High torque tenovirus (TTV) load before first vaccine dose is associated with poor serological response to COVID-19 vaccination in lung transplant recipients

BACKGROUND: : Serological responses to COVID-19 vaccination are diminished in recipients of solid organ transplants, especially in lung transplant recipients (LTR), probably as result of immunosuppressive treatment. There is currently no marker of immunosuppression that can be used to predict the COVID-19 vaccination response. Here, we study whether torque tenovirus (TTV), a highly prevalent virus can be used as an indicator of immunosuppression. METHODS: : The humoral response to the mRNA 1273 vaccine was assessed in 103 LTR, who received a transplant between 4 and 237 months prior to vaccination, by measuring Spike (S)-specific IgG levels at baseline, 28 days after first, and 28 days after the second vaccination. TTV loads were determined by RT-PCR and Pearson's correlation coefficient was calculated to correlate serological responses to TTV load. RESULTS: : Humoral responses to COVID-19 vaccination were observed in 41/103 (40%) LTR at 28 days after the second vaccination. 62/103 (60%) were non-responders. Lower TTV loads at baseline (significantly) correlated with higher S-specific antibodies and a higher percentage of responders. Lower TTV loads also strongly correlated with longer time since transplantation, indicating that participants with lower TTV loads were longer after transplantation. CONCLUSIONS: : This study shows a better humoral response to the SARS-CoV-2 vaccine in subjects with a lower TTV load pre-vaccination. In addition, TTV load correlates with the time after transplantation. Further studies on the use of TTV load in vaccination efficacy studies in immunocompromised cohorts should provide leads for the potential use of this marker for optimizing vaccination response

Humoral and cellular immune responses after COVID-19 vaccination of lung transplant recipients and patients on the waiting list:a 6-month follow-up

Background: Data on cellular response and the decay of antibodies and T cells in time are scarce in lung transplant recipients (LTRs). Additionally, the development and durability of humoral and cellular immune responses have not been investigated in patients on the waitlist for lung transplantation (WLs). Here, we report our 6-month follow-up of humoral and cellular immune responses of LTRs and WLs, compared with controls. Methods: Humoral responses to two doses of the mRNA-1273 vaccination were assessed by determining spike (S)-specific IgG antibodies and neutralizing antibodies. Cellular responses were investigated by interferon gamma (IFN-γ) release assay (IGRA) and IFN-γ ELISpot assay at 28 days and 6 months after the second vaccination. Results: In LTRs, the level of antibodies and T-cell responses was significantly lower at 28 days after the second vaccination. Also, WLs had lower antibody titers and lower T-cell responses compared with controls. Six months after the second vaccination, all groups showed a decrease in antibody titers and T-cell responses. In WLs, the rate of decline of neutralizing antibodies and T-cell responses was significantly higher than in controls. Conclusion: Our results show that humoral and cellular responses in LTRs, if they develop, decrease at rates comparable with controls. In contrast, the inferior cellular responses and the rapid decay of both humoral and cellular responses in the WL groups imply that WLs may not be protected adequately by two vaccinations and repeat boostering may be necessary to induce protection that lasts beyond the months immediately post-transplantation.</p

DIALysis or not: Outcomes in older kidney patients with GerIatriC Assessment (DIALOGICA): rationale and design

Background: The incidence and prevalence of older patients with kidney failure who are dependent on dialysis is increasing. However, observational studies showed limited or no benefit of dialysis on mortality in subgroups of these patients when compared to conservative care. As the focus is shifting towards health-related quality of life (HRQoL), current evidence of effects of conservative care or dialysis on HRQoL in older patients is both limited and biased. Dialysis comes with both high treatment burden for patients and high costs for society; better identification of patients who might not benefit from dialysis could result in significant cost savings. The aim of this prospective study is to compare HRQoL, clinical outcomes, and costs between conservative care and dialysis in older patients. Methods: The DIALysis or not: Outcomes in older kidney patients with GerIatriC Assessment (DIALOGICA) study is a prospective, observational cohort study that started in February 2020. It aims to include 1500 patients from 25 Dutch and Belgian centres. Patients aged ≥70 years with an eGFR of 10–15 mL/min/1.73m2 are enrolled in the first stage of the study. When dialysis is initiated or eGFR drops to 10 mL/min/1.73m2 or lower, the second stage of the study commences. In both stages nephrogeriatric assessments will be performed annually, consisting of questionnaires and tests to assess most common geriatric domains, i.e. functional, psychological, somatic, and social status. The primary outcome is HRQoL, measured with the Twelve-item Short-Form Health Survey. Secondary outcomes are clinical outcomes (mortality, hospitalisation, functional status, cognitive functioning, frailty), cost-effectiveness, and decisional regret. All outcomes are (repeated) measures during the first year of the second stage. The total follow-up will be a maximum of 4 years with a minimum of 1 year in the second stage. Discussion: By generating more insight in the effects of conservative care and dialysis on HRQoL, clinical outcomes, and costs, findings of this study will help patients and physicians make a shared decision on the best individual treatment option for kidney failure. Trial registration: The study was registered in the Netherlands Trial Register (NL-8352) on 5 February 2020

Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study.

Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease

A multidimensional approach to older patients during COVID-19 pandemic: a position paper of the Special Interest Group on Comprehensive Geriatric Assessment of the European Geriatric Medicine Society (EuGMS)

Purpose: The COVID-19 pandemic has been a dramatic trigger that has challenged the intrinsic capacity of older adults and of society. Due to the consequences for the older population worldwide, the Special Interest Group on Comprehensive Geriatric Assessment (CGA) of the European Geriatric Medicine Society (EuGMS) took the initiative of collecting evidence on the usefulness of the CGA-based multidimensional approach to older people during the COVID-19 pandemic. Methods: A narrative review of the most relevant articles published between January 2020 and November 2022 that focused on the multidimensional assessment of older adults during the COVID-19 pandemic. Results: Current evidence supports the critical role of the multidimensional approach to identify older adults hospitalized with COVID-19 at higher risk of longer hospitalization, functional decline, and short-term mortality. This approach appears to also be pivotal for the adequate stratification and management of the post-COVID condition as well as for the adoption of preventive measures (e.g., vaccinations, healthy lifestyle) among non-infected individuals. Conclusion: Collecting information on multiple health domains (e.g., functional, cognitive, nutritional, social status, mobility, comorbidities, and polypharmacy) provides a better understanding of the intrinsic capacities and resilience of older adults affected by SARS-CoV-2 infection. The EuGMS SIG on CGA endorses the adoption of the multidimensional approach to guide the clinical management of older adults during the COVID-19 pandemic

Comprehensive geriatric assessment in older people : an umbrella review of health outcomes

Background: Comprehensive geriatric assessment (CGA) has been in use for the last three decades. However, some doubts remain regarding its clinical use. Therefore, we aimed to capture the breadth of outcomes reported and assess the strength of evidence of the use of comprehensive geriatric assessment (CGA) for health outcomes in older Methods: Umbrella review of systematic reviews of the use of CGA in older adults searching in Pubmed, Embase, Scopus, Cochrane library and CINHAL until 05 November 2021. All possible health outcomes were eligible. Two independent reviewers extracted key data. The grading of evidence was carried out using the GRADE for intervention studies, whilst data regarding systematic reviews were reported as narrative findings. Results: Among 1,683 papers, 31 systematic reviews (19 with meta-analysis) were considered, including 279,744 subjects. Overall, 13/53 outcomes were statistically significant (P &amp;lt; 0.05). There was high certainty of evidence that CGA reduces nursing home admission (risk ratio [RR] = 0.86; 95% confidence interval [CI]: 0.75–0.89), risk of falls (RR = 0.51; 95%CI: 0.29–0.89), and pressure sores (RR = 0.46; 95%CI: 0.24–0.89) in hospital medical setting; decreases the risk of delirium (OR = 0.71; 95%CI: 0.54–0.92) in hip fracture; decreases the risk of physical frailty in community-dwelling older adults (RR = 0.77; 95%CI: 0.64–0.93). Systematic reviews without meta-analysis indicate that CGA improves clinical outcomes in oncology, haematology, and in emergency department. Conclusions: CGA seems to be beneficial in the hospital medical setting for multiple health outcomes, with a high certainty of evidence. The evidence of benefits is less strong for the use of CGA in other settings