Molecular Mechanisms Lead to Sex-Specific COVID-19 Prognosis and Targeted Therapies.

Clinical and epidemiological studies have identified male sex as an important risk factor for COVID-19 clinical outcomes and mortality. This raises the question as to how this risk factor can be addressed in the prognosis, clinical management, and the treatment of patients with Coronavirus disease 2019 (COVID-19). Currently, there are no guidelines or protocols to help alter the course of sex-specific COVID-19 prognosis, especially in severe disease presentations. This is partly due to the lack of research studies characterizing the differences in male vs. female host response to the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection and a lack of a well-rounded understanding of the molecular mechanisms involved. Here, we discuss three distinct but interconnected molecular-level differences in males and females that likely play an essential role in the COVID-19 prognosis. We review interactions of SARS-CoV-2 with host cell angiotensin-converting enzyme 2 (ACE2) in the viral entry between males vs. females and discuss the differential regulation of the renin-angiotensin system (RAS) between the two sexes. Next, we present immune response disparities and how immune function and endocrine regulation may render males increasingly vulnerable to severe COVID-19. We describe the interconnected roles of these three regulatory systems in males and females in response to SARS-CoV-2 infection. Finally, we highlight the clinical implications of these mechanisms to patients with COVID-19 and propose putative targeted therapies that can help reduce COVID-19 severity in those critically ill.

Biopsychosocial and Spiritual Implications of Patients With COVID-19 Dying in Isolation.

Critically ill patients with the Coronavirus disease 2019 (COVID-19) are dying in isolation without the comfort of their family or other social support in unprecedented numbers. Recently, healthcare teams at COVID-19 epicenters have been inundated with critically ill patients. Patients isolated for COVID-19 have had no contact with their family or loved ones and may have likely experienced death without closure. This situation highlights concerns about patients' psychological and spiritual well-being with COVID-19 and their families, as they permanently part ways. While palliative care has advanced to adequately address these patients' needs, the COVID-19 pandemic presents several barriers that force healthcare teams to deprioritize these essential aspects of patient care. The severe acute respiratory syndrome (SARS) outbreak in 2003 gave us a glimpse of these challenges as these patients were also isolated in hospitals. Here, we discuss the importance of the biopsychosocial spiritual model in end-of-life care and its implications on patients dying with COVID-19. Furthermore, we outline an integrative approach to address the unique and holistic needs of critically ill patients dying with COVID-19. These include intentional and increased coordination with trained palliative care staff, early and frequent goals of care including discussion of end-of-life plans, broader use of technology to improve connectedness, and shared decision making with patients' families.

Central nervous system infections due to vancomycin-resistant enterococci: case series and review of the literature.

OBJECTIVES: To evaluate reported cases of central nervous system (CNS) infections due to vancomycin-resistant enterococci (VRE) and describe the data necessary to better understand clinical characteristics of this rare disease process. METHODS: We report two cases of VRE CNS infection and review 36 cases reported in the literature. RESULTS: Eighty-two percent (31/38) of cases were due to Enterococcus faecium. The median length of stay prior to diagnosis was 14 days (interquartile range 9-33). Fifty-eight percent (22/38) of cases had significant underlying non-malignant CNS disease processes and 63% (24/38) had CNS devices in situ. Forty percent (15/38) of patients had other positive culture sites. Ninety-two percent (35/38) of patients experienced microbiological cure and 74% (28/38) experienced clinical and microbiological cure following a variety of antimicrobial therapies. Seventy-four percent (14/19) of patients who experienced clinical/microbiological cure with CNS devices had them either removed or replaced. Eighteen percent (7/38) died from VRE CNS infections. CONCLUSIONS: VRE CNS infections are uncommon nosocomial infections that most commonly affect patients with underlying CNS disease processes. The vast majority of cases are due to E. faecium, and many cases involve multiple positive culture sites. Optimal antimicrobial therapy remains undefined, but should be coupled with removal or replacement of indwelling CNS devices.