SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study

Background

Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood.

Objectives

COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination.

Methods

Individuals on immunoglobulin replacement therapy or with an IgG less than 4 g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs.

Results

A total of 5.6% (n?=?320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n?=?168) compared with 100% of healthy controls (n?=?205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs. 48.0%, p?=?0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs. 2.39, p?=?0.0003). T cell responses post vaccination was demonstrable in 46.2% of participants and were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine.

Conclusion

SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection.

     

National audit of continence care for older people: results of a pilot study*

INTRODUCTION AND AIM: Bladder and bowel problems are common in the elderly and are associated with a considerable morbidity and impact on quality of life. Inequalities in service provision and access to services have been recognized but there has been no systematic approach to measuring the quality of continence care for older people. This study aimed to develop quality standards, to assess the reliability and utility of the resulting audit package and to report on the standards of care provided in primary care, secondary care and care home setting. METHOD: Fifteen sites in secondary care, primary care and in long-term care settings were randomly selected to pilot the audit package. Data collectors completed audit questionnaires relating to the structure [organization] of care, the outcomes of care, and the process of care for 20 subjects with urinary incontinence and 10 subjects with faecal or double incontinence. RESULTS: The audit tool was reliable (median kappa score of 0.7). Access to integrated continence services, as defined by Good Practice in Continence Services was inadequate. Eighty-five per cent of hospitals had no written policy for continence care. There were deficiencies in obtaining information, in carrying out basic and specialist examinations and investigations and in determining the cause of incontinence. There was a high prevalence of catheter use in secondary care settings. CONCLUSION: The pilot has indicated significant inadequacies in continence care and demonstrates that in many sites the National Service Framework milestone for integrated continence services has not been met. A national audit of continence care is required to determine the extent of inadequate continence care.     

A national benchmark for the initial assessment of men with LUTS: data from the 2010 Royal College of Physicians National Audit of Continence Care

Objective

To assess the degree of adherence to the current National Institute for Health and Clinical Excellence (NICE) guidelines on the management of urinary incontinence (UI) in men.

Design

Retrospective survey of male patients with UI in primary and acute hospital (AH) care as part of a national audit.

Setting

NHS AH and primary care (PC) trusts.

Sample

Twenty-five men <65 years old and 25 men ≥65 years old from each participating site.

Methods

All NHS trusts in England, Wales Northern Ireland and Channel Islands were eligible to participate. A web-based data collection form aligned to the NICE guidelines was constructed for the study. All data submitted to the audit were anonymous, and access to the web tool was password protected for confidentiality.

Results

Data were returned by 80 % (128/161) of acute trusts and 52 % (75/144) of PC trusts in England, and 71 % (10/14) of combined trusts from Northern Ireland, Wales and the Channel Islands including data on 559 men <65 and 1271 65+ from 141 sites within acute hospitals and 445 men <65 and 826 men 65+ in PC, a total of 3101 participants.

Conclusion

The majority of men seen within the NHS with LUTS do not receive management according to evidence-informed NICE guidelines; in general, older men are less likely to receive care that meets guideline standards than younger men.

     

Oral pharmacotherapy for overactive bladder in older patients: mirabegron as a potential alternative to antimuscarinics

Objective Overactive bladder (OAB) is a particular challenge to treat in older adults with co-morbid conditions taking multiple medications. Antimuscarinics (e.g., solifenacin, fesoterodine) and β₃-adrenergic receptor agonists (mirabegron) are similarly efficacious; however, antimuscarinics may be associated with side effects that result in poor persistence and contribute to anticholinergic burden, particularly in those taking other medications with anticholinergic properties. With a mechanism of action distinct from antimuscarinics, mirabegron has a different tolerability profile and does not contribute to anticholinergic burden. The objective of this review was to compare and contrast the tolerability profiles of antimuscarinics and mirabegron in older patients to inform practice.

Methods Prospective trials or retrospective subgroup analyses of antimuscarinics for the treatment of OAB in older patients were identified through a search of PubMed. Tolerability data and results of subgroup analyses of mirabegron in patients aged ≥65 and ≥75 years from a pooled analysis of three trials each of 12 weeks and a 1 year trial are described.

Results Anticholinergic adverse events (AEs) including dry mouth and constipation were more frequent with antimuscarinics versus mirabegron. In patients aged ≥65 years, dry mouth occurred with a six-fold higher incidence with tolterodine extended-release (ER) 4?mg than with mirabegron 25?mg or 50?mg over 12 weeks, and a three-fold higher incidence with tolterodine ER than mirabegron 50?mg over 1 year. Mirabegron had a low incidence of central nervous system effects. A systematic review of the cardiovascular safety profile of mirabegron has not identified any clinically significant effects on blood pressure or pulse rate at therapeutic doses amongst patients aged ≥65 years.

Conclusions Mirabegron has a more favorable tolerability profile than antimuscarinics amongst older patients and may provide an improved benefit-to-risk ratio and therefore be considered as an alternative to antimuscarinics for older patients.