Sex differences in the immune response to acute COVID-19 respiratory tract infection.

BACKGROUND: Sex differences in COVID-19 are increasingly recognized globally. Although infection rates are similar between the sexes, men have more severe illness. The mechanism underlying these sex differences is unknown, but a differential immune response to COVID-19 has been implicated in several recent studies. However, how sex differences shape the immune response to COVID-19 remains understudied. METHODS: We collected demographics and blood samples from over 600 hospitalized patients diagnosed with COVID-19 from May 24th 2020 to April 28th, 2021. These patients were divided into two cohorts: Cohort 1 was further classified into three groups based on the severity of the disease (mild, moderate and severe); Cohort 2 patients were longitudinally followed at three time points from hospital admission (1 day, 7 days, and 14 days). MultiPlex and conventional ELISA were used to examine inflammatory mediator levels in the plasma in both cohorts. Flow cytometry was conducted to examine leukocyte responses in Cohort 2. RESULTS: There were more COVID+ males in the total cohort, and the mortality rate was higher in males vs. females. More male patients were seen in most age groups (in 10-year increments), and in most ethnic groups. Males with severe disease had significantly higher levels of pro-inflammatory cytokines (IL-6, IL-8, MCP-1) than females; levels of IL-8, GRO, sCD40L, MIP-1ß, MCP-1 were also significantly higher in severe vs. mild or control patients in males but not in females. Females had significantly higher anti-inflammatory cytokine IL-10 levels at 14 days compared to males, and the level of IL-10 significantly increased in moderate vs. the control group in females but not in males. At 7 days and 14 days, males had significantly more circulating neutrophils and monocytes than females; however, B cell numbers were significantly higher in females vs. males. CONCLUSION: Sex differences exist in hospitalized patients with acute COVID-19 respiratory tract infection. Exacerbated inflammatory responses were seen in male vs. female patients, even when matched for disease severity. Males appear to have a more robust innate immune response, and females mount a stronger adaptive immune response to COVID-19 respiratory tract infection.

The Relationship Between Plasma Oxytocin and Executive Functioning in Huntington's Disease: A Pilot Study.

The role of oxytocin (OT) in social cognition of patients with Huntington's disease (HD) has been studied, but its impact on executive functioning has not been explored yet. Healthy controls, premanifest HD, and manifest HD participants underwent executive functioning assessment and OT plasma measurement. There were no significant group differences in plasma OT levels. Higher OT levels were associated with better executive functioning in premanifest HD participants. Our findings revealed an association between OT levels and depressive symptoms in premanifest and manifest HD participants. The potential role of OT in HD deserves further investigation.

Small-molecule G-quadruplex stabilizers reveal a novel pathway of autophagy regulation in neurons.

Guanine-rich DNA sequences can fold into four-stranded G-quadruplex (G4-DNA) structures. G4-DNA regulates replication and transcription, at least in cancer cells. Here, we demonstrate that, in neurons, pharmacologically stabilizing G4-DNA with G4 ligands strongly downregulates the Atg7 gene. Atg7 is a critical gene for the initiation of autophagy that exhibits decreased transcription with aging. Using an in vitro assay, we show that a putative G-quadruplex-forming sequence (PQFS) in the first intron of the Atg7 gene folds into a G4. An antibody specific to G4-DNA and the G4-DNA-binding protein PC4 bind to the Atg7 PQFS. Mice treated with a G4 stabilizer develop memory deficits. Brain samples from aged mice contain G4-DNA structures that are absent in brain samples from young mice. Overexpressing the G4-DNA helicase Pif1 in neurons exposed to the G4 stabilizer improves phenotypes associated with G4-DNA stabilization. Our findings indicate that G4-DNA is a novel pathway for regulating autophagy in neurons.