ABSTRACT
Background: Polyethylene glycols (PEGs) are hydrophilic polyethers widely used in pharmaceutical, cosmetic, food, and household products. PEG is usually safe and allergic reactions are rare, however according to literature, hypersensitivity is most likely underestimated and mild to life-threatening immediate-type hypersensitivity to PEG have been reported. PEG 2000 is an ingredient in some of the COVID-19 vaccines and is a possible cause of rare cases of adverse reactions to the vaccines that have been reported*. PEG hypersensitivity seems to depend on molecular weight (MW) and higher MW PEGs appear to be more allergenic. Based on this, we developed two ImmunoCAP PEG tests with different MW:s of PEG for measurement of anti-PEG specific IgE (sIgE) and specific IgG antibodies. Method(s): ImmunoCAP PEG 2000 and PEG 10000 Research Use Only (RUO) tests were developed according to conventional methods. As PEG is structurally related to polysorbates, a specific polysorbate 20 free washing solution was developed. The analytical characteristics of the ImmunoCAP PEG tests have been determined and an accelerated stability study has been performed. Result(s): The developed RUO ImmunoCAP PEG 2000 and PEG 10000 tests fulfilled internal standard RUO specifications using the polysorbate 20 free washing solution. Intra-and inter assay performance were evaluated at three concentrations from low to high on the sIgE measuring range (0-100 kUA/L). Overall results for intra-and inter assay performance were <=6.0 %CV and <=9.5 %CV, respectively. Anti-PEG IgG have been reported in human plasma samples with levels reaching up to 6.5 mug/mL (median 49.3 ng/mL). No anti-PEG IgG interference could be detected for these PEG tests when assayed with an anti-PEG IgG positive control in concentrations up to 6.5 mug/mL. An accelerated stability study indicated a shelf-life of two years for both PEG tests. Conclusion(s): Two ImmunoCAP PEG tests have been developed. These tests have been used as a complementary research tool to evaluate the risk for hypersensitivity reactions to PEG and to determine sIgE sensitization pattern in patient serum. In addition, studies have shown sIgE levels >0.1 kUA/L using these ImmunoCAP PEG tests for patients with a history of reactions to PEG together with positive skin prick testing. *It is important to understand that these reactions are extremely rare and should not discourage the general public from vaccination.
ABSTRACT
We studied the clinical and immunological outcomes of covid-19 infection in strictly consecutive patients with CLL from a well-defined area during the first 13 months of the pandemic. Sixty patients with a median age of 71 years (range 43-97) were identified. Median CIRS was 8 (4-20), median BMI 25 (19-42) and 65% were men. Patients had indolent CLL (n=38), were previously treated (n=12) or had ongoing therapy (n=10, among which seven received BTKi). Forty-six patients (77%) were hospitalized due to severe covid-19 and among them, 11 (24%) were admitted to the intensive care unit (ICU). Severe covid-19 was equally distributed across subgroups irrespective of age, gender, BMI, CLL status except for comorbidities (CIRS >6, p<0.05). Fourteen patients (23%) died;age ≥75 years was the only significant risk factor (p<0.05, uni- and multivariate analyses). Comparing months 1-6 vs. 7-13 of the pandemic, death rates were reduced from 32 to 18%, ICU admission from 37 to 15% and hospitalizations remained frequent (86 vs. 71%). Seroconversion occurred in 34/41 tested patients (83%) and anti-SARS-CoV-2 antibodies remained detectable at 6 and 12 months of follow-up in 17/22 and 8/11 patients, respectively. In-depth immunological analysis revealed that 13/17 tested patients had neutralizing antibodies (including all 12 patients that were also seropositive in conventional serology in this cohort), and 19/28 (68%) had antibodies in saliva. SARS-CoV- 2-specific T-cells (IFN-gamma ELISpot) were detected in 14/17 patients (82%). We conclude that covid-19 in non-selected CLL patients continued to result in a high admission rate even among young early-stage patients. A robust and durable B and/or T cell immunity was observed in most convalescents.
ABSTRACT
The current SARS-CoV-2 pandemic have led to an increased use of medical devices such as face masks and nitrile gloves, within occupational groups of medical care as well as within the general population. Consequently, the incidence reports of adverse effects associated with use of such medical devices have increased manyfold, including reports of allergic skin reactions. The cause of allergic skin reactions, referred to as Allergic Contact Dermatitis (ACD) is the immunological process known as skin sensitization, which is induced by so-called chemical sensitizers. Assessment of skin sensitizing potential of leachables from medical devices is a part of biocompatibility testing of medical devices and is typically performed by use of the Guinea Pig Maximization Test (GPMT), in accordance with the ISO 10993 series of standards. However, recent developments of in vitro assays for assessment of chemical sensitizers motivates the exploration of such methods in the context of rapid pandemic-associated testing. The GARDskin assay [1] is a next-generation in vitro assay for hazard assessment of skin sensitizers, currently progressing towards regulatory acceptance. The method evaluates the transcriptional patterns of a genomic biomarker signature in a human dendritic-like cell line following exposure, in order to provide hazard assessments of tested substances. The method has been adapted to testing of solid materials from e.g. medical device products, by application of extraction protocols using polar- and non-polar extraction vehicles, in accordance with ISO 10993-12. Here, we present results from testing of a commonly used face mask and a nitrile glove in the GARDskin Medical Device assay. Results indicate that the face mask does not leach any compounds with skin sensitizing potential (among four different batches tested), while the nitrile glove was classified as a skin sensitizer. These results harmonize with preexisting experience of similar models of nitril gloves, which are known to be associated with adverse skin reactions, potentially induced by skin sensitization. Furthermore, these results may have implications on the continued use of similar medical devices throughout the pandemic and beyond, as the appropriate application and removal of face masks may indeed benefit from the discontinued simultaneous use of nitrile gloves.
ABSTRACT
The COVID-19 pandemic, and its management, is markedly impacting the management of osteoporosis as judged by access to online FRAX fracture risk assessments. Globally, access was 58% lower in April than in February 2020. Strategies to improve osteoporosis care, with greater use of fracture risk assessments, offer a partial solution. INTRODUCTION: The COVID-19 pandemic is having a significant detrimental impact on the management of chronic diseases including osteoporosis. We have quantified the global impact by examining changes in the usage of online FRAX fracture risk assessments before and after the declaration of the pandemic (11 March 2020). METHODS: The study comprised a retrospective analysis using GoogleAnalytics data on daily sessions on the FRAX® website ( www.sheffield.ac.uk/FRAX ) from November 2019 to April 2020 (main analysis period February-April 2020), and the geographical source of that activity. RESULTS: Over February-April 2020, the FRAX website recorded 460,495 sessions from 184 countries, with 210,656 sessions in February alone. In March and April, the number of sessions fell by 23.1% and 58.3% respectively, a pattern not observed over the same period in 2019. There were smaller reductions in Asia than elsewhere, partly related to earlier and less-marked nadirs in some countries (China, Taiwan, Hong Kong, South Korea and Vietnam). In Europe, the majority of countries (24/31, 77.4%) reduced usage by at least 50% in April. Seven countries showed smaller reductions (range - 2.85 to - 44.1%) including Poland, Slovakia, Czech Republic, Germany, Norway, Sweden and Finland. There was no significant relationship between the reduction in FRAX usage and measures of disease burden such as COVID-attributed deaths per million of the population. CONCLUSION: This study documents a marked global impact of the COVID-19 pandemic on the management of osteoporosis as reflected by FRAX online fracture risk assessments. The analysis suggests that impact may relate to the societal and healthcare measures taken to ameliorate the pandemic.