Evans, Rachel, Leavy, Olivia C, Richardson, Matthew, Elneima, Omer, McAuley, Hamish J C, Shikotra, Aarti, Singapuri, Amisha, Sereno, Marco, Saunders, Ruth, Hart, Nick, Hurst, John R, Raman, Betty, Harrison, Ewen, Wain, Louise V, Brightling, Christopher and Calder, Philip , (2022) Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study. The Lancet Respiratory Medicine. (doi:10.1016/S2213-2600(22)00127-8).
Abstract
Background
There are currently no effective pharmacological or non-pharmacological interventions for Long-COVID. We aimed to describe recovery one year after hospital discharge for COVID-19 and identify factors associated with patient-perceived recovery. 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 post-discharge. Inflammatory protein profiling from plasma at the 6-m visit was performed. 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.
Findings
2,320 participants have been assessed at 6m post-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 (25.6%) and one-year (28.5%). Risk factors for not reporting full recovery at one year were: female sex OR=0.55 (95% CI 0.33-0.90); obesity OR=0.69 (95% CI 0.49-0.97); and IMV OR=0.43 (95% CI 0.21-0.86). Cluster analysis (n=1,636) corroborated the previously reported four groups relating to the severity of physical, mental health and cognitive impairments at six months. Interleukin-6 (IL-6) and other inflammatory mediators of tissue damage and repair, including Trefoil Factor 2 and Transforming Growth Factor Alpha, were elevated at five-months in the ‘very severe’ versus ‘mild’ clusters. Overall, there was a substantial deficit in EQ5D-5L utility index from pre-COVID (0.88 (95% CI 0.74-1.00)), five months (0.74 (95% CI 0.60-0.88)) to one year (0.74 (95% CI 0.59-0.88)), with minimal improvements across all measurements at one year post-discharge in the whole cohort and in 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.
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