Long COVID is associated with severe cognitive slowing

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 Thuringer 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). ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by funding from the Wellcome Trust, NIHR Oxford Health Biomedical Research Centre, and the Thuringer Aufbaubank (2021 FGI 0060). S.Z. and M.H. were funded by the Wellcome Trust (206330/Z/17/Z). E.M.M. was funded by Ph.D. scholarship Landesgraduiertenstipendium of Friedrich-Schiller-University Jena. K.F. was funded by German Forschungsgemeinschaft (DFG, FI 1424/2-1) and the Horizon 2020 Framework Programme of the European Union (ITN SmartAge, H2020-MSCA-ITN-2019-859890). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics committee of Jena University Hospital (Approval Reference: 5082-02/17) and South Central Oxford A Research Ethics Committee (Approval Reference: 18/SC/0448) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes De-identified data supporting this study may be shared based on reasonable written requests to the corresponding author. Access to de-identified data will require a Data Access Agreement and IRB clearance, which will be considered by the institutions who provided the data for this research. The simple reaction time task and the number vigilance task can be tried online at [https://octalportal.com/pcc]. The source code is shared using a Creative Commons NC-ND 4.0 international licence upon reasonable written request to the corresponding author and publicly available at [https://octalportal.com/pcc].