Long COVID is associated with severe cognitive slowing
Authors: Zhao Sijia , Martin Eva Maria , Reuken Philipp A. , Scholcz Anna , Ganse-Dumrath Akke , Srowig Annie , Utech Isabelle , Kozik Valeska , Radscheidt Monique , Brodoehl Stefan , Stallmach Andreas , Schwab Matthias , Fraser Emily , Finke Kathrin , Husain Masud 
Published: December 2023

Background

COVID-19 survivors may suffer from a wide range of chronic cognitive symptoms for months or years as part of post-COVID-19 conditions (PCC). To date, there is no definitive objective cognitive marker for PCC. We hypothesised that a key common deficit in people with PCC might be generalised cognitive slowing.

Methods

To examine cognitive slowing, PCC patients completed two short web-based cognitive tasks, Simple Reaction Time (SRT) and Number Vigilance Test (NVT). 270 patients diagnosed with PCC at two different clinics in UK and Germany were compared to two control groups: individuals who contracted COVID-19 before but did not experience PCC after recovery (No-PCC group) and uninfected individuals (No-COVID group).

Findings

We identified pronounced cognitive slowing in PCC patients, which distinguished them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. Cognitive slowing was evident even on a 30-second task measuring simple reaction time (SRT), with PCC patients responding to stimuli ∼3 standard deviations slower than healthy controls. This finding was replicated across two clinic samples in Germany and the UK. Comorbidities such as fatigue, depression, anxiety, sleep disturbance, and post-traumatic stress disorder did not account for the extent of cognitive slowing in PCC patients. Furthermore, cognitive slowing on the SRT was highly correlated with the poor performance of PCC patients on the NVT measure of sustained attention.

Interpretation

Together, these results robustly demonstrate pronounced cognitive slowing in people with PCC, which distinguishes them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. This might be an important factor contributing to some of the cognitive impairments reported in PCC patients.

Funding

Wellcome Trust (206330/Z/17/Z), NIHR Oxford Health Biomedical Research Centre, the Thüringer Aufbaubank (2021 FGI 0060), German Forschungsgemeinschaft (DFG, FI 1424/2-1) and the Horizon 2020 Framework Programme of the European Union (ITN SmartAge, H2020-MSCA-ITN-2019-859890).

Research in context

Evidence before this study

We searched Google Scholar and PubMed for original research or review articles about the cognitive impairment after COVID-19, published up to 3 December 2023. We used terms relating to COVID-19 (SARS-CoV-2, influenza), post-acute symptoms (long COVID, post-COVID conditions, Post-Acute COVID Syndrome) and cognitive impairment (brain fog, cognitive deficit). Previous studies have shown that some people who recovered from the acute symptoms of COVID-19 might nevertheless experience deficits across an array of cognitive functions, including sustained attention, cognitive flexibility, and memory. However, most reports lacked consensus on the precise definition of post-COVID conditions and a common cognitive signature of post-COVID conditions remains unknown.

Added value of this study

In this investigation, we identified moderate to severe cognitive slowing in most patients with PCC, but not in most people who previously suffered COVID without developing PCC. This was replicated across two post-COVID clinics in Germany and the UK. To our knowledge, this is the first robust demonstration of cognitive slowing as a cognitive signature of post-COVID conditions.

Implications of all the available evidence

Using a 30-second web-based, self-administered psychomotor task, cognitive slowing in PCC can be reliably and easily measured as part of diagnostic work-up, and has potential to be a biomarker to track the progress of rehabilitation of PCC. To encourage researchers and clinicians to employ this task, we have ensured that it is available online with online feedback and all of our code is publicly accessible.