Defining the preadmission factors that modify risk of acute complications, survival and long-term recovery from COVID-19: prospective, longitudinal, multisite, cohort study based in England.

OBJECTIVES: To understand the pre-admission factors associated with COVID-19 clinical outcome with and without controlling for acute COVID-19 severity score. DESIGN: We ran a prospective, longitudinal, multicentre cohort study. SETTING: Patients were recruited from four hospitals and one community General Practice in England PARTICIPANTS: 425 patients with COVID-19 from the start of the UK pandemic in April 2020 through the first three waves with study completing in 2022. PRIMARY AND SECONDARY OUTCOME MEASURES: Data were collected and analysed to identify demographic factors and preadmission symptoms for hospitalised patients that were associated with COVID-19 disease severity at recruitment, acute clinical course and long-term recovery. Analysis methods included logistic regression, time-to-event analysis, mixed-effect models and K-medoids clustering. RESULTS: The cohort was skewed to patients with severe COVID (60%). Preadmission symptom cluster was associated with risk of thrombosis (OR 2.7 (95% CI 1.6 to 6.1), p=0.021) and renal disease (OR 3.3 (95% CI 1.4 to 8.0), p=0.008). Duration of symptoms less than 1 week was associated with pneumothorax (OR 3.1 (95% CI 1.2 to 8.3), p=0.025). Renal complications were more likely to be seen in the first wave compared with the second wave of the pandemic (OR 3.4 (95% CI 1.5 to 7.5), p=0.003). Using a logistic regression model, survival to discharge was associated with white (vs unknown) ethnicity (OR 6.6 (95% CI 2.8 to 15.2), p<0.0001), lower age (<40 years vs >60 years, OR 4.9 (95% CI 1.2 to 20.0), p=0.027) and absence of comorbidities (OR 2.7 (95% CI 1.2 to 5.9), p=0.016). However, using a survival model, hazard of death was increased for all hospitalised who had duration of symptoms less than 1 week (HR 5.6 (95% CI 1.3 to 24.4), p=0.023) or had comorbidities (HR 33.3 (95% CI 3.1 to 333.3), p=0.0035). Over 80% of patients reported long-term sequelae with neuromuscular and cognitive effects dominating early on and mood disturbance and breathlessness persisting to 12 months. Gender had the strongest association with dyspnoea (OR 99.8 (95% CI 2.4 to 4123.1, p=0.02) and persistent mood disorder (OR 8.3 (95% CI 1.7 to 39.9), p=0.008) and associated with persistent gastrointestinal problems (loose bowels (OR 3.3 (95% CI 1.1 to 10.8), p=0.045), abdominal pain (OR 5.0 (95% CI 1.4 to 18.1), p=0.014), constipation (OR 3.8 (95% CI 1.6 to 9.2), p=0.003)) and cognitive problems (OR 2.3 (95% CI 1.1 to -4.8), p=0.024). CONCLUSIONS: These results support an association between specific demographic factors and early infection symptoms that impact on acute and long-term outcomes of COVID-19 in this cohort after accounting for COVID-19 disease severity at enrolment. Understanding the disease mechanisms that explain these relationships is needed to inform targeted therapeutics to prevent and/or manage these complications.