COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

A supercritical carbon dioxide route to protein loaded microparticles for pulmonary drug delivery

In recent years, advances in biotechnology and molecular biology have produced many new protein and peptide based drugs. The pulmonary route potentially offers an efficient and convenient method of systemic drug delivery. One approach is to encapsulate the proteins or peptides into microparticles for more efficient administration. However, the sensitive nature of these molecules can result in their denaturation during traditional microparticle production techniques. The production of microparticles using supercritical carbon dioxide (SCC02) provides an attractive alternative, particularly the Particles from Gas Saturated Solutions (PGSS) method which uses scC02 to liquefy polymers and other excipients at physiological temperatures and in the absence of solvents. The overall aim of this work was to investigate the production of protein loaded microparticles with the optimum characteristics for pulmonary drug delivery using the PGSS technique. Preliminary investigations into suitable materials for particle production highlighted three classes of potentially useful materials; fatty acids, poly(ethylene glycol) (PEG) and PEG stearates. These materials showed a considerable depression in melting temperature in the presence of scC02, allowing microparticles of these materials to be prepared using a high pressure particle rig. The molecular weight of PEG and type of fatty acid used were discovered to have an effect on the size of the microparticles. The properties of PEG stearate microparticles were studied and found to be different from those made from corresponding mixtures of PEG and stearic acid. 11 Abstract Insulin was introduced as a model protein to microparticies consisting of myristic acid with PEG or PEG stearate. It was discovered that varying the concentration of myristic acid had an effect on the particie characteristics. The encapsulation efficiency of insulin was high and the release from the microparticies was complete within the first 10 minutes of the study. In vitro aerosolisation studies using a Next Generation Impactor were carried out to assess the aerodynamic properties of the insulin loaded microparticies. The final section of this thesis deals with extending the time over which this insulin was released from the microparticies prepared using the PGSS process. Poly(iactic acid) (PLA), a biodegradable polymer, was added to formulations containing myristic acid and PEG stearate. In order to facilitate the investigation, a mixture design and statistical software package were used. The addition of PLA was found to notably reduce the initial burst release of insulin from the microparticies.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A supercritical carbon dioxide route to protein loaded microparticles for pulmonary drug delivery

In recent years, advances in biotechnology and molecular biology have produced many new protein and peptide based drugs. The pulmonary route potentially offers an efficient and convenient method of systemic drug delivery. One approach is to encapsulate the proteins or peptides into microparticles for more efficient administration. However, the sensitive nature of these molecules can result in their denaturation during traditional microparticle production techniques. The production of microparticles using supercritical carbon dioxide (SCC02) provides an attractive alternative, particularly the Particles from Gas Saturated Solutions (PGSS) method which uses scC02 to liquefy polymers and other excipients at physiological temperatures and in the absence of solvents. The overall aim of this work was to investigate the production of protein loaded microparticles with the optimum characteristics for pulmonary drug delivery using the PGSS technique. Preliminary investigations into suitable materials for particle production highlighted three classes of potentially useful materials; fatty acids, poly(ethylene glycol) (PEG) and PEG stearates. These materials showed a considerable depression in melting temperature in the presence of scC02, allowing microparticles of these materials to be prepared using a high pressure particle rig. The molecular weight of PEG and type of fatty acid used were discovered to have an effect on the size of the microparticles. The properties of PEG stearate microparticles were studied and found to be different from those made from corresponding mixtures of PEG and stearic acid. 11 Abstract Insulin was introduced as a model protein to microparticies consisting of myristic acid with PEG or PEG stearate. It was discovered that varying the concentration of myristic acid had an effect on the particie characteristics. The encapsulation efficiency of insulin was high and the release from the microparticies was complete within the first 10 minutes of the study. In vitro aerosolisation studies using a Next Generation Impactor were carried out to assess the aerodynamic properties of the insulin loaded microparticies. The final section of this thesis deals with extending the time over which this insulin was released from the microparticies prepared using the PGSS process. Poly(iactic acid) (PLA), a biodegradable polymer, was added to formulations containing myristic acid and PEG stearate. In order to facilitate the investigation, a mixture design and statistical software package were used. The addition of PLA was found to notably reduce the initial burst release of insulin from the microparticies.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Swellable, water- and acid-tolerant polymer sponges for chemoselective carbon dioxide capture

To impact carbon emissions, new materials for carbon capture must be inexpensive, robust, and able to adsorb CO2 specifically from a mixture of other gases. In particular, materials must be tolerant to the water vapor and to the acidic impurities that are present in gas streams produced by using fossil fuels to generate electricity. We show that a porous organic polymer has excellent CO2 capacity and high CO2 selectivity under conditions relevant to precombustion CO2 capture. Unlike polar adsorbents, such as zeolite 13x and the metal–organic framework, HKUST-1, the CO2 adsorption capacity for the hydrophobic polymer is hardly affected by the adsorption of water vapor. The polymer is even stable to boiling in concentrated acid for extended periods, a property that is matched by few microporous adsorbents. The polymer adsorbs CO2 in a different way from rigid materials by physical swelling, much as a sponge adsorbs water. This gives rise to a higher CO2 capacities and much better CO2 selectivity than for other water-tolerant, nonswellable frameworks, such as activated carbon and ZIF-8. The polymer has superior function as a selective gas adsorbent, even though its constituent monomers are very simple organic feedstocks, as would be required for materials preparation on the large industrial scales required for carbon capture

Swellable, Water- and Acid-Tolerant Polymer Sponges for Chemoselective Carbon Dioxide Capture

To impact carbon emissions, new materials for carbon capture must be inexpensive, robust, and able to adsorb CO₂ specifically from a mixture of other gases. In particular, materials must be tolerant to the water vapor and to the acidic impurities that are present in gas streams produced by using fossil fuels to generate electricity. We show that a porous organic polymer has excellent CO₂ capacity and high CO₂ selectivity under conditions relevant to precombustion CO₂ capture. Unlike polar adsorbents, such as zeolite 13x and the metal–organic framework, HKUST-1, the CO₂ adsorption capacity for the hydrophobic polymer is hardly affected by the adsorption of water vapor. The polymer is even stable to boiling in concentrated acid for extended periods, a property that is matched by few microporous adsorbents. The polymer adsorbs CO₂ in a different way from rigid materials by physical swelling, much as a sponge adsorbs water. This gives rise to a higher CO₂ capacities and much better CO₂ selectivity than for other water-tolerant, nonswellable frameworks, such as activated carbon and ZIF-8. The polymer has superior function as a selective gas adsorbent, even though its constituent monomers are very simple organic feedstocks, as would be required for materials preparation on the large industrial scales required for carbon capture