Immunotherapy: FAMILIAL CD45RA DEPLETED T CELLS TO TREAT SEVERE REFRACTORY INFECTIONS IN IMMUNOCOMPROMISED PATIENTS

Background & Aim: Immunocompromised patients are susceptible to high-risk opportunistic infections and malignant diseases. If available, most antiviral and antifungal drugs are quite toxic, relatively ineffective, and induce resistance in the long term. Methods, Results & Conclusion(s): We have previously demonstrated the safety of adoptive cell therapy for COVID-19 patients with CD45RA negative cells containing SARS-CoV-2-specific T cells from a donor, chosen based on HLA compatibility and cellular response to SARS-CoV-2 peptide pools. After finishing a Phase 2 randomized multicenter clinical trial (RELEASE, NCT04578210), we concluded that the infusion is safe, effective, accelerates lymphocyte recovery and shows hallmarks of an immune response. To use adoptive cell therapy to treat COVID-19 it would be necessary to develop a biobank of living drugs. For that, we examined the immune evolution performing a longitudinal analysis from previously SARS-CoV-2 infected and infection- naive individuals covering 21 months from infection. Cellular responses were maintained over time while humoral responses increased after vaccination but were gradually lost. Therefore, the best donors would be recovered individuals and two months after vaccination. We also evaluated the effect of dexamethasone (current standard of care treatment for COVID-19 and other infections involving lymphopenia) and Interleukin-15 (cytokine involved in T-cell maintenance and survival) on CD45RA negative. Dexamethasone did not alter cell functionality, proliferation or phenotype at a clinical-practice concentration, while interleukin-15 increased the memory T-cell and T-regulatory cell activation state, and interferon gamma release. Furthermore, we applied the adoptive passive transfer of CD45RA negative cells containing pathogen-specific memory T-cells to other infectious diseases characterized by sustained lymphopenia. We infused six immunocompromised patients with Cytomegalovirus, BK virus, Aspergillus, and Epstein-Barr virus lymphoproliferative disease. Patients experienced pathogen clearance, resolution of symptoms and lymphocyte increase. Transient microchimerism was detected in three patients. The use of CD45RA negative cells containing specific memory T cells of a third-party donor for treating severe pathogenic diseases in immunocompromised patients is feasible, safe, and effective, and has an advantage over other cell therapies such as lower costs and a less complex regulatory environment.Copyright © 2023 International Society for Cell & Gene Therapy

Biological accidents among healthcare professionals during the SARS-CoV-2 pandemic: 2019 to 2021

Objective: to describe the tendency of biological exposures among healthcare professionals during the years 2019-2021. Method: a retrospective descriptive epidemiological study with 400 biological accidents among the staff of the Clínico-Malvarrosa Health Department (Valencia) from 2019 to 2021. The information was collected by the Occupational Risk Prevention Service through the REBA and EOLAS databases. The type of variables collected were: type of accident, setting where it occurred, characteristics of the worker involved, safety measures applied, and serological parameters of source and worker. Results: the distribution of accidents per year was n= 132 in 2019 (33%), n= 121 in 2020 (30.25%) and n= 147 in 2021 (36.75%). The professionals who experienced more accidents in all years were nurses, specifically those with <5 years of experience, 25-to-34-year old, and under temporary contract. The services that reported more accidents were Primary Care and Surgery in all these years, particularly the morning shifts. Over 20% of the staff were not wearing gloves at the time of the accident in any of these three years. There was an increase in the use of face masks from 24% in 2019 to 100% in 2021, as well as an increase in facial protection measures from 0% to 7%. Of these accidents, 96% could be recorded without seroconversion cases among workers exposed in any of these years. Conclusions: apparently, the COVID-19 pandemic has not altered the tendency towards accidental biological exposures among healthcare workers. The most significant fluctuations could be due to the reduction in surgical activity during 2020. © 2023 DAE Editorial, Grupo Paradigma. All rights reserved.

Is an allergic study to trometamol necessary before the administration of the SARS-CoV- 2 vaccines including this excipient?

Background: Trometamol is an excipient present in radiological contrast media, antibiotic drugs such as fosfomycin, and some NSAIDs formulations (namely ketorolac and desketoprofen). Patients with previous hypersensitivity reactions to these drugs could be at a higher risk after the administration of a SARS-CoV- 2 vaccine formulation including trometamol (SARS/Trometamol vaccine) Method: Patients with a previous history of hypersensitivity reactions to drugs including trometamol as excipient, were sent to our Department for assessment, before receiving a SARS/Trometamol vaccine from December 2021 to January 2022 Allergic study included prick-tests with SARS/Trometamol vaccine and trometamol. According to skin-tests results, a controlled administration of SARS/ Trometamol vaccine was performed. Result(s): A total of 59 patients, 42 women (71.2%) and 17 men (28.8%), were included in our study, with a mean age of 57.3 years. Nineteen patients (32.2%) reported a previous history of hypersensitivity reactions to radiological contrast media, thirty-five patients (59.3%) had reacted to NSAIDS, and five patients had suffered reactions to both drug groups (8.5%) None of the studied patients showed a positive skin-test to neither SARS/Trometamol vaccine nor trometamol. Corresponding SARS/Trometamol vaccine doses were administered to all the patients, and no hypersensitivity reactions were observed. Conclusion(s): According to our results, a previous history of hypersensitivity reactions to drugs including trometamol does not seem to increase the allergic risk after the administration of a SARS-CoV- 2 vaccine formulation containing trometamol. Thus, it would not be necessary to perform an allergic study routinely previous to the vaccination of this kind of patients. However, since trometamol allergy is rather rare, more patients should be studied before this conclusion can be generalized.

Does Timing of Smoking Cessation Have an Impact on Covid-19 Outcomes?

INTRODUCTION: The relationship between smoking and increased morbidity/mortality with COVID19 is well documented;however, there is little data on the relationship between former smokers (FS) and COVID19. Risk stratification of FS is dependent on years since smoking cessation (SC). We conducted a study to determine, if years since SC influenced COVID19 outcomes. METHOD(S): A retrospective cohort study at a single institution. Inclusion criteria: age >= 18 and admitted to the hospital from Jan 2020 to Nov 2021 for COVID19. Patients were divided into two categories;SC < 15 years, and SC > 15 years. The primary outcome was mortality, with secondary outcomes: requirement of nasal cannula (NC), NIV, and mechanical ventilation (MCV). Odds ratios (OR) were calculated for all outcomes. Post-hoc age-adjusted odds ratios (AOR) for age < 75, were calculated for all outcomes. Mortality data was collected on all patients, and OR were calculated between FS, smokers (CS), and non-smokers (NS). RESULT(S): The total number of patients was 608 with 256 being FS, 308 non-smokers, 30 CS, and 14 unknown smoking status. The mean age of FS was 70. There were 154 males (60%) 102 females (40%). Total FS < 75 was 152. Obesity rates were 64.1% and 67.6%, T2DM (Diabetes Mellitus) rates were 34.3% and 59.5% in SC < 15 and SC > 15, respectively. There was no difference in mortality between the two groups, OR (OR 0.81, CI 0.46-1.40, p=0.45) and AOR (AOR 0.79, 0.37-1.69, p=0.54). There was an increased risk of MCV for the SC < 15 group (OR 2.1, CI 1.02-4.57, p=0.04). AOR did not replicate this trend. There was no difference in patients requiring NC (AOR 1.38, CI 0.70-2.74, p=0.36) or MCV (AOR 1.65, CL 0.69- 3.91, p=0.25) between the two groups. SC < 15 had lower rates of NIV (AOR 0.36, CI 0.15-0.90, p=0.029). There was no difference in mortality between FS and CS (OR 1.69, CI 0.70-4.19, p=0.24). The FS group had higher rates of mortality than NS (OR 1.43, CI 1.00-2.05, p=0.048). CONCLUSION(S): Regardless of the timing of SC, FS have the same mortality and MCV rates with COVID19. High comorbidity burden was noted in both population groups, with the SC > 15 group having higher rates of T2DM. Further studies are needed to determine the full effect of SC on COVID19 outcomes, including effect of pack years.

Math Anxiety in Primary Education during Covid-19 Confinement: Influence on Age and Gender

Background: The closure of schools in Spain due to the Covid-19 pandemic confronted teachers, students, and families with a new reality. Previous studies have shown that anxiety levels increase during pandemic times. Therefore, it highlights the interest of the affective domain in primary education. Objectives: To analyse some general aspects of math anxiety, such as primary school students’ fear, nervousness, and blockage before mathematics both at the educational centre and at home during the Covid-19 confinement. Design: Quantitative study using a closed questionnaire of seven questions with a Likert-type scale. Settings and participants: 496 Spanish primary school students. Data collection: Through the questionnaire hosted in Google Forms and provided by the teachers responsible for the students one month after the closure of all the educational centres and the confinement of all the participating children. Results: Fear of math increases during primary education, with the highest levels of fear and restlessness in the third and sixth grades;the girls presented the highest levels in all aspects, except for nervousness during classes. Conclusions: The general aspects of math anxiety are intimately linked and evolve increasingly throughout primary education. These facts are justified based on the proximity of the change in the educational stage and its influence on teaching, as well as the students’ social conditions. © 2022 Lutheran University of Brazil. All rights reserved.

Evaluation of emergency remote teaching during covid-19 lockdown in a Spanish university

The lockdown caused by the pandemic resulted in the closure of schools and universities. Professors had to adapt their subjects to be taught remotely to continue their classes, and students had to cope with various personal situations such as isolation, and returning to their countries. Ensuring that the quality of teaching was maintained would usually have required months of planning and design. In contrast, these changes had to be made in a few days, which is why this situation could be considered as Emergency Remote Teaching (ERT). The objective of this article is to evaluate the teaching of our faculty during this period using the CIPP model (Context, Input, Procedure and Product), which is especially focused on educational projects among others. The university was able to maintain teaching during this period despite the difficulties of the transition. In addition, evaluation surveys show that the satisfaction of professors and students was also maintained. This was possible thanks to the order and clarity transmitted from university authorities and the commitment of the professors, despite their increased workload. This knowledge is important to ensure a better response by universities in future emergencies. Practitioner Notes 1. The lockdown produced by the Covid-19 pandemic forced universities to design and develop Emergency Remote Teaching (ERT) responses. 2. Emergency Remote Teaching (ERT) and policies should be evaluated. 3. The creation of a committee to manage and organise the transition to ERT releases professors from these tasks. 4. Online assessment is the biggest barrier during ERT due to the different concerns of professors and students. © 2022, University of Wollongong. All rights reserved.

DEMPOWER STUDY: EVALUATION OF THE EFFECT OF A PATIENT EMPOWERMENT AND COMMUNICATION DIGITAL TOOL ON METABOLIC CONTROL IN T2DM PATIENTS

Background and Aims: There is still a high number of inadequately controlled T2DM patients. Therefore, it is essential to develop innovative solutions to improve patient's empowerment by increasing patient-physician communication and their selfmanagement. The aim of this study was to analyze the effect of a home digital patient empowerment tool (Figure 1), on metabolic control in T2DM patients. Methods: Multicentric, randomized prospective clinical trial including adult T2DM patients without adequate glycemic control treated according to usual clinical practice across Spain. Figure 2 summarizes the study design and study population. The primary endpoint was the comparison of the proportion of patients who did not achieve the study glycemic target (defined as HbA1c levels ≤7.5% with a reduction in HbA1c ≥0.5 from baseline) at week 24 between groups 1 and 2. It was also performed a comparison of mean HbA1c changes from baseline to week 24 between groups 1 and 2. Results: The COVID-19 pandemic led to a premature study closure since patient's enrollment and follow-up were active during the 2020 lockdown. In total, 50 patients completed week 24 visit. Figure 3 shows the main study results. 46% patients from group 1 achieved study glycemic target vs 18% in group 2 (p = 0.067), whereas the difference in the HbA1c reduction between group 1 and 2 was -0.66% (p < 0.05). Conclusions: Our results suggest the patient empowerment through a home digital tool might allow an improvement in metabolic control and consequently a more effective management of T2DM.

Impact of lockdown on lifestyle: Healthcare professionals and overall population

Objective: to explore the effects of lockdown for the COVID-19 pandemic on the lifestyles of the overall population and healthcare professionals (HCPs). Method: a cross-sectional descriptive study. Non-probability snowball sampling was conducted through WhatsApp. After the pilot survey, an ad-hoc questionnaire was distributed on sociodemographic, clinical and lifestyle variables during lockdown. The parametric tests used for analysis were Student- Fisher's t and Pearson's Chi-squared test, and odds ratio with CI95%. Results: the study included 184 HCPs and 460 non-HCPs. The median age of the sample was 40.4 (SD: 12.8) years, they were mostly women (66.9%) with university education (65.8%). More HCPs had positive test results for COVID-19, OR= 17.1 (9.1- 32.1) or symptoms compatible with COVID-19, OR= 2.1 (1.4- 3.1). The psychological impact of lockdown was higher in HCPs, OR= 1.5 (1.0-2.1). There were no significant differences in the activities carried out during quarantine, except for telework (p< 0.001). The degree of concern self-reported by 68.0% of the non-HCP population was "Very concerned" and "Highly concerned", similarly to HCPs (65.8%) (p= 0.218). Healthy lifestyles were maintained during lockdown, except for physical exercise which was worse in both groups (66.3% of HCPs and 66.4% of non-HCPs). Smoking and/or alcohol intake increased between 20 and 30% in both groups. Conclusions: changes were perceived among HCPs and non- HCPs regarding occupation during lockdown, psychological impact or tendency to get infected. It is essential to introduce resources for mental healthcare, particularly for HCPs. © 2022 DAE Editorial, Grupo Paradigma. All rights reserved.

2020 antimicrobial consumption indicators: analysis compared with previous years

Background and importanceA reference panel of antimicrobial consumption indicators was published in 2019 by a committee from the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).Aim and objectivesTo calculate 2020 hospital antimicrobial consumption indicators and carry out a comparative analysis of these consumption indicators with those observed in the previous 2 years.Material and methodsBased on the panel, 10 antimicrobial consumption indicators were selected. The unit of measurement for the consumption was the number of defined daily doses per 100 stays (DDD/100e).ResultsAntibacterials overall consumption (OC) 1.5% (86.5 to 85.2) decrease in 2019;and 4.7% increase in 2020 compared to 2019 (89.2).Antifungals OC 3% decrease in 2019 (7.05 to 6.84);26% increase in 2020 compared to 2019 (8.65).Carbapenems: in 2019, consumption decreased by 4.2% (10.17 to 9.74);in 2020 it increased by 2% compared to 2019 (9.94).Fluoroquinolones: maintained overall 37.4% decrease (13.01 in 2018, 10.83 in 2019 and 8.14 in 2020).Fosfomycin: maintained overall increase of 27.6% (0.49 in 2018, 0.65 in 2019 and 0.62 in 2020).Aminoglycosides: maintained overall decrease of 40.7% (3.27 in 2018, 2.32 in 2019 and 1.94 in 2020).Colistin: 12.8% decrease in 2019 (1.09 to 0.95), and an 8.4% increase in 2020 compared to 2019 (1.03).Anti-pseudomonal cephalosporins: maintained overall increase of 19% (2.11 in 2018, 2.47 in 2019 and 2.51 in 2020).Amoxicillin-clavulanate/piperacillin-tazobactam ratio: maintained decrease of 47% compared to 2018 (4.34 in 2018, 3.54 in 2019 and 2.26 in 2020).Fluconazole/equinocandins ratio: 24% rise in 2019 (4.14 to 5.45);in 2020 it decreased by 16% (4.57).Conclusion and relevanceDuring 2020, a change in trend has been perceived in a series of antimicrobial consumption indicators, with higher antibacterials and antifungals OC, carbapenems and colistin consumption, and a decreased fluconazole/equinocandins ratio. This change in trend could be related to the increase of multiresistant bacterial and fungal infections associated with COVID-19.The downward trend in the consumption of fluoroquinolones and aminoglycosides and the upward trend in anti-pseudomonal cephalosporins and fosfomycin was maintained. Interventions carried out through the antimicrobial stewardship programme aimed at optimising and/or de-escalating empirical antimicrobial treatment may be behind this trend.The amoxicillin-clavulanate/piperacillin-tazobactam ratio may have been influenced by frequent piperacillin-tazobactam stock-outs in the years studied.References and/or acknowledgements1. Gutiérrez-Urbón JM.Indicadores del uso hospitalario de antimicrobianos basados en el consumo. Farm Hosp 2019;43(3):94–100.Conflict of interestNo conflict of interest

Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study.

AIMS: To examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: A multicentre observational study was performed at Greater Paris University hospitals. The sample involved 14 381 patients hospitalised for COVID-19. A total of 686 (4.8%) inpatients received a BZRA at hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (standard deviation (s.d.) = 25.4). The study baseline was the date of admission, and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, medical comorbidities and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW). RESULTS: Over a mean follow-up of 14.5 days (s.d. = 18.1), the primary endpoint occurred in 186 patients (27.1%) who received BZRAs and in 1134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (hazard ratio (HR) = 3.20; 95% confidence interval (CI) = 2.74-3.74; p < 0.01) and in the IPW analysis (HR = 1.61; 95% CI = 1.31-1.98, p < 0.01), with a significant dose-dependent relationship (HR = 1.55; 95% CI = 1.08-2.22; p = 0.02). This association remained significant in sensitivity analyses. Exploratory analyses indicate that most BZRAs may be associated with an increased mortality among patients hospitalised for COVID-19, except for diazepam, which may be associated with a reduced mortality compared with any other BZRA treatment. CONCLUSIONS: BZRA use may be associated with an increased mortality among patients hospitalised for COVID-19, suggesting the potential benefit of decreasing dose or tapering off gradually these medications when possible.

A Nationwide Survey of COVID-19 Management in the Dominican Republic over the Course of the Pandemic

Background. COVID-19 was declared a global Public Health Emergency by the WHO in January 2020. Limited treatment options existed early in the pandemic. As COVID-19 spread across the globe and new therapeutics emerged, different interpretations of the literature grew, and major societies relayed conflictive recommendations. There is a paucity of data on COVID-19 management in low- and middle-income countries. As a result, we performed a nationwide survey of local treatment practices in the Dominican Republic (DR). Methods. We performed an anonymous survey of infectious diseases specialists in the DR and US. The survey collected hospital characteristics and COVID-19 management protocols during different quarters of 2020-21. Management was categorized by drug and disease severity based on supplemental oxygen requirements. A convenience sample in the US representing community and academic sites was surveyed for point comparison between the US and DR. Results. The survey was completed by physicians from a total of 11 sites located in 4 cities of the DR: Santo Domingo (3), Santiago (4), La Vega (2) and San Francisco (2). These cities were representative of all regions in the country. The survey included 7 (64%) hospitals with < 200 beds, 3 (27%) with 201-300 beds, and 1 (9%) with >400 beds. Seven (47%) were private, 2 (13%) public, and 6 (40%) were teaching hospitals. In the US, 2 academic hospitals with >400 beds and 2 community hospitals with < 200 beds in a major city were surveyed. Management of COVID-19 at sites in the DR and US throughout the pandemic is plotted in Figure 1. Remdesivir use by disease severity is plotted in Figure 2. Conclusion. Throughout the pandemic, as therapeutic options evolved, hospitals and physicians had to adapt to changing guidelines and availability of novel drugs. Variability between countries and sites emerged. The use of hydroxychloroquine and convalescent plasma waned more rapidly in the US. Dexamethasone was widely used at all sites. Tocilizumab and remdesivir were used more liberally in the DR. Antimicrobial stewardship limited these agents at US sites to more narrow therapeutic windows which could explain the discrepancies seen between the US and DR. Uncertainty of benefit in certain disease states, limited availability, and cost may also play a role.

COVID-19 vaccines: An allergological study

Background: In order to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) an active approach is necessary. On December 2020 the commercialization of the COVID-19 vaccines was made. In Spain the first one to arrive was Pfizer-BioNtech vaccine. Initially, several reports of anaphylactic reactions due to the vaccine in the USA and in the UK were reported, which lead to an early recommendation to avoid the administration in patients with allergic history. The objective of this study is to describe and characterize the allergenic profiles of patients attended in our clinic for allergy testing to prevent reactions with the COVID-19 vaccine. Method: The allergological profile of 85 patients diagnosed with previous history of allergic disorders was analysed between January 18th and March 16th 2021. The allergological study included skin-prick test with polyethylene glycol (PEG), Tween 20, Tween 80, and COVID-19 vaccine (Pfizerâ), together with latex and other allergens when necessary. After the double dose of vaccine was completed, a follow up was done by telephone. Results: Risk stratification and approach is exposed in figure 1. Clinical and allergological characteristics of 85 patients are shown in table 1. Out of them, 88.2% had an allergic comorbidity and 48.2% had drug allergy. The reason for consultation was in 92.9% due to their allergic history, 76.5% were referred from the Occupational Health Service, and 80.6% of the patients have had previous vaccination with other anti-infective vaccines without reactions. Also, table 1 shows the prick-test results with COVID vaccine an its excipients, without any positive result. 70.7% of our population has completed the vaccination. Only 9 patients had a possible allergic reaction to the first dose, 8 of them had cutaneous and the remaining had respiratory symptoms. Out of these 9 patients, 6 had their second dose without any symptoms. Conclusion: None of the patients studied showed a positive test for neither the components of the vaccine nor the vaccine itself. More studies are required with a larger sample size to reach final conclusions. (Table Presented).

Incidence of SARS-COV-2 infection incancer patients undergoing active treatment

Introduction and Objectives: Cancer patients are more susceptible to infections because of the active treatmentthat they need to treat their disease. A new coronavirus, called SARS-CoV-2, has caused a global pandemic wherecancer patients have an increased risk of morbidity and mortality associated with COVID-19. However, the incidencedata of COVID-19 in cancer patient with active treatment are not known, although the main oncology societiesrecommend a delay and/or stop in active cancer treatment during this pandemic. Whether this stop will have animpact on the future evolution of their disease is also not known. Therefore, a study of the incidence of COVID-19 inthis type of patient can help us to organize the protocols and the treatment in these high-risk patient group. Materials and Methods: We conducted a prospective clinical study of cancer patients within active treatment(chemotherapy, palliative hormonotherapy, radiotherapy, target therapies, or immunotherapy), analyzing the numberof COVID-19 diagnoses between February 26 and May 13 in two oncology services of the Andalusian community. Adescriptive analysis of 692 patients with active treatment was carried out. In addition, the cumulative incidence andthe differences between groups were calculated using the SPSS vs 18. Results: A total of 692 cancer patients undergoing active treatment at the Hospital Costa del Sol (Marbella) and atthe Hospital San Cecilio (Granada) were analyzed. Sixty four percent were men with a mean age of 60 years. Fortyone percent had a breast cancer diagnosis, 12.9% had lung cancer, and 14.5% had colorectal tumor. Fifty threepercent of them received treatment for stage IV disease, and up to 43% were delayed treatment due to pandemic.The total number of infections was 9, a cumulative incidence of 1.3%, 95% CI (0.384-2.217), and 22% of them diedafter developing the infection. Advanced age (p = 0.011), an admission in the 3 months prior to the diagnosis ofCOVID-19 (p = 0.031), and active treatment with chemotherapy (p = 0.003) were the factors that were associated with an increased risk of developing COVID-19. Conclusions: The incidence of SARS-CoV-2 in cancer patients on active treatment is low but the mortality is high, as previously reported for these patients. Given that the incidence of COVID-19 in patients with treatment is low, wecannot conclude any role of treatment delay in the development of COVID-19 in these patients..