Purpose Survivors of severe COVID-19 commonly experience post-intensive care syndrome (PICS), which includes depression and fatigue. Fatigue is far more common and may inflate depression severity given overlapping symptoms. We sought to disentangle fatigue from depression in PICS.

Methods We conducted a cross-sectional analysis of the RAFT COVID study, a national multicenter longitudinal cohort of severe prolonged COVID-19 survivors. We included participants who completed validated surveys at 1-year from hospitalization for depression (PHQ-9) and fatigue (FACIT-Fatigue). We described correlation of FACIT-fatigue with the PHQ9, and separately with PHQ-2 and PHQ-7, which both omit the two items we hypothesized are influenced by fatigue—tiredness and sleeping. Using a MIMIC model, we performed differential item functioning to evaluate the impact of fatigue on depression directly through these two questions and indirectly with the latent depression construct. We then compared PHQ-7 to PHQ-9 scores by fatigue status.

Results Among 82 participants, 61.0% reported fatigue (reverse-scored FACIT-Fatigue ≥9), and 15.9% moderately severe depression (PHQ-9 ≥10). FACIT-fatigue was strongly correlated with PHQ-9 (r=.87, p<.001), but less so for PHQ-2 (r=.76, p<.001) and PHQ-7 (r=.82, p<.001). The MIMIC model identified significant direct effects on tiredness (λ=.89, p<.001) and sleep (λ=.52, p<.001). Among fatigued participants, the rescaled PHQ-7 was lower than the PHQ-9 (median of 4.5, IQR 1.50-9.75, vs 7, IQR 4-9.75).

Conclusions Fatigue significantly inflated depression symptoms in severe COVID-19 survivors through tiredness and sleeping PHQ-9 items. PHQ-2 may better screen for true depressive symptoms in PICS, minimizing the risk of misdiagnosis and overtreatment.

PLAIN ENGLISH SUMMARY Survivors of severe COVID-19 illness commonly experience post-intensive care syndrome (PICS), which includes depression and fatigue. Fatigue is far more common and may inflate depression severity given overlapping symptoms. We sought to disentangle fatigue from depression in PICS. We found that the presence of fatigue inflated depression severity through symptoms of tiredness and difficulty sleeping, which are two of the nine items of a commonly used depression screening tool, known as the Patient Health Questionnaire-9 (PHQ-9). Depression screening tools that omit these two items, such as the PHQ-2, may better screen for depressive symptoms in PICS, minimizing the risk of overestimating depression symptoms and potentially misdiagnosis.

The authors have declared no competing interest.

This work was funded by grants from the NIH/NIA (K23AG052603), the UCSF Research Evaluation and Allocation Committee (REAC) (Carson and Hampton Research Funds), and the National Association of Long Term Hospitals (NALTH).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Research Evaluation and Allocation Committee of University of California, San Francisco gave ethical approval for this work. The University of California, San Francisco Institutional Review Board approved the RAFT COVID study on June 18, 2020 (#20-31060).

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Funding Disclosures & Conflicts of Interest: This work was supported by grants from the NIH/NIA (K23AG052603), the UCSF Research Evaluation and Allocation Committee (REAC) (Carson and Hampton Research Funds), and the National Association of Long Term Hospitals (NALTH). We have no conflicts of interest to disclose.

All data produced in the present study are available upon reasonable request to the authors