Enhancer deregulation inTET2-mutant clonal hematopoiesis is associated with increased COVID-19 severity and mortality

Background: COVID-19 causes significant morbidity and mortality, albeit with considerable heterogeneity among affected individuals. It remains unclear which host factors determine disease severity and survival. Given the propensity of clonal hematopoiesis (CH) to promote inflammation in healthy individuals, we investigated its effect on COVID-19 outcomes. Method(s): We performed a multi-omics interrogation of the genome, epigenome, transcriptome, and proteome of peripheral blood mononuclear cells from COVID-19 patients (n=227). We obtained clinical data, laboratory studies, and survival outcomes. We determined CH status and TET2-related DNA methylation. We performed single-cell proteogenomics to understand clonal composition in relation to cell phenotype. We interrogated single-cell gene expression in isolation and in conjunction with DNA accessibility. We integrated these multi-omics data to understand the effect of CH on clonal composition, gene expression, methylation of cis-regulatory elements, and lineage commitment in COVID-19 patients. We performed shRNA knockdowns to validate the effect of one candidate transcription factor in myeloid cell lines. Result(s): The presence of CH was strongly associated with COVID-19 severity and all-cause mortality, independent of age (HR 3.48, 95% CI 1.45-8.36, p=0.005). Differential methylation of promoters and enhancers was prevalent in TET2-mutant, but not DNMT3A-mutant CH. TET2- mutant CH was associated with enhanced classical/intermediate monocytosis and single-cell proteogenomics confirmed an enrichment of TET2 mutations in these cell types. We identified celltype specific gene expression changes associated with TET2 mutations in 102,072 single cells (n=34). Single-cell RNA-seq confirmed the skewing of hematopoiesis towards classical and intermediate monocytes and demonstrated the downregulation of EGR1 (a transcription factor important for monocyte differentiation) along with up-regulation of the lncRNA MALAT1 in monocytes. Combined scRNA-/scATAC-seq in 43,160 single cells (n=18) confirmed the skewing of hematopoiesis and up-regulation of MALAT1 in monocytes along with decreased accessibility of EGR1 motifs in known cis-regulatory elements. Using myeloid cell lines for functional validation, shRNA knockdowns of EGR1 confirmed the up-regulation of MALAT1 (in comparison to wildtype controls). Conclusion(s): CH is an independent prognostic factor in COVID-19 and skews hematopoiesis towards monocytosis. TET2-mutant CH is characterized by differential methylation and accessibility of enhancers binding myeloid transcriptions factors including EGR1. The ensuing loss of EGR1 expression in monocytes causes MALAT1 overexpression, a factor known to promote monocyte differentiation and inflammation. These data provide a mechanistic insight to the adverse prognostic impact of CH in COVID-19.

Evaluation of the perception of physical and emotional health of ophthalmologists in Spain and the influence of the COVID-19 pandemic.

OBJECTIVE: The main objective was to study the perception of physical and emotional health of Spanish ophthalmologists and their health habits, as well as the possible influence of the COVID-19 pandemic. METHODS: An observational, cross-sectional, non-randomized and uncontrolled study was carried out among at Spanish ophthalmologists through an online survey of 47 questions on eating habits, tobacco, alcohol, physical exercise, workload, and perception of physical and emotional state. RESULTS: Of a total of 2,179 ophthalmologists, 260 (11.9%) of whom 55% were men responded to the survey, with a mean age of 52.9±11.4 years. 5.8% were smokers. In total, 51.5% reported good physical health, with a mean Body Mass Index of 24.4kg/m2. Overall, 53.5% reported depression, 66.9% tiredness, 34.6% difficulty sleeping, and 57.3% considered their work hard. Up to 28.5% of those surveyed had thought about leaving their job and 60.8% about reorganizing their workload. In total, 91.9% would continue to choose Ophthalmology as a specialty. In total, 36.2% reported an increase in workload, 42.3% worsening of physical state and 63.8% worsening of emotional state as a consequence of the COVID-19 pandemic. CONCLUSIONS: Spanish ophthalmologists have a positive perception of their physical and emotional health, despite having life habits that are not always healthy and feeling mostly down. The COVID-19 pandemic has had a negative influence on the physical and emotional health of ophthalmologists.

Descriptive observational study of rheumatic patients receiving rituximab during one year of covid19 pandemic

Objectives: To describe the rate of COVID19 infection in rheumatic patients receiving rituximab (RTX) and the prognosis of these patients. Methods: Descriptive study of patients from our Rheumatology service who received RTX for any rheumatic disease during 2020, it was retrospectively analyzed the presence of confirmed COVID19 infection, as well as its demographic and clinical variables, through digital medical records. Results: During 2020, 20 patients (7 vasculitis, 4 AR, 4 IIM, 3 MCTD, 1 SLE and 1 pSS) received RTX (12 women (60%) and 8 men (40%);mean age 51.05 years). The mean time since the first dose of RTX was 58.6 months with a mean cumulative dose per patient of 5936 mg and the last dose of 666 mg. Nasopharyngeal PCR test was performed on 13 patients, of which 8 were positive (6 after COVID19 symptoms and 2 after COVID19 + contact) and 5 negative (3 after COVID19 + contact and 2 due to hospital admission). Comparing the 8 patients who had COVID19 infection versus the 12 who did not, there were no differences regarding age, sex, mean time of exposure to RTX, mean accumulated dose of the drug or last dose. There were no differences between patients infected or not by COVID19 with respect to those considered as risk factors for complicating this infection, nor with respect to DMARDs associated with RTX (Table 1). 7 (87.5%) of the 8 patients with COVID19 infection developed bilateral pneumonia and required admission for a mean time of first hospitalization of 36 days. The pharmacological treatment they received is shown in Table 2. The mean COVID19 infection severity index in our patients was 5.25, according the WHO classification (1). Nasopharyngeal PCR became negative in a mean of 47 days, and no SARS-CoV-2 IgG has developed to date. Three patients required NIV and two were admitted in ICU. After hospital discharge, 3 patients were readmitted several times due to clinical worsening, with a new nasopharyngeal PCR test positive and the need for hospital retreatment. One patient died due to an intestinal perforation. Conclusion: A high percentage (40%) of our patients who received RTX for 1 year had SARS CoV-2 infection. They did not present any known risk factors for complication from this infection;despite this, the COVID-19 severity was high in the majority, requiring prolonged hospitalization and even the need for readmission. The PCR test became negative very late and no patient developed IgG SARS CoV-2.

Generalities, Clinical and Prevention Aspects of COVID-19: Mexico and Latin America

SARS-CoV2 is a coronavirus. It was first identified by the end of 2019 in Wuhan, China in people suffering from severe pneumonia. Eventually, it spread worldwide causing the COVID-19 pandemic as well as 2, 871, 642 deaths by April 2021 around the world and placing Brazil and Mexico in the second and third place in terms of the death toll. The infection may generate a great amount of clinical manifestations due to the presence of its receptor, ACE2, in the cells of the respiratory, intestinal, cardiovascular, renal, hepatic and testicular systems of the host, which causes an initial immunitary response that, if uncontrolled, produces a cytokine storm, systemic inflammatory deterioration and, in some cases, multi-organ failure;which makes it an extremely complex disease. The diagnostic test is the RT-PCR;however, serological and rapid antigen tests have proven useful as well. The medical treatment will be determined according to the severity of the disease and the clinical status of each patient. The observation of some personal protection guidelines is necessary in order to control the pandemic while the process of creation of efficient vaccines is ongoing. Some of them have already been approved for use in case of health emergency though.

Modalities of care and educational inequality in pandemic times: the Sierra Tarahumara experience

The purpose of this paper is to document the experiences faced by a group of basic education teachers in the Sierra Tarahumara in the State of Chihuahua, Mexico facing the health contingency caused by COVID-19. Data collection was carried out through a multiple response electronic questionnaire and a semi-structured interview to determine if the remedial strategies promoted by the Ministry of Public Education respond to the characteristics of a region distinguished by marginality, technological precariousness and communication problems. This study uses a mixed methodology based on the narrative technique, which is complemented with a description of absolute frequencies and percentages connected with the difficulties shared by the teachers. The research results reveal intensification in daily activities, a remarkable commitment to the profession and also reveals the challenges that teachers face in containing learning losses. Furthermore, the most critical findings can be used as input for the design of educational public policy measures aimed at inclusive care of students at risk of school failure.

Perceived stress associated with the COVID-19 pandemic in the city of Guayaquil, Ecuador

The new coronavirus pandemic is the biggest public health crisis the world has faced in more than a century. The fears and uncertainties generated by the sudden arrival, high danger and exponential growth of the disease together with subsequent measures such as isolation that drastically modified the routine, standard of living and economy of each individual greatly influenced the mental health of the patients. people, raising the reports of anxiety, depression and stress in the population. In order to diagnose the levels of the latter associated with the COVID-19 pandemic, a non-probability sampling was applied to students and professors of the Faculty of Medical Sciences of the University of Guayaquil (Ecuador) and health professionals, applying the Perceived Stress Scale (EEP-10), adapted and validated to the context of COVID-19, with quantitative, descriptive and transversal approaches. A total of 860 surveys were accepted, predominantly female (68.6%), and where 61% of the participants reported being a student while 27.8% work in health care. 13% of the respondents showed high levels of perceived stress with a mean of x = 17.017 (± 7.15) between a minimum value of 0 and a maximum of 40. In the multivariate analysis it was determined that gender (-2,399), having a family member with chronic diseases (-1,61), family member diagnosed with COVID-19 (-1,764) and family member who died with COVID-19 (-2,3) are variables that significantly influence the level of perceived stress. © 2021 Instituto de Altos Estudios de Salud Publica. All rights reserved.

Neurological damage in SARS-CoV-2 infections

The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has severely impacted the economy and health care system in more than 180 countries around the world in an unprecedented event, which since its inception has resulted in countless case reports focusing on the potentially fatal systemic and respiratory manifestations of the disease. However, the full extent of possible neurological manifestations caused by this new virus is not yet known. Understanding the interaction of SARS-CoV-2 with the nervous system is essential to assessing likely short- and long-term pathologic consequences. This review seeks to gather and discuss evidence on the occurrence of neurological manifestations and/or nervous system involvement in SARS-CoV-2 infected patients.

Loneliness, Anxiety, Depression, and Adoption of the Role of Caregiver of Older Adults with Chronic Diseases during COVID-19

Objective: To determine the effect of loneliness, anxiety, and depression on adopting the role of caregiver of older adults with chronic conditions in a sample of Mexican caregivers during the COVID-19 pandemic. Materials and method: Predictive and correlational design. The study was conducted with 157 caregivers through the dyad characterization scale, the HADS scale, the UCLA scale, and the Caregiver role adoption scale. The analysis used descriptive and inferential statistics. Results: Most participants were female, with a mean care time of seven months. Mostly, the caregivers have anxiety as a clinical problem (27 %), doubtful depression (14.9 %), profound loneliness (66.2 %), and satisfactory adoption of the role (71.2 %). We found that the more significant the role of adoption, the lower the anxiety, depression, and loneliness levels (p <.05). The psychosocial factors, the age of the person cared for, the age of the informal caregiver, and the care time explained 36 % of the variance in role adoption (F = 13.12;p <.01), with loneliness as a predictive variable. Conclusion: The COVID-19 pandemic has impacted the caregivers’ mental health and caused profound loneliness, the latter being a predictor for adopting the role. © 2022, Universidad de La Sabana. All rights reserved.

Effect of Fear, Concern, and of Risk Factors for Complicated Covid-19 on Self-Care in People in Pre-elderly and Elderly Stages

Objective. The work sought to determine the effect of the risk factors, fear, and concern on self-care regarding COVID-19 in people in pre-elderly and elderly stages. Methods. Correlational-predictive study, gathered through convenience sampling. The study applied the scale of fear of COVID-19 (Huarcaya et al.), the scale of concern about COVID-19 (Ruiz et al.,), and the scale of self-care during the COVID-19 confinement (Martinez et al.,). Descriptive and inferential statistics were applied as the mediation model based on regression. Results. The study had the participation of 333 people, with the majority being women (73.9%). Correlation was found between self-care with the scores from the scale of fear (r = -0.133, p <0.05) and of concern (r = -0.141, p<0.05) regarding COVID-19. The direct effect of the model was c' = 0.16, [95% BCa CI = -0.28, -0.09]. The standardized value for the indirect effect was estimated as c = -0.14, [95% BCa CI= -0.23,-0.09]), which shows existence of a 14.0% effect of the mediating variable on self-care conducts in the prediction model. Conclusion. A direct effect exists of risk factors for COVID-19 complication on self-care, mediated by concern and fear, besides explaining by 14% the self-care conducts for COVID-19. Recommendation is made to address other emotional variables to consider if these increase the prediction.

Genomic diversity in SARS-CoV-2: Mutations and variants

Background: The genetic variability of SARS-CoV-2 has increased notably since the pandemic was declared, which has allowed it to represent a continuous challenge for health policies aimed at its control. Objective. Describe the genomic nomenclature used for general and scientific communication about SARS-CoV-2, as well as describe the mutations, evolution, origin and variants of the virus. Material and Methods. A narrative literature review was carried out, for which a search and analysis of the information was carried out until December 15, 2021. 74 sources selected from the MEDLINE / PubMed, SciELO, LILACS databases and official web pages were reviewed;no language restrictions. Results. Mutations are changes in the nucleotide sequence of the viral genome, which, by affecting the epidemiological dynamics in a population, give rise to variants, and these in turn to differentiated clades. Among the variants of interest, Lambda and Mu stand out, identified for the first time in Peru and Colombia, respectively. While, the variants of concern, in chronological order, are Alpha (British), Beta (South African), Gamma (Brazilian), Delta (Indian) and recently Ómicron. Conclusions. It is concluded that the genomic diversity of SARS-CoV-2 is due to its high rate of mutations that can constitute variants and clades. A better understanding of this diversity allows more effective control measures to be taken, guiding the development and use of vaccines, therapies, diagnostics and health policies. © The Author(s), 2021.