SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Additional file 1: of Orbital T-cell lymphoma in youngest recorded patient – early diagnosis, management, and successful outcome: a case report and review of the literature

Timeline of the patient's clinical history starting from the date of presentation to the date of last follow up. (JPEG 172 kb

Orbital T-cell lymphoma in youngest recorded patient – early diagnosis, management, and successful outcome: a case report and review of the literature

Abstract Background Primary orbital peripheral T-cell lymphoma, not otherwise specified is an exceedingly rare disorder with a very poor outcome, and to the best of our knowledge only a few cases have been reported in the English literature. We present the youngest reported case describing the successful outcome after management with a thorough review of the English literature of all the reported cases of primary peripheral T-cell lymphoma, not otherwise specified. Case presentation Our patient is a 3-year-old Syrian boy who presented with gradual progressive orbital swelling. A physical examination showed a left orbital dystopia and a superior medial displacement of the globe. Extraocular motility was limited in upward elevation of his left eye. A computed tomography scan and magnetic resonance imaging of his orbit showed a mass involving the lateral and inferior walls of his left orbit and extending intraconally. A diagnosis of peripheral T-cell lymphoma, not otherwise specified was made by careful histopathological examination and Berlin-Frankfurt-Munster protocol was initiated. A 6-month follow up with orbital magnetic resonance imaging showed no sign of orbital or brain involvement. Conclusions Through this report we emphasize two takeaway lessons: (1) always have a high level of suspicion of this entity regardless of the age of the patient; and (2) careful histopathological examination is very important for prompt confirmation of the diagnosis and early commencement of proper treatment

Impact of Comorbidities on Treatment Patterns and Disease Outcomes in Rheumatoid Arthritis: Findings from the Kuwait Registry for Rheumatic Diseases (KRRD)

Background: Comorbidities are common in rheumatoid arthritis (RA) and adversely affect outcomes, yet data from Middle Eastern populations remain limited. We aimed to evaluate the impact of comorbidity burden on prescribing patterns and disease activity in a large national RA cohort. Methods: We conducted a retrospective cohort study using the Kuwait Registry for Rheumatic Diseases (2011–2025). Adults with RA fulfilling ACR/EULAR criteria were stratified by comorbidity burden using the Kuwait Rheumatoid Arthritis Comorbidity Index (KRRD-CI): low (<3) vs high ([Formula: see text]3). Outcomes included prescribed medications (csDMARDs, bDMARDs, tsDMARDs), treatment regimens at baseline and last visit, and changes in DAS28 and CDAI. Results: Among 1,305 patients (937 low-comorbidity; 368 high-comorbidity), high-comorbidity patients were older (61.6 vs 45.3 years, p<0.001), more often female (81% vs 70%, p<0.001), and had longer disease duration (6.7 vs 3.8 years, p<0.001). Frequent comorbidities included hypertension (61%), diabetes (52%), osteoporosis (22%), and thyroid disease (25%). At baseline, methotrexate ([Formula: see text]57%) was most prescribed. Low-comorbidity patients more often received sulfasalazine (15% vs 11%) and hydroxychloroquine (28% vs 22%), while high-comorbidity patients more frequently received adalimumab (13% vs 7%), rituximab (4% vs 1%), and infliximab (6% vs 3%). tsDMARD use was rare (<2%). Treatment patterns differed: low-comorbidity patients were more often on csDMARD monotherapy (55% vs 41%) or untreated (19% vs 10%), whereas high-comorbidity patients more often received bDMARD monotherapy (19% vs 10%) or csDMARD[Formula: see text]bDMARD combinations (29% vs 16%). Over time, csDMARD monotherapy declined (53%[Formula: see text]36%), while bDMARD monotherapy (16%[Formula: see text]24%) and csDMARD[Formula: see text]bDMARD combinations (24%[Formula: see text]33%) increased. Both groups achieved significant disease activity improvements. DAS28 improved by 0.79 in low-comorbidity vs 0.61 in high-comorbidity; CDAI improved by 4.57 ([Formula: see text]46%) vs 4.55 ([Formula: see text]43%), respectively. Effect sizes were modest and comparable. Conclusions: High-comorbidity RA patients were more likely to receive biologics and combination DMARDs, while low-comorbidity patients often remained on csDMARD monotherapy or untreated. Despite greater biologic use in high-comorbidity patients, disease activity improvements were similar, suggesting therapeutic inertia or treatment resistance

Pharmaceutical Advertising and Public Perceptions in Saudi Arabia

Introduction: As the pharmaceutical advertising landscape evolves with digital advancements, this study examines public awareness and perceptions of medication advertisements in Saudi Arabia. It focuses on the effects of regulatory frameworks and evaluates how they influence public understanding and attitudes toward these advertisements. Method: A cross-sectional study was conducted using an electronic survey in Saudi Arabia in December 2023. The survey was distributed on social media platforms and reached a diverse sample of 440 participants. It covered public perception and attitudes toward drug advertisements, knowledge of regulatory laws, and preferences regarding advertising mediums. Results: Out of the 440 participants in the study, who were primarily employees with bachelor’s degrees, there was a clear awareness of drug advertisements. The average age of the group was 33 years, and a significant portion (71.1%) held a bachelor’s degree, with 51.1% being employed. The findings revealed that 25.5% of participants frequently noticed drug ads, while 22.7% saw them very often. Although many found the ads informative, there were significant concerns about unrealistic expectations and the risk of overmedication; 89.8% believed the ads set unrealistic expectations about the effectiveness of medications. Additionally, 60.7% thought that celebrity endorsements might mislead the audience, and 91.1% felt that ads should provide more detailed information about potential risks and side effects. Regarding preferred advertising platforms, mobile apps and websites were favored (47%), followed closely by social media (46.4%). A striking 93.2% of participants believed that drug ads on social media should be subject to stricter regulations, and 96.4% wanted more proactive monitoring of online advertising. Many also reported using other sources, such as medical review sites, to verify medication information. Conclusions: Pharmaceutical advertising in Saudi Arabia must balance ethical transparency with educational value. The influence of digital platforms underscores the necessity for stricter regulation and accurate information dissemination. A collaborative approach is essential to align advertising practices with public health interests and regulatory standards

Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study

OBJECTIVES: Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs. DESIGN: A multicentre, international, collaborative cohort study. SETTING: 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020. PARTICIPANTS: Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, Wilms' tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer. MAIN OUTCOME MEASURE: All-cause mortality at 30 days and 90 days. RESULTS: 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001). CONCLUSIONS: The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally