Preprint Disentangling Fatigue from Depression among Survivors of Severe COVID-19, 2026, Cabrera et al.

[SNT Gatchaman]

Disentangling Fatigue from Depression among Survivors of Severe COVID-19

Spoiler: Authors

Juan R Cabrera; Peter Pham; W John Boscardin; Anil N Makam

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.

Web | DOI | PDF | Preprint: MedRxiv | Open Access

 

[Utsikt]

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.

Good to have some data on this, even though it should be obvious from reading the questionnaires. PHQ-2 still had an r-value of 0.76, so it’s probably not very useful.

These are the questions:

Over the last 2 weeks, how often have you been bothered by any of the following problems?​

1. Little interest or pleasure in doing things​

2. Feeling down, depressed, or hopeless​

If you get symptoms from doing things, you’ll be flagged by 1. If you’re sick and there are no treatments, you’ll be flagged by 2.

 

[rvallee]

Fatigue is far more common and may inflate depression severity given overlapping symptoms.

The main takeaway from this is that depression diagnoses are so unreliable that the most common symptom in all of medicine can all by itself create loads of false positives even though it's obvious incorrect.

Someone ought to look into that. Well, someone who doesn't want to inflate mental health diagnoses, which is clearly super popular for some reason. Some understand that as a risk, and the authors of this paper appear to, while others see it as an opportunity.

The PHQ should not be used on sick people for this reason, full stop. It's the exact same mindless process by which almost every description of symptoms ends up with cancer as a possibility on WebMD. This is the total ethical and intellectual rot at the heart of "liaison psychiatry" and other nonsense. Mental health questionnaires mostly lead to false positives, unless they are applied with a bias towards risk, while they more often than not are applied because of the opportunity to throw away patients.

 

[Trish]

So this study is not about there being any real difficulty separating depression and fatigue in patients, it's about problematic questionnaire design. And about the risks of using questionnaires for diagnosis.

Something that we know well in ME/CFS, with pwME being described as having high rates of depression and anxiety and a long string of othe psych problems on the basis of flawed questionnaires.

And I say again, we would be much better off if all questionnaires were dumped, especially ones trying to assess psych issues.