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1.
Front Cell Infect Microbiol ; 13: 1155938, 2023.
Article in English | MEDLINE | ID: covidwho-20234677

ABSTRACT

Background: The SARS-CoV-2 virus has caused unprecedented mortality since its emergence in late 2019. The continuous evolution of the viral genome through the concerted action of mutational forces has produced distinct variants that became dominant, challenging human immunity and vaccine development. Aim and methods: In this work, through an integrative genomic approach, we describe the molecular transition of SARS-CoV-2 by analyzing the viral whole genome sequences from 50 critical COVID-19 patients recruited during the first year of the pandemic in Mexico City. Results: Our results revealed differential levels of the evolutionary forces across the genome and specific mutational processes that have shaped the first two epidemiological waves of the pandemic in Mexico. Through phylogenetic analyses, we observed a genomic transition in the circulating SARS-CoV-2 genomes from several lineages prevalent in the first wave to a dominance of the B.1.1.519 variant (defined by T478K, P681H, and T732A mutations in the spike protein) in the second wave. Conclusion: This work contributes to a better understanding of the evolutionary dynamics and selective pressures that act at the genomic level, the prediction of more accurate variants of clinical significance, and a better comprehension of the molecular mechanisms driving the evolution of SARS-CoV-2 to improve vaccine and drug development.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , Pandemics , Mexico/epidemiology , Phylogeny , Genome, Viral , Mutation
2.
Cad. Bras. Ter. Ocup ; 31: e3363, 2023. tab
Article in Spanish | WHO COVID, LILACS (Americas) | ID: covidwho-2299625

ABSTRACT

Resumen Introducción Los años de universidad son un periodo de desarrollo crucial para la transición de la adolescencia a la adultez, por eso existe una creciente preocupación sobre la salud mental de los estudiantes. El COVID-19 puso en situación de vulnerabilidad a esta población, con aumento del riesgo de depresión, ansiedad o estrés. Objetivo Aunque los estudios sobre los efectos de la pandemia y sus consecuencias sobre la salud mental se publican de manera exponencial, existen pocos centrados en estudiantes de ciencias de la salud. Por ello, se enfoca esta temática en estudiantes de Grado en Terapia Ocupacional para explorar los efectos sobre la salud mental en la etapa de confinamiento inicial. Método Partiendo de la hipótesis de que el confinamiento ha podido poner en situación vulnerable a los estudiantes universitarios, se realizó un estudio cuantitativo longitudinal con estudiantes del Grado de Terapia Ocupacional en base a los cuestionarios General Health Questionnaire (GHQ-28), Patient Health Questionnaire (PHQ-9), Escala de Felicidad Subjetiva (SHS) y la Escala de Desesperanza de Beck. Resultados Los resultados mostraron una mejoría en las diferentes escalas entre los años 2019 y 2020, con relaciones estadísticamente significativas entre el estado de confinamiento y una reducción del riesgo de depresión a su finalización. Conclusiones Esta relación sugiere dudas sobre la temporalidad y la medición de los resultados siendo posible queque el confinamiento tuviera aspectos positivos en algunas de las dimensiones de la salud mental, dada su relación con la falta de aislamiento social en muchos casos, el establecimiento de rutinas y la reincorporación a la docencia presencial.


Resumo Introdução Os anos universitários são um período de desenvolvimento crucial para a transição da adolescência para a idade adulta, razão pela qual é crescente a preocupação com a saúde mental dos estudantes. A COVID-19 coloca esta população numa situação vulnerável, com risco acrescido de depressão, ansiedade ou stress. Objetivo Embora estudos sobre os efeitos da pandemia e suas consequências na saúde mental sejam publicados de forma exponencial, poucos são os voltados para estudantes de ciências da saúde. Por este motivo, aborda-se esta temática em alunos de graduação em terapia ocupacional para explorar os efeitos na saúde mental em fase inicial de confinamento. Método Partindo da hipótese de que o confinamento tem sido capaz de colocar estudantes universitários em situação de vulnerabilidade, foi realizado um estudo quantitativo longitudinal com estudantes do Curso Graduação em Terapia Ocupacional com base no General Health Questionnaire (GHQ-28), Patient Health Questionnaire (PHQ-9), Escala de Felicidade Subjetiva (SHS) e Escala de Desesperança de Beck. Resultados Os resultados mostraram uma melhora nas diferentes escalas entre os anos de 2019 e 2020, com relações estatisticamente significativas entre o estado de confinamento e a redução do risco de depressão ao final. Conclusão Esta relação sugere dúvidas sobre a temporalidade e a mensuração dos resultados, sendo possível que o confinamento tenha tido aspectos positivos em algumas das dimensões da saúde mental, dada sua relação com a falta de isolamento social, em muitos casos, o estabelecimento de rotinas e o retorno ao ensino presencial.


Abstract Introduction The university years are a crucial period of development for the transition from adolescence to adulthood, which is why there is a growing concern for the mental health of students. COVID-19 places this population in a vulnerable situation, with an increased risk of depression, anxiety, or stress. Objective Although studies on the effects of the pandemic and its consequences on mental health are published exponentially, few studies focus on students in health sciences. Therefore, we aimed the approach of these issues regarding undergraduates from the Degree of Occupational Therapy to explore the effects of the national lockdown on mental health. Method Based on the hypothesis that confinement may have made university students vulnerable, a quantitative longitudinal study was conducted with students of the Occupational Therapy Degree based on the General Health Questionnaire (GHQ-28), Patient Health Questionnaire (PHQ-9), Subjective Happiness Scale (SHS) and Beck's Scale of Hopelessness (BSH). Results The results showed an improvement in the different scales between 2019 and 2020, with statistically significant relationships between the state of confinement and a reduction in the risk of depression at its end. Conclusions This relationship suggests doubts about the temporality and measurement of the results since it is possible that confinement had positive aspects in some of the dimensions of mental health, given its relationship with the lack of social isolation in many cases, the establishment of routines and the return to face-to-face teaching.

3.
J Interferon Cytokine Res ; 42(8): 430-443, 2022 08.
Article in English | MEDLINE | ID: covidwho-2278024

ABSTRACT

Interferon-induced transmembrane (IFITM) proteins mediate protection against enveloped viruses by blocking membrane fusion at endosomes. IFITM1 and IFITM3 are crucial for protection against influenza, and various single nucleotide polymorphisms altering their function have been linked to disease susceptibility. However, bulk IFITM1 and IFITM3 mRNA expression dynamics and their correlation with clinical outcomes have not been extensively addressed in patients with respiratory infections. In this study, we evaluated the expression of IFITM1 and IFITM3 in peripheral leukocytes from healthy controls and individuals with severe pandemic influenza A(H1N1) or coronavirus disease 2019 (COVID-19). Comparisons between participants grouped according to their clinical characteristics, underlying disease, and outcomes showed that the downregulation of IFITM1 was a distinctive characteristic of severe pandemic influenza A(H1N1) that correlated with outcomes, including mortality. Conversely, increased IFITM3 expression was a common feature of severe pandemic influenza A(H1N1) and COVID-19. Using a high-dose murine model of infection, we confirmed not only the downregulation of IFITM1 but also of IFITM3 in the lungs of mice with severe influenza, as opposed to humans. Analyses in the comparative cohort also indicate the possible participation of IFITM3 in COVID-19. Our results add to the evidence supporting a protective function of IFITM proteins against viral respiratory infections in humans.


Subject(s)
Antigens, Differentiation , COVID-19 , Influenza, Human , Membrane Proteins , RNA-Binding Proteins , Animals , Antigens, Differentiation/genetics , Antigens, Differentiation/metabolism , COVID-19/genetics , Humans , Influenza A Virus, H1N1 Subtype , Influenza, Human/genetics , Leukocytes/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism
4.
J Interferon Cytokine Res ; 42(8): 352-368, 2022 08.
Article in English | MEDLINE | ID: covidwho-2277657

ABSTRACT

The costs of coronavirus disease 2019 (COVID-19) are devastating. With millions of deaths worldwide, specific serological biomarkers, antiviral agents, and novel therapies are urgently required to reduce the disease burden. For these purposes, a profound understanding of the pathobiology of COVID-19 is mandatory. Notably, the study of immunity against other respiratory infections has generated reference knowledge to comprehend the paradox of the COVID-19 pathogenesis. Past studies point to a complex interplay between cytokines and other factors mediating wound healing and extracellular matrix (ECM) remodeling that results in exacerbated inflammation, tissue injury, severe manifestations, and a sequela of respiratory infections. This review provides an overview of the immunological process elicited after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Also, we analyzed available data about the participation of matrix metalloproteinases (MMPs) and transforming growth factor-beta (TGF-ß) in immune responses of the lungs. Furthermore, we discuss their possible implications in severe COVID-19 and sequela, including pulmonary fibrosis, and remark on the potential of these molecules as biomarkers for diagnosis, prognosis, and treatment of convalescent COVID-19 patients. Our review provides a theoretical framework for future research aimed to discover molecular hallmarks that, combined with clinical features, could serve as therapeutic targets and reliable biomarkers of the different clinical forms of COVID-19, including convalescence.


Subject(s)
COVID-19 , Matrix Metalloproteinases , Transforming Growth Factor beta , Biomarkers , COVID-19/immunology , Cost of Illness , Humans , Matrix Metalloproteinases/immunology , SARS-CoV-2 , Transforming Growth Factor beta/immunology
5.
Int J Environ Res Public Health ; 19(22)2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2110070

ABSTRACT

The purpose of this study was to analyze the changes in physical activity and physical fitness between the beginning of the first academic year after a confinement (November 2020) and the beginning of the second academic year after a confinement ("new normality": November 2021) in a cohort of adolescents. Moreover, the evolution of physical fitness after controlling for physical activity was examined. A total of 687 students (M = 15.35, SD = 1.677) from a high school located in a rural town in northern Spain gave information on their physical activity (PA) levels in two different periods. Linear mixed models were used to examine these changes. The results indicated that vigorous physical activity (VPA) and the metabolic equivalent of task (MET) significantly increased between the two periods. A growth tendency of several components of fitness (upper body power, strength endurance, cardiovascular fitness, flexibility, and eye-hand coordination) was also observed. Finally, the results indicated that belonging to a sports club and getting involved in more VPA better explained the development in cardiovascular and muscle fitness between the two time points. Thus, the results of this study highlighted the relevance of membership in a sports club and vigorous PA in order to mitigate the potential negative effect of social distancing measures on physical fitness.


Subject(s)
COVID-19 , Sports , Humans , Adolescent , COVID-19/epidemiology , Communicable Disease Control , Physical Fitness/physiology , Exercise/physiology
6.
Environ Sci Pollut Res Int ; 29(31): 46487-46508, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1906477

ABSTRACT

Devices based on lateral flow assay (LFA) have been gaining more and more space in the detection market mainly due to their simplicity, speed, and low cost. These devices have excellent sensing format versatility and make these strips an ideal choice for field applications. The COVID-19 pandemic boosted the democratization of this method as a "point of care testing" (POCT), and the trend is that these devices become protagonists for the monitoring of pesticides in the environment. However, designing LFA devices for detecting and monitoring pesticides in the environment is still a challenge. This is because analytes are small molecules and have only one antigenic determinant, which makes it difficult to apply direct immunoassays. Furthermore, most LFA devices provide only qualitative or semi-quantitative results and have a limited number of applications in multi-residue analysis. Here, we present the state of the art on the use of LFA in the environmental monitoring of pesticides. Based on well-documented results, we review all available LFA formats and strategies for pesticide detection, which may have important implications for the future of monitoring pesticides in the environment. The main advances, challenges, and perspectives of these devices for a direction in this field of study are also presented.


Subject(s)
COVID-19 , Pesticides , Humans , Immunoassay/methods , Pandemics , Point-of-Care Testing
7.
Int J Environ Res Public Health ; 19(11)2022 06 01.
Article in English | MEDLINE | ID: covidwho-1892876

ABSTRACT

This study looks into the relationship between mental health and social exclusion scenarios, paying special attention to employment-related factors. Previous studies have shown the relationship between mental health, social exclusion and poverty. For this study, authors have used data from the VIII Report on social development and exclusion in Spain, with a sample of 11,655 households. The SPSS Statistics programme was used for statistical analysis. Several factors that could pose a risk or be a protection for the presence of mental health conditions were designed. By means of a binary logistic regression the impact of these factors on mental health issues was scored. The results show that a deteriorated social network and a negative interpretation of reality are the most influential factors related to the presence of mental health conditions in a given household. On the contrary, positive social relationships protect households and function as a support when mental health conditions are already present. Thus, the support of positive and committed social relationships is a key element to protect the mental health of households.


Subject(s)
Employment , Mental Health , Cross-Sectional Studies , Employment/psychology , Interpersonal Relations , Protective Factors
8.
Biology (Basel) ; 11(4)2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1776122

ABSTRACT

The sanitary crisis of the past two years has focused the public's attention on quantitative indicators of the spread of the COVID-19 pandemic. The daily reproduction number Rt, defined by the average number of new infections caused by a single infected individual at time t, is one of the best metrics for estimating the epidemic trend. In this paper, we provide a complete observation model for sampled epidemiological incidence signals obtained through periodic administrative measurements. The model is governed by the classic renewal equation using an empirical reproduction kernel, and subject to two perturbations: a time-varying gain with a weekly period and a white observation noise. We estimate this noise model and its parameters by extending a variational inversion of the model recovering its main driving variable Rt. Using Rt, a restored incidence curve, corrected of the weekly and festive day bias, can be deduced through the renewal equation. We verify experimentally on many countries that, once the weekly and festive days bias have been corrected, the difference between the incidence curve and its expected value is well approximated by an exponential distributed white noise multiplied by a power of the magnitude of the restored incidence curve.

9.
Proc Natl Acad Sci U S A ; 118(50)2021 12 14.
Article in English | MEDLINE | ID: covidwho-1562323

ABSTRACT

The COVID-19 pandemic has undergone frequent and rapid changes in its local and global infection rates, driven by governmental measures or the emergence of new viral variants. The reproduction number Rt indicates the average number of cases generated by an infected person at time t and is a key indicator of the spread of an epidemic. A timely estimation of Rt is a crucial tool to enable governmental organizations to adapt quickly to these changes and assess the consequences of their policies. The EpiEstim method is the most widely accepted method for estimating Rt But it estimates Rt with a significant temporal delay. Here, we propose a method, EpiInvert, that shows good agreement with EpiEstim, but that provides estimates of Rt several days in advance. We show that Rt can be estimated by inverting the renewal equation linking Rt with the observed incidence curve of new cases, it Our signal-processing approach to this problem yields both Rt and a restored it corrected for the "weekend effect" by applying a deconvolution and denoising procedure. The implementations of the EpiInvert and EpiEstim methods are fully open source and can be run in real time on every country in the world and every US state.


Subject(s)
Basic Reproduction Number , COVID-19/transmission , COVID-19/epidemiology , Computer Simulation , Forecasting , Humans , Incidence , Models, Theoretical , SARS-CoV-2
11.
J Infect Dis ; 224(1): 21-30, 2021 07 02.
Article in English | MEDLINE | ID: covidwho-1379462

ABSTRACT

The differentiation between influenza and coronavirus disease 2019 (COVID-19) could constitute a diagnostic challenge during the ongoing winter owing to their clinical similitude. Thus, novel biomarkers are required to enable making this distinction. Here, we evaluated whether the surfactant protein D (SP-D), a collectin produced at the alveolar epithelium with known immune properties, was useful to differentiate pandemic influenza A(H1N1) from COVID-19 in critically ill patients. Our results revealed high serum SP-D levels in patients with severe pandemic influenza but not those with COVID-19. This finding was validated in a separate cohort of mechanically ventilated patients with COVID-19 who also showed low plasma SP-D levels. However, plasma SP-D levels did not distinguish seasonal influenza from COVID-19 in mild-to-moderate disease. Finally, we found that high serum SP-D levels were associated with death and renal failure among severe pandemic influenza cases. Thus, our studies have identified SP-D as a unique biomarker expressed during severe pandemic influenza but not COVID-19.


Subject(s)
COVID-19/genetics , Gene Expression , Host-Pathogen Interactions/genetics , Influenza A Virus, H1N1 Subtype , Influenza, Human/genetics , Pulmonary Surfactant-Associated Protein D/genetics , SARS-CoV-2 , Adult , Aged , Biomarkers , COVID-19/blood , COVID-19/diagnosis , COVID-19/virology , Coinfection , Enzyme-Linked Immunosorbent Assay , Female , Humans , Influenza, Human/diagnosis , Influenza, Human/virology , Male , Middle Aged , Prognosis , Pulmonary Surfactant-Associated Protein D/blood , Severity of Illness Index , Symptom Assessment , Young Adult
12.
EClinicalMedicine ; 37: 100959, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1275282

ABSTRACT

BACKGROUND: There are limited antiviral options for the treatment of patients with COVID-19. Ivermectin (IVM), a macrocyclic lactone with a wide anti-parasitary spectrum, has shown potent activity against SARS-CoV-2 in vitro. This study aimed at assessing the antiviral effect of IVM on viral load of respiratory secretions and its relationship with drug concentrations in plasma. METHODS: Proof-of-concept, pilot, randomized, controlled, outcome-assessor blinded trial to evaluate antiviral activity of high-dose IVM in 45 COVID-19 hospitalized patients randomized in a 2:1 ratio to standard of care plus oral IVM at 0·6 mg/kg/day for 5 days versus standard of care in 4 hospitals in Argentina. Eligible patients were adults with RT-PCR confirmed SARS-CoV-2 infection within 5 days of symptoms onset. The primary endpoint was the difference in viral load in respiratory secretions between baseline and day-5, by quantitative RT-PCR. Concentrations of IVM in plasma were measured. Study registered at ClinicalTrials.gov: NCT04381884. FINDINGS: 45 participants were recruited (30 to IVM and 15 controls) between May 18 and September 9, 2020. There was no difference in viral load reduction between groups but a significant difference was found in patients with higher median plasma IVM levels (72% IQR 59-77) versus untreated controls (42% IQR 31-73) (p = 0·004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r: 0·47, p = 0·02). Adverse events were similar between groups. No differences in clinical evolution at day-7 and day-30 between groups were observed. INTERPRETATION: A concentration dependent antiviral activity of oral high-dose IVM was identified at a dosing regimen that was well tolerated. Large trials with clinical endpoints are necessary to determine the clinical utility of IVM in COVID-19. FUNDING: This work was supported by grant IP-COVID-19-625, Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación, Argentina and Laboratorio ELEA/Phoenix, Argentina.

14.
Front Immunol ; 12: 593595, 2021.
Article in English | MEDLINE | ID: covidwho-1229174

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1ß, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic.


Subject(s)
COVID-19 , Cytokines , Influenza A Virus, H1N1 Subtype , Influenza, Human , Matrix Metalloproteinase 1 , Matrix Metalloproteinase 3 , Receptors, Immunologic , Adult , Aged , COVID-19/blood , COVID-19/epidemiology , COVID-19/immunology , Cytokines/blood , Cytokines/immunology , Female , Humans , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H1N1 Subtype/metabolism , Influenza, Human/blood , Influenza, Human/epidemiology , Influenza, Human/immunology , Male , Matrix Metalloproteinase 1/blood , Matrix Metalloproteinase 1/immunology , Matrix Metalloproteinase 3/blood , Matrix Metalloproteinase 3/immunology , Middle Aged , Prospective Studies , Receptors, Immunologic/blood , Receptors, Immunologic/immunology , Th1 Cells/immunology , Th2 Cells/immunology
15.
Front Immunol ; 12: 633297, 2021.
Article in English | MEDLINE | ID: covidwho-1133913

ABSTRACT

The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.


Subject(s)
Biomarkers/metabolism , Chemokines, CXC/metabolism , Influenza A Virus, H1N1 Subtype/physiology , Influenza, Human/diagnosis , Lung/metabolism , Mycobacterium tuberculosis/physiology , SARS-CoV-2/physiology , Adult , Aged , COVID-19/diagnosis , COVID-19/mortality , Chemokines, CXC/genetics , Chemokines, CXC/immunology , Cohort Studies , Disease Progression , Female , Humans , Influenza, Human/mortality , Lung/pathology , Male , Mexico , Middle Aged , Pandemics , Patient Outcome Assessment , Prognosis , Survival Analysis , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/mortality , Young Adult
16.
Commun Biol ; 4(1): 290, 2021 03 05.
Article in English | MEDLINE | ID: covidwho-1118820

ABSTRACT

SARS-CoV-2 virus has infected more than 92 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19). Using a rhesus macaque model of SARS-CoV-2 infection, we have characterized the transcriptional signatures induced in the lungs of juvenile and old macaques following infection. Genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs, while pathways associated with collagen formation are downregulated, as also seen in lungs of macaques with tuberculosis. In COVID-19, increasing age is a significant risk factor for poor prognosis and increased mortality. Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. Together, our transcriptomic studies have delineated disease pathways that improve our understanding of the immunopathogenesis of COVID-19.


Subject(s)
COVID-19/immunology , Cell Degranulation , Interferons/physiology , Neutrophils/physiology , SARS-CoV-2 , Aged , Animals , CD36 Antigens/physiology , COVID-19/etiology , Collagen/metabolism , Disease Models, Animal , Female , Gene Expression Regulation , Humans , Lung/metabolism , Macaca mulatta , Male , Middle Aged , Receptors, Notch/physiology , Signal Transduction/physiology , Transforming Growth Factor beta/physiology , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor A/physiology
17.
J Pharm Sci ; 110(6): 2501-2507, 2021 06.
Article in English | MEDLINE | ID: covidwho-1046101

ABSTRACT

Recently published data indicates that high ivermectin (IVM) concentrations suppress in vitro SARS-CoV-2 replication. Nasal IVM spray administration may contribute to attaining high drug concentrations in nasopharyngeal tissue, a primary site of virus entrance/replication. The safety and pharmacokinetic performances of a novel IVM spray formulation were assessed in a pig model. Piglets received IVM either orally (0.2 mg/kg) or by one or two nasal spray doses. The overall safety, and histopathology of the IVM-spray application site tissues, were assessed. The IVM concentration profiles measured in plasma and respiratory tract tissues after the nasal spray were compared with those achieved after the oral administration. Animals tolerated well the nasal spray formulation. No local/systemic adverse events were observed. After nasal administration, the highest IVM concentrations were measured in nasopharyngeal and lung tissues. The nasal/oral IVM concentration ratios in nasopharyngeal and lung tissues markedly increased by repeating (12 h apart) the spray application. The fast attainment of high and persistent IVM concentrations in nasopharyngeal tissue is the main advantage of the nasal over the oral route. These original results support the undertaking of future clinical trials to evaluate the safety/efficacy of the nasal IVM spray application in the prevention and/or treatment of COVID-19.


Subject(s)
COVID-19 , Ivermectin , Administration, Oral , Animals , Humans , Ivermectin/toxicity , Nasal Sprays , SARS-CoV-2 , Swine
18.
Rev. cienc. med. Pinar Rio ; 24(3):e4509-e4509, 2020.
Article in Spanish | LILACS (Americas) | ID: grc-741682

ABSTRACT

RESUMEN Introducción: los coronavirus llevan su nombre por las peculiares partículas virales con forma de corona que recubren su superficie, varias especies son de reciente investigación y existe poca información sobre la transmisión, gravedad e impacto clínico. Objetivo: caracterizar pacientes pediátricos con la COVID-19 atendidos en Pinar del Río. Métodos: se realizó un estudio observacional, descriptivo y transversal de 15 pacientes con enfermedad por coronavirus 2019, ingresados en el Hospital Clínico-Quirúrgico Docente "León Cuervo Rubio", desde el 26 de marzo hasta el 12 de mayo de 2020. La muestra fue seleccionada mediante un muestreo no probabilístico. Para el procesamiento de la información obtenida se emplearon las técnicas de estadística descriptiva. Resultados: el grupo de edad más representado fue el de siete a 12 años y el sexo masculino (60 vs 40 %). El 53,3 % de los pacientes debutó con infección no complicada y el asma bronquial resultó la comorbilidad más frecuente. El síntoma más notificado al ingreso fue la fiebre (60 %). En la radiografía de tórax el engrosamiento hiliar mostró mayor presentación, sin alteraciones significativas en los estudios de laboratorio. El total de casos estudiados recibió tratamiento con Oseltamivir oral. Conclusiones: la enfermedad por la COVID-19 se ha convertido rápidamente en una amenaza mundial para la salud. Los escolares masculinos fueron más propensos al contagio y debutaron como síndromes clínicos no severos. ABSTRACT Introduction: coronaviruses are named for the peculiar crown-shaped viral particles that cover their surface, several species are newly investigated and there is little information about transmission, severity and clinical effects. Objective: to characterize pediatric patients with COVID-19 attended in Pinar del Río province. Methods: an observational, descriptive and cross-sectional study of 15 patients with COVID-19 admitted to Dr. Leon Cuervo Rubio Clinical-Surgical Teaching Hospital was conducted from March 26th to May 12th, 2020. The studied was completed by means of a non-probabilistic sampling. Descriptive statistical methods were applied to process the information collected. Results: the most represented age group was seven -12 years old and male gender (60 vs. 40 %);53,3% of patients developed a non-complicated infection and bronchial asthma was the most frequent comorbidity. The most reported symptom on admission was fever (60 %). In the chest X-ray the hilar thickening showed a greater presentation, without significant alterations in the laboratory studies. The total number of cases studied was treated with oral Oseltamivir. Conclusions: COVID-19 has rapidly become a global health threat. Male schoolchildren were more prone to infection and the disease presented non-severe clinical syndromes.

19.
Educ. med. super ; 34(2):e2385-e2385, 2020.
Article in Spanish | LILACS (Americas) | ID: grc-741501

ABSTRACT

RESUMEN Introducción: La educación médica es un elemento de vital importancia para mejorar el desempeño de los profesionales de la salud en la lucha contra la pandemia de COVID-19. Objetivo: Identificar los elementos fundamentales relacionados con la educación médica en su relación con la atención médica a pacientes con COVID-19, y las estrategias de prevención y control. Desarrollo: Los aspectos relacionados con la atención médica de pacientes sospechosos y confirmados, y con la prevención y el control de la transmisión de infecciones en entornos comunitarios o en centros de salud, se describen como áreas fundamentales para la educación médica. Asimismo, después de controlar la pandemia, los educadores de salud tienen el desafío de evaluar la modificación requerida en los programas de capacitación de profesionales de la salud para lograr un alto rendimiento en los nuevos entornos epidemiológicos. Por este motivo se realizó una sistematización del conocimiento relacionado con los desafíos y el papel de la educación médica en la lucha contra la COVID-19. Conclusiones: Los educadores han tenido un desafío durante la epidemia de COVID-19 en la educación de los profesionales de la salud para enfrentar la epidemia, que será un mayor en el futuro debido a la necesidad de lograr la sostenibilidad de la educación y la revisión de los programas de capacitación para enfrentar la nueva realidad epidemiológica. ABSTRACT Introduction: Medical education is vitally important for improving the performance of health professionals in the fight against the COVID-19 pandemic. Objective: To identify the fundamental elements related to medical education in its relationship with medical care of patients with COVID-19, as well as prevention and control strategies. Development: Aspects related to medical care of suspected and confirmed patients, as well as to the prevention and control of infection transmission in the community settings or in health centers, are described as fundamental areas for medical education. Furthermore, after controlling the pandemic, health educators are challenged to assess the required modification to health professional training programs in order to achieve high performance in new epidemiological settings. Therefore, a systematization was carried out of knowledge related to the challenges and the role of medical education in the fight against COVID-19. Conclusions: Educators have faced a challenge during the COVID-19 epidemic in educating health professionals to face the epidemic, which will be even greater in the future due to the need to achieve sustainability of education and revision of training programs to face the new epidemiological reality.

20.
Rev. habanera cienc. méd ; 19(supl.1):e3318-e3318, 2020.
Article in Spanish | LILACS (Americas) | ID: grc-741500

ABSTRACT

RESUMEN Introducción: En el proceso de cuidados de paciente con sospecha de infección por el nuevo coronavirus (COVID-19) se incluyen elementos que deben ser considerados en las estrategias de prevención de la transmisión. Objetivo: Describir, a partir de la presentación de un caso confirmado con COVID-19, la cronología de los cuidados del paciente sospechoso o confirmado con la enfermedad y la necesidad de optimizar los tiempos de diagnóstico en la prevención de su transmisión. Presentación de caso: Paciente masculino de 59 años de edad con antecedentes de Hipertensión arterial y gota, y de profesión taxista. Siete días anteriores al ingreso comienza con los síntomas clínicos y se le realiza prueba rápida para COVID-19, la cual resultó negativa. Al quinto día de ingreso de aislamiento en habitación privada se le realiza PCR y se confirma la infección por coronavirus. Se traslada a institución dedicada a la atención de estos pacientes donde presenta recuperación sin complicaciones. Se describen los intervalos de tiempo en relación con los cuidados en especial énfasis a la demora diagnóstica. Conclusiones: Se requiere un monitoreo de la dinámica de los cuidados de los pacientes sospechosos de COVID-19 con un especial enfoque en el fortalecimiento de la prevención de la transmisión nosocomial y en la comunidad. ABSTRACT Introduction: In the process of caring for patients with suspected coronavirus infection (COVID-19), elements that must be considered in transmission prevention strategies are included. Objective: To describe, based on the presentation of a case confirmed with COVID-19, the chronology of patients suspected or confirmed with the disease and the need to optimize diagnosis times in the transmission prevention. Case presentation: Fifty-nine-year-old male patient with a history of high blood pressure and gout, working as a taxi driver. Seven days before admission, he began with symptoms. A rapid test for COVID-19 was performed, which was negative. On the fifth day of isolation in a private room, PCR was performed and coronavirus infection was confirmed. He was moved to an institution dedicated to the care of these patients where he recovered without complications. Time intervals concerning care are described with special emphasis on diagnostic delay. Conclusion: Monitoring of the care dynamics of patients suspected of COVID-19 is required with a special focus on strengthening the prevention of nosocomial transmission and the prevention of the spreading of the disease in the community.

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