# Greater fatigue is more strongly associated with reduced reward sensitivity in the long-term phase of coronavirus disease (COVID-19) than in the early phase

## TL;DR

Long-term fatigue after COVID-19 is linked to reduced sensitivity to rewards, more so than in the early stages of the disease.

## Contribution

The study reveals that reward sensitivity is more strongly affected by fatigue in the long-term phase of COVID-19 compared to the early phase.

## Key findings

- Participants with long-term post-COVID-19 fatigue showed significantly lower reward sensitivity compared to those in the early phase or with no prior infection.
- Fatigue was more strongly associated with reduced reward sensitivity in the long-term group than in the early phase group.
- Older age, unhealthy lifestyle, and worrying during the early phase of COVID-19 predicted lower reward sensitivity in the long-term group.

## Abstract

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-19 infection. Infections have been shown to change decisions about engaging in effortful and rewarding activities, but it is currently unclear whether fatigue and depressive symptoms are similarly associated with decision making during early and persistent phases after a COVID-19 infection. Here, we investigated whether fatigue and depressive mood are associated with altered weighting of reward and effort in decision making at different timepoints after COVID-19 infection.

We conducted an online cross-sectional study between March 2021 and March 2022, in which 242 participants (18–65 years) with COVID-19 < 4 weeks ago (n = 62), COVID-19 > 12 weeks ago (n = 81), or no prior COVID-19 (n = 90; self-reported) performed an effort-based decision-making task. In this task, participants accepted or rejected offers in which they could exert physical effort (ticking boxes on screen, 5 levels) to gain rewards (money to be gained in a voucher-lottery, 5 levels). State fatigue and depressive mood were measured with the Profile of Mood States (POMS) prior to the task. We used mixed binomial regression analysis to test whether fatigue and depressive mood were related to acceptance rates for reward and effort levels and whether this differed between the groups.

Compared with no COVID-19 and COVID-19 < 4 weeks groups, the COVID-19 > 12 weeks group reported higher state fatigue (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-19 > 12 weeks group, fatigue was more negatively associated with reward sensitivity compared to the COVID-19 < 4 weeks group (Reward∗Fatigue∗Group: OR 0.47 (95 %CI 0.25, 1.13), p = 0.022) and the no COVID-19 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. There were also no group differences for the relationship between depressive mood and effort or reward sensitivity. Higher age, lower BMI, unhealthy lifestyle, and worrying during the early phase of COVID-19 each predicted lower 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).

The finding that fatigue is related to lower reward sensitivity > 12 weeks after COVID-19 suggests potential reward deficits in post-COVID-19 fatigue. Moreover, higher age, unhealthy lifestyle, and worrying during the early phase of COVID-19 are potential risk factors for developing lower reward sensitivity. These findings are in line with previous observations that long-term inflammation induces dysregulations in neural reward processing, which should be investigated in future studies.

•We tested how fatigue and mood relate to decision making after COVID-19 or no COVID.•Fatigue was greater and reward sensitivity smaller >12wk than <4wk post-COVID.•Fatigue was more related to lower reward sensitivity in >12wk than <4wk post-COVID.•Depressive mood >12wk post-COVID was not associated with altered decision making.•Older age, unhealthy lifestyle, and worrying predicted lower reward sensitivity.

We tested how fatigue and mood relate to decision making after COVID-19 or no COVID.

Fatigue was greater and reward sensitivity smaller >12wk than <4wk post-COVID.

Fatigue was more related to lower reward sensitivity in >12wk than <4wk post-COVID.

Depressive mood >12wk post-COVID was not associated with altered decision making.

Older age, unhealthy lifestyle, and worrying predicted lower reward sensitivity.