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Summary Background ChAdOx1-vectored vaccine candidates against several pathogens have been developed and tested in clinical trials and ChAdOx1 nCoV-19 has now been licensed for emergency use for COVID-19. We assessed the safety and immunogenicity of the ChAdOx1 MERS vaccine in a phase 1b trial in healthy Middle Eastern adults. Method MERS002 is an open-label, non-randomised, dose-escalation, phase 1b trial. Healthy Middle Eastern adults aged 18–50 years were included in the study. ChAdOx1 MERS was administered as a single intramuscular injection into the deltoid muscle of the non-dominant arm at three different dose groups: 5·0 × 109 viral particles in a low-dose group, 2·5 × 1010 viral particles in an intermediate-dose group, and 5·0 × 1010 viral particles in a high-dose group. The primary objective was to assess the safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited and unsolicited adverse events after vaccination for up to 28 days and occurrence of serious adverse events up to 6 months. The study is registered with ClinicalTrials.gov, NCT04170829. Findings Between Dec 17, 2019, and June 1, 2020, 24 participants were enrolled (six to the low-dose, nine to the intermediate-dose, and nine to the high-dose group) and received a dose; 23 were available for follow-up at 6 months. The one dose of ChAdOx1 MERS vaccine was well tolerated with no serious adverse event reported during the 6 months of follow-up. Most adverse events were mild (67, 74%) and moderate (17, 19%). Six (7%) severe adverse events were reported by two participants in the intermediate-dose group (two feverish, two headache, one joint pain, and one muscle pain). Pain at the injection site was the most common local and overall adverse event, reported by 15 (63%) of the 24 participants. The most common systemic adverse event was headache, reported by 14 (58%), followed by muscle pain reported by 13 (54%). The vaccine induced both antibody and T cell immune responses in all volunteers; antibodies peaked at day 28 and T cell responses peaked at day 14; and continued until the end of follow-up at 6 months. Interpretation The acceptable safety and immunogenicity data from this phase 1b trial of ChAdOx1 MERS vaccine candidate in Healthy Middle Eastern adults, combined with previous safety and immunogenicity data from a trial in the UK, support selecting the ChAdOx1 MERS vaccine for advancement into phase 2 clinical evaluation. Funding UK Department of Health and Social Care, using UK Aid funding, managed by the UK National Institute for Health Research; and King Abdullah International Medical Research Center.

Few studies examine health-related quality of life (HRQoL) in Arabic-speaking multiple sclerosis (MS) patients. However, HRQoL tools such as the Short Form-36 QoL instrument (SF-36) and the Multiple Sclerosis International QoL (MusiQoL) questionnaire have been validated in other languages. The primary objective of this study was to prospectively assess HRQoL using the MusiQoL questionnaire among Arabic-speaking MS patients treated with subcutaneous interferon (sc IFN β-1a) over 12 months, as part of a prospective, multinational, multicenter cohort study. Patients’ clinical parameters and HRQoL were assessed at baseline, 6 months, and 12 months. Changes in MusiQoL total and subdomain scores were compared using a Friedman test. Correlation between MusiQoL total score and Expanded Disability Status Score (EDSS) was also evaluated. In total, 439 patients from four Arabic-speaking countries were included. The mean age was 32.44 (±0.34) years, 71.5% were female, and 63.1% had an education level of university or above. The mean MS duration was 4.13 (±0.12) years, mean age at first attack was 27.35 (±0.26) years, and mean baseline EDSS score was 2.05 (±0.04). MusiQoL total score significantly improved at 6 months; however, this diminished at 12 months ( 65.67 ± 0.8 at baseline vs. 67.21 ± 0.79 at 6 months and 65.75 ± 0.8 at 12 months; p = 0.0015 ). Several aspects of patients’ HRQoL including activity of daily living, physical well-being, symptoms, and coping improved. Overall HRQoL measured using SF-36 remained generally unchanged over time ( p = 0.215 ). There was a statistically significant inverse relationship between change in EDSS score over time and change in overall MusiQoL score over time. In summary, findings confirm the utility of using MusiQoL for assessing changes in HRQoL during treatment with sc IFN β-1a in Arabic-speaking patients with MS.

Objective: Genome-Wide association studies (GWAS) showed an association between subset of single-nucleotide polymorphism (SNPs) and multiple sclerosis. Our study aims to study this association in Saudi familial multiple sclerosis patients. Methods: Four subject groups were used in this study: sporadic MS (MS patients without family history), FMS (MS patients who have at least one family member diagnosed with MS), related controls (relatives of FMS patients who appear to be free of the disease) and independent controls (healthy volunteers). Subjects were genotyped for 15 SNPs. The variation in the genotype distribution was analyzed across study groups by using logistic regression. Results: 342 subjects were included. 99 were in the sporadic MS group, 22 were FMS, 89 were related control, and 132 were independent control. SNPS rs3135388, rs7577363, rs1321172, rs6897932, rs6498169, rs12487066, and rs4763655were associated with MS when MS and independent control groups were compared. Same SNPS were identified but with stronger association when the FMS and independent control groups were compared. Finally, when the patients and the controls were selected from a much more homogenous genetic pool from which it would be expected that only SNPs highly linked to MS would persist, only two SNPs rs6498169[OR 4.26, CI (1.17 – 15.51)];, and rs10984447 [OR 13.63, CI(1.54, 120.83) ][were associated with MS. Conclusions: Our results suggest that using a more homogenous genetic pool of cases and controls could help to identify the most significant MS-associated SNPs. Our finding is in agreement with other studies including larger sample size and more diverse populations.

Parental consanguinity (PC) may be a risk factor for familial multiple sclerosis (FMS) throughout inbred communities. The objective of this report was to estimate prevalence of FMS and rate of PC among FMS versus non-FMS patients. All Saudi MS patients were identified from our registry. The history of PC was analyzed as a case-control study. In total 141 MS patients were identified. Of these, 30 (21%) reported having at least one affected relative, 37.6% reported PC and 16% presented first-degree PC. In addition, FMS patients were more likely than non-FMS patients to report PC. In conclusion, FMS is prevalent among Saudi MS patients. MS patients with a history of PC were more likely to have FMS, suggesting a potential role of consanguinity.