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

Effects of the COVID-19 pandemic on food purchase and consumption in college students.

Background: The world has experienced a pandemic in the last 100 years which has caused abrupt changes in mobility and lifestyle habits. Objective(s): To identify the effects of the COVID-19 pandemic on the purchase and consumption of food in university students. Method(s): Prospective, cross-sectional, descriptive study of 335 university students. The evaluation instrument consisted of general data, food shortages and price increase, changes in habits and healthy eating, with 11 questions in total. An analysis was made with descriptive statistics and Pearson's Chi-square with statistical significance level of p<0.05. Result(s): The most used modality of purchase before and during the confinement was face-to-face (53.73%), showed a significant relationship between the consumption of food of low biological value (junk) under factors of anxiety, depression, boredom and a relationship between students' eating and interest in healthy eating with Pearson's Chi-square values of 26.09 and 72.81 respectively. Conclusion(s): There were no changes in the modality of acquiring their food, modifications are observed in the consumption of junk food and interest in maintaining a healthier diet during the confinement by COVID-19.Copyright © 2022 Sociedad Espanola de Nutricion Comunitaria. All rights reserved.

Comparative in silico design and validation of GPS™ CoVID-19 dtec-RT-qPCR test.

AIMS: Providing a ready-to-use reverse transcriptase qPCR (RT-qPCR) method fully validated to detect the SARS-CoV-2 with a higher exclusivity than this shown by early published RT-qPCR designs. METHODS AND RESULTS: The specificity of the GPS™ CoVID-19 dtec-RT-qPCR test by analysis of sequence alignments was approached and compared with other RT-qPCR designs. The GPS™ CoVID-19 dtec-RT-qPCR test was validated following criteria of UNE/EN ISO 17025:2005 and ISO/IEC 15189:2012. Diagnostic validation was achieved by two independent reference laboratories, the Instituto de Salud Carlos III, (Madrid, Spain), the Public Health England (Colindale, London, UK), and received the label CE-IVD. The GPS design showed the highest exclusivity and passed all parameters of validation with strict acceptance criteria. Results from reference laboratories 100% correlated with these obtained by using reference methods and showed 100% of diagnostic sensitivity and specificity. CONCLUSIONS: The CE-IVD GPS™ CoVID-19 dtec-RT-qPCR test, available worldwide with full analytical and diagnostic validation, is the more exclusive for SARS-CoV-2 by far. SIGNIFICANCE AND IMPACT OF THE STUDY: Considering the CoVID-19 pandemic status, the exclusivity of RT-qPCR tests is crucial to avoid false positives due to related coronaviruses. This work provides of a highly specific and validated RT-qPCR method for detection of SARS-CoV-2, which represents a case of efficient transfer of technology successfully used since the pandemic was declared.

Intelligent Screening from X-Ray Digital Images Based on Deep Learning

Coronavirus disease (Covid-19) is an infectious respiratory disease caused by SARS-CoV-2. Among the symptoms, the respiratory system of the sufferer is affected. This respiratory condition suggests that the chest imaging plays a key role in the diagnosis of the disease. Several pre-trained deep learning models have been developed to detect Covid-19 through chest radiographs. These models provide high precision for binary detection, however, when combined with other diseases such as pneumonia that also affect the respiratory system and lungs, they offer poorer quality performance and reduce screening performance. In this study, we analyze some neural networks models for binary and multiclass classification of X-ray images in order to find out the best accuracy of classification. The models are based on deep learning methodology to learn and classify images. They are extracted from well-known repositories such as Kaggle. The conducted experiments compare their performance in several scenarios: a multiclass classification model versus the combination of several binary classification models. Two methods for combining the output of the binary models are proposed to achieve the best performance. The results show that the best results are obtained with a well-trained multiclass model. However, a preliminary screening can be obtained from the binary models without creating and training a more complex model. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

The effect of COVID-19 on patients with preexisting autoimmune diseases

In December 2019, a new Coronavirus called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), appeared in China, spreading rapidly around the globe and becoming a pandemic. SARS-CoV-2 is the cause of a serious life-threatening disease known as COVID-19. The risk of SARS-CoV-2 infection in patients with preexisting systemic autoimmune diseases (AID) appears to be slightly higher than in the general population, but the clinical course does not appear to be different. However, we must bear in mind that the use of corticosteroids, immunomodulatory drugs, and biological therapy in patients with AID can modulate the risk of hospitalization and death. The alterations in the innate and adaptive immune response found in patients with cytokine storm due to COVID-19 are the reasons for the high morbidity and mortality. Thus, clinicians should early identify the symptoms and closely monitor patients with risk factors for developing these complications and the interactions with other systems such as the immune-neuro-endocrine system. © 2023 Elsevier Inc. All rights reserved.

Side effects of the COVID-19 vaccines

The ability to eradicate deadly diseases and decrease the mortality of others makes vaccines one of the most important discoveries of the last century. Despite already having effective vaccines, scientific advances continue developing new antigens capable of producing more significant immune responses to achieve stronger immunity. © 2023 Elsevier Inc. All rights reserved.

Family Relations of University Students in Times of Pandemic by COVID-19: Feelings and Tensions

Objective: The objective of this research was to reveal the feelings and tensions that characterize the family relationships of university students in times of pandemic and confinement conditions due to COVID-19. Method(s): The method was qualitative, and the feelings and tensions in the family and educational context of 584 university students were evaluated, from a qualitative proposal and a hermeneutic approach, anchored to the question: How have the affective manifestations been, in terms of feelings and tensions, in the family relationships of university students, academically active, in the Caribbean Region of Colombia, during the mandatory confinement process derived from the COVID 19 pandemic? The methodological design was structured from the concepts of the Grounded Theory, applied to the data obtained through virtual techniques and instruments, such as an online survey. The organization of the information to generate the results was made from descriptive, analytical and interpretive coding, supported by matrices and theoretical maps. Results and Discussion: There are feelings and tensions in three directions: Negative Feelings (in tension) such as anxiety, stress and depression;positive feelings, joy, adaptation and ambiguous feelings, which show ambivalence and variability, which are reflected in family relationships and three senses: They have improved, remain the same and have worsened, according to each type, dynamics and characteristics of the family, associated with gender, coping mechanisms and socioeconomic level. Conclusion(s): Families were transformed due to the pandemic, and relationships and interactions were found that exacerbated tensions or factors of protection and care among family members, with emotional overload, with stress from work and study.Copyright © 2023 Bentham Science Publishers.

What is going on within google earth engine? A systematic review and meta-analysis

Google Earth Engine (GEE) is a geospatial processing platform based on geo-information applications in the ‘cloud'. This platform provides free access to huge volumes of satellite data for computing, and offers support tools to monitor and analyse environmental features on a large scale. Such facilities have been widely used in numerous studies about land management and planning. Considering the current lack of relevant overviews, it may be useful to evaluate the utilization paths of GEE and its impact on the scientific community. For this purpose, a systematic review has been conducted using the PRISMA methodology based on 343 articles published from 2020 to 2022 in high-impact scientific journals, selected from the Scopus and Google Scholar databases. After an overview of the publishing context, an analysis of the frequency of satellite features, processing methods, applications are carried out, and a special attention is given to the COVID-19 studies. Finally, the geographical distribution of the reviewed articles is evaluated, and the citation impact metrics is analysed. On a bibliometric approach, 90 journals published articles on GEE in the reference period (January 2020 to April 2022), and this large number of journals reveals the multidisciplinary application of GEE platform as well as the interest of publishers towards this topic of relevance for the international scientific community. The results of the meta-analysis following the systematic review showed that: (i) the Landsat 8 was the most widely-used satellite (25%);(i) the non-parametric classification methods, mainly Random Forest, were the most recurrent algorithms (31%);and (iii) the water resources assessment and prediction were the most common methodological applications (22%). A low number of articles about COVID-19, in spite of the planetary importance of the pandemic effects. The reviewed articles were geographically distributed among 86 countries, China, United States, and India accounting for the large number. ‘Remote Sensing' and ‘Remote Sensing of Environment' were the leading journals in the citation impact metrics, while the Random Forest method and the agriculture-related applications being the mostly cited. It is expected that these results might change over the mid to long term, due to fast progress in environmental and spatial information technologies, although currently our findings may be worthwhile and useful for assessing the current global deployment of GEE platform. © 2022 The Authors

Efficacy of Approved versus Unapproved Vaccines for SARS-CoV-2 Infection in Randomised Blinded Clinical Trials

Background. Five SARS-CoV-2 vaccines are approved in North America and/or Europe: Pfizer/BioNTech, Moderna, Janssen, Oxford-AstraZeneca and Novavax. Other vaccines have been developed, including Sinopharm, SinoVac, QazVac, Covaxin, Soberana, Corbevac, Medicago, Clover and Cansino, but are not approved in high income countries. This meta-analysis compared the efficacy of approved and unapproved vaccines in randomised clinical trials (RCTs). Methods. A systematic review of clinical trial registries, PUBMED and EMBASE identified placebo-controlled RCTs of SARS-CoV-2 vaccines prospectively evaluating risks of symptomatic or severe infection with clearly defined endpoints. For each trial, risk of bias was assessed using Cochrane tool 2.0 and the CONSORT checklist. In the pre-defined meta-analysis, relative risks of symptomatic infection and severe disease were compared for each vaccine versus placebo, using Cochrane-Mantel Haenszel Tests (random effects method). Results. There were 21 RCTs assessing efficacy of the COVID-19 vaccines identified. One RCT was excluded for high risk of bias. Ten RCTs in 206,667 participants evaluated 5 approved vaccines;10 RCTs in 158,599 participants evaluated 8 unapproved vaccines. In the meta-analysis, prevention of symptomatic infection was 84% (95% C.I. 68-92%) for approved vaccines versus 72% (95% C.I. 65-77%) for unapproved vaccines, with no significant difference between vaccine types (p=0.13). Prevention of severe SARS-CoV-2 infection was 95% (95% C.I. 78-99%) for approved vaccines versus 84% (95% C.I. 72-91%) for unapproved vaccines (p=0.12). In addition, the risk of serious adverse events was similar between vaccine types (p=0.49). Efficacy of approved and unapproved SARS-CoV-2 vaccines Percentage efficacy of approved and unapproved SARS-CoV-2 vaccines against symptomatic infection (Panel A) and severe disease (Panel B). Vaccines are arranged by approval-status (approved vaccines to the left and unapproved vaccines to the right of discontinuous line) and colour-coded by vaccine type. Error bars represent 95% confidence intervals. RIBSP, Research Institute for Biological Safety Problems;IFV, Instituto Finlay de Vacunas. Conclusion. This meta-analysis of 20 RCTs in 365,266 participants, showed no significant difference in efficacy between the approved and unapproved SARS-CoV-2 vaccines for endpoints of either symptomatic or severe infection. Differences in study design, end-point definitions, variants and prevalence of infection may have influenced the results. Head-to-head RCTs will be required to make definitive conclusions. If efficacy is proved definitively, new patent-free vaccines could lower costs of worldwide SARS-CoV-2 vaccination campaigns significantly.

Factors Associated to Decrease in Quality of Life After Mild-Moderate COVID-19: A Cross-Sectional Study

Background. Post-COVID-19 alterations have been recognized even after mild disease. We aimed to assess which factors are the main contributors to a decrease in quality of life(QOL) of patients with different times elapsed from the COVID-19 diagnosis. Methods. A cross-sectional study from January 2021 to April 2021 in a Referral Center in Mexico City. Patients were invited for a follow-up visit in which a structured questionnaire about symptoms, the EQ-5D-5L QOL for QOL, and an objective olfactory evaluation with The Sniffin' Sticks Screening 12 test. Results. We included 179 patients, 64% were female with a median age of 33 years. The median time since COVID-19 diagnosis until the evaluation was 219 days (IQR, 94-255). Persistent symptoms were present up to in 158/179 (88%), fatigue, pain/discomfort and cognitive alterations were present in 61%, the median EQ-5D-5L index value preCOVID-19 was 1 (IQR, 0.94-1) and post- COVID-19 was 0.87 (IQR, 0.80-0.94), P< 0.001. There were 101/179 (56%) patients with decreased QOL;In the multivariate analysis, post-COVID-19 pain (aOR, 2.5;P= 0.01), anxiety (aOR, 13;P= 0.03), and the persistence of three or more symptoms (aOR, 2.6;P= 0.05) were factors associated with decreased QOL. Conclusion. Within the post- COVID-19 alterations, psychological and physical factors such as Pain/discomfort, anxiety, and persistent symptoms explained the decreased QOL in the post-COVID-19 patient. These alterations were present as early as 30 days to more than eight months.

Overview of coronavirus pandemic

During the last months of 2019, numerous cases of respiratory illness such as pneumonia and acute respiratory distress syndrome were described in Wuhan, the capital city of Hubei province in China. At the same time, several research groups identified and reported the etiological agent, that included within the Coronaviridae family and the order Nidovirales, named SARS-CoV-2. Subsequently, the pathological and clinical status caused by the pathogen is commonly known as Coronavirus disease 2019 (COVID-19). In a short period, the outbreak of emerging spread across the world. Therefore the World Health Organization declared a public health emergency of international concern on January 30, 2020, and as a pandemic on March 11, 2020. Many different public health and epidemiological studies have been published since the COVID-19 outbreak, but fatality rates (those that relate the number of cases to mortality) are difficult to assess with certainty. Mean and median case-fatality rates worldwide are near to 3% and 2%, respectively. The median infection fatality calculated from serologic prevalence varies from 0.00% to 1.63% but is mostly estimated between 0.27% and 0.9%. These indexes are influenced by geographic location, socioeconomic status, sex, age, and health conditions, among others. © 2022 Elsevier Inc. All rights reserved.

DIFFERENT HUMORAL but SIMILAR CELLULAR RESPONSES of PATIENTS with AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES under DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS after COVID-19 VACCINATION

Background: The interplay between humoral and cellular response after vaccination against SARS-CoV-2 in patients (pts.) with autoimmune infammatory rheumatic diseases (AIRD) remains unknown. Objectives: To investigate the impact of different immunosuppressive therapies on the development of humoral and cellular immune responses to full 2-dose SARS-CoV-2 vaccination in AIRD pts. with stable low disease activity. Methods: The immune reactivity to COVID-19 vaccination was investigated in a prospectively recruited AIRD cohort with rheumatoid arthritis, axial spondy-loarthritis or psoriatic arthritis which received a therapy with IL-17i, TNFi, JAKi or MTX (alone or in combination). Almost all patients received mRNA-based vaccine, only 4 patients had a heterologous scheme. Anti-spike(S) antibodies(ab.) and sera neutralizing capacity (neutralization dilution 50;ND50) were measured 4 weeks after the frst (prime+4w) and 4 weeks after the second vaccination (boost+4w). Vaccine-specifc cellular immunity was evaluated by quantifying expression of activation markers on T cells as well as their production of key cytokines, at prime+4w and boost+4w. Results: Overall, a total of 92 pts. were included in the fnal cohort. 31 (33.7%) pts. were on TNFi, 24 (26.1%) on IL-17i, 24 (26.1%) on JAKi, each group encompassing pts. receiving drug inhibitors alone or in combination with MTX.13 (14.1%) were treated with MTX alone. The median time between the vaccination and blood sampling was 31 [IQR: 28-34] days after prime+4w and 28 [IRQ: 28-28] days after boost+4w. Although at prime+4w only 34/90 (37.8%) of pts. presented neutralizing ab., the majority (86/91, 94.5%), developed them at boost+4w. The highest neutralization titer developed the pts. on IL-17i both at prime+4w (74 [IQR: 13-91]) and boost+4w (798 [IQR: 511-1344]), while no statistically signifcant differences were found in the neutralization titer at boost+4w for the TNFi, JAKi, and MTX groups: 207 ND50 [IQR: 120-576], 319 [IQR: 133-461] and 749 [IQR: 264-1920], respectively. 81/90 (90.0%) pts. developed IgG ab. against SARS-CoV-2 S-protein at prime+4w and 91/92 (98.9%) at boost+4w. Pts. receiving IL-17i developed higher ab. titers (8295 U/mL [IQR: 4586-11,237]) compared to the other three groups: JAKi (4405 U/mL [IQR: 1436-7265], TNFi (2313 [IQR: 1156-3630] U/mL) and MTX (2010 U/mL [IQR: 693-9254]). Neutralization capacity correlated well with the titer of anti-S ab. at both timepoints. Co-administration of biologic/tsDMARDs and MTX led to lower titers compared to biologic/tsDMARDs mon-otherapy. All therapies left frequencies of CD154+CD137+ CD4+ T cells and CD137+ CD8+ T cells at prime+4w and boost+4w unchanged. Polyfunction-ality and T cell cytokine profiles across therapies did not signifcantly vary at boost+4w. Conclusion: Even after insufficient seroconversion for neutralizing capacity and ab. response against SARS-CoV-2 S-proteins between pts. of different mod of action agents, particularly for MTX and JAKi after frst vaccination, a second vaccination covered almost all pts. regardless of DMARDs therapy, with better outcomes in those on IL-17I. T cell immunity revealed similar frequencies of activated T cells in all modes of action after the second vaccination.

A phase 1/2 trial of lurbinectedin (L) in combination with pembrolizumab (P) in relapsed small cell lung cancer (SCLC): The LUPER study

Background: L is a novel anticancer agent that inhibits trans-activated transcription and modulates the tumor microenvironment. L is approved by the FDA for metastatic SCLC patients (pts) with progressive disease (PD) on or after platinum-based chemotherapy (CT). The LUPER study is assessing the safety, tolerability, and preliminary efficacy of L+P as second-line regimen for SCLC pts after failure of platinum- based CT. Phase 1 data are presented here. Methods: In this phase 1/2 trial (NCT04358237), adult pts with histologically confirmed SCLC, PD to a previous CT-containing regimen (≥4 weeks before study initiation), no prior exposure to immunotherapy, ECOG PS of 0-1, and measurable disease as per RECIST 1.1 are eligible. Pts with treated, stable, and asymptomatic brain metastases (BMs) are allowed. A 3+3 dose-escalation was done to determine the recommended phase 2 dose (RP2D) of L+P. L was dosed at 2.4 mg/m2 and 3.2 mg/m2 IV Q3W in the dose level (DL)1 and 2, respectively, in combination with fixed dose of P (200 mg IV Q3W). The RP2D was the highest DL at which 0/3 pts or ≤1/6 pts experienced dose-limiting toxicities (DLTs) during the first cycle. Treatment was administered until PD, unacceptable toxicity, or consent withdrawal. Secondary endpoints include safety as per CTCAE 5.0, preliminary efficacy, and pharmacokinetics. Results: Thirteen pts were enrolled across 3 hospitals in Spain (DL1, n = 7;DL2, n = 6). Median age was 66 (range 43-78) years, 46.2% were female, 61.5% had ECOG PS of 1, 38.5% had platinum-free interval < 90 days, 30.8% had LDH > upper normal limit, and 15.4% had BMs. One DLT (G3 asthenia) and one G4 neutropenia lasting > 3 days (controlled with G-CSF prophylaxis upon C2, without requiring dose delay or modification) occurred in the DL1. No DLT were reported in the DL2. The RP2D was identified as 3.2 mg/m2 L and 200 mg P IV Q3W. At data cutoff (Jan 21, 2022), 5 (38.4%) pts remained on treatment (1 pt in DL1 discontinued due to COVID-19 in cycle 1). Median duration of treatment was 2.1 (0-11.8) months, 5 (38.5%) pts had ≥8 cycles, and median relative dose intensity of L and P were 91.1% and 95.7%, respectively. Immune-related AEs (G2 pneumonitis;G3 ALT increased) led to P discontinuation in 2 (15.4%) pts. Responses were shown in both DLs, with ORR of 30.8% (1 confirmed complete response and 3 partial responses);3 pts had stable disease (SD;including 1 patient with SD > 12 weeks) and 5 (38.5%) pts experienced PD. Conclusions: This is the first report to demonstrate a manageable safety profile and preliminary efficacy of second-line L+P for relapsed SCLC pts. This combination warrants further confirmation in the ongoing expansion phase 2.

The impact of the COVID-19 pandemic on blood supply management in Region III, Philippines

Background: Over the years, transfusion therapy has profited healthcare in improving health outcomes of a wide spectrum of patients. However, the stability and availability of adequate blood supply is not always ensured. Disasters such as the COVID-19 pandemic may pose significant threats to blood supply management- which may also affect the performance of healthcare systems. Recent studies and news have highlighted the effect of the COVID- 19 crisis to blood supply management but not much has been studied on the trends in blood supply management in a Philippine setting which may provide information on how blood supply is being managed locally in the presence of challenges amid the COVID-19 pandemic. Aims: The current study aimed to explore the trends in blood collection, utilization and wastage in Region III, Philippines in the years 2019 and 2020 to describe the impact of the pandemic on local blood supply management. Methods: Secondary data from the Department of Health-Central Luzon, Philippines was used to calculate the proportion of decrease or increase in blood donation, usage, and wastage during the pandemic. Results: During the course of the pandemic, five out of the six provinces included in the study had decreased voluntary blood donations (-31.87%) while four out of six had increased replacement donations (28.82%), which reduced the total blood donation output in the region (-14.46%). In addition, a lower utilization of whole blood (-21.53%) and platelet concentrate units (-19.70%) caused an overall decrease in blood usage (-5.29%). Lastly, a high wastage of fresh frozen plasma units (52.35%) largely contributed to the general increase in unused blood products (10.91%). Summary/Conclusions: A shift in the sources of blood donations (i.e., increased replacement donations) was observed in Region III, Philippines during the COVID-19 pandemic. This can be attributed to the implementation of social restrictions that prevented mass blood donations and rendered replacement donations as the 'safer' option in preventing the spread of COVID-19. Moreover, the demand for blood utilization decreased during the pandemic which relates to the efforts of blood supply managers to balance the demand and supply of blood products since the pandemic reduced the blood donation output in the region. However, this attempt to decrease blood demand resulted in an increased wastage of blood products. The findings of this study calls for the establishment of preparedness plans to efficiently combat against disasters such as the COVID-19 pandemic.