Pronounced cognitive slowing distinguished people with long COVID from others, a cross-sectional study showed.
On a 30-second task measuring simple reaction time, moderate-to-severe cognitive slowing was evident among long COVID patients compared with age-matched healthy individuals who had previous symptomatic SARS-CoV-2 infection and recovered, reported Sijia Zhao, PhD, at the University of Oxford in England, and co-authors in eClinicalMedicine.
Long COVID patients responded to visual stimuli at about 3 standard deviations slower than healthy controls, Zhao and colleagues said. More than half (53.5%) of long COVID patients had a response speed slower than 2 standard deviations from the control mean, suggesting that slow reaction time was a common cognitive deficit.
The study represents the first robust demonstration of slowing as a cognitive signature of post-COVID conditions, the researchers said.
It’s also the first objective cognitive marker found for long COVID, Zhao told MedPage Today. “Importantly, this marker can be reliably and easily measured using a 30-second web-based task, so it has potential to be a marker to track the progress of rehabilitation of long COVID,” she said.
Zhao and colleagues studied 270 patients diagnosed with post-COVID condition (also called long COVID) at two different clinics and compared them with two control groups: those who had SARS-CoV-2 infection but did not experience long COVID after recovery, and those who were never infected.
All long COVID patients completed the study from May 2021 through July 2023 at Jena University Hospital in Germany or the long COVID clinic at Oxford and met the National Institute for Health and Care Excellence (NICE) requirements for long COVID. Mean time from COVID-19 diagnosis was 326 days, and 20% were hospitalized when they had acute SARS-CoV-2 infection.
Participants completed two short web-based cognitive tasks, the Simple Reaction Time (SRT) task and the Number Vigilance Test (NVT).
The SRT task required participants to press the space bar when a large red circle appeared in the center of the screen. After they pressed the space bar, the red circle disappeared and would reappear after randomized intervals that ranged from 0.5 to 2 seconds. The total number of trials was 16 (the first two trials were not included in the analysis).
This task was performed by 119 long COVID patients (mean age about 47 and 67.2% were female), 63 COVID patients who had recovered, and 75 people who never had COVID. The average reaction time for healthy controls (both recovered COVID and no COVID groups) was 0.34 seconds. Long COVID patients responded significantly more slowly at an average of 0.49 seconds. Depression and other mental health symptoms did not predict cognitive slowing.
A total of 194 participants completed the NVT, an online visual sustained attention task used in other studies of long COVID brain fog. Participants had to remain alert and monitor a rapidly changing stream of numbers, then press the space bar when they spotted the uncommon target “0”. After each minute during testing, they reported their level of fatigue and motivation on a visual analogue scale.
Similar to their performance on the SRT, long COVID patients took substantially longer to react to targets on the NVT compared with both groups of healthy controls. This slowness was maintained throughout the entire course of 9 minutes and could not be explained by trading off speed for accuracy.
Long COVID patients who were not hospitalized with acute infection also showed significant cognitive slowing compared with non-hospitalized COVID patients who didn’t develop long COVID. “This indicates that the cognitive slowing observed in post-COVID-19 conditions was not merely due to the acute illness of COVID-19,” Zhao and colleagues noted.
Study limitations included a lack of comprehensive neuropsychological assessments for both long COVID patients and controls. Some long COVID patients could have peripheral neuropathy or joint problems that might have affected their motor responses, the researchers acknowledged. In addition, cognitive symptoms are not always present in long COVID patients.
Disclosures
This research was supported by funding from the Wellcome Trust, NIHR Oxford Health Biomedical Research Centre, German Forschungsgemeinschaft, and the Thüringer Aufbaubank.
Zhao and a co-author were funded by the Wellcome Trust. Co-authors were supported by Friedrich-Schiller-University Jena, German Forschungsgemeinschaft, and the Horizon 2020 Framework Programme of the European Union.
Primary Source
eClinicalMedicine
Source Reference: Zhao S, et al “Long COVID is associated with severe cognitive slowing: a multicentre cross-sectional study” EClinicalMedicine 2024; DOI: 10.1016/j.eclinm.2024.102434.
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