Increased vitamin D levels, as reflected by 25-hydroxy vitamin D (25OHD) measurements, have been proposed to protect against COVID-19 based on in vitro, observational, and ecological studies. ...However, vitamin D levels are associated with many confounding variables, and thus associations described to date may not be causal. Vitamin D Mendelian randomization (MR) studies have provided results that are concordant with large-scale vitamin D randomized trials. Here, we used 2-sample MR to assess evidence supporting a causal effect of circulating 25OHD levels on COVID-19 susceptibility and severity.
Genetic variants strongly associated with 25OHD levels in a genome-wide association study (GWAS) of 443,734 participants of European ancestry (including 401,460 from the UK Biobank) were used as instrumental variables. GWASs of COVID-19 susceptibility, hospitalization, and severe disease from the COVID-19 Host Genetics Initiative were used as outcome GWASs. These included up to 14,134 individuals with COVID-19, and up to 1,284,876 without COVID-19, from up to 11 countries. SARS-CoV-2 positivity was determined by laboratory testing or medical chart review. Population controls without COVID-19 were also included in the control groups for all outcomes, including hospitalization and severe disease. Analyses were restricted to individuals of European descent when possible. Using inverse-weighted MR, genetically increased 25OHD levels by 1 standard deviation on the logarithmic scale had no significant association with COVID-19 susceptibility (odds ratio OR = 0.95; 95% CI 0.84, 1.08; p = 0.44), hospitalization (OR = 1.09; 95% CI: 0.89, 1.33; p = 0.41), and severe disease (OR = 0.97; 95% CI: 0.77, 1.22; p = 0.77). We used an additional 6 meta-analytic methods, as well as conducting sensitivity analyses after removal of variants at risk of horizontal pleiotropy, and obtained similar results. These results may be limited by weak instrument bias in some analyses. Further, our results do not apply to individuals with vitamin D deficiency.
In this 2-sample MR study, we did not observe evidence to support an association between 25OHD levels and COVID-19 susceptibility, severity, or hospitalization. Hence, vitamin D supplementation as a means of protecting against worsened COVID-19 outcomes is not supported by genetic evidence. Other therapeutic or preventative avenues should be given higher priority for COVID-19 randomized controlled trials.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic urticaria is one of the most commonly diagnosed dermatoses. Following diagnosis, correct identification and proper treatment significantly reduces disease activity, thereby improving the ...patient’s quality of life. However, there is an extensive differential diagnosis for chronic urticaria that, if missed, can lead to life-threatening sequelae. Many of the diseases that masquerade as urticaria are rare and often have a significant delay in diagnosis. This paper aims to fill the gap in the literature by clearly characterising the cutaneous eruptions and atypical findings in many of the most common mimickers of chronic urticaria. Conditions such as erythema marginatum seen in conjunction with hereditary angioedema, urticaria vasculitis, autoinflammatory cryopyrin-associated periodic syndromes, adult-onset Still’s disease and systemic onset juvenile arthritis, Schnitzler syndrome, erythema multiforme, and cutaneous mastocytosis will be discussed.
PURPOSE OF REVIEWOcular allergies affect an estimated 40% of the population, 98% of which are because of allergic conjunctivitis. With the current advent of both repurposed drugs for ocular ...allergies, as well as novel drugs and methods of administration, there is a need for an updated review of current available medications. A clear characterization of each treatment will ultimately allow treating physicians to restore patients’ quality of life and decrease burden of disease.
RECENT FINDINGSCurrently, there are a number of reformulated antihistamines, with cetrizine being the most recent ophthalmic solution available. Nevertheless, there is ongoing research in the field of immunotherapy, steroids, flavonoids, cannabis, and drug-delivery systems.
SUMMARYAlthough dual-activity agents remain the keystone for treatment, newer drugs and drug-delivery systems offer other novel directions for delivering appropriate relief with minimal adverse effects.
Data on anaphylaxis cases in pre‐hospital settings is limited. As part of the Cross Canada Anaphylaxis Registry (C‐CARE), we assessed anaphylaxis cases managed by paramedics in Outaouais, Quebec. A ...software program was developed to prospectively record demographic and clinical characteristics as well as management of cases meeting the definition of the anaphylaxis. Univariate and multivariate logistic regressions were compared to assess factors associated with severity of reactions and epinephrine use. Among 33,788 ambulance calls of which 23,486 required transport, 104 anaphylaxis cases were identified (anaphylaxis rate of 0.31% 95%CI, 0.25%, 0.37% among all ambulance calls and 0.44% 95%CI, 0.36%, 0.54% among those requiring transport). The median age was 46.8 years and 41.3% were males. The common triggers included food (32.7% 95%CI, 24.0%, 42.7%), drugs (24.0% 16.4%, 33.6%), and venom (17.3% 10.8%, 26.2%). Among all reactions, 37.5% (95%CI, 28.4%, 47.6%) were severe. Epinephrine was not administered in 35.6% (95%CI, 26.6%, 45.6%) of all cases. Males were more likely to have severe reactions (Odds ratio OR: 2.50 95%CI, 1.03, 6.01). Venom‐induced reactions and severe anaphylaxis were more likely to be managed with epinephrine (OR: 6.9 95%CI, 1.3, 35.3 and 4.2 95%CI, 1.5, 12.0, respectively). This is the first prospective study evaluating anaphylaxis managed by paramedics. Anaphylaxis accounts for a substantial proportion of the cases managed by paramedics in Outaouais, Quebec and exceeds prior reports of the proportion of Quebec emergency room visits attributed to anaphylaxis. Although guidelines recommend prompt use of epinephrine for all cases of anaphylaxis, more than a third of cases did not receive epinephrine. It is crucial to develop educational programs targeting paramedics to promote the use of epinephrine in all cases of anaphylaxis regardless of the specific trigger.
This is the first prospective paper assessing anaphylaxis treated by paramedics. Our results reveal high rates of anaphylaxis, mainly triggered by food and under use of epinephrine.
To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds ...of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation (odds ratio (OR) = 0.54, P = 7 × 10
), hospitalization (OR = 0.61, P = 8 × 10
) and susceptibility (OR = 0.78, P = 8 × 10
). Measuring OAS1 levels in 504 individuals, we found that higher plasma OAS1 levels in a non-infectious state were associated with reduced COVID-19 susceptibility and severity. Further analyses suggested that a Neanderthal isoform of OAS1 in individuals of European ancestry affords this protection. Thus, evidence from MR and a case-control study support a protective role for OAS1 in COVID-19 adverse outcomes. Available pharmacological agents that increase OAS1 levels could be prioritized for drug development.
Predicting COVID-19 severity is difficult, and the biological pathways involved are not fully understood. To approach this problem, we measured 4701 circulating human protein abundances in two ...independent cohorts totaling 986 individuals. We then trained prediction models including protein abundances and clinical risk factors to predict COVID-19 severity in 417 subjects and tested these models in a separate cohort of 569 individuals. For severe COVID-19, a baseline model including age and sex provided an area under the receiver operator curve (AUC) of 65% in the test cohort. Selecting 92 proteins from the 4701 unique protein abundances improved the AUC to 88% in the training cohort, which remained relatively stable in the testing cohort at 86%, suggesting good generalizability. Proteins selected from different COVID-19 severity were enriched for cytokine and cytokine receptors, but more than half of the enriched pathways were not immune-related. Taken together, these findings suggest that circulating proteins measured at early stages of disease progression are reasonably accurate predictors of COVID-19 severity. Further research is needed to understand how to incorporate protein measurement into clinical care.
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