Assessing frailty in care practices: quick reminders in the light of the Covid-19 pandemic.

The Covid-19 pandemic has brought the concept of frailty back to the centre of debate, particularly for its relevance as a determinant of health outcomes. Frailty is concept that has long been a used gerontology. Today, several theoretical models of frailty are proposed in the literature, with as many tools to operationalize it. This article provides a brief outline of the three main models of frailty and the corresponding measurement instruments. The choice of the model as well as the choice of the assessment tool are discussed in the light of the clinical objectives pursued by health professionals. More generally, this article highlights the value of assessing frailty in routine practice to determine health outcomes and adapt care to individual needs.Copyright © 2020 Editions Medecine et Hygiene. All rights reserved.

Detection of SARS-CoV-2 Spike-Protein-Specific Antibodies after Vaccination via Nasal and Buccal Swabs: Prospects for Mass Scale Immunity-Screening in Large Populations

Background: Humoral immunity after SARS-CoV-2 vaccination has been extensively investigated in blood. Far less is known, however, about the potentially induced mucosal immunity. Aim of this study was to develop an ELISA method in order to determine the prevalence of IgG and IgA SARS-CoV-2 spike-protein-specific antibodies (Abs) in buccal and nasal surfaces of vaccinees after full vaccination with BNT162b2, mRNA-1273, ChAdOx1 or combination. Method(s): To this end, we prospectively analyzed 69 adult individuals after signed written consent who received their first vaccine dose between February and July 2021. Detection of IgG and IgA Abs was performed using the semi-quantitative ELISA assay from EUROIMMUN for both blood and swab samples after protocol modification for the latter. The eluates of the nasal and buccal swabs were analyzed undiluted while the same cut-off was set as for the serum assay. The samples were taken at regular intervals to ensure systematic recording of Ab course before and after each vaccination dose. Result(s): After second dose all study subjects developed IgG anti spike Abs in serum, yet 5.9% of them remained negative for IgA. In buccal swabs, positivity rates were 81.2% and 53.1% and in nasal swabs 84.1% and 90.6% for IgG and IgA, respectively. The IgG Abs in buccal swabs correlated more consistently with the respective measurements in blood with a correlation coefficient of r=0.74 while the IgA assay gave less concordant results. It is of note that IgA Abs appeared to be significantly more prevalent in the nasal compared to the buccal mucosa. Adjustment of the assay cut-off as to IgG antibody detection in buccal swabs from 1.1 to 0.2 conferred a sensitivity of 91.8% and a specificity of 100% in a total of 520 comparison measurements. Conclusion(s): In conclusion, our findings confirm a weaker yet clear prevalence of Abs in mucosal surfaces after full vaccination against SARSCoV- 2 with IgA anti-spike Abs being significantly more prevalent in the nasal cavity. Our method for IgG Ab detection in buccal swabs could be expanded to other pathogens of interest and serve as a reliable alternative to standard serum assays especially in the context of immunity screening of large populations.

A Randomised Open-Label Trial of Early, Very High-Titre Convalescent Plasma Therapy in Clinically Vulnerable Individuals with Mild COVID-19 as model of early treatment in a pandemia with a new pathogen: Experience from collection of very high-titer plasma from superimmunized individuals

Background: COVID-19 convalescent plasma (CCP) remains a potential therapy of COVID-19, e.g. for new variants and for patients with impaired immune response. The trial COVIC-19 takes into account lessons learned from previous trials and combines it to a novel approach: * CCP with very high levels of SARS-CoV-2 antibodies from donors with previous SARS-CoV-2 infection (inf) and vaccination (vax) * Treatment early after symptom onset * Treatment of vulnerable persons (e.g. immunocompromised) * Study of immune escape Methods: We report the initial experience of collection of very high-titer plasma units (defined as >=4.000 BAU/ml in the QuantiVac ELISA) for this COVIC-19 trial. We recruited 348 potential donors (151 male, 197 female) who had passed initial eligibility check. S-Ab were measured by anti-SARS-CoV-2 QuantiVac ELISA (Euroimmun): mean 4229 BAU/ml (IQR 2.239-5.486 BAU/ml). High S-Ab in the QuantiVac assay correlated with high neutralizing capacity in the GenScript surrogat neutralization assay. S-Ab was >=4.000 BAU/ml in 25.1% of the individuals and did not significantly differ by gender or ABO type, but were higher among those who had received 3 vax (median 4.231 BAU/ml) or 2 vax (median 2.954 BAU/ml) or 1 vax (median 1.832 BAU/ml)(p<0.01). Result(s): We analyzed the association between the order of immunizing events and S-Ab. Highest S-Ab were observed among those with a breakthrough infection after 2 vax, followed by a booster (3rd dose post inf.) (median 5.840 BAU/ml;76.7% >=4.000 BAU/ml) or breakthrough inf after 3 vax (no further booster;median 3.841 BAU/ml;47.9% >=4.000 BAU/ml). S-Ab were lower in those with inf before vax followed by 1 vax (median 1.806 BAU/ml;18.1% >=4.000 BAU/ml) or >1 vax (median 2.586 BAU/ ml). S-Ab declined rapidly: 42% of donors with S-Ab >=4.000 BAU/ml had declined below this threshold in the short interval until 1st plasmapheresis and further 6% until 2nd apheresis. Further follow-up will be presented. Conclusion(s): Taking into account all eligibility criteria only 8.6% of individuals willing to donate could provide plasma units meeting the criteria of high-titer plasma for COVIC-19. Collection of very-high titer plasma from super-immunized individuals with previous infection and vaccination is feasible, but requires substantial donor selection and rapid screening and immediate start of apheresis to take advantage of the short period of very high mAb.

BNT162b2 booster vaccination elicits cross-reactive immunity against SARS-CoV-2 variants B.1.1.529 and B.1.617.2 in convalescents of all ages

Background: Among the greatest challenges of the current pandemic with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is its ongoing evolution, resulting in variants of interest (VOI) and variants of concern (VOC) with an enhanced capacity for immune escape. The likelihood for the emergence of such variants exponentially rises with the time a host is infected with the virus and the virus is reproduced without being properly controlled by the immune system. Method(s): In this prospective observational cohort study we analyzed cellular and serological immune response parameters against SARS-CoV-2 and current variants of concern (VOC) in 147 COVID-19-convalescent and 39 COVID-19-naive individuals before and after BNT162b2 booster vaccination. End points included anti-SARS-CoV-2 IgG and IgA titers, neutralization capacities against wild type SARS-CoV-2 and the VOCs B.1.1.529 and B.1.617.2 as well as SARS-CoV-2-specific T cell IFN-gamma responses. Result(s): No significant differences regarding immunological response parameters were observed between younger and older individuals. Booster vaccination induced full recovery of both cellular and serological response parameters including IFN-g secretion and anti-spike antibody titers with strong neutralization capacities against wild type SARS-COV-2 and Delta. Surprisingly, even serological neutralization capacity against Omicron was detectable one month after second vaccination and four months before it had been first observed in South Africa. As a result, more than 90% of convalescent individuals exhibited detectable and 75% strong Omicron neutralization capacity after booster vaccination, compared with 72% and 46% of COVID-19-naive individuals. Conclusion(s): Broad and cross-reactive immune memory against SARSCoV- 2 including currently known VOCs can be established by booster vaccination with spike-based mRNA vaccines like BNT162b2, particularly in COVID-19-convalescent individuals of all ages. Nevertheless, especially in COVID-19-naive individuals future variants escaping the memory immune response may require vaccine approaches such as inactivated whole virus vaccines, which include all antigenic components of the virus. (Figure Presented).

B CELL CHARACTERISTICS at BASELINE PREDICT HUMORAL RESPONSE UPON SARS-COV-2 VACCINATION among PATIENTS TREATED with RITUXIMAB

Background: Vaccination is considered efficient in controlling infections incl. SARS-CoV-2. Prior studies showed that patients receiving rituximab (RTX) with low B cell counts are at increased infectious risk (1) and risk of inadequate vaccination responses (2, 3). Thus, the ability to further defne and predict vaccination responses in these patients may guide their optimal protection. Objectives: To assess predictive biomarkers of vaccination responses upon SARS-CoV-2 vaccination in RTX treated patients. Methods: B cell characteristics before vaccination were evaluated to predict responses in 15 patients with autoimmune infammatory rheumatic diseases receiving RTX. 11 patients with rheumatoid arthritis on other therapies (RA), 11 kidney transplant recipients (KTR) and 15 healthy volunteers (HC) served as controls. A multidimensional analysis of B cell subsets and a correlation matrix were performed to identify predictive biomarkers. Results: Signifcant differences regarding absolute B cell counts and specifc subset distribution pattern between the groups were validated at baseline. Here, the majority of B cells from vaccination responders of the RTX group (RTX IgG+) comprised naïve and transitional B cells, whereas vaccination non-responders (RTX IgG-) carried preferentially plasmablasts and double negative (CD27-IgD-) B cells (Figure 1). Moreover, there was a positive correlation between neutralizing antibodies and absolute B cell numbers with B cells expressing HLA-DR and CXCR5 (involved in antigen presentation and germinal center formation) as well as an inverse correlation with CD95 expression and CD21low expression (marker for activation and exhaustion) on B cells. Conclusion: Substantial repopulation of naïve B cells upon RTX therapy appears to be essential for an adequate vaccination response requiring germinal center formation. In contrast, expression of exhaustion markers (CD21low, CXCR5-, CD95+) indicate negative predictors of vaccination responses. These results may guide optimized vaccination strategies in RTX treated patients clearly requiring antigen-inexperienced B cells for appropriate protection.

Pilot Trial of the My Hematology Oncology Patient Experience (MyHOPE™) for Multiple Myeloma (MM) Digital Solution in Patients with MM

Background: There is growing evidence to suggest that continuous monitoring and a proper use of patient-reported outcomes (PROs) in the clinical setting may improve patient care by facilitating doctor-patient communication, promoting individualized supportive care, and increasing patient satisfaction (Velikova, J Clin Oncol. 2004;22(4):714-24;Yang, Support Care Cancer. 2018 Jan;26(1):41-60). This may be of particular importance for patients with MM, a condition characterized by considerable heterogeneity in PROs at different timepoints within a patient's disease journey (TA King et al, Semin Oncol Nurs. 2017;33(3):299-315;R Abonour et al, Ann Hematol. 2018;97(12):2425-36). There is also a growing body of evidence to support that digital platforms in healthcare can have an impact on patients' lives and improve the patient care experience across diverse medical settings. Web-based platforms that provide education and allow patients to track data have demonstrated improvement across a range of PROs measuring empowerment, self-efficacy, and mastery when compared against standard of care in a variety of disease states (MR Fu et al, Internet Interv. 2016;5:56-64;G Bouma et al, Support Care Cancer. 2017;25(7):2075-2083). This may be particularly relevant in light of the current coronavirus disease 2019 (COVID-19) global pandemic. Patient-reported outcome data (e.g., symptoms) that can be readily shared with healthcare professionals (HCPs) can support clinical decision making and impact patient outcomes (E Basch et al, JAMA. 2017 Jul 11;318(2):197-8). Data collected through wearables (such as emoji scales and activity) have been shown to be correlated with traditional, validated PRO measures in patients with cancer (CA Thompson et al, Blood. 2017;130(Suppl 1):2179). Digital medication tracking has led to better medication adherence, increased prescription refills, and better clinical outcomes. Centralized disease management digital platforms have shown potential to reduce patients’ risk of complications (S Kumar et al, Abstract for the 77th American Diabetes Association. 2017). Despite this body of evidence supporting the potential impact of the use of digital platforms, there is little evidence specifically in MM. The MyHOPE™ for MM Solution is a validated investigational digital technology platform designed to provide patients with a comprehensive set of tools and resources to support the patient throughout their overall experience with MM and to collect biometrics and self-reported data such as symptom tracking, medication adherence, and health-related quality of life (HRQoL) with the ability to share this data with the patient's care team. MyHOPE™ for MM is the first prospective study evaluating the impact of a digital intervention for patients with hematological malignancies. Study Design and Methods: This is a multi-center, randomized, pilot trial of the MyHOPE™ for MM Solution. Approximately 126 adult patients (≥ 18 years of age) with a diagnosis of MM and who reside in the USA will be recruited from approximately 30 study sites within the USA, reflecting both community and academic centers. Patients will be stratified according to disease status (newly-diagnosed multiple myeloma transplant-eligible or ineligible, newly-diagnosed multiple myeloma in patients undergoing their first autologous stem cell transplant, or relapsed and/or refractory) and will be randomized in a 2:1 manner to either the Patient App + HCP Portal (Cohort 1) or Patient App Alone (Cohort 2). Primary objectives include feasibility of the platform and patient empowerment and self-efficacy. Other objectives include user satisfaction with the platform, health-related quality of life, and clinical outcomes. Enrolled patients will receive MM-treament regimen according to their physician's care plan. The study is in start-up and recruitment is expected through 2021. Disclosures: Raje: Celgene: Consultancy. Nadeem: Amgen: Membership on an entity's Board of Directors or advisory committees;Adaptive: Membership on an entity's Board of Direct rs or advisory committees;Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees;Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES;Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES;Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Mikhael: Amgen, Celgene, GSK, Janssen, Karyopharm, Sanofi, Takeda: Honoraria. Ludwig: Bristol Myers Squibb: Consultancy. Agarwal: Bristol-Myers Squibb Company: Current Employment, Current equity holder in publicly-traded company. Inumerable: Bristol Myers Squibb: Current Employment. Ong: Bristol Myers Squibb: Current Employment. Jagannath: BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy.

Privacy-protecting, reliable response data discovery using COVID-19 patient observations.

OBJECTIVE: To utilize, in an individual and institutional privacy-preserving manner, electronic health record (EHR) data from 202 hospitals by analyzing answers to COVID-19-related questions and posting these answers online. MATERIALS AND METHODS: We developed a distributed, federated network of 12 health systems that harmonized their EHRs and submitted aggregate answers to consortia questions posted at https://www.covid19questions.org. Our consortium developed processes and implemented distributed algorithms to produce answers to a variety of questions. We were able to generate counts, descriptive statistics, and build a multivariate, iterative regression model without centralizing individual-level data. RESULTS: Our public website contains answers to various clinical questions, a web form for users to ask questions in natural language, and a list of items that are currently pending responses. The results show, for example, that patients who were taking angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, within the year before admission, had lower unadjusted in-hospital mortality rates. We also showed that, when adjusted for, age, sex, and ethnicity were not significantly associated with mortality. We demonstrated that it is possible to answer questions about COVID-19 using EHR data from systems that have different policies and must follow various regulations, without moving data out of their health systems. DISCUSSION AND CONCLUSIONS: We present an alternative or a complement to centralized COVID-19 registries of EHR data. We can use multivariate distributed logistic regression on observations recorded in the process of care to generate results without transferring individual-level data outside the health systems.

Privacy-Protecting, Reliable Response Data Discovery Using COVID-19 Patient Observations.

There is an urgent need to answer questions related to COVID-19's clinical course and associations with underlying conditions and health outcomes. Multi-center data are necessary to generate reliable answers, but centralizing data in a single repository is not always possible. Using a privacy-protecting strategy, we launched a public Questions & Answers web portal (https://covid19questions.org) with analyses of comorbidities, medications and laboratory tests using data from 202 hospitals (59,074 COVID-19 patients) in the USA and Germany. We find, for example, that 8.6% of hospitalizations in which the patient was not admitted to the ICU resulted in the patient returning to the hospital within seven days from discharge and that, when adjusted for age, mortality for hospitalized patients was not significantly different by gender or ethnicity.

Privacy-Protecting, Reliable Response Data Discovery Using COVID-19 Patient Observations (preprint)

There is an urgent need to answer questions related to COVID-19s clinical course and associations with underlying conditions and health outcomes. Multi-center data are necessary to generate reliable answers, but centralizing data in a single repository is not always possible. Using a privacy-protecting strategy, we launched a public Questions & Answers web portal (https://covid19questions.org) with analyses of comorbidities, medications and laboratory tests using data from 202 hospitals (59,074 COVID-19 patients) in the USA and Germany. We find, for example, that 8.6% of hospitalizations in which the patient was not admitted to the ICU resulted in the patient returning to the hospital within seven days from discharge and that, when adjusted for age, mortality for hospitalized patients was not significantly different by gender or ethnicity. One Sentence SummaryPublicly Sharing Knowledge on COVID19 Without Sharing Patient-Level Data: A Privacy-Protecting Multivariate Analysis Approach

[Assessing frailty in care practices : quick reminders in the light of the Covid-19 pandemic]

The Covid-19 pandemic has brought the concept of frailty back to the centre of debate, particularly for its relevance as a determinant of health outcomes. Frailty is concept that has long been a used gerontology. Today, several theoretical models of frailty are proposed in the literature, with as many tools to operationalize it. This article provides a brief outline of the three main models of frailty and the corresponding measurement instruments. The choice of the model as well as the choice of the assessment tool are discussed in the light of the clinical objectives pursued by health professionals. More generally, this article highlights the value of assessing frailty in routine practice to determine health outcomes and adapt care to individual needs.