{"title":"百日咳体液免疫对学龄儿童 covid-19 病程影响的特殊性","authors":"H. Pavlyshyn, O. Panchenko, K. Kozak","doi":"10.24061/2413-4260.xiii.4.50.2023.7","DOIUrl":null,"url":null,"abstract":"Coronavirus disease remains one of the most serious diseases in the world. The percentage of severe and fatal cases inchildren is lower than in adults. The search for biomarkers of disease severity continues. There is evidence of heterologousimmunity between the causative agent of coronavirus infection and some other infectious agents. Both Bordetella pertussis and SARS-CoV-2 cause damage to the respiratory system. It should be noted that the incubation period and transmission mechanism are similar for these two microorganisms. Pertussis vaccinations are given in childhood.The purpose of the study is to fi nd the charcteristics of the course of COVID-19 in school-aged children depending on thestate of humoral immunity against pertussis toxin, assessing their level of immunoglobulin G against pertussis.Material and methods. 92 pediatric patients aged 6 to 17 years were studied, including 30 children without signs of thedisease in the control group and 62 children with manifestations of laboratory- confi rmed COVID-19. The clinical features of the disease and laboratory indicators (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells, D-dimer) were evaluated, as well as the levels of free salivary cortisol and vitamin D. According to the severity of the disease, 3 groups were formed: the fi rst – 20 children with a mild course of COVID-19, the second – 33 patients with a moderate course of the disease, the third – 9 with a severe course of the disease.All children were tested for immunoglobulin G (Ig G) to pertussis toxin by enzyme- linked immunosorbent assay (VIROTECHB. pertussis PT Ig G ELISA, Rüsselsheim, Germany). The result was considered negative (no increase in the titer of specifi c class G antibodies to pertussis toxin), borderline, and positive (there is an increase in the titer of immunoglobulin G to pertussis toxin). Statistical analysis was performed using the program «Stat Plus» (Shapiro- Wilk test, mean SD (standard deviation) with correct distribution of characteristics; median, upper and lower quartiles with incorrect distribution, Chi-square test, Man-Whitney test, Fisher’s test).The study was conducted in accordance with the rules of patient safety and ethical principles of scientifi c medical researchinvolving human subjects (2000). The permission to conduct this study was given by the Bioethics Commission (Protocol No. 61 of 13.11.2020). The parents (legal representatives) of the patients gave their written consent to the conduct of this study.This study is a fragment of research work «An Integrated Approach to Symptom Control, Long- Term Prognosis in the Context of Comorbid Pathology in the Clinic of Internal Diseases and Family Doctor Practice» (state registration No. 0118U000361).Results. The mean age of the patients was 11.573.82 years. The study groups did not diff er in sex (x2=4.97, p=0.174) andage (p=0.490) composition. The level of humoral immunity against pertussis toxin diff ered signifi cantly between the study groups. A positive and borderline result for the presence of specifi c immunoglobulin G to tetanus toxin was found in 75.86 % of children without signs of disease. At the same time, only 41.51 % of children with COVID-19 manifestations had a positive and borderline result (p=0.005). A positive and borderline result for the presence of specifi c immunoglobulin G to tetanus toxin was seen in 66.67 % of children with mild infection, 33.33 % of patients with moderate disease, and only 12.50 % of patients with severe disease (X2=16.91, P=<0.001).Children with a negative result for immunoglobulin G to pertussis toxin have signifi cantly higher WBC count (1.3-fold), ESR(2.4-fold), D-dimer (3.4-fold), and CRP (1.5-fold) compared to patients with positive and borderline levels of these antibodies.In children with a negative result, there was a 6.25-fold increase in salivary free cortisol (p<0.001) and a 2.0-fold decrease invitamin D levels (p<0.001).Conclusions. In children with COVID-19 manifestations, there was a signifi cantly higher percentage of negative test resultsfor the presence of IgG to pertussis toxin compared to the control group, indicating a lower level of humoral immunity to tetanus in this group of patients. In children with mild disease, there was a signifi cantly higher percentage of positive and borderline test results for the presence of IgG to pertussis toxin (indicating a higher level of humoral immunity against this pathogen) compared to the groups of children with moderate and severe disease. The absence of specifi c immunoglobulins G to pertussis toxin is associated with an increase in the level of pro-infl ammatory markers (leukocyte count, ESR, CRP) and D-dimer, which also indicates a more severe course of COVID-19. Patients who are negative for pertussis toxin antibodies have elevated cortisol levels as a marker of stress and decreased vitamin D levels. Both biologically active substances are involved in the immune response to infectious agents and may serve as additional non-specifi c markers of COVID-19 severity. Therefore, low humoral immunity to pertussis contributes to the increase in COVID-19 severity in childhood.","PeriodicalId":162458,"journal":{"name":"Neonatology, surgery and perinatal medicine","volume":"231 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"PECULIARITIES OF THE COURSE OF COVID-19 IN SCHOOL-AGE CHILDREN AS A FUNCTION OF HUMORAL IMMUNITY AGAINST PERTUSSIS\",\"authors\":\"H. Pavlyshyn, O. Panchenko, K. Kozak\",\"doi\":\"10.24061/2413-4260.xiii.4.50.2023.7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Coronavirus disease remains one of the most serious diseases in the world. The percentage of severe and fatal cases inchildren is lower than in adults. The search for biomarkers of disease severity continues. There is evidence of heterologousimmunity between the causative agent of coronavirus infection and some other infectious agents. Both Bordetella pertussis and SARS-CoV-2 cause damage to the respiratory system. It should be noted that the incubation period and transmission mechanism are similar for these two microorganisms. Pertussis vaccinations are given in childhood.The purpose of the study is to fi nd the charcteristics of the course of COVID-19 in school-aged children depending on thestate of humoral immunity against pertussis toxin, assessing their level of immunoglobulin G against pertussis.Material and methods. 92 pediatric patients aged 6 to 17 years were studied, including 30 children without signs of thedisease in the control group and 62 children with manifestations of laboratory- confi rmed COVID-19. The clinical features of the disease and laboratory indicators (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells, D-dimer) were evaluated, as well as the levels of free salivary cortisol and vitamin D. According to the severity of the disease, 3 groups were formed: the fi rst – 20 children with a mild course of COVID-19, the second – 33 patients with a moderate course of the disease, the third – 9 with a severe course of the disease.All children were tested for immunoglobulin G (Ig G) to pertussis toxin by enzyme- linked immunosorbent assay (VIROTECHB. pertussis PT Ig G ELISA, Rüsselsheim, Germany). The result was considered negative (no increase in the titer of specifi c class G antibodies to pertussis toxin), borderline, and positive (there is an increase in the titer of immunoglobulin G to pertussis toxin). Statistical analysis was performed using the program «Stat Plus» (Shapiro- Wilk test, mean SD (standard deviation) with correct distribution of characteristics; median, upper and lower quartiles with incorrect distribution, Chi-square test, Man-Whitney test, Fisher’s test).The study was conducted in accordance with the rules of patient safety and ethical principles of scientifi c medical researchinvolving human subjects (2000). The permission to conduct this study was given by the Bioethics Commission (Protocol No. 61 of 13.11.2020). The parents (legal representatives) of the patients gave their written consent to the conduct of this study.This study is a fragment of research work «An Integrated Approach to Symptom Control, Long- Term Prognosis in the Context of Comorbid Pathology in the Clinic of Internal Diseases and Family Doctor Practice» (state registration No. 0118U000361).Results. The mean age of the patients was 11.573.82 years. The study groups did not diff er in sex (x2=4.97, p=0.174) andage (p=0.490) composition. The level of humoral immunity against pertussis toxin diff ered signifi cantly between the study groups. A positive and borderline result for the presence of specifi c immunoglobulin G to tetanus toxin was found in 75.86 % of children without signs of disease. At the same time, only 41.51 % of children with COVID-19 manifestations had a positive and borderline result (p=0.005). A positive and borderline result for the presence of specifi c immunoglobulin G to tetanus toxin was seen in 66.67 % of children with mild infection, 33.33 % of patients with moderate disease, and only 12.50 % of patients with severe disease (X2=16.91, P=<0.001).Children with a negative result for immunoglobulin G to pertussis toxin have signifi cantly higher WBC count (1.3-fold), ESR(2.4-fold), D-dimer (3.4-fold), and CRP (1.5-fold) compared to patients with positive and borderline levels of these antibodies.In children with a negative result, there was a 6.25-fold increase in salivary free cortisol (p<0.001) and a 2.0-fold decrease invitamin D levels (p<0.001).Conclusions. In children with COVID-19 manifestations, there was a signifi cantly higher percentage of negative test resultsfor the presence of IgG to pertussis toxin compared to the control group, indicating a lower level of humoral immunity to tetanus in this group of patients. In children with mild disease, there was a signifi cantly higher percentage of positive and borderline test results for the presence of IgG to pertussis toxin (indicating a higher level of humoral immunity against this pathogen) compared to the groups of children with moderate and severe disease. The absence of specifi c immunoglobulins G to pertussis toxin is associated with an increase in the level of pro-infl ammatory markers (leukocyte count, ESR, CRP) and D-dimer, which also indicates a more severe course of COVID-19. Patients who are negative for pertussis toxin antibodies have elevated cortisol levels as a marker of stress and decreased vitamin D levels. Both biologically active substances are involved in the immune response to infectious agents and may serve as additional non-specifi c markers of COVID-19 severity. Therefore, low humoral immunity to pertussis contributes to the increase in COVID-19 severity in childhood.\",\"PeriodicalId\":162458,\"journal\":{\"name\":\"Neonatology, surgery and perinatal medicine\",\"volume\":\"231 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-10-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neonatology, surgery and perinatal medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.24061/2413-4260.xiii.4.50.2023.7\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neonatology, surgery and perinatal medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.24061/2413-4260.xiii.4.50.2023.7","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
冠状病毒病仍然是世界上最严重的疾病之一。儿童中严重和致命病例的比例低于成人。人们仍在继续寻找疾病严重程度的生物标志物。有证据表明,冠状病毒感染的病原体与其他一些传染源之间存在异源免疫。百日咳杆菌和 SARS-CoV-2 都会对呼吸系统造成损害。值得注意的是,这两种微生物的潜伏期和传播机制相似。本研究的目的是根据学龄儿童对百日咳毒素的体液免疫状态,评估其百日咳免疫球蛋白 G 的水平,找出 COVID-19 在学龄儿童中的病程特点。研究对象为92名6至17岁的儿童患者,其中对照组为30名无疾病症状的儿童,实验室确诊为COVID-19的儿童为62名。研究人员评估了疾病的临床特征和实验室指标(C-反应蛋白(CRP)、红细胞沉降率(ESR)、白细胞、D-二聚体),以及游离唾液皮质醇和维生素 D 的水平。根据病情严重程度分为三组:第一组--20 名 COVID-19 病程较轻的儿童,第二组--33 名病程中等的患者,第三组--9 名病程较重的患者。所有儿童均通过酶联免疫吸附试验(VIROTECHB.检测结果分为阴性(百日咳毒素 G 类特异性抗体滴度没有增加)、边缘性和阳性(百日咳毒素免疫球蛋白 G 滴度增加)。统计分析使用 "Stat Plus "程序(Shapiro- Wilk 检验、特征分布正确时的平均值 SD(标准差)、分布不正确时的中位数、上下四分位数、Chi-square 检验、Man-Whitney 检验、Fisher's 检验)。本研究根据患者安全规则和涉及人类受试者的医学科学研究伦理原则(2000 年)进行。生物伦理委员会(2020 年 11 月 13 日第 61 号协议)批准开展此项研究。本研究是 "内科疾病诊所和家庭医生实践中的症状控制、合并病理学背景下的长期预后综合方法"(国家注册号:0118U000361)研究工作的一个片段。患者的平均年龄为 11.573.82 岁。研究组在性别(x2=4.97,P=0.174)和年龄(P=0.490)组成上没有差异。研究组之间的百日咳毒素体液免疫水平差异显著。在 75.86% 的无疾病征兆的儿童中,破伤风毒素特异性免疫球蛋白 G 呈阳性和边缘性结果。同时,在有 COVID-19 表现的儿童中,只有 41.51% 的儿童的结果为阳性和边缘值(p=0.005)。66.67%的轻度感染患儿、33.33%的中度感染患儿和仅有 12.50%的重度感染患儿(X2=16.91,P=<0.001)出现破伤风毒素特异性免疫球蛋白 G 阳性和边缘结果。百日咳毒素免疫球蛋白 G 阴性结果的儿童与这些抗体水平阳性和边缘水平的患者相比,白细胞计数(1.3 倍)、血沉(2.4 倍)、D-二聚体(3.4 倍)和 CRP(1.5 倍)明显升高。在有COVID-19表现的儿童中,百日咳毒素IgG检测结果呈阴性的比例明显高于对照组,这表明该组患者的破伤风体液免疫水平较低。与中度和重度疾病儿童组相比,轻度疾病儿童中百日咳毒素 IgG 阳性和边缘测试结果的百分比明显更高(表明对该病原体的体液免疫水平更高)。百日咳毒素特异性免疫球蛋白 G 的缺失与促炎症指标(白细胞计数、血沉、CRP)和 D-二聚体水平的升高有关,这也表明 COVID-19 的病程更为严重。百日咳毒素抗体阴性的患者皮质醇水平升高,这是压力的标志,维生素 D 水平降低。
PECULIARITIES OF THE COURSE OF COVID-19 IN SCHOOL-AGE CHILDREN AS A FUNCTION OF HUMORAL IMMUNITY AGAINST PERTUSSIS
Coronavirus disease remains one of the most serious diseases in the world. The percentage of severe and fatal cases inchildren is lower than in adults. The search for biomarkers of disease severity continues. There is evidence of heterologousimmunity between the causative agent of coronavirus infection and some other infectious agents. Both Bordetella pertussis and SARS-CoV-2 cause damage to the respiratory system. It should be noted that the incubation period and transmission mechanism are similar for these two microorganisms. Pertussis vaccinations are given in childhood.The purpose of the study is to fi nd the charcteristics of the course of COVID-19 in school-aged children depending on thestate of humoral immunity against pertussis toxin, assessing their level of immunoglobulin G against pertussis.Material and methods. 92 pediatric patients aged 6 to 17 years were studied, including 30 children without signs of thedisease in the control group and 62 children with manifestations of laboratory- confi rmed COVID-19. The clinical features of the disease and laboratory indicators (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells, D-dimer) were evaluated, as well as the levels of free salivary cortisol and vitamin D. According to the severity of the disease, 3 groups were formed: the fi rst – 20 children with a mild course of COVID-19, the second – 33 patients with a moderate course of the disease, the third – 9 with a severe course of the disease.All children were tested for immunoglobulin G (Ig G) to pertussis toxin by enzyme- linked immunosorbent assay (VIROTECHB. pertussis PT Ig G ELISA, Rüsselsheim, Germany). The result was considered negative (no increase in the titer of specifi c class G antibodies to pertussis toxin), borderline, and positive (there is an increase in the titer of immunoglobulin G to pertussis toxin). Statistical analysis was performed using the program «Stat Plus» (Shapiro- Wilk test, mean SD (standard deviation) with correct distribution of characteristics; median, upper and lower quartiles with incorrect distribution, Chi-square test, Man-Whitney test, Fisher’s test).The study was conducted in accordance with the rules of patient safety and ethical principles of scientifi c medical researchinvolving human subjects (2000). The permission to conduct this study was given by the Bioethics Commission (Protocol No. 61 of 13.11.2020). The parents (legal representatives) of the patients gave their written consent to the conduct of this study.This study is a fragment of research work «An Integrated Approach to Symptom Control, Long- Term Prognosis in the Context of Comorbid Pathology in the Clinic of Internal Diseases and Family Doctor Practice» (state registration No. 0118U000361).Results. The mean age of the patients was 11.573.82 years. The study groups did not diff er in sex (x2=4.97, p=0.174) andage (p=0.490) composition. The level of humoral immunity against pertussis toxin diff ered signifi cantly between the study groups. A positive and borderline result for the presence of specifi c immunoglobulin G to tetanus toxin was found in 75.86 % of children without signs of disease. At the same time, only 41.51 % of children with COVID-19 manifestations had a positive and borderline result (p=0.005). A positive and borderline result for the presence of specifi c immunoglobulin G to tetanus toxin was seen in 66.67 % of children with mild infection, 33.33 % of patients with moderate disease, and only 12.50 % of patients with severe disease (X2=16.91, P=<0.001).Children with a negative result for immunoglobulin G to pertussis toxin have signifi cantly higher WBC count (1.3-fold), ESR(2.4-fold), D-dimer (3.4-fold), and CRP (1.5-fold) compared to patients with positive and borderline levels of these antibodies.In children with a negative result, there was a 6.25-fold increase in salivary free cortisol (p<0.001) and a 2.0-fold decrease invitamin D levels (p<0.001).Conclusions. In children with COVID-19 manifestations, there was a signifi cantly higher percentage of negative test resultsfor the presence of IgG to pertussis toxin compared to the control group, indicating a lower level of humoral immunity to tetanus in this group of patients. In children with mild disease, there was a signifi cantly higher percentage of positive and borderline test results for the presence of IgG to pertussis toxin (indicating a higher level of humoral immunity against this pathogen) compared to the groups of children with moderate and severe disease. The absence of specifi c immunoglobulins G to pertussis toxin is associated with an increase in the level of pro-infl ammatory markers (leukocyte count, ESR, CRP) and D-dimer, which also indicates a more severe course of COVID-19. Patients who are negative for pertussis toxin antibodies have elevated cortisol levels as a marker of stress and decreased vitamin D levels. Both biologically active substances are involved in the immune response to infectious agents and may serve as additional non-specifi c markers of COVID-19 severity. Therefore, low humoral immunity to pertussis contributes to the increase in COVID-19 severity in childhood.