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

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 501/1965 (25·5%) 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.