ileana Octavia Petrescu, Cristina Elena Singer, Lucrețiu Radu, Liliana Anghelina, and Cristian Gheonea. 2025. "Effect of COVID-19 Disease on Serum Vitamin D Status in Children with Asthma—A Retrospective Study" Journal of Clinical Medicine 14, no. 13: 4525. https://doi.org/10.3390/jcm14134525

APA Style

Abdul-Razzak, J., Ionescu, M., Diaconu, R., Popescu, A. D., Niculescu, E. C., Petrescu, I. O., Singer, C. E., Radu, L., Anghelina, L., & Gheonea, C. (2025). Effect of COVID-19 Disease on Serum Vitamin D Status in Children with Asthma—A Retrospective Study. Journal of Clinical Medicine, 14(13), 4525. https://doi.org/10.3390/jcm14134525

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