ABSTRACT
The novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China in late 2019 and has now caused a global pandemic. The disease caused by SARS-CoV-2 is known as COVID-19. To date, few treatments for COVID-19 have proven effective, and the current standard of care is primarily supportive. As a result, novel therapeutic strategies are in high demand. Viral entry into target cells is frequently sensitive to cell membrane lipid composition and membrane organization. Evidence suggests that cell entry of SARS-CoV-2 is most efficient when the target cell plasma membrane is replete with cholesterol; and recent data implicate cholesterol flux through the high-affinity receptor for cholesterol-rich high-density lipoprotein (HDL), called scavenger receptor type B-1 (SR-B1), as critical for SARS-CoV-2 entry. Here, we demonstrate that a cholesterol-poor synthetic biologic high-density lipoprotein (HDL NP) targets SR-B1 and inhibits cell entry of a SARS-CoV-2 spike protein pseudovirus. Human cells expressing SR-B1 are susceptible to SARS-CoV-2 infection, and viral entry can be inhibited by 50-80% using HDL NPs in an SR-B1-dependent manner. These results indicate that HDL NP targeting of SR-B1 is a powerful potential therapy to combat COVID-19 and other viral diseases.
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
Background: COVID-19 can result in a severe viral pneumonia, with high reported mortality rates in patients requiring mechanical ventilation. There is controversy as to whether established therapeutic approaches to acute respiratory distress syndrome are optimal in this condition, and numerous novel therapies have been used, often outside the context of randomised trials. In addition, longer term quality of life outcomes associated with COVID-19 are as yet unknown. The aim of this case series is to describe demographic, physiological and outcome data of patients with COVID-19 admitted to our intensive care units who were treated according to evidence-based guidelines for acute respiratory distress syndrome.Methods: We retrospectively reviewed the records of all patients admitted to intensive care units in our institution with COVID-19 between March and June, 2020. Physiological and laboratory data were recorded at baseline and daily until intensive care discharge or death. Quality of life was assessed at a virtual post-intensive care follow-up clinic around 10 weeks after ICU discharge.Results: 45 patients with COVID-19 were included, 37 (82.2%) of whom were male, with a mean age of 55 years. 42 (93.3%) of this cohort met criteria for acute respiratory distress syndrome at time of admission. Clinical management was consistent with evidence based institutional guidelines introduced for acute respiratory distress syndrome. Median length of intensive care stay was 14 days. The intensive care mortality rate was 8.9%. Functional and psychological morbidity post intensive care was significant: 45.2% of respondents had at least moderate impairment of mobility and 35.5% described at least moderate symptoms of anxiety or depression at the time of follow up.Conclusions : This case series demonstrates low mortality in a cohort of patients treated according to an established evidence-based approach for acute respiratory distress syndrome. However, COVID-19 survivors have a marked functional and psychological morbidity impacting quality of life following ICU admission. The therapeutic goal in the future will be to achieve similar survival outcomes while minimizing the significant morbidity associated with COVID-19 related critical care admission.