Chapter 5 140 compared to the reference value. Changes in fatigue severity following illness onset were compared between baseline and month 6 and between month 6 and month 12 using a Wald Χ2 test obtained from a model that included age, sex and clinical severity. Persistent severe fatigue was modelled using logistic regression. Multivariable model construction was performed as described above. Adjusted odds ratios (aOR) and their 95%CIs are presented. Two sensitivity analyses were performed. Firstly, we restricted our analyses to prospectively-enrolled participants. Secondly, we redefined the outcome as having chronic fatigue (i.e. fatigue present within the first month of illness and persisting up to 6 months after illness onset). Two-sided P-values <0.05 were considered statistically significant. Statistical analyses were performed using Stata (v.15.1, College Station, TX, USA). RESULTS Study population Participant flow is described in Supplementary Figure S1. By 1 August 2021, 350 participants had been enrolled. Forty-seven participants did not complete a fatigue questionnaire. Consequently 303 participants were included in our analyses (Table 1). None of the participants had been vaccinated for COVID-19 prior to enrolment. There were no statistically significant differences in socio-demographic and clinical characteristics between participants who were excluded versus included in our analyses (Supplementary Table S1a). The proportion of missing surveys during follow-up are displayed in Supplementary Figure S2. Between those who were later lost to follow-up and those who remained in the study, the sex (50% male versus 58% [p=0.330]), number of comorbidities (p=0.100), clinical severity (p=0.415), and proportion of participants reporting severe fatigue in their first completed survey (65% versus 50% [p=0.081], respectively) did not differ. However, participants who were lost to follow-up (LTFU) were on average 8 years younger than those who remained in active follow-up (β=-7.96, p=0.003).
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