Case report: VEXAS syndrome: an atypical indolent presentation as sacroiliitis with molecular response to azacitidine.

VEXAS syndrome is a recently described autoinflammatory syndrome caused by the somatic acquisition of UBA1 mutations in myeloid precursors and is frequently associated with hematologic malignancies, chiefly myelodysplastic syndromes. Disease presentation can mimic several rheumatologic disorders, delaying the diagnosis. We describe a case of atypical presentation resembling late-onset axial spondylarthritis, later progressing to a systemic inflammatory syndrome with chondritis, cutaneous vasculitis, and transfusion-dependent anemia, requiring high doses of steroids. Ruxolitinib was used as the first steroid-sparing strategy without response. However, azacitidine showed activity in controlling both inflammation and the mutant clone. This case raises the question of whether azacitidine's anti-inflammatory effects are dependent on or independent of clonal control. We discuss the potential relevance of molecular remission in VEXAS syndrome and highlight the importance of a multidisciplinary team for the care of such complex patients.

The impact of regulatory T cells on the graft-versus-leukemia effect.

Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is the only curative therapy for many hematologic malignancies, whereby the Graft-versus-Leukemia (GVL) effect plays a pivotal role in controlling relapse. However, the success of GVL is hindered by Graft-versus-Host Disease (GVHD), where donor T cells attack healthy tissues in the recipient. The ability of natural regulatory T cells (Treg) to suppress immune responses has been exploited as a therapeutical option against GVHD. Still, it is crucial to evaluate if the ability of Treg to suppress GVHD does not compromise the benefits of GVL. Initial studies in animal models suggest that Treg can attenuate GVHD while preserving GVL, but results vary according to tumor type. Human trials using Treg as GVHD prophylaxis or treatment show promising results, emphasizing the importance of infusion timing and Treg/Tcon ratios. In this review, we discuss strategies that can be used aiming to enhance GVL post-Treg infusion and the proposed mechanisms for the maintenance of the GVL effect upon the adoptive Treg transfer. In order to optimize the therapeutic outcomes of Treg administration in allo-HSCT, future efforts should focus on refining Treg sources for infusion and evaluating their specificity for antigens mediating GVHD while preserving GVL responses.

Differential activation of basal and IL-7-induced PI3K/Akt/mTOR and JAK/STAT5 signaling distinguishes pediatric from adult acute lymphoblastic leukemia.

Not available.

Disseminated intravascular coagulation score evolution in 48 h predicts early death in acute promyelocytic leukemia patients.

INTRODUCTION: Early death (ED) is the unsolved issue of acute promyelocytic leukemia (APL). The disseminated intravascular coagulation (DIC) score has been proposed as a marker of bleeding and death in APL; whether its temporal evolution predicts outcomes in APL is unknown. We evaluated whether an increasing score 48 h after diagnosis associates with ED. METHODS: Retrospective, single-center study, including patients with newly diagnosed APL between 2000 and 2023, treated with all-transretinoic acid (ATRA) plus anthracycline or arsenic trioxide (ATO). "DIC score worsening" was defined as ≥1 point increase in the score after 48 h, and ED as death within 30 days of diagnosis. RESULTS: Eighty-six patients were included, with median age of 46 years (17-82). ED patients (26.7%) more frequently had age >60 years and worsening DIC score after 48 h. These were also the only predictors of ED identified in both univariate and multivariate (OR 4.18, p = .011; OR 7.8, p = .005, respectively) logistic regression analysis. CONCLUSION: This is the first study on DIC score evolution in APL-a worsening DIC score 48 h after diagnosis is a strong independent predictive factor of ED. We propose a reduction of the DIC score from diagnosis as a new treatment goal in APL care.

Full-Dose Azacitidine in 5 Days Versus 7 Days With a Weekend Break in Myelodysplastic Syndromes: A Retrospective Cohort Study.

INTRODUCTION: Apart from transplantation, only azacitidine demonstrated a survival benefit in a phase III study in higher-risk myelodysplastic syndromes (MDS). The approved regimen is 75 mg/m2/day for 7 consecutive days, imposing a logistic challenge for outpatient weekend administration. Schedules with 5 days and 7 days with a weekend break (5 + 2) have been used for convenience despite the lack of strong scientific support. Most studies of alternative schedules were performed in lower-risk MDS and with dose reduction in the 5-day schedules. METHODS: We performed a single-center, retrospective cohort study to compare full-dose azacitidine (7 × 75 mg/m2) administration in 5-day and 5 + 2-day schedules in a higher-risk MDS cohort. We evaluated 100 patients for overall survival and a subsample (49 patients) for acute myeloid leukemia-free survival (AMLFS), probability of infections and transfusion burden. Kaplan-Meier analysis and Cox models were used for survival analyses. Linear and logistic regressions were applied for univariate and multivariate assessment. RESULTS: After a median follow-up of 10.8 months, patients treated with a 5-day schedule had a median overall survival of 12.5 months versus 15.0 months in the 5+2 group: HR 0.95 (95% CI, 0.57-1.56); P= .83. AMLFS was also similar between groups: HR 1.70 (95% CI, 0.70-4.14); P = .24. Azacitidine schedules were not predictive of infections nor number of red blood cell or platelet transfusions in multivariate analyses. CONCLUSIONS: In higher-risk MDS, full-dose azacitidine (7 × 75 mg/m2) can be administered both in 5 days and in 7 days with a weekend break with no significant difference in survival, infection or transfusional outcomes.

HLA frequency distribution of the Portuguese bone marrow donor registry.

Introduction: The Portuguese donor Registry of CEDACE was the fifth largest per capita bone marrow donor Registry of the WMDA as of 2019 and has yet to be thoroughly analyzed. We aimed to characterize its various aspects, including demographics and HLA allele and haplotype frequencies, to evaluate the genetic matching propensity score and ultimately further develop it. Methods: We described and compared characteristics of the donor population with census data and used an Expectation-Maximization algorithm and analyses of molecular variance to assess haplotype frequencies and establish phylogenetic distances between regions and districts within the country. Results: We identified 396545 donors, corresponding to 3.85% of the Portuguese population; the median donor age was 39 years, with 60.4% of female donors. Most donors were Portuguese nationals, although 40 other nationalities were present, with a significant proportion of donors from Brazil and Portuguese-speaking African Countries; almost all donors self-reported as Western, with the second largest group reporting African ancestry. There was an asymmetric contribution of donors from different districts and regions, with most coming from coastal districts and few from the southern districts and autonomous regions; foreign and self-declared non-Western donors were mainly located in the Metropolitan Area of Lisbon and the South. Although most donors were typed in three loci (HLA-A, HLA-B and HLA-DRB1), only 44% were also typed in HLA-C, 1.28% in HLA-DQB1 and only 0.77% in all five loci and in high-resolution. There were varying allele and haplotype frequencies across districts and regions, with the most common three loci, low-resolution haplotypes, being HLA-A*01~B*08~DRB1*03, A*29~B*44~DRB1*07 and HLA-A*02~B*44~DRB1*04; some haplotypes were more prevalent in the South, others in the North and a few in the autonomous regions; African and foreign donors presented relevant differences in haplotype frequency distributions, including rare haplotypes of potential interest. We also report on four loci, low-resolution frequency distributions. Using AMOVA, we compared genetic distances between districts and regions, which recapitulated the country's geography. Discussion: Our analysis showed potential paths to optimization of the Registry, including increasing the male donor pool and focusing on underrepresented districts and particular populations of interest, such as donors from Portuguese-speaking African countries.

Predictors of very early death in acute promyelocytic leukemia: a retrospective real-world cohort study.

Early death (ED) is still the major obstacle to cure in acute promyelocytic leukemia (APL). Most studies focus on 30-day ED; however, little is known on predictors of death before starting APL treatment (very early death - VED) and on predictors of 7-day ED, the period with most deaths due to thrombohemorrhagic diathesis. We hypothesized whether the severity of the coagulopathy of APL could predict VED and 7-day ED. We also aimed to evaluate other characteristics associated with these outcomes. We undertook a retrospective, single-center observational study including newly diagnosed APL patients admitted to our institution between January 2000 and November 2022. Baseline demographical, clinical, and laboratorial data were collected. Statistical analysis was performed using Stata. One hundred four patients were included. The VED rate was 4.8%. A DIC Score ≥ 7 (p = 0.045), serum creatinine > 1.5 mg/dL (p < 0.001%), a DIC Score ≥ 6 within 24 h (p = 0.009), and mechanical ventilation (p < 0.001) were associated with VED. The 7-day ED rate was 12.5%. High-risk (p = 0.007) and hypogranular APL (p = 0.029), DIC Score at diagnosis (p = 0.047), DIC Score ≥ 7 (p = 0.043), DIC Score ≥ 6 within 24 h (p = 0.025), PT prolongation > 6 s (p = 0.002), and creatinine > 1.5 mg/dL (p = 0.004) were associated with 7-day ED. However, only elevated creatinine emerged as an independent predictor of 7-day ED (OR 21.4; p = 0.008). Our study shows that in patients with APL, an elevated creatinine at diagnosis strongly predicts for 7-day ED. A DIC Score ≥ 7 and a Score that remains ≥ 6 within 24 h and a serum creatinine > 1.5 mg/dL significantly associated with VED.

Multi-Approach Characterization of Novel Pyrene-Degrading Mycolicibacterium austroafricanum Isolates Lacking nid Genes.

Polycyclic aromatic hydrocarbons (PAHs) are chemical compounds that are widespread in the environment, arising from the incomplete combustion of organic material, as well as from human activities involving petrol exploitation, petrochemical industrial waste, gas stations, and environmental disasters. PAHs of high molecular weight, such as pyrene, have carcinogenic and mutagenic effects and are considered pollutants. The microbial degradation of PAHs occurs through the action of multiple dioxygenase genes (nid), which are localized in genomic island denominate region A, and cytochrome P450 monooxygenases genes (cyp) dispersed in the bacterial genome. This study evaluated pyrene degradation by five isolates of Mycolicibacterium austroafricanum using 2,6-dichlorophenol indophenol (DCPIP assay), gas chromatography/mass spectrometry (CG/MS), and genomic analyses. Two isolates (MYC038 and MYC040) exhibited pyrene degradation indexes of 96% and 88%, respectively, over a seven-day incubation period. Interestingly, the genomic analyses showed that the isolates do not have nid genes, which are involved in PAH biodegradation, despite their ability to degrade pyrene, suggesting that degradation may occur due to the presence of cyp150 genes, or even genes that have not yet been described. To the best of our knowledge, this is the first report of isolates without nid genes demonstrating the ability to degrade pyrene.

Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathway.

The decision whether endosomes enter the degradative or recycling pathway in mammalian cells is of fundamental importance for pathogen killing, and its malfunctioning has pathological consequences. We discovered that human p11 is a critical factor for this decision. The HscA protein present on the conidial surface of the human-pathogenic fungus Aspergillus fumigatus anchors p11 on conidia-containing phagosomes (PSs), excludes the PS maturation mediator Rab7, and triggers binding of exocytosis mediators Rab11 and Sec15. This reprogramming redirects PSs to the non-degradative pathway, allowing A. fumigatus to escape cells by outgrowth and expulsion as well as transfer of conidia between cells. The clinical relevance is supported by the identification of a single nucleotide polymorphism in the non-coding region of the S100A10 (p11) gene that affects mRNA and protein expression in response to A. fumigatus and is associated with protection against invasive pulmonary aspergillosis. These findings reveal the role of p11 in mediating fungal PS evasion.

Extracorporeal photopheresis as an immunomodulatory treatment modality for chronic GvHD and the importance of emerging biomarkers.

Haematopoietic stem cell transplantation (HSCT) is the treatment of choice for malignant haematological diseases. Despite continuous improvements in pre- and post-transplantation procedures, the applicability of allo-HSCT is limited by life-threatening complications such as graft-versus-host disease (GvHD), engraftment failure, and opportunistic infections. Extracorporeal photopheresis (ECP) is used to treat steroid resistant GvHD with significant success. However, the molecular mechanisms driving its immunomodulatory action, whilst preserving immune function, require further understanding. As ECP is safe to administer with few significant adverse effects, it has the potential for earlier use in the post-HSCT treatment of GvHD. Thus, further understanding the immunomodulatory mechanisms of ECP action may justify more timely use in clinical practice, as well as identify biomarkers for using ECP as first line or pre-emptive GvHD therapy. This review aims to discuss technical aspects and response to ECP, review ECP as an immunomodulatory treatment modality for chronic GvHD including the effect on regulatory T cells and circulating vs. tissue-resident immune cells and consider the importance of emerging biomarkers for ECP response.

Analysis of FOXP3 DNA Methylation Patterns to Identify Functional FOXP3+ T-Cell Subpopulations.

Human regulatory CD4+CD25+FOXP3+ T cells (Tregs) are involved in the suppression of immune responses and play important roles in the maintenance of self-tolerance and immune homeostasis. Abnormal Treg function may result in disease states of varying severity. As FOXP3-expressing Treg cells are phenotypically and functionally heterogeneous, the success of Treg therapies depends on the ability to reliably distinguish subpopulations of T cells bearing a Treg-like phenotype. Methylation of cytosines within CpG dinucleotides is an important epigenetic mechanism involved in regulation (and suppression) of gene expression. On the other hand, demethylation of regulatory DNA sequences, such as promoters and enhancers, is essential for initiation of gene transcription. This protocol shows that bisulfite sequencing (BS) distinguishes methylated and unmethylated cytosines within DNA and reveals the methylation status of individual CpGs in cells within each population, identifying functionally different FOXP3+ subpopulations.

Cell-based therapy in prophylaxis and treatment of chronic graft-versus-host disease.

Hematopoietic allogeneic stem cell transplantation (allo-SCT) is a curative option for patients with hematological malignancies. However, due to disparities in major and minor histocompatibility antigens between donor and recipient, severe inflammatory complications can occur, among which chronic graft-versus-host disease (cGVHD) can be life-threatening. A classical therapeutic approach to the prevention and treatment of cGVHD has been broad immunosuppression, but more recently adjuvant immunotherapies have been tested. This review summarizes and discusses immunomodulatory approaches with T cells, including chimeric antigen receptor (CAR) and regulatory T cells, with natural killer (NK) cells and innate lymphoid cells (ILCs), and finally with mesenchymal stromal cells (MSC) and extracellular vesicles thereof. Clinical studies and pre-clinical research results are presented likewise.

Genetic determinants of fungi-induced ROS production are associated with the risk of invasive pulmonary aspergillosis.

Reactive oxygen species (ROS) are an essential component of the host defense against fungal infections. However, little is known about how common genetic variation affects ROS-mediated antifungal host defense. In the present study, we investigated the genetic factors that regulate ROS production capacity in response to the two human fungal pathogens: Candida albicans and Aspergillus fumigatus. We investigated fungal-stimulated ROS production by immune cells isolated from a population-based cohort of approximately 200 healthy individuals (200FG cohort), and mapped ROS-quantitative trait loci (QTLs). We identified several genetic loci that regulate ROS levels (P < 9.99 × 10-6), with some of these loci being pathogen-specific, and others shared between the two fungi. These ROS-QTLs were investigated for their influence on the risk of invasive pulmonary aspergillosis (IPA) in a disease relevant context. We stratified hematopoietic stem-cell transplant (HSCT) recipients based on the donor's SNP genotype and tested their impact on the risk of IPA. We identified rs4685368 as a ROS-QTL locus that was significantly associated with an increased risk of IPA after controlling for patient age and sex, hematological malignancy, type of transplantation, conditioning regimen, acute graft-versus-host-disease grades III-IV, and antifungal prophylaxis. Collectively, this data provides evidence that common genetic variation can influence ROS production capacity, and, importantly, the risk of developing IPA among HSCT recipients. This evidence warrants further research for patient stratification based on the genetic profiling that would allow the identifications of patients at high-risk for an invasive fungal infection, and who would benefit the most from a preventive strategy.

Hematopoietic Stem Cell Transplantation for Neurological Disorders: A Focus on Inborn Errors of Metabolism.

Hematopoietic stem cells have been investigated and applied for the treatment of certain neurological disorders for a long time. Currently, their therapeutic potential is harnessed in autologous and allogeneic hematopoietic stem cell transplantation (HSCT). Autologous HSCT is helpful in immune-mediated neurological diseases such as Multiple Sclerosis. However, clinical benefits derive more from the immunosuppressive conditioning regimen than the interaction between stem cells and the nervous system. Mainly used for hematologic malignancies, allogeneic HSCT explores the therapeutic potential of donor-derived hematopoietic stem cells. In the neurological setting, it has proven to be most valuable in Inborn Errors of Metabolism, a large spectrum of multisystem disorders characterized by congenital deficiencies in enzymes involved in metabolic pathways. Inborn Errors of Metabolism such as X-linked Adrenoleukodystrophy present with brain accumulation of enzymatic substrates that result in progressive inflammatory demyelination. Allogeneic HSCT can halt ongoing inflammatory neural destruction by replacing hematopoietic-originated microglia with donor-derived myeloid precursors. Microglia, the only neural cells successfully transplanted thus far, are the most valuable source of central nervous system metabolic correction and play a significant role in the crosstalk between the brain and hematopoietic stem cells. After transplantation, engrafted donor-derived myeloid cells modulate the neural microenvironment by recapitulating microglial functions and enhancing repair mechanisms such as remyelination. In some disorders, additional benefits result from the donor hematopoietic stem cell secretome that cross-corrects neighboring neural cells via mannose-6-phosphatase paracrine pathways. The limitations of allogeneic HSCT in this setting relate to the slow turnover of microglia and complications such as graft-vs.-host disease. These restraints have accelerated the development of hematopoietic stem cell gene therapy, where autologous hematopoietic stem cells are collected, manipulated ex vivo to overexpress the missing enzyme, and infused back into the patient. With this cellular drug vehicle strategy, the brain is populated by improved cells and exposed to supraphysiological levels of the flawed protein, resulting in metabolic correction. This review focuses on the mechanisms of brain repair resulting from HSCT and gene therapy in Inborn Errors of Metabolism. A brief mention will also be made on immune-mediated nervous system diseases that are treated with this approach.

MAVS Expression in Alveolar Macrophages Is Essential for Host Resistance against Aspergillus fumigatus.

Our recent data demonstrate a critical role of the RIG-I-like receptor family in regulating antifungal immunity against Aspergillus fumigatus in a murine model. However, the importance of this pathway in humans and the cell types that use this innate immune receptor family to detect A. fumigatus remain unresolved. In this study, using patients who underwent hematopoietic stem cell transplantation, we demonstrate that a polymorphism in human MAVS present in the donor genome was associated with the incidence of invasive pulmonary aspergillosis. Moreover, in a separate cohort of confirmed invasive pulmonary aspergillosis patients, polymorphisms in the IFIH1 gene alter the inflammatory response, including IFN-responsive chemokines. Returning to our murine model, we now demonstrate that CD11c+ Siglec F+ alveolar macrophages require Mavs expression to maintain host resistance against A. fumigatus. Our data support the role of MAVS signaling in mediating antifungal immunity in both mice and humans at least in part through the role of MAVS-dependent signaling in alveolar macrophages.

The effects of mindfulness-based interventions in COVID-19 times: a systematic review / Os efeitos de intervenções baseadas em mindfulness em tempos da COVID-19: uma revisão sistemática

Introduction: the public health crisis caused by COVID-19, a disease caused by SARS-CoV-2, has imposed physical threats and psychological suffering on both infected patients and individuals who experience social isolation and various governmental restrictions, leading to the appearance of symptoms like anxiety, depression, as well as insomnia, stress, and changes in biological rhythm. In face of this stressful scenario, interventions based on mindfulness (MBIs) have proved to be potentially adequate tools in reducing psychological suffering and generating well-being in the general population.Objective: to describe the effects of mindfulness-based interventions during the COVID-19 pandemic. Methods: A systematic literature review was conducted on the effects of mindfulness intervention in times of COVID-19. The articles were searched in four databases (Pubmed, Embase, Scopus, and Science direct) and the PRISMA protocol was used to conduct this review. In total, fourteen articles were included in the study.Results: the use of mindfulness techniques in the population with impaired mental health because of the COVID-19 pandemic proved to be beneficial, with improvement in emotional stress scores and reduction in anxiety symptoms, through formal mindfulness meditation practices such as mindful breathing, body scanning, and application of the mindfulness-based stress reduction strategy (MBSR). Strategies were also applied through smartphone applications that had the objective of promoting the increase of mindfulness and the development of the acceptance without judgment of the traumatic experiences already lived, in addition to an integrated intervention on the internet with the use of mindfulness, the training of respiratory relaxation, refuge skills and Butterfly Hug Method.Conclusion: with the pandemic going through, still with high mortality, continuity of social isolation, and, consequently, intensification of psychic suffering in the population and health professionals, interventions based on mindfulness (MBIs) are being effective to reduce this suffering, prevent the appearance of of chronic mental disorders and promote positive impacts on physical and mental well-being.

Introdução: a crise de saúde pública ocasionada pela COVID-19, doença causada pelo SARS-CoV-2, impôs ameaças físicas e sofrimento psíquico tanto aos pacientes infectados quanto aos indivíduos que vivenciam o isolamento social e as diversas restrições governamentais, propiciando o aparecimento de sintomas de ansiedade, depressão, além de insônia, estresse e alterações do ritmo biológico. Diante desse cenário estressor, as intervenções baseadas em atenção plena (MBIs), se mostraram ferramentas potencialmente adequadas na redução do sofrimento psicológico e na geração de bem-estar da população em geral.Objetivo: descrever os efeitos das intervenções baseadas em mindfulness em tempos da COVID-19.Método: foi realizada uma revisão sistemática da literatura sobre os efeitos da intervenção mindfulness em tempos da COVID-19. Os artigos foram pesquisados em quatro bases de dados (Pubmed, Embase, Scopus e Science direct) e o protocolo PRISMA foi utilizado para realização desta revisão. No total, quatorze artigos foram incluídos no estudo.Resultados: a utilização de técnicas de mindfulness na população com prejuízos na saúde mental em consequência da pandemia da COVID-19 mostraram-se benéficas, ocorrendo melhora no escore de estresse emocional e redução dos sintomas de ansiedade, através de práticas formais de meditação tipo mindfulness, como respiração consciente, escaneamento corporal, e aplicação da estratégia de redução do estresse baseada em atenção plena (MBSR). Estratégias também foram aplicadas através de aplicativos de smartphone que tiveram o objetivo de promover o aumento da atenção plena e o desenvolvimento da aceitação, sem julgamentos, das experiências traumáticas já vividas, além de intervenção integrada na internet com o uso da atenção plena, treinamento de relaxamento respiratório, habilidades de refúgio e método do abraço de borboleta. Conclusão: com o perpassar da pandemia, ainda com elevada mortalidade, continuidade dos isolamentos sociais, e, consequentemente, intensificação do sofrimento psíquico na população e profissionais de saúde, as intervenções baseadas em atenção plena (MBIs) estão sendo eficazes para diminuir esse sofrimento, prevenir aparecimento de transtornos mentais crônicos e promover impactos positivos no bem-estar físico e mental.

A phase 1 study of donor regulatory T-cell infusion plus low-dose interleukin-2 for steroid-refractory chronic graft-vs-host disease.

Chronic graft-versus-host disease (cGVHD) remains a frequent cause of nonrelapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Despite recent advances, options for steroid-refractory (SR) cGVHD are limited. In previous trials of low-dose interleukin-2 (LD IL-2), the immunomodulatory properties of regulatory T cells (Tregs) have been harnessed to treat SR-cGVHD safely and effectively. In the present study, we combined a single infusion of Treg-enriched lymphocytes (Treg DLI) from the original stem cell donor with in vivo Treg expansion using LD IL-2 (1 × 106 IU/m2 per day for 8 weeks) in 25 adult patients with SR-cGVHD. Treg were not expanded ex vivo. Treg DLI was initiated at 0.1 × 106 cells per kg patient and escalated to a maximum dose of 1 × 106 cells per kg. Treg DLI plus LD IL-2 was well tolerated and led to partial responses (PR) in 5 of 25 patients (20%) after 8 weeks of therapy. Ten additional patients (40%) had stable disease with minor responses not meeting PR criteria. Patients at all dose levels had similar Treg expansion without significant changes in CD4+ conventional T cells or CD8+ T cells. High-throughput sequencing of the T-cell receptor ß locus showed selective improvement of Treg diversity. A subset of DLI-derived Treg clones showed preferential expansion at week 8 and long-term persistence 1-year postinfusion. We demonstrate for the first time that infusion of polyclonal healthy donor Tregs followed by expansion with LD IL-2 is safe in patients with SR-cGVHD, thus establishing a foundation for future adoptive Treg therapies in the posttransplant setting. This trial was registered at www.clinicaltrials.gov as #NCT01937468.

Relação entre o medo da COVID-19 e a sobrecarga física e mental de profissionais de saúde que realizam atendimento contínuo de pacientes durante a pandemia do novo coronavírus / Relationship between fear of COVID-19 and physical and mental burden of health professionals in the continuous care of patients during new coronavirus pandemic

Introdução: A pandemia da doença por coronavírus 19 (COVID-19) contribui para a exacerbação do estresse e sofrimento dos profissionais de saúde. Objetivo: Avaliar a relação entre o medo da COVID-19 e a sobrecarga física e mental dos profissionais de saúde em atendimento contínuo de pacientes durante a pandemia de COVID-19 em duas cidades da região do Campo das Vertentes no estado de Minas Gerais. Material e Métodos: Foi realizado um estudo descritivo transversal com 77 profissionais de saúde (32 (14) anos; 67,5% do gênero feminino) que estavam em atendimento contínuo durante a pandemia de COVID-19. Dados sociodemográficos e profissionais foram coletados e o medo foi avaliado pela Escala de Medo da COVID-19 (EMC-19), sintomas depressivos pelo Patient Health Questionnaire-9 (PHQ-9) e síndrome de Burnout pelo Maslach Burnout Inventory ­ Human Services Survey (MBI-HSS). Resultados: O escore total da EMC-19 se correlacionou com a carga horária de trabalho semanal (ρ= 0,395; p<0,001), o PHQ-9 (ρ= 0,332; p= 0,003) e as dimensões exaustão emocional (ρ= 0,253; p= 0,026), despersonalização (ρ= 0,243; p= 0,033) e baixa realização pessoal (ρ= -0,389; p<0,001) do MBI-HSS. No modelo de regressão linear ajustado para potenciais fatores confundidores, a EMC-19 continuou significativamente associada com a baixa realização pessoal apresentando coeficiente de determinação ajustado de 0,372 (p<0,001). Conclusão: O medo da COVID-19 nos profissionais de saúde em atendimento contínuo de pacientes durante a pandemia de COVID-19 nas duas cidades da região do Campo das Vertentes no estado de Minas Gerais se relacionou com sintomas depressivos e as características da síndrome de Burnout de exaustão emocional, despersonalização e baixa realização pessoal.

Introduction: The coronavirus disease 19 (COVID-19) pandemic contributes to the exacerbation of stress and suffering of health professionals. Objective: To evaluate the relationship between fear of COVID-19 and physical and mental burden of health professionals in the continuous care of patients during COVID-19 pandemic in two cities in the Campo das Vertentes region in the state of Minas Gerais. Material and Methods: A descriptive cross-sectional study was carried out with 77 health professionals (32 (14) years; 67.5% female) who were in continuous care during COVID-19 pandemic. Sociodemographic and professional data were collected and the fear of COVID-19 was taken from the Fear of COVID-19 Scale (FCV-19S), depressive symptoms by the Patient Health Questionnaire-9 (PHQ-9) and Burnout syndrome by the Maslach Burnout Inventory ­ Human Services Research (MBI-HSS). Results: The total score of FCV-19S correlated with the weekly workload (ρ= 0.395; p<0.001), the PHQ-9 (ρ= 0.332; p= 0.003) and the emotional exhaustion (ρ= 0.253; p= 0.026), depersonalization (ρ= 0.243; p= 0.033) and low sense of personal accomplishment (ρ= -0.389; p<0.001) dimensions of the MBI-HSS. In the linear regression model adjusted for potential confounders, the FCV-19S continued significantly associated with low sense of personal accomplishment and presented adjusted coefficient of determination of 0.372 (p<0.001). Conclusion: The fear of COVID-19 of health professionals in the continuous care of patients during COVID-19 pandemic in two cities in the Campo das Vertentes region in the state of Minas Gerais was related to depressive symptoms and as characteristics of the Burnout syndrome of emotional exhaustion, depersonalization and with low sense of personal accomplishment.