One year health outcomes associated with systemic corticosteroids for COVID-19: a longitudinal cohort study (preprint)

BackgroundIn patients with COVID-19 requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) one year after discharge. MethodsAdults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies. HRQoL, assessed by EQ-5D-5L utility index, pre-hospital and one year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias. FindingsIn 1,888 participants included in the primary analysis, 1,149 received corticosteroids. There was no between-group difference in EQ-5D-5L utility index at one year (mean difference 0.004, 95% CI: -0.026 to 0.034, p = 0.77). A similar reduction in EQ-5D-5L was seen at one year between corticosteroid exposed and non-exposed groups (mean (SD) change -0.12 (0.22) vs -0.11 (0.22), p = 0.32). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a larger cohort of 109,318 patients admitted to hospital with COVID-19, EQ-5D-5L utility index at one year remained similar between the two groups. InterpretationSystemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL one year after hospital discharge. Treatments to address this are urgently needed. Take home messageSystemic corticosteroids given for acute COVID-19 do not affect health-related quality of life or other patient reported outcomes, physical and mental health outcomes, and organ function one year after hospital discharge

Cohort Profile: Post-hospitalisation COVID-19 study (PHOSP-COVID) (preprint)

Abstract [bullet] PHOSP-COVID is a national UK multi-centre cohort study of patients who were hospitalised for COVID-19 and subsequently discharged. [bullet] PHOSP-COVID was established to investigate the medium- and long-term sequelae of severe COVID-19 requiring hospitalisation, understand the underlying mechanisms of these sequelae, evaluate the medium- and long-term effects of COVID-19 treatments, and to serve as a platform to enable future studies, including clinical trials. [bullet] Data collected covered a wide range of physical measures, biological samples, and Patient Reported Outcome Measures (PROMs). [bullet] Participants could join the cohort either in Tier 1 only with remote data collection using hospital records, a PROMs app and postal saliva sample for DNA, or in Tier 2 where they were invited to attend two specific research visits for further data collection and biological research sampling. These research visits occurred at five (range 2-7) months and 12 (range 10-14) months post-discharge. Participants could also participate in specific nested studies (Tier 3) at selected sites. [bullet] All participants were asked to consent to further follow-up for 25 years via linkage to their electronic healthcare records and to be re-contacted for further research. [bullet] In total, 7935 participants were recruited from 83 UK sites: 5238 to Tier 1 and 2697 to Tier 2, between August 2020 and March 2022. [bullet] Cohort data are held in a Trusted Research Environment and samples stored in a central biobank. Data and samples can be accessed upon request and subject to approvals.

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a prospective, multicentre study (preprint)

ObjectivesTo describe physical behaviours following hospital admission for COVID-19 including associations with acute illness severity and ongoing symptoms. Methods1077 patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and type 2 diabetes were comparators. ResultsValid accelerometer data from 253 women and 462 men were included. Women engaged in a mean{+/-}SD of 14.9{+/-}14.7 minutes/day of moderate-to-vigorous physical activity (MVPA), with 725.6{+/-}104.9 minutes/day spent inactive and 7.22{+/-}1.08 hours/day asleep. The values for men were 21.0{+/-}22.3 and 755.5{+/-}102.8 minutes/day and 6.94{+/-}1.14 hours/day, respectively. Over 60% of women and men did not have any days containing a 30-minute bout of MVPA. Variability in sleep timing was approximately 2 hours in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer sleep duration, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes. ConclusionsPhysical activity and regulating sleep patterns are potential treatable traits for COVID-19 recovery programmes.

Clinical characteristics with inflammation profiling of Long-COVID and association with one-year recovery following hospitalisation in the UK: a prospective observational study (preprint)

Background There are currently no effective pharmacological or non-pharmacological interventions for Long-COVID. To identify potential therapeutic targets, we focussed on previously described four recovery clusters five months after hospital discharge, their underlying inflammatory profiles and relationship with clinical outcomes at one year. Methods PHOSP-COVID is a prospective longitudinal cohort study, recruiting adults hospitalised with COVID-19 across the UK. Recovery was assessed using patient reported outcomes measures (PROMs), physical performance, and organ function at five-months and one-year after hospital discharge. Hierarchical logistic regression modelling was performed for patient-perceived recovery at one-year. Cluster analysis was performed using clustering large applications (CLARA) k-medoids approach using clinical outcomes at five-months. Inflammatory protein profiling from plasma at the five-month visit was performed. Findings 2320 participants have been assessed at five months after discharge and 807 participants have completed both five-month and one-year visits. Of these, 35.6% were female, mean age 58.7 (SD 12.5) years, and 27.8% received invasive mechanical ventilation (IMV). The proportion of patients reporting full recovery was unchanged between five months 501/165 (25.6%) and one year 232/804 (28.9%). Factors associated with being less likely to report full recovery at one year were: female sex OR 0.68 (95% CI 0.46-0.99), obesity OR 0.50 (95%CI 0.34-0.74) and IMV OR 0.42 (95%CI 0.23-0.76). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate/cognitive, mild relating to the severity of physical, mental health and cognitive impairments at five months in a larger sample. There was elevation of inflammatory mediators of tissue damage and repair in both the very severe and the moderate/cognitive clusters compared to the mild cluster including interleukin-6 which was elevated in both comparisons. Overall, there was a substantial deficit in median (IQR) EQ5D-5L utility index from pre-COVID (retrospective assessment) 0.88 (0.74-1.00), five months 0.74 (0.60-0.88) to one year: 0.74 (0.59-0.88), with minimal improvements across all outcome measures at one-year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 remain substantial one year after discharge across a range of health domains with the minority in our cohort feeling fully recovered. Patient perceived health-related quality of life remains reduced at one year compared to pre-hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.

Obesity, Ethnicity, and Covid-19 Mortality: A population-based cohort study of 12.6 Million Adults in England (preprint)

Abstract Importance: Obesity and ethnicity are well characterised risk factors for severe COVID-19 outcomes, but the differential effects of obesity on COVID-19 outcomes by race/ethnicity has not been examined robustly in the general population. Objective: To investigate the association between body mass index (BMI) and COVID-19 mortality across different ethnic groups. Design, Setting, and Participants: This is a retrospective cohort study using linked national Census, electronic health records and mortality data for English adults aged 40 years or older who were alive at the start of pandemic (24th January 2020). Exposures: BMI obtained from electronic health records. Self-reported ethnicity (white, black, South Asian, other) was the effect-modifying variable. Main Outcomes and Measures: COVID-19 related death identified by ICD-10 codes U07.1 or U07.2 mentioned on the death certificate from 24th January 2020 until December 28th 2020. Results: The analysis included white (n = 11,074,708; mean age 61.9 [13.4] years; 54% women), black (n = 416,542; 56.4 [11.7] years; 57% women), South Asian (621,691; 55.7 [12.4] years; 51% women) and other (n = 478,196; 55.3 [11.6] years; 55% women) ethnicities with linked BMI data. The association between BMI and COVID-19 mortality was stronger in ethnic minority groups. Compared to a BMI of 22.5 kg/m2 in white ethnicities, the adjusted HR for COVID-19 mortality at a BMI of 30 kg/m2 in white, black, South Asian and other ethnicities was 0.95 (95% CI: 0.87-1.03), 1.72 (1.52-1.94), 2.00 (1.78-2.25) and 1.39 (1.21-1.61), respectively. The estimated risk of COVID-19 mortality at a BMI of 40 kg/m2 in white ethnicities (HR = 1.73) was equivalent to the risk observed at a BMI of 30.1 kg/m2, 27.0 kg/m2, and 32.2 kg/m2 in black, South Asian and other ethnic groups, respectively. 5 Conclusions: This population-based study using linked Census and electronic health care records demonstrates that the risk of COVID-19 mortality associated with obesity is greater in ethnic minority groups compared to white populations.

Patterns of Multimorbidity and Risk of Severe SARS-CoV-2 Infection: an observational study in the U.K. (preprint)

Background Pre-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. Methods We 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 or 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. Results Among 360,283 participants, the median age was 68 [range, 48-85] years, most were White (94.5%), and 1,706 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 men. Conclusion The risk of severe SARS-CoV-2 infection is higher in individuals with multimorbidity, indicating the need to target research and resources in people with SARS-CoV-2 infection and multimorbidity.

Perceptions of Risk of Attending Hospital During The COVID-19 Pandemic: A UK Public Opinion Survey (preprint)

Background: To inform clinical and research practice in secondary care in the COVID-19 pandemic, we consulted patients and the public on their feelings of safety, factors affecting feelings of safety, intention to participate in research, attitudes to research and comfort with new ways of working in order to inform secondary care policy on restarting research and some clinical activity. Method: An online survey was used to collect public opinions on attending hospitals. The survey link was circulated via the National Institute for Health Research (NIHR) Public Involvement (PPI) Leads network and social media. Results: 402 people completed the survey. Participant age ranged from 18-85+, with the majority (337 [84%]) aged 35-74. There was a higher number of women (77%) compared to men (23%); and participants were mainly White European (91%) compared to Black, Asian and Minority Ethnic (BAME) (6%), or other (2%).Results for feelings of safety scales show bi-polarity, with few respondents in the middle ground. Implementation of COVID-19 related safety measures such as social distancing, use of personal protective equipment (PPE) and cleaning were strongly supported by most respondents. There was ambivalence around less certain measures such as staff antigen and antibody testing. Respondents were most likely to participate in research related to their own condition, COVID-19 and vaccine, but less likely to participate as healthy volunteers, especially female participants, and those suffering from a pre-existing comorbidity identified with increased risk. There was general agreement that participants are comfortable with new ways of working, such as remote consultation, though women and BAME respondents were less comfortable.Conclusions: Findings raise concerns for health inequalities already impacting some groups during the pandemic. The roles of clinical necessity and personal benefit support the reopening of services in line with clinical necessity. Moderate caution in respect of vaccine research relative to patient-participant research presents a challenge for pending recruitment demands. This area would benefit from qualitative research to explore themes and concerns in more depth and support development and targeting of key messaging.

Perceptions of Risk of Attending Hospital During the COVID-19 Pandemic: A UK Public Opinion Survey (preprint)

Background: To inform clinical and research practice in secondary care in the COVID-19 pandemic we consulted patients and the public on their feelings of safety, factors affecting feelings of safety, intention to participate in research, attitudes to research and comfort with new ways of working in order to inform secondary care policy on restarting research and some clinical activity. Method: An online survey was used to collect public opinions on attending hospitals. The survey link was circulated via the National Institute for Health Research (NIHR) Public Involvement (PPI) Leads network and social media.Results: 402 people completed the survey. Participants age ranged from the 18-85+, with the majority (337 (84%)) aged between 35 to 74 years. There were a higher number of women (77%) compared to men (23%); and were mainly White European (91%) compared to Black, Asian and Minority Ethnic (BAME) (6%), or other (2%).Results for feelings of safety scales show bi-polarity with few respondents in the middle ground. Implementation of COVID-19 related safety measures such as social distancing, use of personal protective equipment (PPE) and cleaning were strongly supported by most respondents. There was ambivalence around less certain measures such as staff antigen and antibody testing. Respondents were most likely to participate in research related to their own condition, COVID-19 and vaccine, but less likely to participate as healthy volunteers, especially if suffering from a pre-existing comorbidity identified with increased risk or were female. There was general agreement that participants are comfortable with new ways of working, such as remote consultation, though women and BAME respondents were less comfortable.Conclusions: Findings raise concerns for health inequalities already impacting some groups in the pandemic. The role of clinical necessity and personal benefit support the reopening of services in line with clinical necessity. Moderate caution in respect of vaccine research relative to patient-participant research presents a challenge for pending recruitment demands, and would benefit from qualitative research to explore themes and concerns in more depth and support development and targeting of key messaging.

Obesity, walking pace and risk of severe COVID-19: Analysis of UK Biobank (preprint)

Unstructured abstractObesity is an emerging risk factor for coronavirus disease-2019 (COVID-19). Simple measures of physical fitness, such as self-reported walking pace, could also be important risk factors, but have not been well documented. This analysis includes 414,201 UK Biobank participants with complete covariate and linked COVID-19 data. We analysed the risk of severe (in-hospital) COVID-19 across categories of obesity status and walking pace. As of June 20th 2020 there were 972 cases of severe COVID-19 that had occurred within the cohort. Compared to normal weight individuals, the adjusted odds ratio (OR) for severe COVID-9 in those with obesity was 1.49 (1.24, 1.78). Compared to those with a brisk walking pace, the OR in slow walkers was 1.84 (1.49, 2.27). Slow walkers had the highest risk of severe COVID-19 regardless of obesity status. For example, compared to normal weight brisk walkers, the odds of severe COVID-19 in obese brisk walkers was 1.39 (0.99, 1.98), whereas the odds in normal weight slow walkers was 2.48 (1.56, 3.93). Self-reported walking pace, a simple measure of functional fitness, appears to be a risk factor for severe COVID-19 that is independent of obesity. This may help inform simple pragmatic public health risk stratification and preventative strategies.