The effects of COVID-19 on cognitive performance in a community-based cohort: A COVID Symptom Study Biobank observational study
Authors: Cheetham Nathan J. , Penfold Rose , Giunchiglia Valentina , Bowyer Vicky , Sudre Carole H. , Canas Liane S. , Deng Jie , Murray Benjamin , Kerfoot Eric , Antonelli Michela , Rjoob Khaled , Molteni Erika , Österdahl Marc F. , Harvey Nicholas R. , Trender William R. , Malim Michael H. , Doores Katie J. , Hellyer Peter J. , Modat Marc , Hammers Alexander , Ourselin Sebastien , Duncan Emma L. , Hampshire Adam , Steves Claire J. 
Published: March 2023

Background

Cognitive impairment has been reported after many types of infection, including SARS-CoV-2. Whether deficits following SARS-CoV-2 improve over time is unclear. Studies to date have focused on hospitalised individuals with up to a year follow-up. The presence, magnitude, persistence and correlations of effects in community-based cases remain relatively unexplored.

Methods

Cognitive performance (working memory, attention, reasoning, motor control) was assessed in participants of a voluntary biobank in July, 2021 (Round 1), and April, 2022 (Round 2). Participants, drawn from the COVID Symptom Study smartphone app, comprised individuals with and without SARS-CoV-2 infection and varying symptom duration. Effects of COVID-19 exposures on cognitive accuracy and reaction time scores were estimated using multivariable ordinary least squares linear regression models weighted for inverse probability of participation, adjusting for potential confounders and mediators. The role of ongoing symptoms after COVID-19 infection was examined stratifying for self-perceived recovery. Longitudinal analysis assessed change in cognitive performance between rounds.

Findings

3335 individuals completed Round 1, of whom 1768 also completed Round 2. At Round 1, individuals with previous positive SARS-CoV-2 tests had lower cognitive accuracy (N = 1737, β = −0.14 standard deviations, SDs) than negative controls. Deficits were largest for positive individuals with ≥ 12 weeks of symptoms (N = 495, β = −0.22 SDs). Effects were comparable to hospital presentation during illness (N = 281, β = −0.31 SDs), and 10 years age difference (60-70 years vs. 50-60 years, β = −0.21 SDs) in the whole study population. Stratification by self-reported recovery revealed that deficits were only detectable in SARS-CoV-2 positive individuals who did not feel recovered from COVID-19, whereas individuals who reported full recovery showed no deficits. Longitudinal analysis showed no evidence of cognitive change over time, suggesting that cognitive deficits for affected individuals persisted at almost 2 years since initial infection.

Interpretation

Cognitive deficits following SARS-CoV-2 infection were detectable nearly two years post infection, and largest for individuals with longer symptom durations, ongoing symptoms, and/or more severe infection. However, no such deficits were detected in individuals who reported full recovery from COVID-19. Further work is needed to monitor and develop understanding of recovery mechanisms for those with ongoing symptoms.

Funding

Chronic Disease Research Foundation, Wellcome Trust, National Institute for Health and Care Research, Medical Research Council, British Heart Foundation, Alzheimer’s Society, European Union, COVID-19 Driver Relief Fund, French National Research Agency.

Research in context

Evidence before this study

Abstracts were screened from a PubMed search query (COVID-19) AND (long COVID) AND (cognitive impairment), which returned 409 results between 2020 and January 20, 2023. Multiple systematic reviews and meta-analyses reported consistent observation of cognitive deficits following SARS-CoV-2 infection. Most studies of cognitive impairment have used small samples of less than 200 participants (including any controls), hospitalised cohorts, and measured cognitive impairment through self-report or dichotomised quantitative scales. Only one study was found with a sample size of more than 1,000 individuals, included cases and controls across both community and hospital settings, and used objective cognitive testing that allowed quantitative estimation of the scale of any cognitive impairment. Previous studies have also been limited insofar as focusing on earlier infections in the first year of the COVID-19 pandemic, prior to introduction of vaccination and emerging variants. Studies focusing on longitudinal follow-up for those hospitalised with COVID-19 or with long COVID have found low rates of full recovery from long-term symptoms at up to one year since infection, including cognitive impairment.

Added value of this study

We report quantitatively on cognitive impairment following SARS-CoV-2 infection, from a large dataset of 4,000 individuals with and without test-confirmed SARS-CoV-2 infection and a range of associated symptom durations, with mostly community-based cases. Importantly, we undertook two rounds of cognitive testing allowing longitudinal tracking of cognitive performance. Our longitudinal methods allowed us to report on deficits up to two years since infection, and following infections with SARS-CoV-2 variants that have emerged over 2021 and 2022, not previously studied in the context of COVID-19 and cognition.

Implications of all the available evidence

This study adds to existing evidence of cognitive deficits following SARS-CoV-2 infection, but finds important exceptions. At initial testing in mid-2021, cognitive deficits are not found for individuals who self-report as feeling recovered from COVID-19, even for those with longest symptom duration. In follow-up testing in mid-2022, we find that deficits appear persistent for those with earlier infections and ongoing symptoms, consistent with previous smaller studies. More research is required to monitor those experiencing persistent cognitive impairment and understand the mechanisms underlying recovery.