Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients.

BACKGROUND: SARS-CoV-2 infection portends a broad range of outcomes, from a majority of asymptomatic cases to a lethal disease. Robust correlates of severe COVID-19 include old age, male sex, poverty, and co-morbidities such as obesity, diabetes, and cardiovascular disease. A precise knowledge of the molecular and biological mechanisms that may explain the association of severe disease with male sex is still lacking. Here, we analyzed the relationship of serum testosterone levels and the immune cell skewing with disease severity in male COVID-19 patients. METHODS: Biochemical and hematological parameters of admission samples in 497 hospitalized male and female COVID-19 patients, analyzed for associations with outcome and sex. Longitudinal (in-hospital course) analyses of a subcohort of 114 male patients were analyzed for associations with outcome. Longitudinal analyses of immune populations by flow cytometry in 24 male patients were studied for associations with outcome. RESULTS: We have found quantitative differences in biochemical predictors of disease outcome in male vs. female patients. Longitudinal analyses in a subcohort of male COVID-19 patients identified serum testosterone trajectories as the strongest predictor of survival (AUC of ROC = 92.8%, p < 0.0001) in these patients among all biochemical parameters studied, including single-point admission serum testosterone values. In lethal cases, longitudinal determinations of serum luteinizing hormone (LH) and androstenedione levels did not follow physiological feedback patterns. Failure to reinstate physiological testosterone levels was associated with evidence of impaired T helper differentiation and augmented circulating classical monocytes. CONCLUSIONS: Recovery or failure to reinstate testosterone levels is strongly associated with survival or death, respectively, from COVID-19 in male patients. Our data suggest an early inhibition of the central LH-androgen biosynthesis axis in a majority of patients, followed by full recovery in survivors or a peripheral failure in lethal cases. These observations are suggestive of a significant role of testosterone status in the immune responses to COVID-19 and warrant future experimental explorations of mechanistic relationships between testosterone status and SARS-CoV-2 infection outcomes, with potential prophylactic or therapeutic implications.

C1 esterase inhibitor and the contact system in COVID-19.

Coronavirus disease 2019 (COVID-19) is frequently associated with severe systemic consequences, including vasculitis, a hyperinflammatory state and hypercoagulation. The mechanisms leading to these life-threatening abnormalities are multifactorial. Based on the analysis of publicly available interactomes, we propose that severe acute respiratory syndrome coronavirus-2 infection directly causes a deficiency in C1 esterase inhibitor, a pathogen-specific mechanism that may help explain significant systemic abnormalities in patients with COVID-19.

Efecto irritante in vitro de formulaciones cosméticas con extracto de camu camu, mediante el método Het Cam / Irritant effect in vitro of cosmetic formulations with camu camu extract by Het Cam method

Objetivo: evaluar el efecto irritante de formulaciones cosméticas con extractos de camu camu. Material y métodos: El presente estudio se realizó con formulaciones cosméticas de extractos de camu camu, proporcionadas por el laboratorio de AYRU COSMETIC; utilizamos la técnica altermativa in vitro, en membrana corioalantoidea en huevos fártiles de gallina (HET CAM, henás egg test chorioallantoic membrane). La implementación de la técnica se realizó en el Centro de Investigación de Medicina Tradicional y Farmacología del Instituto de Investigación de la Facultad de Medicina Humana de la USMP. Resultados: Ninguno de los cosméticos con extracto de camu camu, produjo ruptura de la membrana corioalantoidea, evidenciado por ausencia del colorante absorbido, azul de tripón, detectable a 595nm. Conclusiones: Los índices de irritación (I.I) obtenidos en todas las formulaciones cosméticas permiten clasificarlas como NO IRRITANTES, y constituyen el soporte de la inocuidad, de las mismas, para continuar con pruebas de eficacia.

Objective: To evaluate the irritant effect of cosmetic formulations elaborated with camu camu extracts. Material and Methods: This study was performed with cosmetic on formulations containing camu camu extracts supplied by the AYRU COSMETIC Laboratory. We used the alternative in vitro technic on choriollantoic membrane in fertile hen’s eggs (HET CAM, hen’s egg chorioallantoic membrane test). The techniques was implemented at “Centro Investigaci¢n de Medicina Tradicional y Farmacolog¡a” of the Research Institute of the school of Medicine of San Martin de Porres University. Results: None of the cosmetic with Camu Camu extracts showed chorioallantoic membrane rupture, which was verified by the absence of absorbed trypan blue dye, detectable at 595 nm. Conclusions: the rates of irritation (II) obtained in all cosmetic formulations allow us to classify them as NOT IRRITATING and support the safety of such products to continue clinical efficacy trials.