Patterns of physical activity and SARS-CoV-2 severe pneumonia: A case-control study.

BACKGROUND: Regular physical activity is associated with a low risk of severe community-acquired infections. However, the hypothesis that a physical inactivity pattern is associated with a higher risk for severe COVID-19 has not been completely proven, especially with severe pneumonia. OBJECTIVE: The goal of this study was to confirm the link between physical activity patterns and severe SARS-CoV-2 pneumonia. DESIGN: Case-control study. METHODS: This study involved 307 patients who developed SARS-CoV-2 severe pneumonia and were hospitalized in an intensive care unit. Age- and sex-matched controls (307) were selected from the same population: patients with mild to moderate forms of COVID-19 who were not hospitalized. Physical activity patterns were assessed using the short version of the International Physical Activity Questionnaire. RESULTS: The mean physical activity levels were lower in the SARS-CoV-2 severe pneumonia group as compared to the control group: 1576±2939 vs 2438±2999, metabolic equivalent of task (MET-min/week), p<0.001. A high or moderate physical activity level was more common in the control group, and a low physical activity level was more observed in the case group (p<0.001). Obesity was also associated with severe SARS-CoV-2 pneumonia (p<0.001). Multivariable analysis showed that a low physical activity level was associated with a higher risk for severe SARS-CoV-2 pneumonia, independent of nutritional status (CI 3.7; 2.24-5.99), p<0.001). CONCLUSION: A higher and moderate level of physical activity is linked to a lower risk of SARS-CoV-2 severe pneumonia.

Morphological, cellular, and molecular basis of brain infection in COVID-19 patients.

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.

Misoprostol administered sublingually at a dose of 12.5 µg versus vaginally at a dose of 25 µg for the induction of full-term labor: a randomized controlled trial protocol.

BACKGROUND: Various methods are currently used for the induction of labor. Nevertheless, the most effective method with the fewest side effects remains to be established. Misoprostol, administered vaginally, has been routinely used for this purpose; however, other forms of administration are being proposed, including the use of sublingual tablets. No studies have yet compared the effectiveness and safety of 12.5-µg misoprostol administered sublingually compared to a 25-µg vaginal dose of the drug for the induction of labor. METHODS: A triple-blind, multicenter, placebo-controlled, randomized clinical trial will be conducted in Brazil at the Instituto de Medicina Integral Prof. Fernando Figueira and at the Assis Chateaubriand Maternity Teaching Hospital of the Federal University of Ceará. A total of 140 patients with full-term pregnancies, a live fetus, a Bishop score ≤ 6 and a recommendation of induction of labor will be randomized to one of two groups. One group will receive 12.5-µg sublingual tablets of misoprostol and placebo vaginal tablets, while the other group will receive placebo sublingual tablets and vaginal tablets containing 25 µg of misoprostol. The principal endpoint is the rate of tachysystole. The secondary endpoints are vaginal delivery within 24 h of induction, uterine hyperstimulation, Cesarean section, severe neonatal morbidity or perinatal death, severe maternal morbidity or maternal death, and maternal preference regarding the route of administration of the drug. Student's t-test, and the chi-square test of association or Fisher's exact test, as appropriate, will be used in the data analysis. Risk ratios and their respective 95% confidence intervals will be calculated. DISCUSSION: Misoprostol has been identified as a safe, inexpensive, easily administered option for the induction of labor, with satisfactory results. An experimental study has shown that misoprostol administered sublingually at a dose of 25 µg appears to be effective and is associated with greater maternal satisfaction when labor is induced in women with an unfavorable cervix. Nevertheless, the rate of tachysystole remains high; therefore, further studies are required to determine the ideal dose and the ideal interval of time between doses. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01406392 .