Regional variations are found in the incidence and severity of the COVID-19 infection. Human leukocyte antigen (HLA) polymorphism is one of the genetic factors that might have an impact on the outcome of the disease. This study explored the association between the HLA genotype and the severity of COVID-19 among patients from South Asia. Blood samples from 95 Asians (Bangladeshis, Indians, and Pakistanis) with COVID-19 were collected. The patients were divided according to the severity of their infection: mild (N = 64), severe (N = 31), and fatal (N = 20). DNA was extracted from all samples, and HLA genotyping was performed for both class I (A, B, and C) and class II (DRB1, DQA1, and DQB1) using the PCR-rSSO (polymerase chain reaction-reverse sequence-specific oligonucleotide) molecular method. The frequency of HLA-B*51 was significantly higher among patients in the fatal group than among those in the mild infection group (15% vs. 4.7%, p = 0.027). Additionally, the frequency of HLA-B*35 was significantly higher in the mild infection group than in the fatal group (21.1% vs. 7.5%, p = 0.050 [a borderline p-value]). In terms of HLA class II, DRB1*13 was significantly observed in the fatal group than in the mild infection group (17.5% vs. 11.3%, p = 0.049). However, the p-value for all alleles became insignificant after a statistical correction for the p-values (p c = 0.216, p c = 0.4, and p c = 0.49, respectively). Compared with all published data, this study highlights that the association between the HLA system and the COVID-19 outcome might be ethnic-dependent. Genetic variation between populations must be examined on a wider scale to assess infection prognosis and vaccine effectiveness.
The chicken anaemia virus-derived protein Apoptin/VP3 (CAV-Apoptin) has the important ability to induce tumour-selective apoptosis in a variety of human cancer cells. Recently the first human Gyrovirus (HGyV) was isolated from a human skin swab. It shows significant structural and organisational resemblance to CAV and encodes a homologue of CAV-Apoptin/VP3. Using overlapping primers we constructed a synthetic human Gyrovirus Apoptin (HGyV-Apoptin) fused to green fluorescent protein in order to compare its apoptotic function in various human cancer cell lines to CAV-Apoptin. HGyV-Apoptin displayed a similar subcellular expression pattern as observed for CAV-Apoptin, marked by translocation to the nucleus of cancer cells, although it is predominantly located in the cytosol of normal human cells. Furthermore, expression of either HGyV-Apoptin or CAV-Apoptin in several cancer cell lines triggered apoptosis at comparable levels. These findings indicate a potential anti-cancer role for HGyV-Apoptin.
Key Points• There is 100% concordance in the cytogenetic and mutation profile between PB and BM in myelodysplastic syndrome.Recent studies have shown that more than 80% of bone marrow (BM) samples from patients with myelodysplastic syndrome (MDS) harbor somatic mutations and/or genomic aberrations, which are of diagnostic and prognostic importance. We investigated the potential use of peripheral blood (PB) and serum to identify and monitor BM-derived genetic markers using high-resolution single nucleotide polymorphism array (SNP-A) karyotyping and parallel sequencing of 22 genes frequently mutated in MDS. This pilot study showed a 100% SNP-A karyotype concordance and a 97% mutation concordance between the BM and PB. In contrast, mutation analysis using Sanger sequencing of PB and serum-derived DNA showed only 65% and 42% concordance to BM, respectively. Our results show the potential utility of PB as a surrogate for BM for MDS patients, thus avoiding the need for repeated BM aspirates particularly in elderly patients and those with fibrotic or hypocellular marrows. (Blood. 2013;122(4):567-570) IntroductionThe myelodysplastic syndromes (MDSs) are clonal disorders of hematopoiesis that occur predominantly in the elderly (median age 72 years) and are characterized by morphologic dysplasia, ineffective hematopoiesis, peripheral blood (PB) cytopenias, chromosomal aberrations, and propensity to myeloid leukemic transformation. The advent of high-throughput and high-resolution techniques for genetic analysis has shown that more than 80% of MDS patients harbor somatic mutations and/or genomic aberrations in their bone marrow (BM), which provide pathogenetic as well as diagnostic and prognostic insights into this disease.1-4 Frequent BM aspirates may be required for morphological 5 and genetic assessment, especially after BM transplant. In addition, in a significant patient proportion, the BM is hypocellular (10% to 15%) 6 and/or fibrotic (17%), 7 making the aspiration procedure painful and uncomfortable, especially in the elderly. In MDS the molecular analysis of copy number changes and genetic mutations has been done primarily on BM-derived DNA samples. Previous studies that used fluorescent in situ hybridization (FISH) and single nucleotide polymorphism arrays (SNP-As) to compare the karyotype concordance between BM and PB showed the usefulness of this approach. However, a comprehensive genetic analysis to compare the karyotype and mutation profile between BM and PB in MDS has not been performed. [8][9][10][11] In this pilot study we investigated the presence of BM-derived genetic markers in both PB and serum from the same patients using high-resolution SNP-A karyotyping, 454 parallel sequencing (454-PS), and Sanger sequencing of 22 genes most frequently mutated in MDS and acute myeloid leukemia (AML). Study designGenomic DNA from PB and BM was extracted (Qiagen) from frozen cell pellets and 100 ng was whole genome amplified (WGA; Qiagen), both per manufacturer's protocols. Serum DNA was purified from 200 mL of serum ...
HLA polymorphism is one of the genetic factors that may be associated with variations in susceptibility to COVID-19 infection. In this study, the frequency of HLA alleles among Saudi patients infected with COVID-19 was examined. The association with infection susceptibility and mortality was evaluated. This study included 135 Saudi COVID-19-infected patients (106 recovered and 29 died) who were admitted to hospitals because of their symptoms, and 135 healthy controls. HLA class I (A, B, C) and class II (DRB1, DQB1) genotyping was performed using the molecular method (PCR-rSSO). In this study, there was a significant increase in the frequency of HLA-A*01, B*56 and C*01 among infected patients compared to the control group (12.1% vs. 5.2%, p = 0.004, 3.7% vs. 0%, p = 0.006, 4.4% vs. 1.5%, p = 0.042, respectively). Moreover, there was a significant increase in the frequency of HLA-A*03 and C*06 among fatal patients compared to infected patients (13.8% vs. 5.7%, p = 0.036, 32.8% vs. 17.5%, p = 0.011, respectively). In terms of HLA class II, HLA-DRB1*04 was significantly higher in the control group compared to infected patients (27.4% vs. 16.3%, p = 0.002), while HLA-DRB1*08 was significantly higher in the infected group compared to the control (4.8% vs. 0.7%, p = 0.004). After statistical correction of the p value, A*01, B*56, DRB1*04 and DRB1*08 remained statistically significant (p c = 0.04, p c = 0.03, p c = 0.014 and p c = 0.028). This initial data suggested that individual HLA genotypes might play a role in determining susceptibility to COVID-19 infection and infection outcome. However, examining a larger sample size from different populations is required to determine a powerful association for clinical application.
The increasing number of COVID-19 patients has increased health care professionals’ workloads, making the management of dynamic patient information in a timely and comprehensive manner difficult and sometimes impossible. Compounding this problem is a lack of health care professionals and trained medical staff to handle the increased number of patients. Although Saudi Arabia has recently improved the quality of its health services, there is still no suitable intelligent system that can help health practitioners follow the clinical guidelines and automated risk assessment and treatment plan remotely, which would allow for the effective follow-up of patients of COVID-19. The proposed system includes five sub-systems: an information management system, a knowledge-based expert system, adaptive learning, a notification and follow-up system, and a mobile tracker system. This study shows that, to control epidemics, there is a method to overcome the shortage of specialists in the management of infections in Saudi Arabia, both today and in the future. The availability of computerized clinical guidance and an up-to-date knowledge base play a role in Saudi health organizations, which may not have to constantly train their physician staff and may no longer have to rely on international experts, since the expert system can offer clinicians all the information necessary to treat their patients.
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