Abstract
Context:
One of the emerging diseases that has spread in 2019 is COVID-19.Objectives:
The present systematic review (SR) was performed to evaluate the status of laboratory and radiological findings in the age group of children and adolescents with COVID-19.Methods:
In this SR study, three of the research team members conducted searches in SCOPUS, PUBMED, Science Direct, and ISI international sites. The keywords that were searched included children- pediatric- adolescents- coronavirus- COVID-19- Novel coronavirus SARS-CoV-2-epidemiology- diagnostic findings- laboratory findings- CT SCAN- computed tomography- percentage of lymphocyte- alanine aminotransferase- white blood cell count (WBC). The combination of search keywords with AND as well as OR was performed. For analysis, descriptive data reporting was performed using EndNote software.Results:
The analysis of the laboratory and radiology findings of 197 patients of 12 studies included in the SR study showed notable changes in the lung CT scan and laboratory ranges that confirm the COVID-19 infection in these patients.Conclusions:
This systematic review provides information on the laboratory and radiology findings of children and adolescents with COVID-19 for the health care team.Keywords
COVID-19 Coronavirus Pediatric Laboratory Radiologic Systematic Review
1. Context
Children and adolescents have a number of physiological, psychological, and social needs, one of which is their health (1-3). However, their health may be affected by diseases such as cancer (4), cardiovascular disease (5), thalassemia (6, 7), liver disease (8), rickets (8), and orthopedic diseases (9). They may also be exposed to various diseases that threaten their lives, like other age groups (6, 7, 9).
In order to maintain the health of patients, it is essential to diagnose the disease promptly and take appropriate proceedings to treat it (10, 11). For treating a disease, the disease must first be properly diagnosed, and the medical team must have knowledge about its laboratory and radiologic findings (12-14). Many of the diagnostic findings of various diseases can be extracted from reference books or articles and. But in emerging diseases, it is necessary to inform the nurses and the physicians about its diagnostic strategy (15-17).
It is important to pay attention to infectious diseases in children (18). One of the emerging diseases that has spread in 2019 is COVID-19 (19, 20). Nurses and physicians have enough knowledge about the laboratory and radiologic findings of previous infectious diseases, but COVID-19’s laboratory and radiology findings are not fully available due to their emergence (21-23). Children and adolescents also don’t self-report about illness and clinical symptoms for reasons such as lack of awareness, inadequate health literacy, and other factors affecting younger age. For this reason, laboratory and radiological findings are more important (24-26).
2. Objectives
The present SR study was performed to evaluate the status of laboratory and radiological findings in patients with COVID-19 in the age group of children and adolescents worldwide.
3. Methods
3.1. Study Protocol
The study protocol is based on the SR (PRISMA) study protocol (27). Two members of the team performed the search, and in the event of a dispute between the two, the third person searched again, and the conclusion was made in consultation with all members of the research.
3.2. Inclusion Criteria
Inclusion criteria were according to PICO: 1- Population (published articles about COVID-19), Intervention (laboratory and radiological diagnostic procedures in children and adolescents), comparison (alanine aminotransferase, percentage of lymphocytes, WBC, CRP, and CT), outcome (studies on diagnostic findings in COVID-19).
3.3. Exclusion Criteria
1) Articles containing incomplete information; 2) meta-analysis articles; 3) qualitative studies; 4) duplicates; 5) lack of connection with the purpose of the research.
3.4. Search Strategy
Three of the research team searched all articles from 2019 to 2020 at SCOPUS, PUBMED, Science Direct, ISI international sites. The keywords that were searched included children- pediatric- adolescents- coronavirus- COVID-19- Novel coronavirus SARS-CoV-2-epidemiology- diagnostic findings- laboratory findings- CT SCAN- computed tomography- percentage of lymphocyte- alanine aminotransferase- white blood cell count (WBC). The combination of search keywords with AND as well as OR was performed (Table 1).
Characteristics of Studies Entered Into the SRa
Author | Age | Country | Number | CT | CRP | WBC | Percentage of Lymphocyte | Alanine Aminotransferase | |
---|---|---|---|---|---|---|---|---|---|
1 | Xia et al. (28) | Pediatric | China | 20 | chest CT: Chest CT with abnormality = 20% (4); pulmonary lesions (bilateral) = 50% (10); pulmonary lesions (unilateral) = 30% (6); pulmonary lesions: Null = 4 (20); unilateral = 6 (30); bilateral = 10 (50) | ≤ 3 = 13 (65); > 3= 7 (35) | < 5.50 = 4 (20) (decreased); 5.50 ‐ 12.20 = 14 (70) (normal); > 12.20 = 2 (10) (increased); the unit of measurement was WBC × 109/L. | < 45 = 7 (35) (decreased); 45 - 65 = 10 (50); > 65 = 3 (15) (increased) | ≤ 40 = 15 (75); > 40 = 5 (25) (increased) (ALT, IU/L) |
2 | Zheng et al. (29) | 25 | In 8 (32) of the patients, it was normal, in 5 (20) of the patients, there was unilateral involvement and in 12 (48) of the patients, there was bilateral involvement. | 14.5 (0.93 - 25.04) (mg/L) | 6.2 (4.30 - 9.85) (109/L) | 2.19 (1.15 - 3.31) (109/L) | 12 (10 - 13) (U/L) | ||
3 | Chen et al. (30) | Pediatric | China | 12 | infectious disease | 11.51 (2.39) (mg/L) | 6.33 (1.78), cells, 109/L | ||
4 | Chen et al. | < 18 years | China | 31 | The findings of the primary Chest-Xray and CT was ground-glass, high-density shadows or hazy patchy shadows that generally were in the subpleural field. | > 8 mg/L = 4 (12.9) | < 5 × 109/L = 12 (38.7); > 12 × 109/L = 1 (3.2) | < 1.1 × 109/L = 0 (0); > 3.2× 109/L = 8 (25.8) | > 45 U/L = 2 (6.5) |
5 | Cai et al. | children | China | 10 | unilateral patchy infiltrate = 4 (40) | 7.5 mg/L | 7.35 × 109/L | Unilateral patchy infiltrate = 4 (40) | - |
6 | Ma et al. (31) | children | China | 50 | Overall, patients with CT rates were 43 (86), local patchy shadowing rate of 16 (32), ground-glass opacity rate of 29 (58), bilateral patchy shadowing rate of 9 (18) and interstitial rate abnormalities were 3 (6). | - | In the evaluation of patients, 8 (16) had thrombocytopenia and 10 (20) had lymphopenia. Also, 4 (8) patients had lymphocytosis, and 8 (16) had thrombocytosis. | - | - |
7 | Qui et al. (32) | Children | China | 36 | Infectious disease | 5 (2) had a level of less than 8 mg/L | Unit of measurement: (4 - 10 × 109 cells per L); WBC Rate: 6 1 (2 ·1) | Unit of measurement: 1 1 - 3 = 2 × 109 cells per L); Lymphocytes Rate: 2 ·4 (0·8); | 21 (14) have a level less than 40 U/L |
8 | Du et al. (33) | Children | China | 14 | Infectious disease | Unit of measurement: 0.068 to 8.2 mg/L; CRP rate: 9.05 ± 15.81 | Unit of measurement: 4 - 10 × 109/L; WBC rate:5.93 ± 2.52 | Unit of measurement: 0.8 - 4 ×109/L; lymphocytes rate: 3.68 ± 2.04 | - |
9 | Sun et al. (34) | Pediatric | China | 8 | Of the 8 children studied, 6 were children with bilateral pneumonia. Also, 2 of them had unilateral pneumonia. Further examination of these CTs showed that 6 of them had ground-glass opacity, 7 patients had multiple patch-like shadows, and one had pleural effusion. | In 8 patients studied were: 6.48 - 57.9 - 103 - 0.75 - 27.02 - 1 - 9.9 - 0.5. Unit of measurement: 0 - 3 mg /L | - | In patients under study were: 0.69 - 1.96 - 2.7 - 6.41 - 3.6 - 4.04 - 1.7 - 2.8; Unit of measurement: 1.15 - 4 × 109/L | In patients under study were: 58 - 6 6 - 36 - 100 - 55 - 9 - 16 - 8; Unit of measurement: 15 - 46 U/L |
10 | Liu et al. (2020) (35) | children | China | 4 | The result of CT one was normal, one with single consolidation, one with single pure GGO, and one in multiple consolidation. | In 3 patients, it was normal, and in one, it was Increased. | In 3 patients, it was normal, and in one, it was decreased. | Lymphocyte count was increased in 2 patients and normal in two patients. Increased lymphocyte ratio in 2 patients, normal in one patient and in one patient, was deceased. | - |
11 | Li et al. (35) | children | China | 5 | Patchy ground-glass opacities = 60% (3); Normal = 2 (40) | It was evaluated in 5 patients and was equal: 9.4, 0.6, 0.2, 0,7, 0.9; CRP at presentation, mg/L (normal reference values 0 - 3) | WBC was evaluated in 5 patients and were:9.2, 14.8, 15, 6.6, and 5.3. The unit of measurement was WBC × 109/L (normal reference values 4.5 - 11) | - | - |
12 | Liu et al. (27) | Children | China | 6 | In 4 patients, there was bilateral lung involvement. In one patient, the lung was healthy and in one patient NA. | - | - | - | - |
3.5. Data Extraction
The checklist included demographic data of extracted articles and information about Alanine aminotransferase, percentage of lymphocytes, WBC, CRP, and CT (Figure 1).
Flowcharts for SR
3.6. Statistical Analysis
Descriptive reporting was performed using EndNote software.
4. Results
In the initial search, 197 articles were extracted, of which 88 were eliminated in the first step, evaluation of the title and abstract of the article. Also, 84 articles overlapped in the search results, and 13 articles did not meet the inclusion criteria. Finally, 12 articles entered the SR phase (Figure 1). According to the findings, 12 articles were extracted, of which 8 articles were related to the original articles, and 4 articles were related to the articles of case series. Also, COVID-19 disrupts the laboratory range of WBC and other variables in the study, and these changes confirm infection in these patients.
5. Discussion
This study is the first SR study in the world to evaluate the laboratory and radiologic findings of COVID-19 in children and adolescents. According to the findings, this infection in these age groups creates changes in their CT, which confirmed the lung infection of these patients. Studies in the adults with COVID-19 also demonstrates these changes, as shown in the study of Ai et al. (36). In the study of Bernheim et al. (37) infection caused by COVID-19 leads to changes in the lung CT of these patients and is consistent with the results of this study.
In the studies included in this SR study, there is an increase in the level of CRP in patients with COVID-19, which is consistent with the results of Yang et al. (38), and Li et al. (39) studies in the adults with COVID-19 with an increase in CRP. Other changes in laboratory variables such as alanine aminotransferase, percentage of lymphocytes, and WBC are the same as the other studies in this area in other age groups (40-42).
One of the limitations of this study is the variation in laboratory units that did not allow the meta-analysis to provide more comprehensive data. Another limitation of this study is the small sample size in the studies. It should be noted that in this study only articles published in English were examined, so it is suggested to do an SR study on the Chinese-language articles given the fact that the epicenter of COVID-19 was in China.
6. Conclusions
This SR provides information on the laboratory and radiologic findings of children and adolescents with COVID-19 for the health care team.
References
-
1.
Sadeghi N. Effect of Drawing Distraction on Children's Preoperative Anxiety: A Clinical Trail. Journal of Mazandaran University of Medical Sciences. 2019;29(175):86-97.
-
2.
Mehrdadi A, Sadeghian S, Direkvand-Moghadam A, Hashemian A. Factors affecting happiness: a cross-sectional study in the Iranian youth. Journal of clinical diagnostic research: JCDR. 2016;10(5):VC01. [PubMed ID: 27437333].
-
3.
Mohammadi M, Raiegani V, Akbar A, Jalali R, Ghobadi A, Abbasi P. Prevalence of behavioral disorders in Iranian children. Journal of Mazandaran University of Medical Sciences. 2019;28(169):181-91.
-
4.
Vazifeh MD, Hojjati H, Farhangi H. Effect of Spiritual Care Based on Ghalbe Salim on Anxiety in Adolescent with Cancer. Journal of religion health. 2019.
-
5.
Arvind B, Ramakrishnan S. Rheumatic Fever and Rheumatic Heart Disease in Children. The Indian Journal of Pediatrics. 2020:1-7.
-
6.
Sadeghloo A, Shamsaee P, Hesari E, Akhondzadeh G, Hojjati H. The effect of positive thinking training on the quality of life of parents of adolescent with thalassemia. International journal of adolescent medicine. 2019. [PubMed ID: 31525156].
-
7.
Yolme ABS, Hojjati H, Akhoundzadeh G. The effect of Islamic semanticism on self-reporting and lifestyles of mothers of adolescents with thalassemia. International Journal of Adolescent Medicine Health. 2020;1(ahead-of-print). [PubMed ID: 32031975].
-
8.
Kalvandi G, Honar N, Geramizadeh B, Ataollahi M, Rahmani A, Javaherizadeh H. Serum C-reactive protein in children with liver disease and ascites. Hepatitis monthly. 2016;16(8). [PubMed ID: 27795726].
-
9.
Lethbridge M, Anderson E. Anesthesia for Orthopedic Surgery in Children. A Guide to Pediatric Anesthesia. Germany: Springer; 2020. p. 373-80.
-
10.
Møller AM. Clinical Examination Skills in the Adult Critically Ill Patient. Anesthesia Analgesia. 2020;130(1). e24.
-
11.
Elameer M, Price CI. Neuroimaging Methods for Acute Stroke Diagnosis and Treatment. Stroke Biomarkers. Germany: Springer; 2020. p. 297-333.
-
12.
Carvalho JC, Mestrinho HD, Guillet A, Maltz M. Radiographic Yield for Clinical Caries Diagnosis in Young Adults: Indicators for Radiographic Examination. Caries Research. 2020:1-11. [PubMed ID: 32101874].
-
13.
Lipsky BA, Senneville É, Abbas ZG, Aragón‐Sánchez J, Diggle M, Embil JM, et al. Guidelines on the diagnosis and treatment of foot infection in persons with diabetes (IWGDF 2019 update). Diabetes/Metabolism Research Reviews. 2020;36. e3280. [PubMed Central ID: PMC7154668].
-
14.
Crumley I, Halton J, Greig J, Kahunga L, Mwanga J, Chua A, et al. The impact of computed radiography and teleradiology on patients’ diagnosis and treatment in Mweso, the Democratic Republic of Congo. Plos one. 2020;15(1). e0227773. [PubMed ID: 31940418].
-
15.
Qian G, Yang N, Ding F, Ma AHY, Wang Z, Shen Y, et al. Epidemiologic and Clinical Characteristics of 91 Hospitalized Patients with COVID-19 in Zhejiang, China: A retrospective, multi-centre case series. QJM: An International Journal of Medicine. 2020.
-
16.
Wu JT, Leung K, Bushman M, Kishore N, Niehus R, de Salazar PM, et al. Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China. Nature Medicine. 2020;26(4):506-10. [PubMed ID: 32284616].
-
17.
Jiang F, Deng L, Zhang L, Cai Y, Cheung CW, Xia Z. Review of the clinical characteristics of coronavirus disease 2019 (COVID-19). Journal of General Internal Medicine. 2020:1-5. [PubMed ID: 32133578].
-
18.
Shahramian I, Kalvandi G, Javaherizadeh H, Khalili M, Noori NM, Delaramnasab M, et al. The effects of prebiotic supplementation on weight gain, diarrhoea, constipation, fever and respiratory tract infections in the first year of life. Journal of paediatrics child health. 2018;54(8):875-80. [PubMed ID: 29579345].
-
19.
Fauci AS, Lane HC, Redfield RR. Covid-19—navigating the uncharted. Mass Medical Soc; 2020. Contract No.: 0028-4793.
-
20.
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet respiratory medicine. 2020;8(4):420-2.
-
21.
Chan JF, Yip CC, To KK, Tang TH, Wong SC, Leung K, et al. Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse transcription-PCR assay validated in vitro and with clinical specimens. Journal of Clinical Microbiology. 2020;58(5). [PubMed ID: 32132196].
-
22.
Pérez-Cantero A, Guarro J. Current knowledge on the etiology and epidemiology of Scopulariopsis infections. Medical Mycology. 2020;58(2):145-55. [PubMed ID: 31329937].
-
23.
Wu C, Gardner G, Chang AM. Nursing students’ knowledge and practice of infection control precautions: an educational intervention. Journal of advanced nursing. 2009;65(10):2142-9. [PubMed ID: 20568319].
-
24.
Arvanitis M, Davis MM, Wolf MS. Topical review: Proposing a developmentally informed research agenda for the Study of Health Literacy in Children. Journal of Pediatric Psychology. 2020;45(3):266-70. [PubMed ID: 31693133].
-
25.
Bollweg TM, Okan O. Measuring children’s health literacy: Current approaches and challenges. International Handbook of Health Literacy. 2019:83.
-
26.
Porta G, de Carvalho E, Santos JL, Gama J, Borges CV, Seixas RB, et al. Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes. Jornal de pediatria. 2019;95(4):419-27.
-
27.
Liu W, Zhang Q, Chen J, Xiang R, Song H, Shu S, et al. Detection of Covid-19 in children in early January 2020 in Wuhan, China. New England Journal of Medicine. 2020;382(14):1370-1. [PubMed ID: 32163697].
-
28.
Xia W, Shao J, Guo Y, Peng X, Li Z, Hu D. Clinical and CT features in pediatric patients with COVID‐19 infection: Different points from adults. Pediatric Pulmonology. 2020. [PubMed ID: 32134205].
-
29.
Zheng F, Liao C, Fan Q, Chen H, Zhao X, Xie Z, et al. Clinical characteristics of children with coronavirus disease 2019 in Hubei, China. Current medical science. 2020:1-6.
-
30.
Chen J, Zhang Z, Chen Y, Long Q, Tian W, Deng H, et al. The clinical and immunological features of pediatric COVID-19 patients in China. Genes Diseases. 2020. [PubMed ID: 32363222].
-
31.
Ma H, Hu J, Tian J, Zhou X, Li H, Laws MT, et al. Visualizing the Novel Coronavirus (COVID-19) in Children: What We Learn from Patients at Wuhan Children's Hospital. SRN Electronic Journal. 2020.
-
32.
Qiu H. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. Lancet. 2019;5.
-
33.
Du W, Yu J, Wang H, Zhang X, Zhang S, Li Q, et al. Clinical Characteristics of COVID-19 in Children Compared with Adults Outside of Hubei Province in China. SRN Electronic Journal. 2020.
-
34.
Sun D, Li H, Lu X, Xiao H, Ren J, Zhang F, et al. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center’s observational study. World Journal of Pediatrics. 2020:1-9.
-
35.
Li W, Cui H, Li K, Fang Y, Li S. Chest computed tomography in children with COVID-19 respiratory infection. Pediatric Radiology. 2020:1-4. [PubMed ID: 32163697].
-
36.
Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W, et al. Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology. 2020:200642. [PubMed ID: 32101510].
-
37.
Bernheim A, Mei X, Huang M, Yang Y, Fayad ZA, Zhang N, et al. Chest CT findings in coronavirus disease-19 (COVID-19): relationship to duration of infection. Radiology. 2020:200463. [PubMed ID: 32077789].
-
38.
Yang W, Cao Q, Qin L, Wang X, Cheng Z, Pan A, et al. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): A multi-center study in Wenzhou city, Zhejiang, China. Journal of Infection. 2020. [PubMed ID: 32112884].
-
39.
Li L, Li S, Xu M, Zheng S, Duan Z, Chen Y, et al. The level of plasma C-reactive protein is closely related to the liver injury in patients with COVID-19. medRxiv. 2020.
-
40.
Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel medicine infectious disease. 2020:101623. [PubMed ID: 32179124].
-
41.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet respiratory medicine. 2020.
-
42.
Cao W. Clinical features and laboratory inspection of novel coronavirus pneumonia (COVID-19) in Xiangyang, Hubei. medRxiv. 2020.