Prevalence of olfactory dysfunction and quality of life in hospitalised patients 1 year after SARS-CoV-2 infection: a cohort study.

OBJECTIVES: To determine the long-term prevalence of olfactory and/or gustatory dysfunction (OD±GD), associated risk factors and impact on quality of life (QoL) in previously hospitalised patients with COVID-19 1 year after infection. DESIGN: A single-centre cohort study. SETTING: Patients admitted at a large central London hospital with COVID-19 infection between 10 February 2020 and 22 May 2020. PARTICIPANTS: 150 adult subjects with previously confirmed SARS-CoV-2 infection were recruited between 10 December 2020 and 29 January 2021. Participants were predominantly male (102/150, 68.0%); mean age 58.0±15.9 years and 41.2% (56/136) were of black, Asian and minority ethnic backgrounds. MAIN OUTCOME MEASURES: EQ-5D-5L values and Sino-Nasal Outcome Test-22 (SNOT-22) scores. RESULTS: Long-term prevalence of OD±GD was 12.8% (19/149) at median time of 264.5 days following SARS-CoV-2 infection onset. Patients with OD±GD had a significantly higher median total SNOT-22 score (46.1; Q1-Q3: 23.0-60.0; 95% CI 23.0 to 60.0) compared with those without (16.0; Q1-Q3: 5.0-30.5; 95% CI 12.0 to 18.0) (p=0.0002), reflecting poorer QoL, particularly psychological well-being (p=0.0004), which was not alleviated with time (p=0.4977). Median EQ-5D-5L value was not significantly different between patients with OD±GD (0.70; Q1-Q3: 0.38-0.83; 95% CI 0.38 to 0.83) and those without (0.83; Q1-Q3: 0.61-0.94; 95% CI 0.75 to 0.89) (p=0.0627). Age, sex, ethnicity, smoking status, highest C reactive protein value, intubation and ventilation, and oxygen supplementation were not found to influence OD±GD (p>0.05). CONCLUSIONS: 12.8% of previously hospitalised patients with COVID-19 in London still report persistent problems with smell or taste up to a year after infection, impacting their QoL. Increased holistic support including psychological therapy and olfactory rehabilitation for affected patients may help to reduce long-term morbidity.

Low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in db/db mice.

The aim of this study was to determine whether low dose doxycycline as an anti-inflammatory agent could improve glucose metabolism in diabetic animals. Therefore, doxycycline was supplemented in drinking water to 6-week-old male db/db mice for 10 weeks. Doxycycline reduced perirenal/epididymal fat, Lee's index, and liver cholesterol. Blood HDL-cholesterol increased, but total cholesterol and aspartate transaminase decreased. Glucose and insulin tolerances were improved, accompanying with reduced fasting blood glucose, insulin, HOMA-IR and advanced glycation end products. Islet number, ß-cell percentage and mass increased, while islet size decreased. Consistently, less apoptosis but more ß-cell proliferation were found in islets of treated mice. Freshly isolated islets from treated mice showed higher insulin content and enhanced glucose stimulated insulin secretion (GSIS). In addition, purified islets of Balb/c mice showed increased GSIS after cultivation in vitro with doxycycline, but not with chloramphenicol and levofloxacin. Inflammation markers, including lipopolysaccharides (LPS) and C-reactive protein (CRP) in serum as well as CD68-positive cells in treated islets, decreased significantly. Finally, LPS stimulated the production of inflammatory factors but inhibited GSIS of MIN6 cells; however, the effects were completely reversed by doxycycline. The results support further study of possible long-term usage of sub-antimicrobial doxycycline in diabetic patients.

Incorporation of Viral Glycoprotein VSV-G Improves the Delivery of DNA by Erythrocyte Ghost into Cells Refractory to Conventional Transfection.

The objective of this study was to formulate a novel gene delivery system based on the erythrocyte ghost (EG) integrated with fusogenic viral glycoprotein vesicular stomatitis virus glycoprotein G (VSV-G). VSV-G proteins were harvested as condition medium of Ad293 cells carrying a VSV-G transgene and then incorporated into EG. Plasmid DNA was condensed by various transfection reagents. A luciferase expression construct (pGL3-control) and a DsRed expression cassette (pCMV-DsRed) were used to evaluate the delivery efficiency of DNA/EG/VSV-G complexes. VSV-G proteins could be incorporated into EG in static incubation under acidic conditions as evidenced by the Western blot analysis. Condensed plasmid DNA was bound mostly to the outer surface of EG, which could be detected by electromicroscopy and measured by electrophoresis. EG/VSV-G complexes stimulated the delivery of pGL3-control into Ad293 cells significantly with the luciferase activity increased about 4-fold as compared to that of the control. The delivery of pCMV-DsRed was also enhanced with the percentage of DsRed-positive Ad293 cells increased from 55 % to about 80 %. Moreover, the transfection efficiency in 3T3, HeLa, INS-1, and bone marrow stem cell (BMSC) cells increased about 2-3-fold. Finally, confocal microscopy analysis showed that incorporation of VSV-G significantly enhanced the endocytosis of EG into target cells. In the present study, a novel type of non-viral DNA delivery vehicle consisting of EG and fusogenic VSV-G proteins was formulated, which showed superior transfection efficiency even in cells resistant to classical transfection.