Reported Adverse Effects and Attitudes among Arab Populations Following COVID-19 Vaccination: A Large-Scale Multinational Study Implementing Machine Learning Tools in Predicting Post-Vaccination Adverse Effects Based on Predisposing Factors.

Background: The unprecedented global spread of coronavirus disease 2019 (COVID-19) has imposed huge challenges on the healthcare facilities, and impacted every aspect of life. This has led to the development of several vaccines against COVID-19 within one year. This study aimed to assess the attitudes and the side effects among Arab communities after receiving a COVID-19 vaccine and use of machine learning (ML) tools to predict post-vaccination side effects based on predisposing factors. Methods: An online-based multinational survey was carried out via social media platforms from 14 June to 31 August 2021, targeting individuals who received at least one dose of a COVID-19 vaccine from 22 Arab countries. Descriptive statistics, correlation, and chi-square tests were used to analyze the data. Moreover, extensive ML tools were utilized to predict 30 post vaccination adverse effects and their severity based on 15 predisposing factors. The importance of distinct predisposing factors in predicting particular side effects was determined using global feature importance employing gradient boost as AutoML. Results: A total of 10,064 participants from 19 Arab countries were included in this study. Around 56% were female and 59% were aged from 20 to 39 years old. A high rate of vaccine hesitancy (51%) was reported among participants. Almost 88% of the participants were vaccinated with one of three COVID-19 vaccines, including Pfizer-BioNTech (52.8%), AstraZeneca (20.7%), and Sinopharm (14.2%). About 72% of participants experienced post-vaccination side effects. This study reports statistically significant associations (p < 0.01) between various predisposing factors and post-vaccinations side effects. In terms of predicting post-vaccination side effects, gradient boost, random forest, and XGBoost outperformed other ML methods. The most important predisposing factors for predicting certain side effects (i.e., tiredness, fever, headache, injection site pain and swelling, myalgia, and sleepiness and laziness) were revealed to be the number of doses, gender, type of vaccine, age, and hesitancy to receive a COVID-19 vaccine. Conclusions: The reported side effects following COVID-19 vaccination among Arab populations are usually non-life-threatening; flu-like symptoms and injection site pain. Certain predisposing factors have greater weight and importance as input data in predicting post-vaccination side effects. Based on the most significant input data, ML can also be used to predict these side effects; people with certain predicted side effects may require additional medical attention, or possibly hospitalization.

Genome-Wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A and Identification of ZBTB10 and Three Distinct HLA Associations.

To investigate the genetics of late-onset myasthenia gravis (LOMG), we conducted a genome-wide association study imputation of>6 million single nucleotide polymorphisms (SNPs) in 532 LOMG cases (anti-acetylcholine receptor [AChR] antibody positive; onset age≥50 years) and 2,128 controls matched for sex and population substructure. The data confirm reported TNFRSF11A associations (rs4574025, P = 3.9 × 10-7, odds ratio [OR] 1.42) and identify a novel candidate gene, ZBTB10, achieving genome-wide significance (rs6998967, P = 8.9 × 10-10, OR 0.53). Several other SNPs showed suggestive significance including rs2476601 (P = 6.5 × 10-6, OR 1.62) encoding the PTPN22 R620W variant noted in early-onset myasthenia gravis (EOMG) and other autoimmune diseases. In contrast, EOMG-associated SNPs in TNIP1 showed no association in LOMG, nor did other loci suggested for EOMG. Many SNPs within the major histocompatibility complex (MHC) region showed strong associations in LOMG, but with smaller effect sizes than in EOMG (highest OR ~2 versus ~6 in EOMG). Moreover, the strongest associations were in opposite directions from EOMG, including an OR of 0.54 for DQA1*05:01 in LOMG (P = 5.9 × 10-12) versus 2.82 in EOMG (P = 3.86 × 10-45). Association and conditioning studies for the MHC region showed three distinct and largely independent association peaks for LOMG corresponding to (a) MHC class II (highest attenuation when conditioning on DQA1), (b) HLA-A and (c) MHC class III SNPs. Conditioning studies of human leukocyte antigen (HLA) amino acid residues also suggest potential functional correlates. Together, these findings emphasize the value of subgrouping myasthenia gravis patients for clinical and basic investigations and imply distinct predisposing mechanisms in LOMG.

Spectrum of Phenotypes Associated with Mutations in LRBA.

To date, several germline mutations have been identified in the LRBA gene in patients suffering from a variety of clinical symptoms. These mutations abolish the expression of the LRBA protein, leading to autoimmunity, chronic diarrhea, B-cell deficiency, hypogammaglobulinemia, functional T-cell defects and aberrant autophagy. We review the clinical and laboratory features of patients with LRBA mutations and present five novel mutations in eight patients suffering from a multitude of clinical features.

Novel mutations in TNFRSF7/CD27: Clinical, immunologic, and genetic characterization of human CD27 deficiency.

BACKGROUND: The clinical and immunologic features of CD27 deficiency remain obscure because only a few patients have been identified to date. OBJECTIVE: We sought to identify novel mutations in TNFRSF7/CD27 and to provide an overview of clinical, immunologic, and laboratory phenotypes in patients with CD27 deficiency. METHODS: Review of the medical records and molecular, genetic, and flow cytometric analyses of the patients and family members were performed. Treatment outcomes of previously described patients were followed up. RESULTS: In addition to the previously reported homozygous mutations c.G24A/p.W8X (n = 2) and c.G158A/p.C53Y (n = 8), 4 novel mutations were identified: homozygous missense c.G287A/p.C96Y (n = 4), homozygous missense c.C232T/p.R78W (n = 1), heterozygous nonsense c.C30A/p.C10X (n = 1), and compound heterozygous c.C319T/p.R107C-c.G24A/p.W8X (n = 1). EBV-associated lymphoproliferative disease/hemophagocytic lymphohistiocytosis, Hodgkin lymphoma, uveitis, and recurrent infections were the predominant clinical features. Expression of cell-surface and soluble CD27 was significantly reduced in patients and heterozygous family members. Immunoglobulin substitution therapy was administered in 5 of the newly diagnosed cases. CONCLUSION: CD27 deficiency is potentially fatal and should be excluded in all cases of severe EBV infections to minimize diagnostic delay. Flow cytometric immunophenotyping offers a reliable initial test for CD27 deficiency. Determining the precise role of CD27 in immunity against EBV might provide a framework for new therapeutic concepts.