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

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

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

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Histological Comparison of Postoperative Wound Care Regimens for Laser Resurfacing in a Porcine Model

Background. The use of short‐pulsed CO2 lasers for skin resurfacing is routinely performed, but few studies have examined postsurgical care. Objective To determine which postoperative treatments are most beneficial in promoting optimal healing after laser resurfacing. Methods. Four pigs received laser resurfacing. The laser sites were randomly left untreated or treated with petroleum‐based ointment or dressed with 1 of the following occlusive dressings: hydrocolloid, hydrogel or foam. Biopsies were taken from each treatment group on Days 2, 3, 4, 5, 8, 12, and 19. All samples were stained with hematoxylin and eosin. Each histological slide was evaluated by a blinded investigator. Results. Differences were observed between treatment groups in the amount of cellular infiltrate, presence of necrotic tissue, progression of the epidermal sheet, maturation of the epidermis, presence of rete ridges, and appearance of new collagen. Conclusion. Postoperative treatments after laser resurfacing vary in their ability to influence the quality of healing

Laser Resurfacing: Usual and Unusual Complications

The use of the carbon dioxide laser for skin resurfacing was initially described in 1989. 1 Since that time, several reports have shown it to be highly effective in the treatment of photodamaged skin and acne scarring. 2,3,4,5 Advances in laser technology have simplified the procedure and minimized adverse sequelae. Laser skin resurfacing has become a very popular technique, and recently several patient series have been published on the use of different resurfacing lasers to treat photodamaged skin. 3,4 However, very little has been written about its complications. Adequate patient selection, sound medical judgement, proper training with experience and knowledge of skin physiology and wound care are important factors for successful outcomes. Interested physicians across a broad range of subspecialties have expressed concern about the rate of adverse outcomes and management of complications. We report seven representative cases of complications referred to our dermatology clinics from outside physicians, in the hope of educating clinicians regarding the usual and unusual side effects of this procedure

Efficacy of Dupilumab in Different Racial Subgroups of Adults With Moderate-to-Severe Atopic Dermatitis in Three Randomized, Placebo-Controlled Phase 3 Trials

Dupilumab, a monoclonal antibody that blocks the shared receptor subunit for interleukin (IL)-4 and IL-13, is currently approved for the treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis (AD). The efficacy and safety of dupilumab for AD among racial subgroups is unknown. This post hoc analysis from three phase 3 trials assessed the efficacy and safety of dupilumab vs placebo by racial subgroup (White, Asian, Black/African American). Data from LIBERTY AD SOLO 1 (NCT02277743), SOLO 2 (NCT02277769), and CHRONOS (NCT02260986) were pooled. Outcomes included mean and percent change from baseline to week 16 in the key therapeutic domains Eczema Area and Severity Index (EASI), Peak Pruritus Numerical Rating Scale (NRS), Dermatology Life Quality Index (DLQI), and Patient-Oriented Eczema Measure, as well as Investigator’s Global Assessment and pain or discomfort assessed by the European Quality of Life-5 Dimensions 3 level questionnaire. A total of 2,058 patients (White n=1,429, Asian n=501, Black/African American n=128) were included in the current analysis. Baseline demographics and disease characteristics were balanced between treatment groups and racial subgroups. In the three trials, dupilumab significantly (P\u3c0.0001) improved all assessed outcomes compared with placebo in the White and Asian subgroups. In the smaller Black/African American subgroup, dupilumab significantly (P\u3c0.0001) improved EASI endpoints and mean changes in Peak Pruritus NRS and DLQI vs placebo, with positive numeric trends favoring dupilumab in all other endpoints. Dupilumab was generally well tolerated, with an acceptable safety profile in all racial subgroups. Serious adverse events occurred more frequently with placebo; treatment discontinuations due to adverse events were rare in all treatment groups. Significant clinical improvement and a favorable benefit-risk profile can be achieved with dupilumab treatment in patients of White, Asian, and Black/African American racial subgroups with moderate-to-severe AD inadequately controlled with topical medications. ClinicalTrials.gov identifiers: NCT02277743, NCT02277769, NCT0226098