Vaccine effectiveness for prevention of covid-19 related hospital admission during pregnancy in England during the alpha and delta variant dominant periods of the SARS-CoV-2 pandemic: population based cohort study

OBJECTIVE: To estimate vaccine effectiveness for preventing covid-19 related hospital admission in individuals first infected with the SARS-CoV-2 virus during pregnancy compared with those of reproductive age who were not pregnant when first infected with the virus. DESIGN: Population based cohort study. SETTING: Office for National Statistics Public Health Data Asset linked dataset, providing national linked census and administrative data in England, 8 December 2020 to 31 August 2021. PARTICIPANTS: 815 477 females aged 18-45 years (mean age 30.4 years) who had documented evidence of a first SARS-CoV-2 infection in the NHS Test and Trace or Hospital Episode Statistics data. MAIN OUTCOME MEASURES: Hospital admission where covid-19 was recorded as the primary diagnosis. Cox proportional hazards models, adjusted for calendar time of infection, sociodemographic factors, and pre-existing health conditions related to uptake of the covid-19 vaccine and risk of severe covid-19 outcomes, were used to estimate vaccine effectiveness as the complement of the hazard ratio for hospital admission for covid-19. RESULTS: Compared with pregnant individuals who were not vaccinated, the adjusted rate of hospital admission for covid-19 was 77% (95% confidence interval 70% to 82%) lower for pregnant individuals who had received one dose and 83% (76% to 89%) lower for those who had received two doses of vaccine. These estimates were similar to those found in the non-pregnant group: 79% (77% to 81%) for one dose and 83% (82% to 85%) for two doses of vaccine. Among those who were vaccinated >90 days before infection, having two doses of vaccine was associated with a greater reduction in risk than one dose. CONCLUSIONS: Covid-19 vaccination was associated with reduced rates of hospital admission in pregnant individuals infected with the SARS-CoV-2 virus, and the reduction in risk was similar to that in non-pregnant individuals. Waning of vaccine effectiveness occurred more quickly after one than after two doses of vaccine

Vaccine effectiveness for prevention of covid-19 related hospital admission during pregnancy in England during the alpha and delta variant dominant periods of the SARS-CoV-2 pandemic:population based cohort study

Objective To estimate vaccine effectiveness for preventing covid-19 related hospital admission in individuals first infected with the SARS-CoV-2 virus during pregnancy compared with those of reproductive age who were not pregnant when first infected with the virus. Design Population based cohort study. Setting Office for National Statistics Public Health Data Asset linked dataset, providing national linked census and administrative data in England, 8 December 2020 to 31 August 2021. Participants 815 477 females aged 18-45 years (mean age 30.4 years) who had documented evidence of a first SARS-CoV-2 infection in the NHS Test and Trace or Hospital Episode Statistics data. Main outcome measures Hospital admission where covid-19 was recorded as the primary diagnosis. Cox proportional hazards models, adjusted for calendar time of infection, sociodemographic factors, and pre-existing health conditions related to uptake of the covid-19 vaccine and risk of severe covid-19 outcomes, were used to estimate vaccine effectiveness as the complement of the hazard ratio for hospital admission for covid-19. Results Compared with pregnant individuals who were not vaccinated, the adjusted rate of hospital admission for covid-19 was 77% (95% confidence interval 70% to 82%) lower for pregnant individuals who had received one dose and 83% (76% to 89%) lower for those who had received two doses of vaccine. These estimates were similar to those found in the non-pregnant group: 79% (77% to 81%) for one dose and 83% (82% to 85%) for two doses of vaccine. Among those who were vaccinated >90 days before infection, having two doses of vaccine was associated with a greater reduction in risk than one dose. Conclusions Covid-19 vaccination was associated with reduced rates of hospital admission in pregnant individuals infected with the SARS-CoV-2 virus, and the reduction in risk was similar to that in non-pregnant individuals. Waning of vaccine effectiveness occurred more quickly after one than after two doses of vaccine

Patterns of multimorbidity and risk of severe SARS-CoV-2 infection: an observational study in the U.K.

Funder: National Institute for Health Research; Grant(s): Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014), NIHR Applied Research Collaboration East Midlands (ARC EM), NIHR Leicester Biomedical Research CentreBackgroundPre-existing comorbidities have been linked to SARS-CoV-2 infection but evidence is sparse on the importance and pattern of multimorbidity (2 or more conditions) and severity of infection indicated by hospitalisation or mortality. We aimed to use a multimorbidity index developed specifically for COVID-19 to investigate the association between multimorbidity and risk of severe SARS-CoV-2 infection.MethodsWe used data from the UK Biobank linked to laboratory confirmed test results for SARS-CoV-2 infection and mortality data from Public Health England between March 16 and July 26, 2020. By reviewing the current literature on COVID-19 we derived a multimorbidity index including: (1) angina; (2) asthma; (3) atrial fibrillation; (4) cancer; (5) chronic kidney disease; (6) chronic obstructive pulmonary disease; (7) diabetes mellitus; (8) heart failure; (9) hypertension; (10) myocardial infarction; (11) peripheral vascular disease; (12) stroke. Adjusted logistic regression models were used to assess the association between multimorbidity and risk of severe SARS-CoV-2 infection (hospitalisation/death). Potential effect modifiers of the association were assessed: age, sex, ethnicity, deprivation, smoking status, body mass index, air pollution, 25-hydroxyvitamin D, cardiorespiratory fitness, high sensitivity C-reactive protein.ResultsAmong 360,283 participants, the median age was 68 [range 48-85] years, most were White (94.5%), and 1706 had severe SARS-CoV-2 infection. The prevalence of multimorbidity was more than double in those with severe SARS-CoV-2 infection (25%) compared to those without (11%), and clusters of several multimorbidities were more common in those with severe SARS-CoV-2 infection. The most common clusters with severe SARS-CoV-2 infection were stroke with hypertension (79% of those with stroke had hypertension); diabetes and hypertension (72%); and chronic kidney disease and hypertension (68%). Multimorbidity was independently associated with a greater risk of severe SARS-CoV-2 infection (adjusted odds ratio 1.91 [95% confidence interval 1.70, 2.15] compared to no multimorbidity). The risk remained consistent across potential effect modifiers, except for greater risk among older age. The highest risk of severe infection was strongly evidenced in those with CKD and diabetes (4.93 [95% CI 3.36, 7.22]).ConclusionThe multimorbidity index may help identify individuals at higher risk for severe COVID-19 outcomes and provide guidance for tailoring effective treatment

Living with early-stage dementia: a review of qualitative studies

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Obesity, chronic disease, age, and in-hospital mortality in patients with covid-19: analysis of ISARIC clinical characterisation protocol UK cohort.

BACKGROUND: Although age, obesity and pre-existing chronic diseases are established risk factors for COVID-19 outcomes, their interactions have not been well researched. METHODS: We used data from the Clinical Characterisation Protocol UK (CCP-UK) for Severe Emerging Infection developed by the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC). Patients admitted to hospital with COVID-19 from 6th February to 12th October 2020 were included where there was a coded outcome following hospital admission. Obesity was determined by an assessment from a clinician and chronic disease by medical records. Chronic diseases included: chronic cardiac disease, hypertension, chronic kidney disease, chronic pulmonary disease, diabetes and cancer. Mutually exclusive categories of obesity, with or without chronic disease, were created. Associations with in-hospital mortality were examined across sex and age categories. RESULTS: The analysis included 27,624 women with 6407 (23.2%) in-hospital deaths and 35,065 men with 10,001 (28.5%) in-hospital deaths. The prevalence of chronic disease in women and men was 66.3 and 68.5%, respectively, while that of obesity was 12.9 and 11.1%, respectively. Association of obesity and chronic disease status varied by age (p < 0.001). Under 50 years of age, obesity and chronic disease were associated with in-hospital mortality within 28 days of admission in a dose-response manner, such that patients with both obesity and chronic disease had the highest risk with a hazard ratio (HR) of in-hospital mortality of 2.99 (95% CI: 2.12, 4.21) in men and 2.16 (1.42, 3.26) in women compared to patients without obesity or chronic disease. Between the ages of 50-69 years, obesity and chronic disease remained associated with in-hospital COVID-19 mortality, but survival in those with obesity was similar to those with and without prevalent chronic disease. Beyond the age of 70 years in men and 80 years in women there was no meaningful difference between those with and without obesity and/or chronic disease. CONCLUSION: Obesity and chronic disease are important risk factors for in-hospital mortality in younger age groups, with the combination of chronic disease and obesity being particularly important in those under 50 years of age. These findings have implications for targeted public health interventions, vaccination strategies and in-hospital clinical decision making

Obesity, Ethnicity, and Risk of Critical Care, Mechanical Ventilation, and Mortality in Patients Admitted to Hospital with COVID-19: Analysis of the ISARIC CCP-UK Cohort.

OBJECTIVE: The aim of this study was to investigate the association of obesity with in-hospital coronavirus disease 2019 (COVID-19) outcomes in different ethnic groups. METHODS: Patients admitted to hospital with COVID-19 in the United Kingdom through the Clinical Characterisation Protocol UK (CCP-UK) developed by the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) were included from February 6 to October 12, 2020. Ethnicity was classified as White, South Asian, Black, and other minority ethnic groups. Outcomes were admission to critical care, mechanical ventilation, and in-hospital mortality, adjusted for age, sex, and chronic diseases. RESULTS: Of the participants included, 54,254 (age = 76 years; 45.0% women) were White, 3,728 (57 years; 41.1% women) were South Asian, 2,523 (58 years; 44.9% women) were Black, and 5,427 (61 years; 40.8% women) were other ethnicities. Obesity was associated with all outcomes in all ethnic groups, with associations strongest for black ethnicities. When stratified by ethnicity and obesity status, the odds ratios for admission to critical care, mechanical ventilation, and mortality in black ethnicities with obesity were 3.91 (3.13-4.88), 5.03 (3.94-6.63), and 1.93 (1.49-2.51), respectively, compared with White ethnicities without obesity. CONCLUSIONS: Obesity was associated with an elevated risk of in-hospital COVID-19 outcomes in all ethnic groups, with associations strongest in Black ethnicities

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19

OBJECTIVE: To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications. RESEARCH DESIGN AND METHODS: In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors. RESULTS: Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication. CONCLUSIONS: Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19

ObjectiveTo investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications.Research design and methodsIn this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors.ResultsCardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age ConclusionsIncreased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes

Association between household size and COVID-19: A UK Biobank observational study.

OBJECTIVE: To assess the association between household size and risk of non-severe or severe COVID-19. DESIGN: A longitudinal observational study. SETTING: This study utilised UK Biobank linked to national SARS-CoV-2 laboratory test data. PARTICIPANTS: 401,910 individuals with available data on household size in UK Biobank. MAIN OUTCOME MEASURES: Household size was categorised as single occupancy, two-person households and households of three or more. Severe COVID-19 was defined as a positive SARS-CoV-2 test on hospital admission or death with COVID-19 recorded as the underlying cause; and non-severe COVID-19 as a positive test from a community setting. Logistic regression models were fitted to assess associations, adjusting for potential confounders. RESULTS: Of 401,910 individuals, 3612 (1%) were identified as having suffered from a severe COVID-19 infection and 11,264 (2.8%) from a non-severe infection, between 16 March 2020 and 16 March 2021. Overall, the odds of severe COVID-19 was significantly higher among individuals living alone (adjusted odds ratio: 1.24 [95% confidence interval: 1.14 to 1.36], or living in a household of three or more individuals (adjusted odds ratio: 1.28 [1.17 to 1.39], when compared to individuals living in a household of two. For non-severe COVID-19 infection, individuals living in a single-occupancy household had lower odds compared to those living in a household of two (adjusted odds ratio: 0.88 [0.82 to 0.93]. CONCLUSIONS: Odds of severe or non-severe COVID-19 infection were associated with household size. Increasing understanding of why certain households are more at risk is important for limiting spread of the infection

Secreted production of an elastin-like polypeptide by Pichia pastoris

Elastin-like polypeptides (ELPs) are biocompatible designer polypeptides with inverse temperature transition behavior in solution. They have a wide variety of possible applications and a potential medical importance. Currently, production of ELPs is done at lab scale in Escherichia coli shake flask cultures. With a view to future large scale production, we demonstrate secreted production of ELPs in methanol-induced fed-batch cultures of Pichia pastoris and purification directly from the culture medium. The production of ELPs by P. pastoris proved to be pH dependent within the experimental pH range of pH 3 to 7, as an increasing yield was found in cultures grown at higher pH. Because ELP produced at pH 7 was partly degraded, a pH optimum for production of ELP was found at pH 6 with a yield of 255 mg of purified intact ELP per liter of cell-free medium