Fatigue >12 weeks after coronavirus disease (COVID) is associated with reduced reward sensitivity during effort-based decision making

Background Fatigue and depressive mood is inherent to acute disease, but a substantial group of people report persisting disabling fatigue and depressive symptoms long after a COVID infection. Acute infections have shown to change decisions to engage in effortful and rewarding activities, but it is currently unclear whether fatigue and depressive symptoms similarly affect decision making during acute and persistent phases of a COVID infection. Here, we investigated whether fatigue and depressive mood are associated with altered weighting of effort and reward in decision-making during different timepoints after COVID infection. Methods We conducted an online cross-sectional study between March 2021 and March 2022. 242 Participants (18-65 years) with COVID <4 weeks ago (n=62), COVID >12 weeks ago (n=81), or no prior COVID (self-reported) (n=90) performed an effort-based decision-making task, in which they decided whether they wanted to exert physical effort (ticking boxes on screen, 5 levels) for reward (money to be gained in a voucher-lottery, 5 levels). State fatigue and depressive mood was measured by the Profile of Mood States (POMS) prior to the task. We used multilevel binomial regression analysis to test whether fatigue and depressive mood were related to acceptance rates for effort and reward levels and whether this differed between the groups. Results Compared with no COVID and COVID <4 weeks groups, the COVID >12 weeks group reported higher state fatigue scores (mean±SD: 20±7 vs. 14±7 and 12±6 POMS-score, respectively; both p<0.001) and was less sensitive to rewards (Reward*Group: OR: 0.35 (95%CI 0.20, 0.62), p<0.001 and OR: 0.38 (95%CI 0.20, 0.72), p=0.003). In the COVID >12 weeks group, fatigue was more negatively associated with reward sensitivity compared with the COVID <4 weeks group (Reward*Fatigue*Group: OR 0.47 (95%CI 0.25, 1.13), p=0.022) and the no COVID group (Reward*Fatigue*Group: OR 0.48 (95%CI 4.01, 0.92), p=0.029). No group differences were observed for the relationship between fatigue and effort sensitivity. No group differences were observed for the relationship between depressive mood and effort or reward sensitivity. Higher age, lower BMI, unhealthy lifestyle, and worrying during the acute phase of COVID each predicted decreased reward sensitivity in the >12 weeks group (Age*Reward: OR 0.30 (95%CI 0.19, 0.48), p<0.001; BMI*Reward: OR 1.43 (95%CI 1.01, 2.00), p=0.047); Lifestyle*Reward: OR 1.50 (95%CI 1.06, 2.14), p=0.022; Worrying*Reward: OR 0.59 (95%CI 0.38, 0.94), p=0.025, respectively). Conclusion The finding that fatigue is related to lower reward sensitivity >12 weeks after COVID, suggesting potential reward deficits in post-covid fatigue. These findings are in line with previous observations that long-term inflammation can induce dysregulations in neural reward processing, which should be further investigated in future studies. Highlights We tested if fatigue and mood were related to altered decision making post-COVID Participants post-COVID >12wks ago were more fatigued and less reward sensitive Post-COVID-related fatigue was associated with reduced reward sensitivity Post-COVID-related depressive mood was not associated with altered decision making Higher age, unhealthy lifestyle, and worrying predicted reward deficits