Long COVID patients exhibit significant cognitive slowing, new study finds

In a recent preprint* posted to the medRxiv server, researchers from Germany and the United Kingdom (UK) investigated whether patients with symptoms of long coronavirus disease 2019 (long COVID) showed cognitive slowing as a signature deficit. They found that compared to controls (patients with a history of COVID-19 but no long COVID symptoms), long COVID patients showed moderate-to-severe cognitive slowing.

Study: Long COVID is associated with severe cognitive slowing. Image Credit: p.ill.i / Shutterstock

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

Post-COVID-19 condition (PCC), or long COVID, involves chronic symptoms persisting for two months or more after SARS-CoV-2 infection. Cognitive deficits are highly prevalent among patients with PCC, affecting their cognitive flexibility, sustained attention, and memory, correlating with reduced cortical thickness. The term "brain fog" commonly describes these symptoms, but a robust cognitive signature distinguishing PCC from other post-infection cases is lacking.

Slow processing speed is a notable cognitive abnormality reported in acute as well as chronic phases of COVID-19, particularly in those with cognitive symptoms. However, owing to the lack of consensus in defining PCC and the wide variations in cognitive task design, the potential relationship between PCC and generalized cognitive slowing remains to be understood. Therefore, researchers in the present study used two web-based tasks to examine the presence of generalized cognitive slowing as a common deficit in patients with PCC.

About the study

The present study included 270 patients diagnosed with PCC from two clinics in the UK and Germany. Two concise online cognitive tasks, the "simple reaction time" (SRT) followed by "number vigilance test" (NVT), were employed to assess cognitive slowing in individuals with PCC. The performance of this group was compared to that of two control sets: individuals who had a prior COVID-19 infection without subsequent PCC (No-PCC group) and those who never had symptomatic COVID-19 (No-COVID group).

A total of 119 PCC patients, with a mean age of 46.6 years, completed the SRT test, 67.2% of which were females. Similarly, 63 No-PCC participants and 75 No-COVID participants completed the test. Here, the participants were required to press the spacebar on the computer's keyboard when a sizeable red circle appeared on the monitor screen. 

Next, the NVT was a sustained attention task in which the participants were required to vigilantly monitor a fast-changing stream of numbers on the screen and press the spacebar to identify the rare target "0". The NVT was completed by 194 participants. A visual analog scale (VAS) was used to assess the level of fatigue and motivation in the participants every minute. Additionally, the participants filled out questionnaires assessing their depression level and sleep quality.

The tests were implemented using PsychoPy software, and the analysis was performed using MATLAB and R Studio. The statistical analysis involved the use of t-tests and chi-square tests for group comparisons, Bonferroni-corrected P-values, Bayesian factor, analysis of variance, non-parametric tests, Pearson's and Kendall's correlation methods, logistic regression, z-scores, and generalized linear models. Psychomotor speed lower than 1 standard deviation (SD) from normal average was defined as moderate cognitive slowing, and lower than 2 SD was defined as severe cognitive slowing.

Results and discussion

In the SRT test, the average reaction time (RT) of healthy controls (No-COVID and No-PCC) was 0.34 seconds, significantly lower than the RT of PCC patients (0.49 seconds). While the responses of PCC patients were slower, the variability was found to be low. While 53.3% of patients showed severe cognitive slowing in the PCC group, only 4% of individuals in the No-COVID group showed it. A significantly higher proportion of PCC patients showed moderate-to-severe cognitive slowing as compared to No-COVID (p<0.0001) and No-PCC (p=0.0006) groups. The effects were found to be similar in the UK and Germany clinics. RT was found to be clearly dissociated from the mental health phenotypes as well as sleep disturbance levels.

Further, cognitive slowing and lesser vigilance to visual stimuli were noted in PCC patients in the results of NVT, a cognitively more demanding task. No association was found between these results and depression. Interestingly, PCC patients with normal response speed in NVT felt significantly more fatigued than other participants with normal speed. Cognitive slowing and depression could be successfully used to distinguish PCC from No-PCC individuals. While hospitalization due to COVID-19 did not seem to affect RT in PCC patients, a prolonged duration of PCC was found to be associated with severe cognitive slowing.

Conclusion

This study was the first to robustly demonstrate cognitive slowing as a cognitive signature of PCC. Further research is required in the field to understand the underlying mechanisms, potentially aiding the development of therapeutic measures for improved patient outcomes.

*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.

Written by

Dr. Sushama R. Chaphalkar

Dr. Sushama R. Chaphalkar is a senior researcher and academician based in Pune, India. She holds a PhD in Microbiology and comes with vast experience in research and education in Biotechnology. In her illustrious career spanning three decades and a half, she held prominent leadership positions in academia and industry. As the Founder-Director of a renowned Biotechnology institute, she worked extensively on high-end research projects of industrial significance, fostering a stronger bond between industry and academia.