Berbamine suppresses intestinal SARS-CoV-2 infection via a BNIP3-dependent autophagy blockade.

SARS-CoV-2, the causative virus of COVID-19, continues to threaten global public health. COVID-19 is a multi-organ disease, causing not only respiratory distress, but also extrapulmonary manifestations, including gastrointestinal symptoms with SARS-CoV-2 RNA shedding in stool long after respiratory clearance. Despite global vaccination and existing antiviral treatments, variants of concern are still emerging and circulating. Of note, new Omicron BA.5 sublineages both increasingly evade neutralizing antibodies and demonstrate an increased preference for entry via the endocytic entry route. Alternative to direct-acting antivirals, host-directed therapies interfere with host mechanisms hijacked by viruses, and enhance cell-mediated resistance with a reduced likelihood of drug resistance development. Here, we demonstrate that the autophagy-blocking therapeutic berbamine dihydrochloride robustly prevents SARS-CoV-2 acquisition by human intestinal epithelial cells via an autophagy-mediated BNIP3 mechanism. Strikingly, berbamine dihydrochloride exhibited pan-antiviral activity against Omicron subvariants BA.2 and BA.5 at nanomolar potency, providing a proof of concept for the potential for targeting autophagy machinery to thwart infection of current circulating SARS-CoV-2 subvariants. Furthermore, we show that autophagy-blocking therapies limited virus-induced damage to intestinal barrier function, affirming the therapeutic relevance of autophagy manipulation to avert the intestinal permeability associated with acute COVID-19 and post-COVID-19 syndrome. Our findings underscore that SARS-CoV-2 exploits host autophagy machinery for intestinal dissemination and indicate that repurposed autophagy-based antivirals represent a pertinent therapeutic option to boost protection and ameliorate disease pathogenesis against current and future SARS-CoV-2 variants of concern.

Professional Quality of Life Among Physicians and Nurses Working in Portuguese Hospitals During the Third Wave of the COVID-19 Pandemic.

BACKGROUND: In the last 2 weeks of January 2021, Portugal was the worst country in the world in incidence of infections and deaths due to COVID-19. As a result, the pressure on the healthcare system increased exponentially, exceeding its capacities and leaving hospitals in near collapse. This scenario caused multiple constraints, particularly for hospital medical staff. Previous studies conducted at different moments during the pandemic reported that COVID-19 has had significant negative impacts on healthcare workers' psychological health, including stress, anxiety, depression, burnout, post-traumatic stress symptoms, and sleep disturbances. However, there are many uncertainties regarding the professional quality of life of hospital nurses and physicians. To address gaps in previous research on secondary traumatic stress, we focused on healthcare workers working in hospitals affected by a major traumatic event: the third wave of COVID-19. OBJECTIVES: The aim of the present study was to identify the contribution of personal and work-related contextual variables (gender, age, parental status, occupation, years of experience, working with patients affected by COVID-19) on professional quality of life of healthcare workers. METHODS: Cross-sectional study with a web-based questionnaire given to physicians and nurses working in a hospital setting. A total of 853 healthcare professionals (276 physicians and 586 nurses; median age 37 years old) participated in the survey assessing professional quality of life compassion satisfaction, secondary traumatic stress, and burnout. Factors of professional quality of life were assessed using regression analysis. RESULTS: Most of the participants showed moderate (80%; n = 684) or high (18%; n = 155) levels of compassion satisfaction, whereas the majority of them experienced moderate levels of burnout (72%; n = 613) and secondary traumatic stress (69%; n = 592). The analyzed variables demonstrated no differences between professionals who were directly or not involved in the care of COVID-19 patients. Parental status was found to be a significant factor in compassion satisfaction. Female gender was significantly associated with more susceptibility to secondary traumatization. Factors that may potentially contribute to burnout include years of professional experience and the number of work hours per week. CONCLUSION: The COVID-19 pandemic has created a new challenge for the healthcare system. Burnout and secondary traumatic stress can lead to medical errors and impact standards of patient care, particularly compromising compassionate care. It is therefore recommended that hospitals develop psychoeducational initiatives to support professionals in dealing with barriers to compassion.

Burnout among Portuguese healthcare workers during the COVID-19 pandemic.

BACKGROUND: During COVID-19 pandemic, healthcare workers (HCWs) have had high workload and have been exposed to multiple psychosocial stressors. The aim of this study was to evaluate HCWs in terms of the relative contributions of socio-demographic and mental health variables on three burnout dimensions: personal, work-related, and client-related burnout. METHODS: A cross-sectional study was performed using an online questionnaire spread via social networks. A snowball technique supported by health care institutions and professional organizations was applied. RESULTS: A total of 2008 subjects completed the survey. Gender, parental status, marriage status, and salary reduction were found to be significant factors for personal burnout. Health problems and direct contact with infected people were significantly associated with more susceptibility to high personal and work-related burnout. Frontline working positions were associated with all three dimensions. Higher levels of stress and depression in HCWs were significantly associated with increased levels of all burnout dimensions. Higher levels of satisfaction with life and resilience were significantly associated with lower levels of all burnout dimensions. CONCLUSIONS: All three burnout dimensions were associated with a specific set of covariates. Consideration of these three dimensions is important when designing future burnout prevention programs for HCWs.