Cognitive impairment and function in SARS-CoV-2 positive patients

By Bhavana KunkalikarReviewed by Danielle Ellis, B.Sc.Jun 9 2022

In a recent study posted to the medRxiv* preprint server, researchers assessed the association between post-acute coronavirus disease 2019 (COVID-19) cognitive impairment and kynurenine pathway activation.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Evidence has suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with cognitive impairment (CI) after acute COVID-19. However, further research is required to understand the magnitude, trajectory, and characteristics of post-COVID-19 CI.

About the study

In the present study, researchers evaluated the prevalence of CI and trajectories of cognitive performances in COVID-19 patients recovering from mild to moderate acute infection over a period of 12 months.

The team enrolled 128 unvaccinated patients diagnosed with SARS-CoV-2 using nasopharyngeal swabs. The present study is ongoing, with the first exam conducted on 14 May 2020 and data censored on 15 September 2021. The study comprised two longitudinal components: (1) the neurocognitive assessment and (2) the medical and blood test visit assessment. For the assessment of neurocognitive activity, 127 patients completed their first assessment post 2.7 months, 121 completed their second assessment post 5.3 months, and 101 completed their third visit 12.9 months after COVID-19 diagnosis.

Furthermore, the study had three cross-sectional components: (1) the mental health assessment, which was performed two months after diagnosis during the time of neurocognitive assessment, (2) medical history recorded when the participant was first enrolled, which was a few days or weeks before the first neurocognitive assessment, and (3) acute COVID-19 illness history recorded and the evaluation of lung function. Moreover, as per the history of acute COVID-19 illness, participants were classified into three disease severity groups, namely, mild, moderate, and severe. 

The team used the CogState computerized battery (CCB) as a validated cognitive screening test. The test targeted cognitive abilities that were impacted by acute respiratory diseases, immune compromise, as well as cerebrovascular diseases. The team also employed the National Institutes of Health (NIH) toolbox odor identification test (OIT) to assess olfactory performance. In this test, the patients were asked to smell nine scratch-and-sniff cards and match the card’s smell to one out of the four depictions provided.

Furthermore, the mental health of the participants was evaluated using screening tools that captured anxio-depressive symptoms during the first assessment, which was conducted two months after the COVID-19 diagnosis. The depression in the medically ill (DMI-10) test involved a 10-item questionnaire that focused on cognitive symptoms of depression and avoided measuring physical symptoms that were common between depression and physical diseases.     

Results

The study cohort included patients aged between 20 and 79 years, with an average age of 46.6 years and 42% women. The subgroup with acute severe COVID-19 comprised older patients who were more likely to be men than the mild and moderate subgroups.

The study results showed that the longitudinal cognitive performance worsened over time across the period of observation post-COVID-19 diagnosis. Months passed since diagnosis and status of impairment were found to be the main predictors of cognitive performance. Altogether, the team noted that the longitudinal performance of both the impaired and the unimpaired patients declined over time while the impaired patients had a lower overall performance than the unimpaired patients.

Notably, no association was found between CI and disease severity, lung function, or the existence of comorbidity. On the other hand, pre-existing and current mental illnesses did not correlate with CI. However, a significant association was observed between CI and anosmia. Moreover, the team found a substantial impact of CI on the performance of daily activities as well as work efficiency two and four months after COVID-19 diagnosis.

Furthermore, the research showed that cognitively impaired cases had slightly higher levels of kynurenine pathway (KP) metabolites compared to cognitively unimpaired patients two months after the COVID-19 diagnosis. Overall, mild cognitive decline was associated with the activation of KP. This suggested the existence of a potential causal correlation, indicating the role of KP as a biomarker and a therapeutic target.

The analyses also found no significant association between cognition and interferon-gamma (IFN-γ), interleukins, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and peripheral brain biomarkers.        

Conclusion

Overall, the study findings showed that the KP activation was a significant biomarker for cognitive impairment or decline after acute COVID-19. This highlighted the potential role of KP as a monitoring tool and a therapeutic target against COVID-19.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.