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.

     

Gerontological nursing roles within the Southeastern Regional Geriatric Program

This paper looks at the varied roles of Registered Nurses (RNs) within the Southeastern Regional Geriatric Program (SERGP) and how these nursing roles influence client care across the continuum of services. More specifically, this paper describes the clinical services of the SERGP, the roles of RNs within these services, and the principles and dimensions of geriatric nursing assessment, treatment, and rehabilitation. The aim of this article is to promote recognition of the complex and stimulating work of RNs in gerontology. Eliopoulos (1997) states the following that reflects this excitement and complexity: Gerontological nurses help older individuals to achieve a sense of wholeness by guiding them in understanding and finding meaning and purpose in life, facilitating harmony of the mind, body, and spirit, mobilizing their internal and external resources, and promoting self-care behaviours.     

Whose life is it, anyway? Supporting clients to live at risk

This paper introduces readers to the concept of (capable) frail elderly clients choosing to live at risk. Promoting client centred care and independence can be particularly challenging where the client's goals are different than those of the health care team, and there are identified risks to the client's health. Discussion includes the ethical principles of autonomy, non-maleficence, benefecence and paternalism, and other factors that influence the assessment of risk, including the degree of risk, probability of risk, and risk of harm to others. Client Centred Care is introduced as a process model to guide decision-making in cases where clients choose to live at risk.     

Assessment of toxicity and potential risk of the anticoagulant rodenticide diphacinone using Eastern screech-owls (<Emphasis Type="Italic">Megascops asio</Emphasis>)

In the United States, new regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides. This action may be offset by expanded use of first-generation compounds (e.g., diphacinone; DPN). Single-day acute oral exposure of adult Eastern screech-owls (Megascops asio) to DPN evoked overt signs of intoxication, coagulopathy, histopathological lesions (e.g., hemorrhage, hepatocellular vacuolation), and/or lethality at doses as low as 130 mg/kg body weight, although there was no dose–response relation. However, this single-day exposure protocol does not mimic the multiple-day field exposures required to cause mortality in rodent pest species and non-target birds and mammals. In 7-day feeding trials, similar toxic effects were observed in owls fed diets containing 2.15, 9.55 or 22.6 ppm DPN, but at a small fraction (<5%) of the acute oral dose. In the dietary trial, the average lowest-observed-adverse-effect-level for prolonged clotting time was 1.68 mg DPN/kg owl/week (0.24 mg/kg owl/day; 0.049 mg/owl/day) and the lowest lethal dose was 5.75 mg DPN/kg owl/week (0.82 mg/kg owl/day). In this feeding trial, DPN concentration in liver ranged from 0.473 to 2.21 μg/g wet weight, and was directly related to the daily and cumulative dose consumed by each owl. A probabilistic risk assessment indicated that daily exposure to as little as 3–5 g of liver from DPN-poisoned rodents for 7 days could result in prolonged clotting time in the endangered Hawaiian short-eared owl (Asio flammeus sandwichensis) and Hawaiian hawk (Buteo solitarius), and daily exposure to greater quantities (9–13 g of liver) could result in low-level mortality. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.     

Altered cutaneous immune parameters in transgenic mice overexpressing viral IL-10 in the epidermis

IL-10 is a pleiotropic cytokine that inhibits several immune parameters, including Th1 cell-mediated immune responses, antigen presentation, and antigen-specific T cell proliferation. Recent data implicate IL-10 as a mediator of suppression of cell-mediated immunity induced by exposure to UVB radiation (280-320 nm). To investigate the effects of IL-10 on the cutaneous immune system, we engineered transgenic mice that overexpress viral IL-10 (vIL-10) in the epidermis. vIL-10 transgenic mice demonstrated a reduced number of I-A(+) epidermal and dermal cells and fewer I-A(+) hapten-bearing cells in regional lymph nodes after hapten painting of the skin. Reduced CD80 and CD86 expression by I-A(+) epidermal cells was also observed. vIL-10 transgenic mice demonstrated a smaller delayed-type hypersensitivity response to allogeneic cells upon challenge but had normal contact hypersensitivity to an epicutaneously applied hapten. Fresh epidermal cells from vIL-10 transgenic mice showed a decreased ability to stimulate allogeneic T cell proliferation, as did splenocytes. Additionally, chronic exposure of mice to UVB radiation led to the development of fewer skin tumors in vIL-10 mice than in WT controls, and vIL-10 transgenic mice had increased splenic NK cell activity against YAC-1targets. These findings support the concept that IL-10 is an important regulator of cutaneous immune function.     

Oral care for the renal transplant patient

Renal transplant patients require immunosuppressive therapy, including a combination of prednisone, methylprednisone, azathioprine, antilymphocyte globulins, cyclosporine, and/or OKT 3. Consequently, they are vulnerable to opportunistic infections, especially in the oral cavity. The infections often seen are candida albicans and herpes simplex virus. Routine oral assessments and oral care need to be performed to provide maximum patient comfort and to prevent or minimize painful complications.     

Granulocyte-macrophage colony-stimulating factor gene transfer to dendritic cells or epidermal cells augments their antigen-presenting function including induction of anti-tumor immunity

Dendritic antigen-presenting cells derived from epidermis (Langerhans cells), bone marrow, and peripheral blood can present a wide variety of antigens, including tumor-associated antigens, for various immune responses. The development and function of dendritic cells is dependent upon a number of cytokines including granulocyte-macrophage-colony-stimulating factor. For example, Langerhans cells can present tumor-associated antigens for the induction of substantial in vivo anti-tumor immunity but only after activation in vitro by granulocyte-macrophage-colony-stimulating factor. Thus, we reasoned that insertion of a cDNA for granulocyte-macrophage-colony-stimulating factor into dendritic antigen-presenting cells may allow for autocrine stimulation and increased antigen-presenting capability. To test this possibility, we utilized an adenovirus vector to insert a cDNA for murine granulocyte-macrophage-colony-stimulating factor into the dendritic cell lines XS52-4D and XS106 (derived from neonatal mouse epidermis), bone marrow-derived dendritic cells, and epidermal cells that contain Langerhans cells. Infection of each of these cell types resulted in release of abundant quantities of granulocyte-macrophage-colony-stimulating factor. XS52-4D and XS106 cells infected with adenovirus granulocyte-macrophage-colony-stimulating factor exhibited prolonged dendrites and greater expression of major histocompatibility complex class II molecules and CD86 compared with cells infected with a null vector. Granulocyte-macrophage-colony-stimulating factor cDNA-containing XS cells, bone marrow-derived dendritic cells, and epidermal cells had more potent alloantigen presenting capability than cells infected with a null vector. Most importantly, granulocyte-macrophage-colony-stimulating factor gene-transferred epidermal cells were able to present tumor-associated antigens for in vivo anti-tumor immunity against challenge with the S1509a spindle-cell tumor whereas null vector-infected cells were unable to prime for immunity. These results suggest that introduction of a cDNA for granulocyte-macrophage-colony-stimulating factor into dendritic cells may be an effective means to augment their antigen-presenting capability and that granulocyte-macrophage-colony-stimulating factor gene-transfer- red epidermal cells may be useful in tumor vaccination strategies.     

Profile of plasma N-terminal proBNP following acute myocardial infarction; correlation with left ventricular systolic dysfunction.

AIMS: The aims of this study were to describe the temporal pattern of plasma N-terminal pro-brain natriuretic peptide, to examine the optimum time of sampling and to compare plasma N-terminal pro-brain natriuretic peptide to clinical criteria in terms of identification of impaired left ventricular systolic function following acute myocardial infarction. METHODS AND RESULTS: Measurements of N-terminal pro-brain natriuretic peptide were made in 60 patients at 14-48 h, 49-72 h, 73-120 h, 121-192 h following myocardial infarction and at 6 weeks in survivors. Left ventricular wall motion index was assessed during hospitalization (WMI-1) and at 6 weeks (WMI-2). N-terminal pro-brain natriuretic peptide levels were elevated at all time points, to a greater extent in anterior compared to inferior infarction (P < 0.05). A biphasic profile of plasma concentration was observed in anterior infarction with peaks at 14-48 h and 121-192 h. This was sustained at 6 weeks. N-terminal pro- brain natriuretic peptide at 73-120 h was the best independent predictor of WMI-1 (P < 0.005). N-terminal pro-brain natriuretic peptide was higher at all times in patients who received ACE inhibitor therapy compared to those who did not (P < 0.005). N-terminal pro-brain natriuretic peptide at 73-120 h (R(2) = 17.7%, P = 0.005) and previous myocardial infarction (R(2) = 5.3%, P < 0.05) were independent predictors of poor outcome (WMI-2 < or = 1.2 or death by 6 weeks). CONCLUSIONS: A biphasic pattern of plasma N-terminal pro-brain natriuretic peptide is seen after anterior myocardial infarction. Plasma level is strongly correlated to wall motion index soon after and remote from acute myocardial infarction. Plasma N-terminal pro-brain natriuretic peptide measured later in hospitalization better predicts poor outcome following myocardial infarction than when it is measured in the immediate post infarction period.     

Langerhans cell expression of neuropeptide Y and peptide YY

Neuropeptide Y (NPY) and peptide YY (PYY) are structurally related peptides with a variety of known functions. The role of these peptides in the skin is largely unknown, although NPY-like immunoreactivity has been reported in the epidermis. The recent report that these peptides have antimicrobial properties suggests that NPY and PYY may contribute to the skin's defense mechanisms against invading microorganisms. We have demonstrated that Langerhans cells (LC) and a certain BALB/c epidermis-derived dendritic cell line contain mRNA for NPY and PYY using RT-PCR. Furthermore, this dendritic cell line as well as an epidermis-derived dendritic cell line from A/J mice were found to produce NPY and PYY and LC produced PYY, as assessed by radioimmunoassay. These data suggest that the protective function of LC include not only antigen presentation, but also production of antimicrobial peptides.     

Tumor antigen presentation by dermal antigen-presenting cells

Several phenotypes of antigen-presenting cells are present in the dermis, where they presumably function to present encountered antigens for immune responses. This study examined the ability of dermal antigen-presenting cells to present tumor-associated antigens for the induction of in vivo antitumor immunity. Total murine dermal cells were exposed either to medium alone or to medium containing tumor-associated antigens from S1509a tumor cells. Subsequently, dermal cells were injected subcutaneously at weekly intervals into na?ve mice for a total of three immunizations. One week following the final immunization, mice were challenged with living tumor cells. In these experiments, dermal cells pulsed with tumor-associated antigens induced protective immunity to tumor growth. Dermal cells exposed to tumor-associated antigens were also able to elicit delayed-type hypersensitivity after footpad injection into mice previously immunized against S1509a tumor cells. The ability to present tumor-associated antigens for both induction of antitumor immunity and elicitation of delayed-type hypersensitivity was dependent on I-A+ cells and was genetically restricted. Finally, dermal cells tended towards eliciting a greater antitumor delayed-type hypersensitivity response than epidermal cells. These results show that the murine dermis contains antigen-presenting cells capable of processing S1509a tumor antigens for the generation of protective antitumor immunity in vivo.