Cellular and humoral immunogenicity of the COVID-19 vaccine and COVID-19 disease severity in individuals with immunodeficiency.

Background: A well-coordinated adaptive immune response is crucial for limiting COVID-19 disease. Some individuals with immunodeficiency are at a high risk of developing severe COVID-19. Therefore, the development of standardized methods for measuring different arms of the vaccine response in the setting of immunodeficiency is of particular interest. In this study, we compared the vaccine response of individuals living with immunodeficiency with healthy controls in terms of interferon gamma (IFN-γ) production and spike protein-specific antibody level post primary COVID-19 vaccination and booster vaccines. Additionally, the disease severity of those individuals who contracted COVID-19 was assessed. Methods: Whole blood was stimulated overnight from 71 participants and 99 healthy controls. Commercially available PepTivator® peptide pool and trimeric spike protein stimulation were used. ELISA was used to analyze IFN-γ levels. The total SARS-CoV-2 spike protein antibody titre was measured using a Roche Elecsys® S total antibody assay. Patient characteristics, COVID-19 infection status and IDDA 2.1 'Kaleidoscope' scores were recorded. Vaccine responses were scored from zero to three. Results: 99% of healthy controls, 89% of individuals with IEI and 76% with secondary immunodeficiency (SID) had an IFN-γ level above the validated reference range after peptide mix stimulation following primary vaccination. There was an increase in IFN-γ levels in patients with inborn errors of immunity (IEI) following the booster vaccine (p = 0.0156). 100% of healthy controls, 70% of individuals living with IEI and 64% of individuals living with SID had detectable spike protein-specific antibody levels following the primary vaccination. 55% of immunodeficiency patients who had mild COVID-19 and 10% with moderate/severe COVID-19 had detectable antibody and IFN-γ levels post vaccine. The mean pre-infection IDDA 2.1 scores were higher in individuals who developed moderate/severe COVID-19 (25.2 compared to 9.41). Conclusions: Covid whole-blood IGRA is a highly accurate, straightforward and robust assay and can be easily adapted to measure cellular response to COVID-19. A complete evaluation of the vaccine response may be particularly important for individuals living with immunodeficiency. A clinical immunodeficiency score and a validated vaccine response score may be valuable tools in estimating COVID-19 disease risk and identifying individuals living with immunodeficiency who may benefit from enhanced vaccination schedules.

Case Study: Impact of Regulatory Restrictions and Tax Policy on Breakeven Analysis and Risk Management

The objective of this case study is to enable students to analyze the financial impact of an unexpected catastrophic event on a retail business and how the strategic operational decisions made in response to regulatory restrictions and changes in tax policy impact the business's risk tolerance and breakeven analysis. To provide students with a context for comparison, this case study provides students with the opportunity to analyze the financial statements of a retail business prior to the occurrence of an unexpected catastrophic event, how the catastrophic event impacted revenue and profitability, and how the risk reduction strategies the business employed contained the adverse impact of the factors brought on by that catastrophic event on breakeven. This case study addresses a core gap in the body of knowledge by analyzing a business in three distinct stages of the business life cycle: (1) in the start-up phase;(2) in pre-crisis operations mode;and (3) in crisis mode confronted with an unexpected catastrophic event amidst governmental shutdowns, state and federal regulatory restrictions, and emergency changes to the tax policy. Examining a fictitious restaurant (a composite of the sales statistics of three actual restaurants located in Long Island, New York from 2019 to 2021) in operation for one year prior to the COVID-19 pandemic, students are given the opportunity to think critically about how strategic operational decisions made to generate sales, to minimize risk, to comply with mandated state government policy, and to take advantage of federal tax relief policy, collectively changed the financial projections and impacted the breakeven analysis of that business. Students are able to evaluate business start-up costs, first year (pre-pandemic) sales and costs, and second year (during pandemic) sales and costs of a retail business. Students then evaluate how the United States' federal PPP relief loan program, along with other pandemic relief programs for businesses and individuals, impacted profitability and business strategy. Students also assess risk, risk tolerance, and how the strategies employed to minimize risk impact a business. The motivation for this case study is to provide students with an illustrative example of an entity at various stages of the business life cycle, to explore the surrounding context of the impact of external environmental events, and to identify the effects of strategic operational responses to the various regulatory changes that were brought on by a catastrophic event. This case study is designed for use in courses that study revenue projection, tax, internal controls, breakeven analysis, and risk management. Teaching Note: While this case study uses a restaurant as a model, prior understanding of the restaurant industry is not necessary. Any student or instructor can use their practical knowledge and experience as a consumer to adequately analyze the issues presented. © 2023 by the authors.

COVID-19 vaccination-related exacerbation of seizures in persons with epilepsy.

Although vaccines are generally safe in persons with epilepsy (PWE), seizures can be associated with vaccination, including COVID-19. This study assessed the occurrence of COVID-19 vaccination-related seizure exacerbations in PWE. Adult PWE who had received a COVID-19 vaccine were consecutively recruited at a tertiary epilepsy clinic between June 2021 and April 2022. Patient demographics, including epilepsy history, vaccination details, and reported adverse effects were recorded. Seizure exacerbation, defined as occurring within one week of vaccination, was assessed. Five hundred and thirty PWE received the COVID-19 vaccine. 75 % received the Comirnaty (Pfizer) vaccine as their initial dose. Most patients (72 %) were taking ≥ 2 antiseizure medications (ASM) and had focal epilepsy (73 %). One-third were 12 months seizure free at their first vaccination. 13 patients (2.5 %) reported a seizure exacerbation following their first vaccination, three of whom required admission. None were seizure-free at baseline. Six of these patients (46 %) had a further exacerbation of seizures with their second vaccine. An additional four patients reported increased seizures only with the second vaccine dose. Seizure exacerbations are infrequently associated with COVID-19 vaccination, mainly in patients with ongoing seizures. The likelihood of COVID-19 infection complications in PWE outweighs the risk of vaccination-related seizure exacerbations.

Evidence-based implementation of our “Structured urinary Continence Assessment and Management Plan” practice change package to improve continence assessment, diagnosis and management on wards admitting patients post-stroke

Background: Urinary continence assessment and management plans are recommended in stroke clinical guidelines, however this care is often not provided. Aim: To determine the proportion of hospitalised patients with continence symptoms who have an assessment, diagnosis and management plan, before, and following the implementation of a practice change intervention. Methods: Fifteen wards (acute=3, rehabilitation=7, acute and rehabilitation= 5), that admit adult patients with stroke at 12 hospitals (metropolitan= 4, regional=8) participated. We implemented our evidence-based Structured urinary Continence Assessment and Management Plan (SCAMP) intervention (clinical decision tool, practice guidelines, webbased clinician education modules) using implementation strategies to overcome identified barriers. Screening and auditing of consecutive medical record for three 3-month periods were undertaken: before implementation (T0);after the 6-month implementation period (T1), and after a 6-month maintenance period (T2). The records of symptomatic inpatients were audited in detail. Descriptive statistics for The proportions of eligible symptomatic inpatients receiving continence assessment, diagnosis and management plans are presented. Results: All wards contributed data at T0, and 11/15 wards at T1 and T2. The onset of COVID19 prevented implementation at two rural wards, and two metropolitan wards closed immediately after implementation was completed. The proportion of symptomatic inpatients relative to all screened was: T0= 33% (283/849), T1= 33% (239/723), T2= 36% (247/695). The characteristics of symptomatic inpatients included: age(years) mean(SD) T0= 79(13), T1= 76(15), T2= 76(14);females T0= 57%(161/283);T1= 55%(132/239);T2= 58%(143/247). The proportions of symptomatic patients receiving components of care were: assessment within 72 hours T0= 38%, T1= 64%, T2= 64%;diagnosis T0= 30%, T1= 70%, T2= 72%;management plan T0= 7%, T1= 25%, T2= 23%. Discussion: From this large, multi-site study we identified implementation of our SCAMP intervention resulted in immediate improvements in continence care, that were sustained six months later. This intervention appears promising to increase access to best-practice continence care.

A Comparison of the Performance of SARS-CoV-2 Antibody Assays in Healthcare Workers with COVID-19

Aims Since its emergence, significant interest surrounds the use of SARS-CoV-2 serological tests as an alternative or as an adjunct to molecular testing. However, given the speed of this pandemic, paralleled with the pressure to develop and provide serological tests in an expediated manner, not every assay has undergone the rigorous evaluation that is usually associated with medical diagnostic assays. We aimed to examine the performance of several commercially available SARS-CoV-2 IgG antibody assays among participants with confirmed COVID-19 disease and negative controls. Methods Serum taken between day 17 and day 40 post onset of symptoms from 41 healthcare workers with RT-PCR confirmed COVID-19 disease, and pre-pandemic serum from 20 negative controls, were tested for the presence of SARS-CoV-2 IgG using 7 different assays including point-of-care (POC) and laboratory-based assays. Results Assay performance varied. The lab-based Abbott diagnostics SARS-CoV-2 IgG assay proved to be the assay with the best positive and negative predictive value, and overall accuracy. The POC Nal von Minden GmbH and Biozek assays also performed well. Conclusion Our research demonstrates the variations in performance of several commercially available SARS-CoV-2 antibody assays. These findings identify the limitations of some serological tests for SARS-CoV-2. This information will help inform test selection and may have particular relevance to providers operating beyond accredited laboratories.

Skin cancer surgery during the COVID-19 pandemic: A national, multicentre, prospective cohort study and survey of plastic surgeons

Skin cancer is the most common malignancy worldwide. The COVID-19 pandemic has caused an unprecedented reorganization of healthcare services. This study established what effect the pandemic has had on the provision of skin cancer surgery by plastic surgeons in the U.K., one of the worst affected countries globally. A national, multicentre, prospective cohort study of nonmelanoma skin cancer excisions was undertaken. Retrospective data were collected on melanoma surgery. Consecutive monthly surveys from plastic surgeons ascertained how national guidance was implemented. The primary outcome was surgical provision by tumour type. In total, 2050 patients (1549 with nonmelanoma skin cancer and 501 with melanoma) from 32 plastic surgery units were enrolled between 16 March and 14 June 2020. Surgeon surveys were received from 34 plastic surgery units. The number of nonmelanoma skin cancers treated per week fell by 27% to 44% during lockdown. The median number of general anaesthetic operating lists per week per institution fell sixfold from three before the pandemic to 0.5 in April (P < 0.001) and gradually increased in May and June but did not reach pre-'lockdown' levels. Excision of squamous cell carcinomas (SCCs) was prioritized over basal cell carcinomas (BCCs). At the peak of the pandemic, SCCs made up 71% of excisions (normally 28%;P < 0.001). Sentinel lymph node biopsies for melanoma (Breslow thickness ≥ 0.8 mm) occurred in only 26%, suggesting many patients were not accurately staged, restricting their access to adjuvant therapy. Two patients (0.7%) developed COVID-19 after melanoma surgery. High-risk tumours were particularly affected, as 77% of surgeons reported Mohs micrographic surgery was stopped and radiotherapy was run at a reduced service in 70% of units. Surgeons reported that surveillance for melanoma and SCC stopped in 10% and operating on BCCs was stopped in 73% of units. All skin cancers suffered a significant and abrupt disruption, but high-risk and complex lesions were worst affected. The majority of changes observed were in line with speciality association pandemic guidelines. In contrast to previous studies, we have demonstrated that operating on skin cancer during the pandemic was safe. To reduce further mortality and morbidity from the COVID-19 pandemic, skin services must be resumed urgently.