Síndromes clínicos en la infección aguda y crónica de la COVID-19 en población nativa y residente de altura durante la primera y segunda ola

Objective: To classify into clinical syndromes the symptoms of acute and chronic COVID-19 infection among a highaltitude population during the first and second waves. Materials and methods: A prospective and longitudinal study. An online questionnaire was administered to people infected with SARS-CoV-2 during the first and second waves from March 2020 to December 2021. The measures of central tendency were expressed as means and percentages with a 95 % confidence interval. The chi-square test associated the variables and considered a p value ≤ 0.05. IBM SPSS Statistics statistical software V22 was used. Results: A total of 87 women and 63 men with an average age of 44.12 (± 14.56) years participated in the research, out of whom 48.70 % and 51.30 % were infected in the first and second waves, respectively. The 59 reported symptoms were grouped into 19 syndromes for the acute phase and 18 for the chronic phase. The most frequent syndromes in the acute phase were incomplete acute toxic infectious disorders (79.30 %), taste and smell disorders (60.70 %) and anxiety and depressive disorders (56.79 %). Chronic COVID was called post-COVID-19 syndrome and was subdivided into three phases: post-acute, chronic and long-haul. In the post-acute and chronic phases, muscle fatigue and weakness as well as pain and aches appeared, persisting until the long-haul phase, where lingering symptoms were considered sequelae. Post-COVID-19 syndrome occurred in 64.55 % of the participants. Conclusions: This study has shown an increased frequency of symptoms affecting the central and peripheral nervous system in both the acute phase and post-COVID-19 syndrome. It is possible that hypobaric hypoxia, by prolonging inflammation and stimulating oxidative stress, may lead to a longer post-COVID-19 syndrome, with a greater impact on the nervous system.Objetivo: Clasificar los síntomas de la infección aguda y crónica de la COVID-19 en síndromes clínicos, en un grupo poblacional que vive en altura, durante la primera y segunda ola. Materiales y métodos: Estudio prospectivo y longitudinal. Se aplicó un cuestionario virtual a personas infectadas por el SARS-CoV-2 durante la primera y segunda ola, en el periodo marzo del 2020 a diciembre del 2021.Las medidas de tendencia central se expresaron en promedios y porcentajes, con un intervalo de confianza del 95 %. La prueba de ji al cuadrado asoció variables y consideró un valor p ≤ 0,05. Se utilizó el paquete estadístico SPSS 22. Resultados: Participaron 87 mujeres y 63 varones, con una edad promedio de 44,12 (±14,56) años. El 48,70 % se contagiaron en la primera ola y 51,30 %, en la segunda. Los 59 síntomas identificados se agruparon en 19 síndromes correspondientes a la fase aguda y 18 correspondientes a la fase crónica. Los síndromes más frecuentes en la fase aguda fueron el tóxico-infeccioso agudo incompleto, con 79,30 %; el de disfunción del gusto y olfato, con 60,70 %, y el ansioso-depresivo, con 56,79 %. La fase crónica se denominó síndrome pos-COVID-19 y fue subdividida en tres fases, la posaguda, la crónica y la de transportador prolongado. En las fases posaguda y crónica aparecen el síndrome de agotamiento muscular y el doloroso, que persisten hasta la fase de transportador prolongado, en donde los síntomas residuales se consideran secuelas. El síndrome pos-COVID-19 se presentó en 64,55 % de los participantes. Conclusiones: Este estudio ha demostrado una frecuencia mayor de síntomas dependientes de la invasión del virus al sistema nervioso central y periférico tanto en la fase aguda como en el síndrome pos-COVID-19. Es posible que la hipoxia hipobárica al prolongar la inflamación y estimular el estrés oxidativo determine un síndrome pos-COVID-19 más prolongado, y que este tenga mayor repercusión en el sistema nervioso

Caracterización de la función cardiorrespiratoria y su relación con el estrés oxidativo en mujeres expuestas al humo de leña residentes de gran altura (3850 m s. n. m.)

Objective: To characterize the cardiorespiratory function and the state of oxidative stress resulting from the exposure to wood smoke in women who live at high altitude (3,850 m a.s.l.). Materials and methods: An observational case-series study. The cardiorespiratory function was analyzed, and thebiomarkers of oxidative stress malondialdehyde (MDA) and carboxyhemoglobin (COHb) were quantified. Measures of central tendency and dispersion were determined. The statistical methods of association and correlation were implemented. Results: Sixty (60) patients were included in the research. Fifty percent (50.00 %) of the participants showed clinical evidence of heart disease and 25.00 % had clinical symptoms of respiratory disease. Forty-five percent (45.00 %) of the spirometries revealed normal values. Thirty-six point six seven percent (36.67 %) showed a decrease in the forced expiratoryvolume in one second (FEV₁), forced expiratory volume in one second/forced vital capacity ratio (FEV₁/FVC) and/or forced expiratory flow 25-75% (FEF25-75). A decrease in FEV₁/FVC, FEF25-75 and FVC occurred in 8.33 %, 3.33 % and 1.67 % of the study participants, respectively. Moreover, a 5.00 % decrease was found in more than two parameters. Sixty percent (60.00 %) of the electrocardiograms revealed normal values, 36.67 % presented an intraventricular conduction disorder and 3.33 % showed dextrorotation of the heart. Eighty-one point six seven percent (81.67 %) of the participants presented an echocardiographic alteration, 73.33% showed valvular insufficiency, 20.00 % presented pulmonary hypertension and 6.67 % had an enlarged right ventricle. The mean MDA was 6 µM/L ± 2, which was positively correlated with the age (p: 0.029). The median COHb accounted for 1.00 % (p25: 0.70 – p75: 1.68). No statistically significant association was found between the COHb concentration and spirometric alterations. A positive correlation was found between MDA values and the right ventriclewall thickness (p: 0.001). Conclusions: The different alterations of the cardiorespiratory function found in the study population show that both chronic exposure to wood smoke derivatives and hypobaric hypoxia are an important source of free radicals and lead to a permanent and sustained state of oxidative stress, which is responsible for the progressive deterioration of the cardiorespiratory function with no early clinical manifestation.Objetivo: Caracterizar la función cardiorrespiratoria y el estado oxidativo consecuente a la exposición al humo de leña en mujeres que viven a gran altura (3850 m s.n.m.). Materiales y métodos: Estudio observacional serie de casos. Se exploró la función cardiorrespiratoria y se cuantificó la concentración sérica de malondialdehido (MDA) y carboxihemoglobina (COHb) como marcadores de estrés oxidativo. Se determinaron medidas de tendencia central y de dispersión. Se aplicaron métodos estadísticos de asociación y correlación. Resultados: Se estudiaron a 60 participantes, de las cuales, 50,00 % presentó clínica de enfermedad cardiaca; 25,00 %, clínica de enfermedad respiratoria. El 45,00 % de las espirometrías fueron normales; 37,67 % mostraron disminución del volumen espiratorio forzado en un segundo (VEF₁), del índice de permeabilidad bronquial central (VEF₁/CVF) y/o de los flujos aéreos periféricos (FEF25-75); 8,33 %, disminución VEF₁/CVF; 3,33 %, disminución del FEF25-75; 1,67 %, disminución de la capacidad vital forzada (CVF), y 5,0 %, disminución de dos o más parámetros. El 60,00 % de los electrocardiogramas eran normales, en 36,67 % se encontró diferentes trastornos de la conducción intraventricular, y en 3,33 % datos de corazón dextrorotado. El 81,67% de las ecocardiografías mostraba algún tipo de alteración: 73,33 % evidenciaron insuficiencias valvulares; un 20,00 % presentó, además de esta condición, hipertensión arterial; mientras que el 67,67 %, dimensión aumentada del ventrículo derecho. La media de MDA fue de 5,62 µM/L ± 2,06, correlación positiva con la edad (p: 0,029). La mediana de COHb fue de 1,05 % (p25:0,70–p75:1,68). No se encontró diferencia estadísticamente significativa entre la concentración de COHb y las alteraciones espirométricas. Se encontró correlación positiva entre los valores de MDA y el grosor del ventrículo derecho (p: 0,001). Conclusiones: Las diferentes alteraciones de la función cardiorrespiratoria encontradas expresan que tanto la exposición crónica a los derivados del humo de leña como la hipoxia hipobárica son fuentes importantes de radicales libres y que establecen un estado permanente y sostenido de estrés oxidativo, responsable del deterioro progresivo de la función cardiorrespiratoria sin expresión clínica precoz

Hypoglycemia and the Origin of Hypoxia-Induced Reduction in Human Fetal Growth

The most well known reproductive consequence of residence at high altitude (HA >2700 m) is reduction in fetal growth. Reduced fetoplacental oxygenation is an underlying cause of pregnancy pathologies, including intrauterine growth restriction and preeclampsia, which are more common at HA. Therefore, altitude is a natural experimental model to study the etiology of pregnancy pathophysiologies. We have shown that the proximate cause of decreased fetal growth is not reduced oxygen availability, delivery, or consumption. We therefore asked whether glucose, the primary substrate for fetal growth, might be decreased and/or whether altered fetoplacental glucose metabolism might account for reduced fetal growth at HA.Doppler and ultrasound were used to measure maternal uterine and fetal umbilical blood flows in 69 and 58 residents of 400 vs 3600 m. Arterial and venous blood samples from mother and fetus were collected at elective cesarean delivery and analyzed for glucose, lactate and insulin. Maternal delivery and fetal uptakes for oxygen and glucose were calculated.The maternal arterial – venous glucose concentration difference was greater at HA. However, umbilical venous and arterial glucose concentrations were markedly decreased, resulting in lower glucose delivery at 3600 m. Fetal glucose consumption was reduced by >28%, but strongly correlated with glucose delivery, highlighting the relevance of glucose concentration to fetal uptake. At altitude, fetal lactate levels were increased, insulin concentrations decreased, and the expression of GLUT1 glucose transporter protein in the placental basal membrane was reduced.Our results support that preferential anaerobic consumption of glucose by the placenta at high altitude spares oxygen for fetal use, but limits glucose availability for fetal growth. Thus reduced fetal growth at high altitude is associated with fetal hypoglycemia, hypoinsulinemia and a trend towards lactacidemia. Our data support that placentally-mediated reduction in glucose transport is an initiating factor for reduced fetal growth under conditions of chronic hypoxemia

Estrés oxidativo por humo de leña en mujeres nativas de gran altura - 3850 m s. n. m.

ABSTRACT Objective: To determine the blood levels of two oxidative stress biomarkers among native women exposed to wood smoke living at high altitude (3,850 m a.s.l.). Malondialdehyde (MDA) levels and carboxyhemoglobin (COHb) percentage in venous blood, which is also a cellular hypoxia biomarker, were analyzed.Materials and methods: A descriptive case-series study conducted in 74 women between 14 and 55 years of age exposed to wood smoke and coming from the rural area of the Copacabana Municipality (La Paz, Bolivia) at 3,850 m a.s.l. Screening was carried out through a survey and a complete physical examination. MDA levels and COHb percentage in venous blood were determined, and the demographic variables and transcutaneous oxygen saturation were measured. A descriptive statistical analysis was performed and measures of central tendency were calculated using IBM SPSS Statistics Version 18.Results: Seventy-four (74) women between 14 and 55 years of age were examined. This examination resulted in a mean level of 5.5 μmol/L ± 2 MDA and a median percentage of 1 % COHb (p25 –p75: 0.7 - 1.6). Women who used to burn a mixture of eucalyptus and cow or sheep dung had a higher mean level of MDA and a median percentage of 2.5 % COHb.Conclusions: Indoor air pollution (CAI) due to wood smoke increases the oxidative stress among this native population living at high altitude. This is demonstrated by the increased levels of MDA, and the difference against the biomarker levels of healthy native populations living at high altitude and at sea level. In addition, MDA levels and COHb percentages were higher among women who used to burn a mixture of wood and cow or sheep dung due to the higher harmful effects of such mixture.Objetivo: Determinar los niveles sanguíneos de dos biomarcadores de estrés oxidativo en mujeres expuestas al humo de leña, nativas y residentes de gran altura (3850 m s. n. m.). Se analizaron el malondialdehido (MDA), y el porcentaje de carboxihemoglobina en sangre venosa (CHOb), que también es un marcador de hipoxia celular.Materiales y métodos: Estudio descriptivo, serie de casos, realizado en 74 mujeres, entre 14 a 55 años, expuestas al humo de leña y oriundas del área rural del municipio de Copacabana (La Paz, Bolivia) a 3850 m s. n. m. La selección se hizo mediante una encuesta y un examen clínico completo. Se determinaron los niveles de MDA y el porcentaje de CHOb en sangre venosa, y se midieron variables demográficas y la saturación transcutánea de oxígeno. Para el análisis estadístico descriptivo y las medidas de tendencia central se empleó el paquete estadístico SPSS versión 18.Resultados: Se estudiaron 74 mujeres entre 14 a 55 años. Se encontró una media de MDA de 5,5 μmol/L ± 2 y una mediana de CHOb de 1 % (p25 –p75: 0,7 – 1,6). Las mujeres que refirieron quemar una mezcla de eucalipto con estiércol de vaca u oveja presentaron una media de MDA mayor y una mediana de CHOb de 2,5 %.Conclusiones: En esta población nativa y residente a gran altura, la contaminación del aire en interiores (CAI) incrementa el estrés oxidativo. Esto se demuestra en el aumento del MDA y en la diferencia con los valores de este biomarcador en la población sana nativa de altura y del llano. Asimismo, los valores de MDA y CHOb son mayores en quienes usaron una mezcla de leña con estiércol de vaca u oveja, por la mayor nocividad de la mezcla

Concentración de malondialdehido en sujetos que residen a gran altitud: estudio exploratorio

RESUMEN El objetivo fue investigar el comportamiento del malondialdehido (MDA), biomarcador de estrés oxidativo, a grandes altitudes (3500-4200 m de altitud). Se realizó un estudio exploratorio en 91 sujetos de las ciudades de La Paz y El Alto seleccionados a través de una encuesta y examen clínico; la determinación de MDA se realizó con una técnica colorimétrica. Las medidas de tendencia central, dispersión y porcentajes se usaron para la descripción de datos, la prueba de Mann Whitney y Kruscal Wallis para explorar diferencias entre varones y mujeres, grupo etario y altitud. La mediana de concentración de MDA fue de 4,1 µmol/L (RIC 2,4-5,4), la mayor concentración se encontró en mayores de 40 años. El valor de la media encontrada es mayor que los referidos para el nivel del mar y supone la influencia de la hipoxia sobre los valores del MDA, sin embargo, no se encontraron diferencias entre sexo y grupos etarios

Where the O2 goes to: preservation of human fetal oxygen delivery and consumption at high altitude

Fetal growth is decreased at high altitude (> 2700 m). We hypothesized that variation in fetal O2 delivery might account for both the altitude effect and the relative preservation of fetal growth in multigenerational natives to high altitude. Participants were 168 women of European or Andean ancestry living at 3600 m or 400 m. Ancestry was genetically confirmed. Umbilical vein blood flow was measured using ultrasound and Doppler. Cord blood samples permitted calculation of fetal O2 delivery and consumption. Andean fetuses had greater blood flow and oxygen delivery than Europeans and weighed more at birth, regardless of altitude (+208 g, P < 0.0001). Fetal blood flow was decreased at 3600 m (P < 0.0001); the decrement was similar in both ancestry groups. Altitude-associated decrease in birth weight was greater in Europeans (−417 g) than Andeans (−228 g, P < 0.005). Birth weight at 3600 m was > 200 g lower for Europeans at any given level of blood flow or O2 delivery. Fetal haemoglobin concentration was increased, decreased, and the fetal / curve was left-shifted at 3600 m. Fetuses receiving less O2 extracted more (r2= 0.35, P < 0.0001). These adaptations resulted in similar fetal O2 delivery and consumption across all four groups. Increased umbilical venous O2 delivery correlated with increased fetal O2 consumption per kg weight (r2= 0.50, P < 0.0001). Blood flow (r2= 0.16, P < 0.001) and O2 delivery (r2= 0.17, P < 0.001) correlated with birth weight at 3600 m, but not at 400 m (r2= 0.04, and 0.03, respectively). We concluded that the most pronounced difference at high altitude is reduced fetal blood flow, but fetal haematological adaptation and fetal capacity to increase O2 extraction indicates that deficit in fetal oxygen delivery is unlikely to be causally associated with the altitude- and ancestry-related differences in fetal growth