Pub Date : 2023-01-01Epub Date: 2023-01-26DOI: 10.1186/s43042-023-00392-3
Fatemeh Arab, Samaneh Mollazadeh, Farnaz Ghayourbabaei, Meysam Moghbeli, Ehsan Saburi
The coronavirus disease 2019 (COVID-19) pandemic has caused human tragedy through the global spread of the viral pathogen SARS-CoV-2. Although the underlying factors for the severity of COVID-19 in different people are still unknown, several gene variants can be used as predictors of disease severity, particularly variations in viral receptor genes such as angiotensin-converting enzyme 2 (ACE2) or major histocompatibility complex (MHC) genes. The reaction of the immune system, as the most important defense strategy in the case of viruses, plays a decisive role. The innate immune system is important both as a primary line of defense and as a trigger of the acquired immune response. The HLA-mediated acquired immune response is linked to the acquired immune system. In various diseases, it has been shown that genetic alterations in components of the immune system can play a crucial role in how the body responds to pathogens, especially viruses. One of the most important host genetic factors is the human leukocyte antigen (HLA) profile, which includes HLA classes I and II and may be symbolic of the diversity of immune response and genetic predisposition in disease progression. COVID-19 will have direct contact with the acquired immune system as an intracellular pathogen after exposure to the proteasome and its components through class I HLA. Therefore, it is assumed that in different genotypes of the HLA-I class, an undesirable supply causes an insufficient activation of the immune system. Insufficient binding of antigen delivered by class I HLA to host lymphocytes results in uncertain identification and insufficient activation of the acquired immune system. The absence of secretion of immune cytokines such as interferons, which play an important role in controlling viral infection in the early stages, is a complication of this event. Understanding the allelic diversity of HLA in people infected with coronavirus compared with uninfected people of one race not only allows identification of people with HLA susceptible to COVID-19 but also provides better insight into the behavior of the virus, which helps to take effective preventive and curative measures earlier.
2019 年冠状病毒病(COVID-19)大流行通过病毒病原体 SARS-CoV-2 的全球传播造成了人类悲剧。尽管不同人群感染 COVID-19 的严重程度的潜在因素尚不清楚,但有几种基因变异可作为疾病严重程度的预测因子,特别是血管紧张素转换酶 2(ACE2)或主要组织相容性复合体(MHC)基因等病毒受体基因的变异。免疫系统的反应是病毒最重要的防御策略,起着决定性的作用。先天性免疫系统既是第一道防线,也是后天免疫反应的触发器。HLA 介导的获得性免疫反应与后天免疫系统有关。在各种疾病中,免疫系统各组成部分的基因改变在机体如何应对病原体(尤其是病毒)方面起着至关重要的作用。人类白细胞抗原(HLA)图谱是最重要的宿主遗传因素之一,它包括 HLA I 类和 II 类,可能象征着免疫反应的多样性和疾病进展中的遗传易感性。COVID-19 通过 I 类 HLA 暴露于蛋白酶体及其成分后,将作为细胞内病原体与获得性免疫系统直接接触。因此,假定在不同的 HLA-I 类基因型中,不良供应会导致免疫系统激活不足。I 类 HLA 递送的抗原与宿主淋巴细胞结合不充分,导致识别不确定和获得性免疫系统激活不充分。免疫细胞因子(如干扰素)在早期控制病毒感染中发挥着重要作用,而这种细胞因子分泌的缺失则是这一事件的并发症。了解冠状病毒感染者与同一种族未感染者相比的 HLA 等位基因多样性,不仅可以识别 HLA 易感 COVID-19 的人群,还能更好地了解病毒的行为,有助于尽早采取有效的预防和治疗措施。
{"title":"The role of HLA genotypes in understanding the pathogenesis of severe COVID-19.","authors":"Fatemeh Arab, Samaneh Mollazadeh, Farnaz Ghayourbabaei, Meysam Moghbeli, Ehsan Saburi","doi":"10.1186/s43042-023-00392-3","DOIUrl":"10.1186/s43042-023-00392-3","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) pandemic has caused human tragedy through the global spread of the viral pathogen SARS-CoV-2. Although the underlying factors for the severity of COVID-19 in different people are still unknown, several gene variants can be used as predictors of disease severity, particularly variations in viral receptor genes such as angiotensin-converting enzyme 2 (ACE2) or major histocompatibility complex (MHC) genes. The reaction of the immune system, as the most important defense strategy in the case of viruses, plays a decisive role. The innate immune system is important both as a primary line of defense and as a trigger of the acquired immune response. The HLA-mediated acquired immune response is linked to the acquired immune system. In various diseases, it has been shown that genetic alterations in components of the immune system can play a crucial role in how the body responds to pathogens, especially viruses. One of the most important host genetic factors is the human leukocyte antigen (HLA) profile, which includes HLA classes I and II and may be symbolic of the diversity of immune response and genetic predisposition in disease progression. COVID-19 will have direct contact with the acquired immune system as an intracellular pathogen after exposure to the proteasome and its components through class I HLA. Therefore, it is assumed that in different genotypes of the HLA-I class, an undesirable supply causes an insufficient activation of the immune system. Insufficient binding of antigen delivered by class I HLA to host lymphocytes results in uncertain identification and insufficient activation of the acquired immune system. The absence of secretion of immune cytokines such as interferons, which play an important role in controlling viral infection in the early stages, is a complication of this event. Understanding the allelic diversity of HLA in people infected with coronavirus compared with uninfected people of one race not only allows identification of people with HLA susceptible to COVID-19 but also provides better insight into the behavior of the virus, which helps to take effective preventive and curative measures earlier.</p>","PeriodicalId":74994,"journal":{"name":"The Egyptian journal of medical human genetics","volume":"24 1","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9878497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9143407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Inter-individual variations in the clinical manifestations of SARS-CoV-2 infection are among the challenging features of COVID-19. The known role of telomeres in cell proliferation and immune competency highlights their possible function in infectious diseases. Variability in telomere length is an invaluable parameter in the heterogeneity of the clinical presentation of diseases.
Result: In this study, our aim was to investigate the possible association between leukocyte telomere length (LTL) and COVID-19 severity. LTL was measured in 100 patients with moderate and severe forms of COVID-19 using the quantitative PCR (q-PCR) method. Statistical analysis confirmed a strong inverse correlation between relative LTL and COVID-19 severity.
Conclusions: These findings suggest that LTL can be a useful parameter for predicting disease severity in patients, as individuals with short telomeres may have a higher risk of developing severe COVID-19.
Supplementary information: The online version contains supplementary material available at 10.1186/s43042-023-00415-z.
{"title":"Association between leukocyte telomere length and COVID-19 severity.","authors":"Ata Mahmoodpoor, Sarvin Sanaie, Maqsoud Eskandari, Nazila Behrouzi, Majid Taghizadeh, Faranak Roudbari, Babak Emamalizadeh, Nasim Sohrabifar, Somayeh Kazeminasab","doi":"10.1186/s43042-023-00415-z","DOIUrl":"10.1186/s43042-023-00415-z","url":null,"abstract":"<p><strong>Background: </strong>Inter-individual variations in the clinical manifestations of SARS-CoV-2 infection are among the challenging features of COVID-19. The known role of telomeres in cell proliferation and immune competency highlights their possible function in infectious diseases. Variability in telomere length is an invaluable parameter in the heterogeneity of the clinical presentation of diseases.</p><p><strong>Result: </strong>In this study, our aim was to investigate the possible association between leukocyte telomere length (LTL) and COVID-19 severity. LTL was measured in 100 patients with moderate and severe forms of COVID-19 using the quantitative PCR (q-PCR) method. Statistical analysis confirmed a strong inverse correlation between relative LTL and COVID-19 severity.</p><p><strong>Conclusions: </strong>These findings suggest that LTL can be a useful parameter for predicting disease severity in patients, as individuals with short telomeres may have a higher risk of developing severe COVID-19.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1186/s43042-023-00415-z.</p>","PeriodicalId":74994,"journal":{"name":"The Egyptian journal of medical human genetics","volume":"24 1","pages":"37"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10225776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9582211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2023-01-22DOI: 10.1186/s43042-023-00390-5
Meryem Fakhkhari, Hayat Caidi, Khalid Sadki
Background: COVID-19 is a respiratory disease caused by a novel coronavirus called as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Detected for the first time in December 2019 in Wuhan and it has quickly spread all over the world in a couple of months and becoming a world pandemic. Symptoms of the disease and clinical outcomes are very different in infected people. These differences highlight the paramount need to study and understand the human genetic variation that occurring viral infections. Human leukocyte antigen (HLA) is an important component of the viral antigen presentation pathway, and it plays an essential role in conferring differential viral susceptibility and severity of diseases. HLA alleles have been involved in the immune response to viral diseases such as SARS-CoV-2.
Main body of the abstract: Herein, we sought to evaluate this hypothesis by summarizing the association between HLA class I and class II alleles with COVID-19 susceptibility and/or severity reported in previous studies among different populations (Chinese, Italian, Iranian, Japanese, Spanish, etc.). The findings of all selected articles showed that several alleles have been found associated with COVID-19 susceptibility and severity. Even results across articles have been inconsistent and, in some cases, conflicting, highlighting that the association between the HLA system and the COVID-19 outcome might be ethnic-dependent, there were some alleles in common between some populations such as HLA-DRB1*15 and HLA-A*30:02.
Conclusion: These contradictory findings warrant further large, and reproducible studies to decipher any possible genetic predisposition underlying susceptibility to SARS-COV-2 and disease progression and host immune response.
{"title":"HLA alleles associated with COVID-19 susceptibility and severity in different populations: a systematic review.","authors":"Meryem Fakhkhari, Hayat Caidi, Khalid Sadki","doi":"10.1186/s43042-023-00390-5","DOIUrl":"10.1186/s43042-023-00390-5","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 is a respiratory disease caused by a novel coronavirus called as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Detected for the first time in December 2019 in Wuhan and it has quickly spread all over the world in a couple of months and becoming a world pandemic. Symptoms of the disease and clinical outcomes are very different in infected people. These differences highlight the paramount need to study and understand the human genetic variation that occurring viral infections. Human leukocyte antigen (HLA) is an important component of the viral antigen presentation pathway, and it plays an essential role in conferring differential viral susceptibility and severity of diseases. HLA alleles have been involved in the immune response to viral diseases such as SARS-CoV-2.</p><p><strong>Main body of the abstract: </strong>Herein, we sought to evaluate this hypothesis by summarizing the association between HLA class I and class II alleles with COVID-19 susceptibility and/or severity reported in previous studies among different populations (Chinese, Italian, Iranian, Japanese, Spanish, etc.). The findings of all selected articles showed that several alleles have been found associated with COVID-19 susceptibility and severity. Even results across articles have been inconsistent and, in some cases, conflicting, highlighting that the association between the HLA system and the COVID-19 outcome might be ethnic-dependent, there were some alleles in common between some populations such as HLA-DRB1*15 and HLA-A*30:02.</p><p><strong>Conclusion: </strong>These contradictory findings warrant further large, and reproducible studies to decipher any possible genetic predisposition underlying susceptibility to SARS-COV-2 and disease progression and host immune response.</p>","PeriodicalId":74994,"journal":{"name":"The Egyptian journal of medical human genetics","volume":"24 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10585178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2023-01-09DOI: 10.1186/s43042-023-00383-4
Peyvand Kashi, Farzaneh Pakdel, Mohammad Hossein Soroush Barhaghi, Mohammad Ahangarzadeh Rezaee, Sepehr Taghizadeh, Javid Sadeghi, Mehdi Yousefi, Reza Ghotaslou, Mohammad Asgharzadeh, Pourya Gholizadeh, Hossein Samadi Kafil
Background: Tuberculosis (TB) is considered one of the most infectious diseases in the world. In this study, we intended to examine the epidemiology of tuberculosis by MIRU-VNTR to define the changes that occur in the transmission of tuberculosis in the region during the COVID-19 era. A total of 120 Mycobacterium tuberculosis isolates were collected from sputum samples of patients referred to East Azerbaijan Center TB from December 2020 to August 2021. Demographic information such as age, sex, place of birth, previous TB history, and relevant medical data was collected. The proportion method was performed for drug susceptibility testing, and the PCR-based MIRU-VNTR method was applied to identify molecular epidemiology relationships.
Results: The isolates were collected from 78 male (65%) and 39 female (32.5%) Iranian patients and 3 (2.5%) Azerbaijani patients. Ninety-three distinct patterns were identified including 15 clustered patterns and 36 unique patterns. The largest cluster was composed of seven isolates. Furthermore, one cluster with 5 members, four clusters with 3 members, and nine clusters with 2 members. In MIRU-VNTR typing, 75 clusters belonged to the Tabriz region and just 3 to the Republic of Azerbaijan. All isolates were sensitive to rifampin, isoniazid, and ethambutol.
Conclusions: Results of the current study showed COVID-19 pandemic had a direct effect on the transmission and diagnosis of tuberculosis. Less diagnosis and less clustering can indicate public controls and hygiene, and the use of masks had a direct effect on the transmission and diagnosis of tuberculosis. However, misidentification and less focus on other respiratory infections are expected during the pandemic. Studies on the co-infection of COVID-19 and tuberculosis and the role of mask and sanitization against TB are strongly recommended.
{"title":"Genetic diversity of <i>Mycobacterium tuberculosis</i> isolates from northwest of Iran during COVID-19 era.","authors":"Peyvand Kashi, Farzaneh Pakdel, Mohammad Hossein Soroush Barhaghi, Mohammad Ahangarzadeh Rezaee, Sepehr Taghizadeh, Javid Sadeghi, Mehdi Yousefi, Reza Ghotaslou, Mohammad Asgharzadeh, Pourya Gholizadeh, Hossein Samadi Kafil","doi":"10.1186/s43042-023-00383-4","DOIUrl":"10.1186/s43042-023-00383-4","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) is considered one of the most infectious diseases in the world. In this study, we intended to examine the epidemiology of tuberculosis by MIRU-VNTR to define the changes that occur in the transmission of tuberculosis in the region during the COVID-19 era. A total of 120 <i>Mycobacterium tuberculosis</i> isolates were collected from sputum samples of patients referred to East Azerbaijan Center TB from December 2020 to August 2021. Demographic information such as age, sex, place of birth, previous TB history, and relevant medical data was collected. The proportion method was performed for drug susceptibility testing, and the PCR-based MIRU-VNTR method was applied to identify molecular epidemiology relationships.</p><p><strong>Results: </strong>The isolates were collected from 78 male (65%) and 39 female (32.5%) Iranian patients and 3 (2.5%) Azerbaijani patients. Ninety-three distinct patterns were identified including 15 clustered patterns and 36 unique patterns. The largest cluster was composed of seven isolates. Furthermore, one cluster with 5 members, four clusters with 3 members, and nine clusters with 2 members. In MIRU-VNTR typing, 75 clusters belonged to the Tabriz region and just 3 to the Republic of Azerbaijan. All isolates were sensitive to rifampin, isoniazid, and ethambutol.</p><p><strong>Conclusions: </strong>Results of the current study showed COVID-19 pandemic had a direct effect on the transmission and diagnosis of tuberculosis. Less diagnosis and less clustering can indicate public controls and hygiene, and the use of masks had a direct effect on the transmission and diagnosis of tuberculosis. However, misidentification and less focus on other respiratory infections are expected during the pandemic. Studies on the co-infection of COVID-19 and tuberculosis and the role of mask and sanitization against TB are strongly recommended.</p>","PeriodicalId":74994,"journal":{"name":"The Egyptian journal of medical human genetics","volume":"24 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9829222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10284774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-09-23DOI: 10.1186/s43042-022-00354-1
Hayder M Al-Kuraishy, Ali I Al-Gareeb, Engy Elekhnawy, Gaber El-Saber Batiha
Background: Coronavirus disease 2019 (Covid-19) is an infectious worldwide pandemic triggered by severe acute respiratory coronavirus 2 (SARS-CoV-2). This pandemic disease can lead to pro-inflammatory activation with associated acute lung injury and acute respiratory distress syndrome.
Main body of the abstract: SARS-CoV-2 infection is linked with inhibition of adenosine and activation of phosphodiesterase. Dipyridamole (DIP) is a nucleoside transport and phosphodiesterase inhibitor so that it may potentially affect SARS-CoV-2 infection and its accompanying inflammations. Therefore, the primary objective of this mini-review study was to elucidate the potential beneficial impacts of DIP on the adenosinergic pathway in Covid-19. A systemic search was done using online databases with relevant keywords. The findings of the present study illustrated that DIP directly or indirectly, through augmentation of adenosine and inhibition of phosphodiesterase, mitigates Covid-19 outcomes.
Conclusion: Our study concluded that DIP has a potential therapeutic effect in the management and treatment of Covid-19. This could be attained either directly, through anti-SARS-CoV-2, anti-inflammatory, and anti-platelets properties, or indirectly, through augmentation of extracellular adenosine, which has anti-inflammatory and immune-regulatory effects. However, extensive randomized clinical trials, and clinical and prospective research in this area are required to demonstrate the safety and therapeutic efficacy of DIP and adenosine modulators in the treatment of Covid-19.
{"title":"Dipyridamole and adenosinergic pathway in Covid-19: a juice or holy grail.","authors":"Hayder M Al-Kuraishy, Ali I Al-Gareeb, Engy Elekhnawy, Gaber El-Saber Batiha","doi":"10.1186/s43042-022-00354-1","DOIUrl":"10.1186/s43042-022-00354-1","url":null,"abstract":"<p><strong>Background: </strong>Coronavirus disease 2019 (Covid-19) is an infectious worldwide pandemic triggered by severe acute respiratory coronavirus 2 (SARS-CoV-2). This pandemic disease can lead to pro-inflammatory activation with associated acute lung injury and acute respiratory distress syndrome.</p><p><strong>Main body of the abstract: </strong>SARS-CoV-2 infection is linked with inhibition of adenosine and activation of phosphodiesterase. Dipyridamole (DIP) is a nucleoside transport and phosphodiesterase inhibitor so that it may potentially affect SARS-CoV-2 infection and its accompanying inflammations. Therefore, the primary objective of this mini-review study was to elucidate the potential beneficial impacts of DIP on the adenosinergic pathway in Covid-19. A systemic search was done using online databases with relevant keywords. The findings of the present study illustrated that DIP directly or indirectly, through augmentation of adenosine and inhibition of phosphodiesterase, mitigates Covid-19 outcomes.</p><p><strong>Conclusion: </strong>Our study concluded that DIP has a potential therapeutic effect in the management and treatment of Covid-19. This could be attained either directly, through anti-SARS-CoV-2, anti-inflammatory, and anti-platelets properties, or indirectly, through augmentation of extracellular adenosine, which has anti-inflammatory and immune-regulatory effects. However, extensive randomized clinical trials, and clinical and prospective research in this area are required to demonstrate the safety and therapeutic efficacy of DIP and adenosine modulators in the treatment of Covid-19.</p>","PeriodicalId":74994,"journal":{"name":"The Egyptian journal of medical human genetics","volume":"23 1","pages":"140"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9510284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-08-23DOI: 10.1186/s43042-022-00331-8
Shaimaa A Elbadri, Nermeen M A Abdallah, Mona El-Shokry, Amr Gaber, Mahmoud Kh Elsayed
Background: Coronavirus disease 2019 (COVID-19) is a devastating pandemic-causing disease with a variable severity among populations. Genetic studies have pinpointed angiotensin-converting enzyme 2 (ACE2), a key enzyme for viral entry, for its possible linkage to the disease progression. The present study aimed to investigate the potential association between single nucleotide polymorphisms (SNPs) of human ACE2 gene with the severity and outcomes of COVID-19 for better patient management.
Methods: In this observational cross-sectional study, COVID-19 confirmed patients were classified into moderate and severe cases according to the "Ain Shams University Hospitals Pocket Guide for COVID-19 Diagnosis." Genetic analysis of ACE2 SNP rs2048683 was carried out using a TaqMan assay with the real-time polymerase chain reaction (PCR) technique.
Results: Among 90 confirmed COVID-19 patients, 78.9% (71/90) were classified as severe, and 21.1% (19/90) were classified as moderate. Laboratory biomarkers were significantly (P = 0.000) higher in the severe group than in the moderate group. Similarly, associated comorbidities such as hypertension were significant (P = 0.000) in the severe group, whereas asthma and deep venous thrombosis were significant in the moderate group (P = 0.007 and 0.006, respectively). Elevated serum ferritin level (odds ratio (OR) 162.589, 95% confidence interval (CI) 8.108-3260.293) and ACE2 rs2048683 genotype GG/G (OR 5.852, 95% CI 1.586-21.591) were both considered independent risk factors for severe disease.
Conclusion: The findings of the present study provide preliminary evidence of an association between ACE2 rs2048683 SNPs and COVID-19 severity in the Egyptian population, which may inform the need for targeted management.
Supplementary information: The online version contains supplementary material available at 10.1186/s43042-022-00331-8.
{"title":"Association between single nucleotide polymorphism of human angiotensin-converting enzyme 2 gene locus and clinical severity of COVID-19.","authors":"Shaimaa A Elbadri, Nermeen M A Abdallah, Mona El-Shokry, Amr Gaber, Mahmoud Kh Elsayed","doi":"10.1186/s43042-022-00331-8","DOIUrl":"10.1186/s43042-022-00331-8","url":null,"abstract":"<p><strong>Background: </strong>Coronavirus disease 2019 (COVID-19) is a devastating pandemic-causing disease with a variable severity among populations. Genetic studies have pinpointed angiotensin-converting enzyme 2 (ACE2), a key enzyme for viral entry, for its possible linkage to the disease progression. The present study aimed to investigate the potential association between single nucleotide polymorphisms (SNPs) of human ACE2 gene with the severity and outcomes of COVID-19 for better patient management.</p><p><strong>Methods: </strong>In this observational cross-sectional study, COVID-19 confirmed patients were classified into moderate and severe cases according to the \"Ain Shams University Hospitals Pocket Guide for COVID-19 Diagnosis.\" Genetic analysis of ACE2 SNP rs2048683 was carried out using a TaqMan assay with the real-time polymerase chain reaction (PCR) technique.</p><p><strong>Results: </strong>Among 90 confirmed COVID-19 patients, 78.9% (71/90) were classified as severe, and 21.1% (19/90) were classified as moderate. Laboratory biomarkers were significantly (<i>P</i> = 0.000) higher in the severe group than in the moderate group. Similarly, associated comorbidities such as hypertension were significant (<i>P</i> = 0.000) in the severe group, whereas asthma and deep venous thrombosis were significant in the moderate group (<i>P</i> = 0.007 and 0.006, respectively). Elevated serum ferritin level (odds ratio (OR) 162.589, 95% confidence interval (CI) 8.108-3260.293) and ACE2 rs2048683 genotype GG/G (OR 5.852, 95% CI 1.586-21.591) were both considered independent risk factors for severe disease.</p><p><strong>Conclusion: </strong>The findings of the present study provide preliminary evidence of an association between ACE2 rs2048683 SNPs and COVID-19 severity in the Egyptian population, which may inform the need for targeted management.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1186/s43042-022-00331-8.</p>","PeriodicalId":74994,"journal":{"name":"The Egyptian journal of medical human genetics","volume":"23 1","pages":"125"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10257432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Congenital heart disease CHD is a significant cause of mortality and morbidity in children worldwide. Patients with congenital heart disease may develop hematological problems, including thrombocytopenia and neutropenia. In addition, several studies indicate the higher frailty of patients with CHDs to infections and malignancies. Nevertheless, the mechanisms of immune system changes in these patients have remained in the shadow of uncertainty. Moreover, very few studies have worked on cytopenia in CHD. This study has assessed the frequency of thrombocytopenia, neutropenia, lymphopenia, and anemia in pediatric patients with acyanotic congenital heart disease ACHD prior to open-heart surgery.
Methods: This cross-sectional study was handled in the Pediatric Cardiology Clinic, Tehran University of Medical Sciences, during pre-operation visits from 2014 till 2019. Two hundred forty-eight children and adolescents with acyanotic congenital heart disease before open-heart surgery met the criteria to enter the study.
Results: A total of 191 (76.7%) patients with Ventricular Septal Defects (VSD), 37 (14.85%) patients with Atrial Septal Defects (ASD), and 20 (8.11%) patients with Patent Ductus Arteriosus (PDA) were enrolled in this study. The median age was 23.87 months. Thrombocytopenia and neutropenia were found, respectively, in 3 (1.2) and 23 (9.2%) patients. Hemoglobin level and lymphocyte count were significantly lower in patients with neutropenia than patients with normal neutrophil count (P value = 0.024 and P value = 0.000). Significant positive correlations were found between neutropenia and anemia. There were no correlations between neutrophil count and Platelets. Also, anemia was found in 48 patients (19.3%). The study also found a statistically significant correlation between the co-existence of VSD and neutropenia in the patients (P value = 0.000).
Conclusion: Although most were mildly neutropenic, there was a significant correlation between neutropenia and Ventricular Septal Defect compared to PDA and ASD groups. Regarding the importance of neutropenia to affect the prognosis of congenital heart defects in infections, it is important to consider further studies on the status of immune system function in these patients.
{"title":"Hematological indices in pediatric patients with acyanotic congenital heart disease: a cross-sectional study of 248 patients.","authors":"Hanieh Mohammadi, Behzad Mohammadpour Ahranjani, Ehsan Aghaei Moghadam, Farzad Kompani, Mona Mirbeyk, Nima Rezaei","doi":"10.1186/s43042-022-00262-4","DOIUrl":"10.1186/s43042-022-00262-4","url":null,"abstract":"<p><strong>Background: </strong>Congenital heart disease CHD is a significant cause of mortality and morbidity in children worldwide. Patients with congenital heart disease may develop hematological problems, including thrombocytopenia and neutropenia. In addition, several studies indicate the higher frailty of patients with CHDs to infections and malignancies. Nevertheless, the mechanisms of immune system changes in these patients have remained in the shadow of uncertainty. Moreover, very few studies have worked on cytopenia in CHD. This study has assessed the frequency of thrombocytopenia, neutropenia, lymphopenia, and anemia in pediatric patients with acyanotic congenital heart disease ACHD prior to open-heart surgery.</p><p><strong>Methods: </strong>This cross-sectional study was handled in the Pediatric Cardiology Clinic, Tehran University of Medical Sciences, during pre-operation visits from 2014 till 2019. Two hundred forty-eight children and adolescents with acyanotic congenital heart disease before open-heart surgery met the criteria to enter the study.</p><p><strong>Results: </strong>A total of 191 (76.7%) patients with Ventricular Septal Defects (VSD), 37 (14.85%) patients with Atrial Septal Defects (ASD), and 20 (8.11%) patients with Patent Ductus Arteriosus (PDA) were enrolled in this study. The median age was 23.87 months. Thrombocytopenia and neutropenia were found, respectively, in 3 (1.2) and 23 (9.2%) patients. Hemoglobin level and lymphocyte count were significantly lower in patients with neutropenia than patients with normal neutrophil count (<i>P</i> value = 0.024 and <i>P</i> value = 0.000). Significant positive correlations were found between neutropenia and anemia. There were no correlations between neutrophil count and Platelets. Also, anemia was found in 48 patients (19.3%). The study also found a statistically significant correlation between the co-existence of VSD and neutropenia in the patients (<i>P</i> value = 0.000).</p><p><strong>Conclusion: </strong>Although most were mildly neutropenic, there was a significant correlation between neutropenia and Ventricular Septal Defect compared to PDA and ASD groups. Regarding the importance of neutropenia to affect the prognosis of congenital heart defects in infections, it is important to consider further studies on the status of immune system function in these patients.</p>","PeriodicalId":74994,"journal":{"name":"The Egyptian journal of medical human genetics","volume":"23 1","pages":"47"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9964940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The processes of drug development and validation are too expensive to be subjected to experimental trial and errors. Hence, the use of the insilico approach becomes imperative. To this effect, the drug-likeness and pharmacokinetic properties of the ten (10) previously designed derivatives of 2-anilino 4-amino substituted quinazolines were carried out. Their predicted ligand binding interactions were also carried out by docking them against the Plasmodium falciparum dihydroorotate dehydrogenase (Pf-DHODH) protein target, and the stability of the complex was determined through dynamic simulations. The drug-likeness and pharmacokinetic characteristics were estimated using the online SwissADME software, while the Molegro Virtual Docker (MVD) software was used for molecular docking. And the dynamic simulation was performed for the duration of 100 ns to verify the stability of the docked complex, with the aid of a Schrödinger program, Desmond.
Results: The designed derivatives were all found to pass the Lipinski test of drug likeness, while the pharmacokinetic studies result that the skin permeability and molar refractivity values of the derivatives are both within the limits. In addition, except for derivative C-01, most of the derivatives have strong gastrointestinal absorptions and lack Pgp substrate. Furthermore, no derivative inhibited CYP1A2, CYP2C9, or CYP2C19. The docking studies show the better binding affinities between the ligands and Pf-DHODH than those between the atovaquone or chloroquine standards. The derivative C-02, {5-((6,7-dimethoxy-4-((3-nitrobenzyl)amino)quinazolin-2-yl)amino)-2-fluorobenzaldehyde} was found to be the most stable derivative, with a re-rank docking score of - 173.528 kcal/mol and interaction energy of - 225.112 kcal/mol. The dynamic simulation analysis shows that the derivative C-02 forms a stable complex with the protein target over the simulation time.
Conclusions: The ability of these ligands to form hydrogen bonds, as well as various other interactions, was cited as a factor responsible for their better binding affinity. These findings could aid further the development of enhanced antimalarial drugs.
{"title":"Virtual screening and molecular dynamic simulations of the antimalarial derivatives of 2-anilino 4-amino substituted quinazolines docked against a <i>Pf</i>-DHODH protein target.","authors":"Zakari Ya'u Ibrahim, Adamu Uzairu, Gideon Adamu Shallangwa, Stephen Eyije Abechi, Sulaiman Isyaku","doi":"10.1186/s43042-022-00329-2","DOIUrl":"10.1186/s43042-022-00329-2","url":null,"abstract":"<p><strong>Background: </strong>The processes of drug development and validation are too expensive to be subjected to experimental trial and errors. Hence, the use of the insilico approach becomes imperative. To this effect, the drug-likeness and pharmacokinetic properties of the ten (10) previously designed derivatives of 2-anilino 4-amino substituted quinazolines were carried out. Their predicted ligand binding interactions were also carried out by docking them against the <i>Plasmodium falciparum</i> dihydroorotate dehydrogenase (<i>Pf-</i>DHODH) protein target, and the stability of the complex was determined through dynamic simulations. The drug-likeness and pharmacokinetic characteristics were estimated using the online SwissADME software, while the Molegro Virtual Docker (MVD) software was used for molecular docking. And the dynamic simulation was performed for the duration of 100 ns to verify the stability of the docked complex, with the aid of a Schrödinger program, Desmond.</p><p><strong>Results: </strong>The designed derivatives were all found to pass the Lipinski test of drug likeness, while the pharmacokinetic studies result that the skin permeability and molar refractivity values of the derivatives are both within the limits. In addition, except for derivative C-01, most of the derivatives have strong gastrointestinal absorptions and lack Pgp substrate. Furthermore, no derivative inhibited CYP1A2, CYP2C9, or CYP2C19. The docking studies show the better binding affinities between the ligands and <i>Pf-</i>DHODH than those between the atovaquone or chloroquine standards. The derivative C-02, {5-((6,7-dimethoxy-4-((3-nitrobenzyl)amino)quinazolin-2-yl)amino)-2-fluorobenzaldehyde} was found to be the most stable derivative, with a re-rank docking score of - 173.528 kcal/mol and interaction energy of - 225.112 kcal/mol. The dynamic simulation analysis shows that the derivative C-02 forms a stable complex with the protein target over the simulation time.</p><p><strong>Conclusions: </strong>The ability of these ligands to form hydrogen bonds, as well as various other interactions, was cited as a factor responsible for their better binding affinity. These findings could aid further the development of enhanced antimalarial drugs.</p>","PeriodicalId":74994,"journal":{"name":"The Egyptian journal of medical human genetics","volume":"23 1","pages":"119"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9964937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-03-17DOI: 10.1186/s43042-022-00268-y
Anas Khaleel, Bayan Alkhawaja, Talal Salem Al-Qaisi, Lubna Alshalabi, Amneh H Tarkhan
Background: Cigarette smoking is the leading preventable cause of death worldwide, and it is the most common cause of oral cancers. This study aims to provide a deeper understanding of the molecular pathways in the oral cavity that are altered by exposure to cigarette smoke.
Methods: The gene expression dataset (accession number GSE8987, GPL96) of buccal mucosa samples from smokers (n = 5) and never smokers (n = 5) was downloaded from The National Center for Biotechnology Information's (NCBI) Gene Expression Omnibus (GEO) repository. Differential expression was ascertained via NCBI's GEO2R software, and Ingenuity Pathway Analysis (IPA) software was used to perform a pathway analysis.
Results: A total of 459 genes were found to be significantly differentially expressed in smoker buccal mucosa (p < 0.05). A total of 261 genes were over-expressed while 198 genes were under-expressed. The top canonical pathways predicted by IPA were nitric oxide and reactive oxygen production at macrophages, macrophages/fibroblasts and endothelial cells in rheumatoid arthritis, and thyroid cancer pathways. The IPA upstream analysis predicted that the TP53, APP, SMAD3, and TNF proteins as well as dexamethasone drug would be top transcriptional regulators.
Conclusions: IPA highlighted critical pathways of carcinogenesis, mainly nitric oxide and reactive oxygen production at macrophages, and confirmed widespread injury in the buccal mucosa due to exposure to cigarette smoke. Our findings suggest that cigarette smoking significantly impacts gene pathways in the buccal mucosa and may highlight potential targets for treating the effects of cigarette smoking.
Supplementary information: The online version contains supplementary material available at 10.1186/s43042-022-00268-y.
{"title":"Pathway analysis of smoking-induced changes in buccal mucosal gene expression.","authors":"Anas Khaleel, Bayan Alkhawaja, Talal Salem Al-Qaisi, Lubna Alshalabi, Amneh H Tarkhan","doi":"10.1186/s43042-022-00268-y","DOIUrl":"10.1186/s43042-022-00268-y","url":null,"abstract":"<p><strong>Background: </strong>Cigarette smoking is the leading preventable cause of death worldwide, and it is the most common cause of oral cancers. This study aims to provide a deeper understanding of the molecular pathways in the oral cavity that are altered by exposure to cigarette smoke.</p><p><strong>Methods: </strong>The gene expression dataset (accession number GSE8987, GPL96) of buccal mucosa samples from smokers (<i>n</i> = 5) and never smokers (<i>n</i> = 5) was downloaded from The National Center for Biotechnology Information's (NCBI) Gene Expression Omnibus (GEO) repository. Differential expression was ascertained via NCBI's GEO2R software, and Ingenuity Pathway Analysis (IPA) software was used to perform a pathway analysis.</p><p><strong>Results: </strong>A total of 459 genes were found to be significantly differentially expressed in smoker buccal mucosa (<i>p</i> < 0.05). A total of 261 genes were over-expressed while 198 genes were under-expressed. The top canonical pathways predicted by IPA were nitric oxide and reactive oxygen production at macrophages, macrophages/fibroblasts and endothelial cells in rheumatoid arthritis, and thyroid cancer pathways. The IPA upstream analysis predicted that the TP53, APP, SMAD3, and TNF proteins as well as dexamethasone drug would be top transcriptional regulators.</p><p><strong>Conclusions: </strong>IPA highlighted critical pathways of carcinogenesis, mainly nitric oxide and reactive oxygen production at macrophages, and confirmed widespread injury in the buccal mucosa due to exposure to cigarette smoke. Our findings suggest that cigarette smoking significantly impacts gene pathways in the buccal mucosa and may highlight potential targets for treating the effects of cigarette smoking.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1186/s43042-022-00268-y.</p>","PeriodicalId":74994,"journal":{"name":"The Egyptian journal of medical human genetics","volume":"23 1","pages":"69"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9964939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-03-16DOI: 10.1186/s43042-022-00220-0
Hadeel Yaseen Abdel-Qader, Dina Adel Fouad, Soha Ahmed Abuelela, Heba Mohamed Atif Ismail, Noha Hussein Boshnaq
Background: Multiple myeloma (MM) is a proliferation of monoclonal plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Cytogenetic analysis is a challenge in MM because of the low mitotic activity and the rapid loss of plasma cells viability in bone marrow culture. Adding mitogens such as interleukin 6 (IL6) is known to promote the in vitro growth of myeloma cell lines and enhance the fluorescence in situ hybridization application. This study aims to evaluate the prognostic impact of cytogenetic abnormalities detected by enhanced interphase fluorescence in situ hybridization (iFISH) technique in Egyptian MM patients.
Results: Patients who had hyperdiploidy significantly presented with higher Hb level and lower calcium levels compared to non-hyperdiploid patients. They were staged as stage I and II by International staging system (ISS) and considered as standard risk showing better response to treatment. On the contrary, features associated with a worse outcome were patients having del 17p and those belonged to intermediate and high risk groups.
Conclusion: In conclusion, adding interleukin 6 to MM cell culture promotes the in vitro growth of myeloma cells and enhances the successful application of FISH technique. A comprehensive FISH probe set investigating high, intermediate and low-risk cytogenetic abnormalities is needed for accurate risk stratification. Hyperdiploid-myeloma is a favorable risk genetic subtype of MM associated with rapid response to therapy compared to patients having del 17p, t(4;14), and other 14q rearrangements rather than t(11;14) and t(6;14).
{"title":"Clonal heterogeneity by fluorescence in situ hybridization in multiple myeloma: enhanced cytogenetic risk stratification.","authors":"Hadeel Yaseen Abdel-Qader, Dina Adel Fouad, Soha Ahmed Abuelela, Heba Mohamed Atif Ismail, Noha Hussein Boshnaq","doi":"10.1186/s43042-022-00220-0","DOIUrl":"10.1186/s43042-022-00220-0","url":null,"abstract":"<p><strong>Background: </strong>Multiple myeloma (MM) is a proliferation of monoclonal plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Cytogenetic analysis is a challenge in MM because of the low mitotic activity and the rapid loss of plasma cells viability in bone marrow culture. Adding mitogens such as interleukin 6 (IL6) is known to promote the in vitro growth of myeloma cell lines and enhance the fluorescence in situ hybridization application. This study aims to evaluate the prognostic impact of cytogenetic abnormalities detected by enhanced interphase fluorescence in situ hybridization (iFISH) technique in Egyptian MM patients.</p><p><strong>Results: </strong>Patients who had hyperdiploidy significantly presented with higher Hb level and lower calcium levels compared to non-hyperdiploid patients. They were staged as stage I and II by International staging system (ISS) and considered as standard risk showing better response to treatment. On the contrary, features associated with a worse outcome were patients having del 17p and those belonged to intermediate and high risk groups.</p><p><strong>Conclusion: </strong>In conclusion, adding interleukin 6 to MM cell culture promotes the in vitro growth of myeloma cells and enhances the successful application of FISH technique. A comprehensive FISH probe set investigating high, intermediate and low-risk cytogenetic abnormalities is needed for accurate risk stratification. Hyperdiploid-myeloma is a favorable risk genetic subtype of MM associated with rapid response to therapy compared to patients having del 17p, t(4;14), and other 14q rearrangements rather than t(11;14) and t(6;14).</p>","PeriodicalId":74994,"journal":{"name":"The Egyptian journal of medical human genetics","volume":"23 1","pages":"66"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9973681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}