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

Infection with SARS-CoV-2 portends a broad range of outcomes, from a majority of asymptomatic cases or mild clinical courses to a lethal disease. Robust correlates of severe COVID-19 include old age, male sex, poverty and co-morbidities such as obesity, diabetes or cardiovascular disease. A precise knowledge is still lacking of the molecular and biological mechanisms that may explain the association of severe disease with male sex. Here, we show that testosterone trajectories are highly accurate individual predictors (AUC of ROC = 0.928, p < 0.0001) of survival in male COVID-19 patients. Longitudinal determinations of blood levels of luteinizing hormone (LH) and androstenedione suggest an early modest inhibition of the central LH-androgen biosynthesis axis in a majority of patients, followed by either full recovery in survivors or a peripheral failure in lethal cases. Moreover, failure to reinstate physiological testosterone levels was associated with evidence of impaired T helper differentiation and decrease of non-classical monocytes. The strong association of recovery or failure to reinstate testosterone levels with survival or death from COVID-19 in male patients is suggestive of a significant role of testosterone status in the immune responses to COVID-19.

Altitude as a Protective Factor from COVID-19 (preprint)

The COVID-19 pandemic had a delayed onset in South America compared to Asia (outside of China), Europe or North America. In spite of the presumed time advantage for the implementation of preventive measures to help contain its spread, the pandemic in that region followed growth rates that paralleled, and currently exceed, those observed several weeks before in Europe. Indeed, in early August 2020, many countries in South and Central America presented among the highest rates in the world of COVID-19 confirmed cases and deaths per million inhabitants. Here, we have taken an ecological approach to describe the current state of the pandemic in Peru and its dynamics. Our analysis supports a protective effect of altitude from COVID-19 incidence and mortality. Further, we provide circumstantial evidence that internal migration through a specific land route is a significant factor progressively overriding the protection from COVID-19 afforded by high altitude. Finally, we show that protection by altitude is independent of poverty indexes and is inversely correlated with the prevalence in the population of risk factors associated with severe COVID-19, including hypertension and hypercholesterolemia. We discuss long-term multisystemic adaptive traits to hypobaric hypoxia as possible mechanisms that may explain the observed protective effect of high altitude from death due to COVID-19.Funding Statement: This study was partially funded by grants from the CSIC (COV19-006) and CIBER-EHD (Spain), awarded to T.M.T. F.C.V is funded by a Wellcome Trust Intermediate Research Fellowship in Public Health and Tropical Medicine (107544/Z/15/Z).Declaration of Interests: All authors declare no conflicts of interest.