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.

ACT NOW a new diabetes foot educational and risk assessment tool for people with diabetes and health care professionals

Background: When a person with diabetes (PwD) develops a foot problem there is often a delay in receiving specialist help, which may result in amputation and health care professionals (HCP) may be accused of medical negligence. Aim: Our aims were to develop an educational tool to recognise the warning signs of foot complications that might lead to amputation and to disseminate the tool and seek endorsement. Method: The delay to specialist help was analysed by the iDEAL group (Insights for Diabetes Excellence, Access and Learning), a multidisciplinary team of diabetes specialists together with a person with diabetes and recommendations were made. Results: An acronym ACT NOW has been devised to act as an educational tool ACT NOW stands for Accident (recent trauma to foot) Change in colour or shape, Temperature change -hot or cold, New pain, Oozing and Wound. The acronym was devised firstly, to help PwD and HCPs recognise the warning signs of foot complications, leading to potential amputation, and secondly, to trigger early and prompt referral to specialist care. On recognising one or more of these features, the PwD can gain confidence, especially during the COVID 19 pandemic, to seek specialist help either directly from a diabetes foot service or through a first contact HCP who can then refer. An ACT NOW tool was also created consisting of the acronym and a a checklist which prompts the PwD, their carers and HCPs to enquire and document the ACT NOW! symptoms or signs and to take possible further information such as a digital photo. The checklist can then be used as a document to facilitate referral to specialist care. Alternatively, the check list can be used when PwDs present for routine assessment with their HCPs. The ACT NOW tool has been disseminated through digital and traditional media and endorsement granted from many organisations, including the IDF. Discussion: Foot ulcers are highly susceptible to infection which can spread rapidly, causing overwhelming tissue destruction or gangrene, necessitating major amputation. The progression from an initial ‘scratch’ to gangrene can take as little as 48 hours. A lack of knowledge and education can lead to a lack of urgency among PwD, carers and HCPs, who may not recognise that they have a foot related problem requiring urgent referral or care interventions. If there are difficulties in accessing a HCP appointment, there is a risk of critical delay in PwD receiving appropriate assessment and treatment. ACT NOW is designed to promote timely referral and save limbs. iDEAL seeks to reduce amputations by 50% in 5 years by encouraging people to use ACT NOW. Prompt assessment and early referral can help reduce this unnecessary suffering. ACT NOW also seeks to reduce stigma often experienced by PwD regarding complications and remove any blame or shame associated with diabetes complications. These changes can be created through encouraging and enabling an environment of education, knowledge and trust using language that enables PwD.

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.

A new diabetes foot educational and risk assessment tool for people with diabetes and health care professionals has been created: ACT NOW: Accident, Change, Temperature, New pain, Oozing, Wound, an acronym to recognise warning signs of foot complications, and reduce delays in much needed and timely specialist intervention(s) to avoid amputation

Aims: When a person with diabetes (PwD) develops a foot problem there is often a delay in receiving specialist help, which may result in amputation and this may be blamed on medical negligence. Our aims were to develop an educational tool to recognise the warning signs of foot complications that might lead to amputation and to disseminate the tool and seek endorsement. Methods: The delay to specialist help was analysed by the iDEAL group (Insights for Diabetes Excellence, Access and Learning), a multidisciplinary team of diabetes specialists together with a PwD and recommendations were made. Results: An educational tool based on the acronym ACT NOW: Accident (recent trauma to foot), Change in colour or shape, Temperature-hot or cold, New pain, Oozing and Wound) was devised to help PwDs and health care professionals (HCPs) recognise the warning signs of foot complications, leading to potential amputation, that should trigger referral to specialist care. On recognising one or more of these features, the PwD can gain confidence, especially during the covid-19 pandemic, to seek specialist help either directly from a diabetes foot service or through a first contact HCP who can then refer. An ACT NOW checklist was also devised to aid the HCP in making the referral. The tool has been disseminated through digital and traditional media and endorsement granted from the Foot in Diabetes UK (FDUK), the English Diabetes Footcare Network and the Primary Care Diabetes Society. Conclusion: ACT NOW has been accepted as an innovative educational tool to reduce delay of foot referral to specialist care.