There is limited information on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) T‐cell immune responses in patients with coronavirus disease 2019 (COVID‐19). Both CD4+ and CD8+ T cells ...may be instrumental in resolution of and protection from SARS‐CoV‐2 infection. Here, we tested 25 hospitalized patients either with microbiologically documented COVID‐19 (n = 19) or highly suspected of having the disease (n = 6) for presence of SARS‐CoV‐2‐reactive CD69+ expressing interferon‐γ (IFN‐γ) producing CD8+ T cells using flow‐cytometry for intracellular cytokine staining assay. Two sets of overlapping peptides encompassing the SARS‐CoV‐2 Spike glycoprotein N‐terminal 1 to 643 amino acid sequence and the entire sequence of SARS‐CoV‐2 M protein were used simultaneously as antigenic stimulus. Ten patients (40%) had detectable responses, displaying frequencies ranging from 0.15 to 2.7% (median of 0.57 cells/µL; range, 0.43‐9.98 cells/µL). The detection rate of SARS‐CoV‐2‐reactive IFN‐γ CD8+ T cells in patients admitted to intensive care was comparable (P = .28) to the rate in patients hospitalized in other medical wards. No correlation was found between SARS‐CoV‐2‐reactive IFN‐γ CD8+ T‐cell counts and SARS‐CoV‐2 S‐specific antibody levels. Likewise, no correlation was observed between either SARS‐CoV‐2‐reactive IFN‐γ CD8+ T cells or S‐specific immunoglobulin G‐antibody titers and blood cell count or levels of inflammatory biomarkers. In summary, in this descriptive, preliminary study we showed that SARS‐CoV‐2‐reactive IFN‐γ CD8+ T cells can be detected in a non‐negligible percentage of patients with moderate to severe forms of COVID‐19. Further studies are warranted to determine whether quantitation of these T‐cell subsets may provide prognostic information on the clinical course of COVID‐19.
Highlights
SARS‐CoV‐2 specific CD8+ T cells can be detected in 40% of COVID‐19 patients.
No correlation was found between SARS‐CoV‐2‐reactive IFN‐γ CD8+ T‐cell countsand SARS‐CoV‐2 S‐specific antibody levels.
No correlation was observed between SARS‐CoV‐2‐reactive IFN‐γ CD8+ T cells and levels of inflammatory biomarkers.
Drug use implies important challenges related to HIV management, particularly due to an increased risk of potential interactions between antiretroviral therapy (ART) and illicit drugs (pDDIs). This ...study analyses the prevalence and severity of pDDIs among people living with HIV (PLHIV). It also explores their awareness of pDDIs and their beliefs about the toxicity that they may cause, as well as the impact of pDDIs on selected health variables. We conducted an on-line cross-sectional survey across 33 Spanish hospitals and NGOs to collect demographics and clinical data. pDDIs were checked against the Interaction Checker developed by Liverpool University. The sample of the present study was composed of 694 PLHIV who used illicit drugs. They represented 49.5% of the 1,401 PLHIV that participated in the survey. After excluding 38 participants due to lack of information on their ART or illicit drug use, 335 (51.1%) participants consuming drugs presented with some potentially significant pDDIs between their ART and illicit drugs, with a mean of 2.1±1.7 (1-10) pDDIs per patient. The drugs most frequently involved in pDDIs were cocaine, cannabis, MDMA and nitrates ("poppers"). The prevalence of pDDIs across ART regimens was: protease inhibitors (41.7%); integrase inhibitor-boosted regimens (32.1%), and non-nucleoside reverse transcriptase inhibitors (26.3%). An awareness of pDDIs and beliefs about their potential toxicity correlated positively with intentional non-adherence (p<0.0001). Participants with pDDIs exhibited a higher prevalence of intentional non-adherence (2.19±1.04 vs. 1.93±0.94; p = 0.001). The presence of pDDIs was not associated with poorer results in the clinical variables analysed. A significant proportion of PLHIV who use drugs experience pDDIs, thereby requiring close monitoring. pDDIs should be considered in the clinical management of HIV patients. Adequate information about pDDIs and indicators about how to manage ART when PLHIV use drugs could improve ART non-adherence.
To analyze the association between prostate cancer (PCa) risk and night shift work, chronotype, and sleep duration in the context of a population-based case-control study of incident prostate cancer ...in Spain, a total of 465 PCa cases and 410 controls were analyzed. Selection criteria were: (i) age 40–80 years, and (ii) residence in the coverage area of the reference hospitals for ≥6 months before recruitment. Exposure variables were: (i) night shift work (permanent or rotating); (ii) chronotype: morning, neither, or evening (Munich ChronoType Questionnaire) and (iii) sleep duration according to the recommendations of the American National Sleep Foundation. PCa aggressiveness was determined according to the International Society of Urology Pathology classification. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were estimated using logistic regression models. Night shift work was associated with PCa, aOR = 1.47 (95% CI 1.02–2.11), especially for rotating night shifts, aOR = 1.73 (95% CI 1.09–2.75). The magnitude of the association between ever night work and PCa was higher in evening subjects with aOR = 3.14 (95% CI 0.91–10.76) than in morning chronotypes with an aOR = 1.25 (95% CI 0.78–2.00). Working night shifts, especially rotating night shifts, could increase PCa risk. This risk may be higher in people with an evening chronotype.
Glial cells are directly or indirectly affected by estradiol and by different estrogenic compounds, such as selective estrogen receptor modulators. Acting on oligodendrocytes, astrocytes and ...microglia, estrogens regulate remyelination, edema formation, extracellular glutamate levels and the inflammatory response after brain injury. In addition, estradiol induces the expression and release of growth factors by glial cells that promote neuronal survival. Therefore, glial cells are important players in the neuroprotective and reparative mechanisms of estrogenic compounds.
To explore the use of illicit drugs by people living with HIV (PLHIV) taking antiretroviral therapy (ART) and their relationship with variables relevant to the management of HIV infection, such as ...knowledge and beliefs about drug-drug interactions (DDIs), ART adherence, quality of life (QoL), and use of health-care resources.
21 PLHIV in Spain who concomitantly took illicit drugs and ART participated in this qualitative study. Eight experts collaborated in the design of the semi-structured interview guide which explored the following topics: illicit drug use, knowledge and beliefs about DDIs and their impact on ART adherence, the effects of using illicit drugs on health, QoL, and use of health-care resources. Four of those experts, who were PLHIV and members of the executive boards of non-government organizations (NGOs) from four Spanish regions, recruited the participants through their NGOs and carried out the face-to-face interviews. Content analysis of the qualitative data was conducted with the support of the MAXQDA 12 program.
Participants were mainly men (85.7%) and only 14.3% of them were heterosexual. Content analysis showed that the most frequently consumed illicit drugs were poppers, cocaine, and cannabis. Participants were polydrug users and this was, in many cases, prior to HIV diagnosis. Most participants presented theoretical potential moderate DDIs that would require monitoring. More than three quarters of them were not aware of these DDIs. Participants reported interactive toxicity beliefs that lead to intentional nonadherence behaviors. In most cases (n = 17), the participant's doctor knew about their drug use, however only six of them had had an open dialogue with their physician about it. Illicit drug use led to some health-related problems, mainly sexually transmitted infections. A positive QoL's self-perception was found among several participants that used recreational illicit drugs.
Adequate information about DDIs and clues about how to manage ART when PLHIV are using illicit drugs could reduce the negative effects of such interactions and improve ART adherence and QoL.
Background: To analyze the course of microglial and macroglial activation in injured and contralateral retinas after unilateral optic nerve crush (ONC). Methods: The left optic nerve of adult ...pigmented C57Bl/6 female mice was intraorbitally crushed and injured, and contralateral retinas were analyzed from 1 to 45 days post-lesion (dpl) in cross-sections and flat mounts. As controls, intact retinas were studied. Iba1+ microglial cells (MCs), activated phagocytic CD68+MCs and M2 CD206+MCs were quantified. Macroglial cell changes were analyzed by GFAP and vimentin signal intensity. Results: After ONC, MC density increased significantly from 5 to 21 dpl in the inner layers of injured retinas, remaining within intact values in the contralateral ones. However, in both retinas there was a significant and long-lasting increase of CD68+MCs. Constitutive CD206+MCs were rare and mostly found in the ciliary body and around the optic-nerve head. While in the injured retinas their number increased in the retina and ciliary body, in the contralateral retinas decreased. Astrocytes and Müller cells transiently hypertrophied in the injured retinas and to a lesser extent in the contralateral ones. Conclusions: Unilateral ONC triggers a bilateral and persistent activation of MCs and an opposed response of M2 MCs between both retinas. Macroglial hypertrophy is transient.
The purpose of this study was to assess the prevalence, associated factors, and impact on mortality of primary respiratory disease in a large systemic lupus erythematosus (SLE) retrospective cohort.
...All adult patients in the RELESSER-TRANS (Registry of Systemic Lupus Erythematosus Patients of the Spanish Society of Rheumatology SER, cross-sectional phase) registry were retrospectively investigated for the presence of primary pleuropulmonary manifestations.
In total 3215 patients were included. At least one pleuropulmonary manifestation was present in 31% of patients. The most common manifestation was pleural disease (21%), followed by lupus pneumonitis (3.6%), pulmonary thromboembolism (2.9%), primary pulmonary hypertension (2.4%), diffuse interstitial lung disease (2%), alveolar hemorrhage (0.8%), and shrinking lung syndrome (0.8%). In the multivariable analysis, the variables associated with the development of pleuropulmonary manifestation were older age at disease onset (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.02-1.04), higher SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) scores (OR 1.03, 95% CI 1.00-1.07), the presence of Raynaud's phenomenon (OR 1.41, 95% CI 1.09-1.84), secondary antiphospholipid syndrome (OR 2.20, 95% CI 1.63-2.97), and the previous or concomitant occurrence of severe lupus nephritis, (OR 1.48, 95% CI 1.12-1.95) neuropsychiatric manifestations (OR 1.49, 95% CI 1.11-2.02), non-ischemic cardiac disease (OR 2.91, 95% CI 1.90-4.15), vasculitis (OR 1.81, 95% CI 1.25-2.62), hematological manifestations (OR 1.31, 95% CI 1.00-1.71), and gastrointestinal manifestations, excluding hepatitis (OR 2.05, 95% CI 1.14-3.66). Anti-RNP positivity had a clear tendency to significance (OR 1.32, 95% CI 1.00-1.75; P = 0.054). The development of pleuropulmonary manifestations independently contributes to a diminished survival (hazard ratio of 3.13). However, not all complications will influence the prognosis in the same way. Whereas the occurrence of pleural disease or pulmonary thromboembolism has a minimal impact on the survival of these patients, the remaining manifestations have a major impact on mortality.
Except for pleural disease, the remaining respiratory manifestations are very uncommon in SLE (<4%). Pleuropulmonary manifestations independently contributed to a decreased survival in these patients.
•Endotheliopathy is a pathological feature associated with thromboinflammation.•Endothelial biomarkers may help the stratification of risk in COVID-19.•Disruption of the adrenomedullin system ...contributes to endothelial dysfunction.•MR-proADM might be useful for early risk stratification of COVID-19.
Thromboinflammation, resulting from a complex interaction between thrombocytopathy, coagulopathy, and endotheliopathy, contributes to increased mortality in COVID-19 patients. MR-proADM, as a surrogate of adrenomedullin system disruption, leading to endothelial damage, has been reported as a promising biomarker for short-term prognosis. We evaluated the role of MR-proADM in the mid-term mortality in COVID-19 patients.
A prospective, observational study enrolling COVID-19 patients from August to October 2020. A blood sample for laboratory test analysis was drawn on arrival in the emergency department. The primary endpoint was 90-day mortality. The area under the curve (AUC) and Cox regression analyses were used to assess discriminatory ability and association with the endpoint.
A total of 359 patients were enrolled, and the 90-day mortality rate was 8.9%. ROC AUC for MR-proADM predicting 90-day mortality was 0.832. An optimal cutoff of 0.80 nmol/L showed a sensitivity of 96.9% and a specificity of 58.4%, with a negative predictive value of 99.5%. Circulating MR-proADM levels (inverse transformed), after adjusting by a propensity score including eleven potential confounders, were an independent predictor of 90-day mortality (HR: 0.162 95% CI: 0.043-0.480)
Our data confirm that MR-proADM has a role in the mid-term prognosis of COVID-19 patients and might assist physicians with risk stratification.
The psychological implications of stress have become an issue of concern for university students around the world over the past decade. It is thought that the perception of stress varies depending on ...students' personality traits and their beliefs about being able to manage their academic life. To investigate this further, a study was conducted with a sample of 200 university students. The main findings of this study were: (1) All of the Big Five Model of personality traits significantly contribute to developing positive academic self-efficacy, with some of these being moderated by gender. Self-efficacy is characterised by agreeableness, conscientiousness, extraversion, emotionally stability and openness to experience. (2) People with high academic self-efficacy are able to take advantage of eustress and manage distress better than people with low academic self-efficacy. (3) There are some personality traits that contribute to distress and eustress. Specifically, people who are introverted and have low emotional stability and low openness to experience tend to suffer from distress more than people who do not have these traits. In contrast, conscientious people tend to experience eustress more than people without these characteristics. All these traits were mediated by self-efficacy, and in some cases were moderated by gender.
HIV infections are still a very serious concern for public heath worldwide. We have applied molecular evolution methods to study the HIV-1 epidemics in the Comunidad Valenciana (CV, Spain) from a ...public health surveillance perspective. For this, we analysed 1804 HIV-1 sequences comprising protease and reverse transcriptase (PR/RT) coding regions, sampled between 2004 and 2014. These sequences were subtyped and subjected to phylogenetic analyses in order to detect transmission clusters. In addition, univariate and multinomial comparisons were performed to detect epidemiological differences between HIV-1 subtypes, and risk groups. The HIV epidemic in the CV is dominated by subtype B infections among local men who have sex with men (MSM). 270 transmission clusters were identified (>57% of the dataset), 12 of which included ≥10 patients; 11 of subtype B (9 affecting MSMs) and one (n = 21) of CRF14, affecting predominately intravenous drug users (IDUs). Dated phylogenies revealed these large clusters to have originated from the mid-80s to the early 00 s. Subtype B is more likely to form transmission clusters than non-B variants and MSMs to cluster than other risk groups. Multinomial analyses revealed an association between non-B variants, which are not established in the local population yet, and different foreign groups.
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