key: cord-1050359-l432jsvd authors: Chai, Shaoqing; Li, Yan; Li, Xuemei; Tan, Jie; Abdelrahim, Mohamed E. A.; Xu, Xiaoxiao title: Effect of age of COVID‐19 inpatient on the severity of the disease: A meta‐analysis date: 2021-08-01 journal: Int J Clin Pract DOI: 10.1111/ijcp.14640 sha: a689be9b8d22464ffe59ffa831b8248ee684e16d doc_id: 1050359 cord_uid: l432jsvd BACKGROUND: Clinical symptoms of adults and paediatric inpatients with COVID‐19 disease are conflicting. This meta‐analysis was conducted to assess the effect of age of COVID‐19 inpatient on the severity of the disease. METHODS: A systematic literature search up to January 2021 was performed and 5 studies included 910 inpatients with COVID‐19 disease at the baseline of the study; 773 of them were adult inpatients, and 137 of them were paediatric inpatients. They reported a comparison between adults and children with COVID‐19 in the level of symptomatic severity, clinical features, computed tomography (CT) results and laboratory results. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated assessing the effect of age of COVID‐19 inpatient on the severity of the disease using the dichotomous method with a random or fixed‐effect model. RESULTS: Adults with COVID‐19 disease had significantly lower number of mild cases (OR, 0.18; 95% CI, 0.04‐0.77, P = .02); higher number severe cases (OR, 4.90; 95% CI, 2.03‐11.83, P < .001); higher number of cases with fever (OR, 4.14; 95% CI, 2.31‐7.43, P < .001); and higher number of cases with CT positive COVID‐19 disease (OR, 2.04; 95% CI, 1.17‐3.55, P = .001) compared with children. However, no significant difference was found between adults and children in number of cases with shortness of breath (OR, 1.44; 95% CI, 0.41‐5.04, P = .57); dry cough (OR, 1.77; 95% CI, 0.64‐4.93, P = .27); leukopenia (OR, 0.89; 95% CI, 0.47‐1.66, P = .71); lymphopenia (OR, 0.96; 95% CI, 0.49‐1.88, P = .91); high platelets (OR, 0.41; 95% CI, 0.17‐1.02, P = .05); and high D‐dimer (OR, 0.82; 95% CI, 0.43‐1.56, P = .54). CONCLUSIONS: Adults with COVID‐19 disease have a much higher level of symptomatic severity, fever and CT‐positive COVID‐19 disease than children. However, as shown in our results, the laboratory data were similar in both groups. the demographics, clinical characters, laboratory indicators and computed tomography imaging characteristics of the adult with COVID-19 disease. 9, 10 But because of the inadequate number of children with COVID-19 disease, a few meta-analysis studies concentrated on children with COVID-19 disease. [11] [12] [13] Though, they did not compare their children's results to adults because of the lack of comparative studies. Further compassion between adults and children on the clinical features of COVID-19 disease is urgently needed to help in the clinical diagnosis and management of the subjects, of different ages, infected with SARS-CoV-2. This meta-analysis aimed to assess the effect of age of COVID-19 inpatient on the severity of the disease. The study performed here followed the meta-analysis of studies in the epidemiology statement, 14 which was conducted following an established protocol. Studies included were observation studies assessing the effect of age of COVID-19 inpatient on the severity of the disease. Only human studies in any language were considered. Inclusion was not limited by study size. Publications excluded were review articles and commentary and studies that did not deliver a measure of an association. Figure 1 shows a schematic diagram of the study procedure. The articles were integrated into the meta-analysis when the following inclusion criteria were met: 1. The study was observational. 2. The target population was subjects with COVID-19 disease. 3. The intervention programme was based on the effect of age of COVID-19 inpatient on the severity of the disease. 4 . The study included a comparison between adults and children. A protocol of search strategies was prepared according to the PICOS principle, 15 Table 1 . All identified studies were pooled in an EndNote file, duplicates were omitted and the title and abstracts were reviewed to exclude studies that did not report an association of effect of age of COVID-19 inpatient on the severity of the disease. Data were abridged on the following bases; study-related and subject-related characteristics onto a standardised form; last name of the primary author, period of study, year of publication, country, region of the studies and study design; population type, the total number of subjects, demographic data, clinical and treatment characteristics, categories, qualitative and quantitative method of evaluation, information source, outcome evaluation and statistical analysis. 17 When there were different data from one study based on the assessment of the effect of age of COVID-19 inpatient on the severity of the disease, we extracted them independently. The risk of bias in these studies; individual studies were evaluated using the two authors independently assessed the methodological quality of the selected studies. The "risk of bias tool" from the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 was used to assess methodological quality. 18 In terms of the assessment criteria, each study was rated and assigned to one of the following three risks of bias: low: if all quality criteria were met, the study was considered to have a low risk of bias; unclear: if one or more of the quality criteria were partially met or unclear, the study was considered to have a moderate risk of bias; or high: if one or more of the criteria were not met, or not included, the study was considered to have a high risk of bias. Any inconsistencies were addressed by a reevaluation of the original article. • Clinical symptoms of adults and paediatric inpatients with COVID-19 disease are conflicting. • This meta-analysis was conducted to assess the effect of age of COVID-19 inpatient on the severity of the disease. • Adults with COVID-19 disease have a much higher level of symptomatic severity, fever and CT-positive COVID-19 disease than children. • However, as shown in our results, the laboratory data were similar in both groups. The main outcome focused on the assessment of the effect of age of COVID-19 inpatient on the severity of the disease, we extracted them independently to form a summary. Sensitivity analyses were limited only to studies reporting the level of symptomatic severity, clinical features, computerised tomography results and laboratory results of children with COVID-19 disease compared with adults; we extracted them independently. For subcategory and sensitivity analysis, we used comparisons between adults and children. The dichotomous method with a random-effect model or fixedeffect was used to calculate the odds ratio (OR) and 95% CI. The I 2 index was calculated; the I 2 index is between 0% and 100%. Values of about 0%, 25%, 50% and 75% indicate no, low, moderate and high heterogeneity, respectively. 19 When I 2 was higher than 50%, A stratified analysis of studies that did and did not adjust for the effect of ethnicity and gender on the results was not performed because no studies reported or adjusted for this factor. Based on the visual inspection of the funnel plot as well as on quantitative measurement using the Egger regression test, there was no evidence of publication bias (P = .87). However, most of the included studies were assessed to be of a low methodological quality. All studies did not have selective reporting bias, and no articles had incomplete outcome data and selective reporting. This meta-analysis study based on 5 studies included 910 inpatients with COVID-19 disease at the baseline of the study; 773 of them were adult inpatients, and 137 of them were paediatric inpatients. [20] [21] [22] [23] [24] The extent of poor outcome in the symptomatic severity, fever and CT positive in adults with COVID-19 disease was higher than that in children and this was statistically significant in all populations studied. 20 disease. 30 Another explanation was based on the risk factors and the co-morbid conditions that mostly occur in adults compared with children. A meta-analysis study has shown that smoking, which mostly occurs in adults, could stimulate the development of COVID-19 disease making the smoking subjects suffer more from COVID-19 disease. 31 Also, the co-morbid diseases which occur more in adults than in children could add some reasons why adults are much more susceptible to COVID-19 disease than children. 32, 33 However, still all of these explanations are suggestions. This metaanalysis showed the effect of age of COVID-19 inpatient on the severity of the disease. Yet, further studies are needed to validate these potential relationships and explain the mechanism of the effect of age of COVID-19 inpatient on the severity of the disease. These studies must comprise larger with more homogeneous samples. Well-conducted studies are needed to assess these factors and the combination of different childhood vaccination, gender, ethnicity and other variants of subjects; since our meta-analysis study could not answer whether different ethnicity and gender are associated with the results. [34] [35] [36] [37] [38] [39] In summary, the data suggest that adults with COVID-19 disease may be at higher risk of the poor level of symptomatic severity, clinical features and computerised tomography results than children. However, the laboratory data were similar in both groups. From the study presented here, we recommend the use of further comparative studies to validate these findings. There may be selection bias in this study since so many of the studies found were excluded from the meta-analysis. However, the studies excluded did not satisfy the inclusion criteria of our meta-analysis. Also, we could not answer whether the results are associated with ethnicity and gender or not. The study designed to assess the effect of age of COVID-19 inpatient on the sever- Adults with COVID-19 disease have a much higher level of symptomatic severity, fever and CT-positive COVID-19 disease than children. However, as shown in our results, the laboratory data were similar in both groups. From the study presented here, we request further comparative studies between adults and children with COVID-19 to validate these findings and find any possible explanation for the insignificant difference in laboratory results. Though, the analysis of outcomes should be done with caution because of the small number of the study found (5 studies) and the low sample size in most of the selected studies (3 studies ≤100 subjects) in our metaanalysis; suggesting the need for more studies to validate these findings or possibly to significantly influences confidence in the effect evaluation. The datasets analysed during this study are available from the corresponding author on reasonable request. Not applicable. The authors declare that they have no competing interests. Conception and design: Xiaoxiao Xu, Mohamed EA Abdelrahim. Administrative support: All authors. Provision of study materials or subjects: All authors. Collection and assembly of data: Shaoqing Chai, Yan Li, Xuemei Li, Jie Tan. Data analysis and interpretation: All authors. Manuscript writing: All authors. Final approval of manuscript: All authors. All authors have read and approved the manuscript. Not required for this study. Not applicable. 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