Dapagliflozin and Kidney Outcomes in Hospitalized Patients with COVID-19 Infection: An Analysis of the DARE-19 Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Patients who were hospitalized with coronavirus disease 2019 (COVID-19) infection are at high risk of AKI and KRT, especially in the presence of CKD. The Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial showed that in patients hospitalized with COVID-19, treatment with dapagliflozin versus placebo resulted in numerically fewer participants who experienced organ failure or death, although these differences were not statistically significant. We performed a secondary analysis of the DARE-19 trial to determine the efficacy and safety of dapagliflozin on kidney outcomes in the overall population and in prespecified subgroups of participants defined by baseline eGFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The DARE-19 trial randomized 1250 patients who were hospitalized (231 [18%] had eGFR <60 ml/min per 1.73 m2) with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. Dual primary outcomes (time to new or worsened organ dysfunction or death, and a hierarchical composite end point of recovery [change in clinical status by day 30]), and the key secondary kidney outcome (composite of AKI, KRT, or death), and safety were assessed in participants with baseline eGFR <60 and ≥60 ml/min per 1.73 m2. RESULTS: The effect of dapagliflozin versus placebo on the primary prevention outcome (hazard ratio, 0.80; 95% confidence interval, 0.58 to 1.10), primary recovery outcome (win ratio, 1.09; 95% confidence interval, 0.97 to 1.22), and the composite kidney outcome (hazard ratio, 0.74; 95% confidence interval, 0.50 to 1.07) were consistent across eGFR subgroups (P for interaction: 0.98, 0.67, and 0.44, respectively). The effects of dapagliflozin on AKI were also similar in participants with eGFR <60 ml/min per 1.73 m2 (hazard ratio, 0.71; 95% confidence interval, 0.29 to 1.77) and ≥60 ml/min per 1.73 m2 (hazard ratio, 0.69; 95% confidence interval, 0.37 to 1.29). Dapagliflozin was well tolerated in participants with eGFR <60 and ≥60 ml/min per 1.73 m2. CONCLUSIONS: The effects of dapagliflozin on primary and secondary outcomes in hospitalized participants with COVID-19 were consistent in those with eGFR below/above 60 ml/min per 1.73 m2. Dapagliflozin was well tolerated and did not increase the risk of AKI in participants with eGFR below or above 60 ml/min per 1.73 m2.

miRNA signatures associated with vulnerability to food addiction in mice and humans.

Food addiction is characterized by a loss of behavioral control over food intake and is associated with obesity and other eating disorders. The mechanisms underlying this behavioral disorder are largely unknown. We aimed to investigate the changes in miRNA expression promoted by food addiction in animals and humans and their involvement in the mechanisms underlying the behavioral hallmarks of this disorder. We found sharp similitudes between miRNA signatures in the medial prefrontal cortex (mPFC) of our animal cohort and circulating miRNA levels in our human cohort, which allowed us to identify several miRNAs of potential interest in the development of this disorder. Tough decoy (TuD) inhibition of miRNA-29c-3p in the mouse mPFC promoted persistence of the response and enhanced vulnerability to developing food addiction, whereas miRNA-665-3p inhibition promoted compulsion-like behavior and also enhanced food addiction vulnerability. In contrast, we found that miRNA-137-3p inhibition in the mPFC did not lead to the development of food addiction. Therefore, miRNA-29c-3p and miRNA-665-3p could be acting as protective factors with regard to food addiction. We believe the elucidation of these epigenetic mechanisms will lead to advances toward identifying innovative biomarkers and possible future interventions for food addiction and related disorders based on the strategies now available to modify miRNA activity and expression.

Impact of the ABCB1 Drug Resistance Gene on the Risk Factors of Patients with COVID-19 and Its Relationship with the Drugs Used.

Objective: In the last two years progress was made in molecular, physio pathological understanding and the form of transmission of COVID-19, and different therapeutic strategies have been explored to deal with the situation of the pandemic. However, the evaluation of certain genes that participate in the metabolism and transport of these drugs has not been fully explored. A lack of response to treatment and a lower survival have been observed that may be due to the presence of the ABCB1 drug resistance gene. Our research group analyzed whether the expression levels of the ABCB1 gene are associated with comorbidities, treatments, overall survival and risk of death in patients with severe COVID-19. Methods: The expression levels of the ABCB1 gene were analyzed by RT-qPCR in 61 patients diagnosed with COVID-19. The association between the levels of expression, the risk variables and different treatments were determined by the Chi-Square test and the Fisher's exact test. Global Survival (GS) was determined by the Kaplan-Meier method. The impact of high levels of expression and the risk of death was performed by odds ratio. Results: The different risk variables showed that patients with either high or absent levels of ABCB1 gene expression presented a greater risk of death (OR 3.08, 95%, CI 1.02-9.26) as well as need for ventilatory support (OR 2.8, 95%, CI 0.98 -8.5). Patients with diabetes and COVID-19, treated with metformin, were associated with a lower risk of death (OR 1.11, 95%, CI 0.38-3.22). OS with respect to high or absent levels of expression of the ABCB1 gene was lower. Conclusion: High levels or null expression of the ABCB1 gene are associated with a higher risk of death or progression of the disease, the use of metformin in patients with COVID-19 confers a lower risk of death.

COVID-19 mRNA Vaccines Preserve Immunogenicity after Re-Freezing.

The massive COVID-19 vaccine purchases made by high-income countries have resulted in important sample losses, mainly due to the complexity of their handling. Here, we evaluated the possibility of preserving the immunogenicity of COVID-19 mRNA vaccines after re-freezing vials, following the extraction of the maximum possible number of samples, as an alternative approach to minimizing their wastage. Thus, we exposed the vaccine vials to different re-freezing conditions and evaluated mRNA integrity and the effects in mice after in vivo administration. We reveal that the mRNA integrity of Comirnaty® and Spikevax® vaccines remained unaffected after re-freezing during 1 month at -20 °C or -80 °C. The immunological responses also remained unchanged in mice after these re-freezing conditions and no apparent side effects were revealed. The preservation of mRNA integrity and immunogenicity under these handling conditions opens the possibility of re-freezing the mRNA COVID-19 vaccine vials to limit their wastage and to facilitate vaccination processes.

SARS-CoV-2 could be spread through hospital medication dispensed to patients: A prospective observational study.

ABSTRACT: Our objective was to analyze in vitro the persistence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the packaging material of the drugs dispensed to hospital wards. Additionally, to evaluate if the protection with a double plastic bag prevents the contamination of the medication dispensed to an intensive care unit (ICU).On the first part, different materials containing different drugs within an ICU were sampled to confirm the lack of contamination by SARS-CoV-2. The confirmation of the virus was performed using real time reverse transcription polymerase chain reaction. As a control group, in the microbiology laboratory we inoculated the virus into the different surfaces containing the same drugs included in the first part. Samples were obtained with a sterile swab at 3, 6, 8, 10, 14, 21, and 30 days after inoculation and analyzed through real time reverse transcription polymerase chain reaction.None of the studied materials containing the drugs within an ICU was contaminated by SARS-CoV-2. In the second part, SARS-CoV-2 was found in all surfaces for up to 30 days.The use of double-bag unit-dose system to deliver medication in a pandemic seems effective to prevent the potential transmission of SARS-CoV-2. A striking SARS-CoV-2 RNA stability of up to 30 days was found in the surfaces containing the drugs.

Reconstituted mRNA COVID-19 vaccines may maintain stability after continuous movement.

OBJECTIVES: There is an urgent need to ameliorate the possibilities of transporting reconstituted mRNA vaccines from the centralized preparation centres to the vaccination sites to improve the efficiency of the vaccination campaign against coronavirus disease 2019 (COVID-19). We have analysed the integrity of the Pfizer-BioNTech and Moderna vaccines under different movement conditions to provide information that may improve the distribution of vaccines to the target population. METHODS: Syringes of reconstituted Pfizer-BioNTech or Moderna COVID-19 vaccines were prepared in a laminar flow chamber to be subjected to a stability analysis in order to evaluate the impact of movement on mRNA integrity. RNA integrity was checked by the lack of RNA peaks under the original mRNA peak in the electropherogram resulting from potential fragments from RNA degradation. Samples were then exposed for 180 min at room temperature (21 ± 1°C, 55 ± 10% humidity) under different movement conditions. RESULTS: We report that the integrity of the mRNA in the reconstituted COVID-19 vaccines after continuous moderate movement at room temperature is maintained for at least 3 hours, with values of fluorescence units (FU) under the original mRNA peak of 0.38 ± 0.06 in the Pfizer-BioNTech vaccine and 0.96 ± 1.18 FU in the Moderna vaccine, equal to the values obtained without movement (0.36 ± 0.08 FU in the Pfizer-BioNTech and 1.12 ± 0.19 FU in the Moderna). In contrast, the integrity of these vaccines exposed to repeated Vortex shaking was significantly impaired (p < 0.001) with values under the original mRNA peak of 1.34 ± 0.31 FU for the Pfizer-BioNTech and 5.03 ± 1.16 FU for the Moderna samples. CONCLUSIONS: The stability of these reconstituted vaccines reported here may improve the efficiency of the ground transportation and distribution of the vaccines, which may lead to shorter and more homogeneous vaccinations in cities and rural areas.

Accidental Interruption of the Cold Chain for the Preservation of the Moderna COVID-19 Vaccine.

Maintenance in restricted cold temperature conditions is a mandatory requirement to preserve the stability of mRNA vaccines [...].

COVID-19 Incidence in Patients With Immunomediated Inflammatory Diseases: Influence of Immunosuppressant Treatments.

The effect of immunosuppressant treatments on the incidence of coronavirus disease (COVID-19) remains largely unknown. We studied the association between the pre-exposure to disease-modifying antirheumatic drugs (DMARDs) that decrease immunological responses and the incidence of COVID-19 to explore the possible effects of these treatments in early manifestations of the disease. For this purpose, we performed a cross-sectional study including 2,494 patients with immunomediated inflammatory diseases (IMIDs) recruited at the outpatient Rheumatology, Dermatology and Gastroenterology services of Hospital del Mar. The primary outcome was the clinical diagnosis of COVID-19 performed by a physician at the hospital or at the primary care center, from the March 1-29, 2020. Multivariable Poisson regression models were fitted to estimate COVID-19 relative risk (RR) adjusted by comorbidities. We revealed that biological (RR = 0.46, CI 95% = 0.31-0.67) and synthetic (RR = 0.62, CI 95% = 0.43-0.91) DMARDs used in IMIDs diminished the incidence of COVID-19. Striking sex differences were revealed with anti-TNFα compounds (RR = 0.50, CI 95% = 0.33-0.75) with higher effects in women (RR = 0.33, CI 95% = 0.17-0.647). Treatment with low glucocorticoid doses also revealed sex differences decreasing the incidence of COVID-19 predominantly in women (RR = 0.72, CI 95% = 0.42-1.22). Our results report a decreased incidence of COVID-19 in patients receiving specific DMARDs with different immunodepressor mechanisms with striking sex differences. These results underline the interest of repurposing specific DMARDs for the possibility of minimizing the severity of disease progression in the early stages of COVID-19.

An International survey on living kidney donation and transplant practices during the COVID-19 pandemic.

The scope of the impact of the Coronavirus disease 19 (COVID-19) pandemic on living donor kidney transplantation (LDKT) practices across the world is not well-defined. We received survey responses from 204 transplant centers internationally from May to June 2020 regarding the impact of the COVID-19 pandemic on LDKT practices. Respondents represented 16 countries on five continents. Overall, 75% of responding centers reported that LDKT surgery was on hold (from 67% of North American centers to 91% of European centers). The majority (59%) of centers reported that new donor evaluations were stopped (from 46% of North American centers to 86% of European centers), with additional 23% of centers reporting important decrease in evaluations. Only 10% of centers reported slight variations on their evaluations. For the centers that continued donor evaluations, 40% performed in-person visits, 68% by video, and 42% by telephone. Center concerns for donor (82%) and recipient (76%) safety were the leading barriers to LDKT during the pandemic, followed by patients concerns (48%), and government restrictions (46%). European centers reported more barriers related to staff limitations while North and Latin American centers were more concerned with testing capacity and insufficient resources including protective equipment. As LDKT resumes, 96% of the programs intend to screen donor and recipient pairs for coronavirus infection, most of them with polymerase chain reaction testing of nasopharyngeal swab samples. The COVID-19 pandemic has had broad impact on all aspects of LDKT practice. Ongoing research and consensus-building are needed to guide safe reopening of LDKT programs.

Influence of anti-osteoporosis treatments on the incidence of COVID-19 in patients with non-inflammatory rheumatic conditions.

Coronavirus disease 19 (COVID-19) is currently a global pandemic that affects patients with other pathologies. Here, we investigated the influence of treatments for osteoporosis and other non-inflammatory rheumatic conditions, such as osteoarthritis and fibromyalgia, on COVID-19 incidence. To this end, we conducted a cross-sectional study of 2,102 patients being treated at the Rheumatology Service of Hospital del Mar (Barcelona, Spain). In our cohort, COVID-19 cumulative incidence from March 1 to May 3, 2020 was compared to population estimates for the same city. We used Poisson regression models to determine the adjusted relative risk ratios for COVID-19 associated with different treatments and comorbidities. Denosumab, zoledronate and calcium were negatively associated with COVID-19 incidence. Some analgesics, particularly pregabalin and most of the studied antidepressants, were positively associated with COVID-19 incidence, whereas duloxetine presented a negative association. Oral bisphosphonates, vitamin D, thiazide diuretics, anti-hypertensive drugs and chronic non-steroidal anti-inflammatory drugs had no effect on COVID-19 incidence in the studied population. Our results provide novel evidence to support the maintenance of the main anti-osteoporosis treatments in COVID-19 patients, which may be of particular relevance to elderly patients affected by the SARS-CoV-2 pandemic.