ABSTRACT
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
Subject(s)
COVID-19ABSTRACT
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.
Subject(s)
COVID-19ABSTRACT
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.
Subject(s)
Obesity , COVID-19 , Inflammation , Cognition DisordersABSTRACT
BackgroundThe impact of COVID-19 varies markedly, not only between individual patients but also between different populations. We hypothesised that differences in human leukocyte antigen (HLA) genes might influence this variation. MethodsUsing next generation sequencing, we analysed the class I and class II classical HLA genes of 147 white British patients with variable clinical outcomes. 49 of these patients were admitted to hospital with severe COVID infection. They had no significant pre-existing comorbidities. We compared the results to those obtained from a group of 69 asymptomatic hospital workers who evidence of COVID exposure based on blood antibody testing. Allelic frequencies in both the severe and asymptomatic groups were compared to local and national healthy controls with adjustments made for age and sex. With the inclusion of hospital staff who had reported localised symptoms only (limited to loss of smell/taste, n=13) or systemic symptoms not requiring hospital treatment (n=16), we carried out ordinal logistic regression modelling to determine the relative influence of age, BMI, sex and the presence of specific HLA genes on symptomatology. FindingsWe found a significant difference in the allelic frequency of HLA-DRB1*04:01 in the severe patient compared to the asymptomatic staff group (5.1% versus 16.7%, p=0.003 after adjustment for age and sex). There was a significantly lower frequency of the haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 in the asymptomatic group compared to the background population (p=0.007). Ordinal logistic regression modelling confirmed the significant influence of DRB1*04:01 on the clinical severity of COVID-19 observed in the cohorts. InterpretationThis study provides evidence that patient age, sex, BMI and HLA genotype interact to determine the clinical outcome of COVID-19 infection. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSHLA genes are implicated in host resistance or susceptibility to a range of pathogens. No studies thus far have compared HLA allele frequencies in patients requiring hospital admission following COVID-19 exposure to a group of asymptomatic individuals. Added value of this studyThe results indicate that the presence of HLA-DRB1*04:01 might confer protection from the development of respiratory failure following exposure to COVID. Individuals remaining asymptomatic following exposure to COVID are less likely to carry the haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 compared to the background population. This may indicate a host defence pathway not primarily dependent on an IgG response for clearance of infection. These findings conflict with larger genome wide association studies which compared HLA allelic frequencies of severely unwell patients with the background population. Implications of all the available evidenceThe findings could have implications for targeted vaccination regimes as well as helping assess the impact of social restrictions on mortality rates in different populations.