Cognitive impairment, depression, and fatigue in post-COVID and post-vaccination syndrome: a large-scale cross-sectional study, 2025, Hanc et al

[forestglip]

Cognitive impairment, depression, and fatigue in post-COVID and post-vaccination syndrome: a large-scale cross-sectional study

Spoiler: Authors

Hanc, Evelyne; Koller, Katharina; Herold, Regina; Erim, Yesim; Morawa, Eva

[Line breaks added]

Background
Persistent cognitive difficulties are among the most prevalent symptoms observed after COVID-19. This study examined the neuropsychological characteristics, mental health and risk factors associated with cognitive impairment in patients with Post-Acute Sequelae of COVID-19 (PASC). In addition, differences regarding the cognitive dysfunctions between individuals with PASC and Post-Vaccination Syndrome (PVS) were explored.

Methods
Participants were consecutively recruited at the Post-COVID Center of the University Hospital Erlangen in Germany (12/2022–02/2025). Assessments included a broad neuropsychological assessment: d2 Test of Attention, digit span backwards from the Wechsler Memory Scale-Revised (WMS-R) and module 1 (formal lexical fluency) of the Regensburger Verbal Fluency Test (RWT), along with assessments of depression, fatigue, and inflammatory markers (C-reactive protein).

Results
The sample (N = 793, mean age: 46.1 ± 12.4 years; 66.8% women) included n = 723 PASC patients and n = 70 PVS patients.

In the total sample, deficits were most frequent in working speed (61.7%), attention (54.7%) and verbal fluency (48.8%); 30.3% showed multidomain impairment. Clinically significant depressive symptoms (64.5%) and fatigue (92.4%) were common.

Cognitive patterns, depressive symptoms and fatigue in the PVS group closely resembled those observed in PASC. In PASC, lower education, older age, depressive symptoms, and elevated CRP were associated with cognitive impairment.

Conclusion
Cognitive impairment is highly prevalent in PASC and PVS and appears to be influenced by both psychological and biological factors. Similar patterns identified in PVS suggest possible shared mechanisms. Further research is needed to clarify trajectories and optimize treatment strategies.

Web | DOI | PDF | European Archives of Psychiatry and Clinical Neuroscience | Open Access

 

[Utsikt]

Participants were included consecutively between 12/2022 and 02/2025 at the Post-COVID Center of the University Hospital of Erlangen, a multidisciplinary outpatient clinic specializing in patients with PASC.

Referral to the Post-COVID Center was possible only through a general practitioner and required a confirmed SARS-CoV-2 infection and persistent symptoms lasting at least three months.

Some potential selection bias that isn’t really acknowledged by the authors.

Cognitive impairment is highly prevalent in PASC and PVS and appears to be influenced by both psychological and biological factors

There is no basis for making claims about causation.

Depressive symptoms​

The Patient Health Questionnaire-9 (PHQ-9) was used to measure depression symptoms. The range of sum scores is 0–27. To identify likely cases of clinically significant levels of depression symptoms, a cut-off value of ≥ 10 was proposed [39].

The prevalence of probable depression (cut-off ≥ 10) was 64.5% (n = 472). The mean score for depressive symptoms was M = 11.5 (SD = 5.1). Mean PHQ-9 scores were 11.6 (SD = 5.1) in the PASC group and 10.4 (SD = 5.0) in the PVS group.

PHQ-9 is prone to flagging any illness as depression. The authors do not acknowledge that limitation at all. Most sick people would score at least 10 on these questions, which is what they found.

Fatigue​

Analyses included 719 participants. A total of 92.4% of participants (n = 664) reported clinically relevant levels of fatigue (cut-off ≥ 36). The average symptom severity was M = 53.9 (SD = 10.5). The mean FSS score was 53.8 (SD = 10.6) in the PASC group and 54.3 (SD = 9.0) in the PVS group.

As expected, they reported feeling quite fatigued.

Lots of cognitive issues:

When comparing the cognitive performance of the study sample with normative data from healthy controls (see Table 4), significantly lower scores were found in the cognitive domains of attention, working speed and formal lexical fluency.

Both age groups (20–39 and 40–60 years) in the study sample showed significantly reduced performance in attention and working speed (d2 test) compared to healthy controls, with particularly large effect sizes in the older age group.

Formal lexical fluency (RWT) was also significantly impaired in the study sample when compared to controls. Subgroup analyses revealed consistent cognitive impairments among PASC patients across all comparisons.

In contrast, significant differences in cognitive performance among PVS patients were predominantly observed in the older age group, while the younger group showed no significant differences from healthy controls in attention and working speed.

 

[rvallee]

appears to be influenced by both psychological

But there are no psychological factors in this study. 'Depressive symptoms' isn't supposed to mean psychological, they ask many questions that are all obviously part of the illness itself, including specifically cognitive impairment! This is obviously not a valid way of assessing this.

I don't even think there is any basis to claim any psychological factors at all, or that they simply don't matter in the big picture. There is simply no basis to say this other than massively flawed interpretation of bad questionnaires. All this does is make everyone lose focus of the problems by having them obsess over downstream problems that they convinced themselves are easier to fix.