Summary: Severe COVID-19 infection results in cognitive impairment similar to that sustained by natural aging between the ages of 50 to 70, and is equivalent to losing 10 IQ points.

Source: University of Cambridge

Cognitive impairment as a result of severe COVID-19 is similar to that sustained between 50 and 70 years of age and is the equivalent to losing 10 IQ points, say a team of scientists from the University of Cambridge and Imperial College London.

The findings, published in the journaleClinicalMedicine, emerge from theNIHR COVID-19 BioResource. The results of the study suggest the effects are still detectable more than six months after the acute illness, and that any recovery is at best gradual.

There is growing evidence that COVID-19 can cause lasting cognitive and mental health problems, with recovered patients reporting symptoms including fatigue, brain fog, problems recalling words, sleep disturbances, anxiety and even post-traumatic stress disorder (PTSD) months after infection. In the UK, a study found that around one in seven individuals surveyed reported having symptoms that included cognitive difficulties 12 weeks after a positive COVID-19 test.

Whileeven mild cases can lead to persistent cognitive symptoms, between a third and three-quarters of hospitalised patients report still suffering cognitive symptoms three to six months later.

To explore this link in greater detail, researchers analysed data from 46 individuals who received in-hospital care, on the ward or intensive care unit, for COVID-19 at Addenbrookes Hospital, part of Cambridge University Hospitals NHS Foundation Trust. 16 patients were put on mechanical ventilation during their stay in hospital. All the patients were admitted between March and July 2020 and were recruited to the NIHR COVID-19 BioResource.

The individuals underwent detailed computerised cognitive tests an average of six months after their acute illness using the Cognitron platform, which measures different aspects of mental faculties such as memory, attention and reasoning. Scales measuring anxiety, depression and post-traumatic stress disorder were also assessed. Their data were compared against matched controls.

This is the first time that such rigorous assessment and comparison has been carried out in relation to the after effects of severe COVID-19.

COVID-19 survivors were less accurate and with slower response times than the matched control population and these deficits were still detectable when the patients were following up six months later.

The effects were strongest for those who required mechanical ventilation. By comparing the patients to 66,008 members of the general public, the researchers estimate that the magnitude of cognitive loss is similar on average to that sustained with 20 years aging, between 50 and 70 years of age, and that this is equivalent to losing 10 IQ points.

Survivors scored particularly poorly on tasks such as verbal analogical reasoning, a finding that supports the commonly-reported problem of difficulty finding words. They also showed slower processing speeds, which aligns with previous observations post COVID-19 of decreased brain glucose consumption within the frontoparietal network of the brain, responsible for attention, complex problem-solving and working memory, among other functions.

Professor David Menon from the Division of Anaesthesia at the University of Cambridge, the studys senior author, said: Cognitive impairment is common to a wide range of neurological disorders, including dementia, and even routine aging, but the patterns we saw the cognitive fingerprint of COVID-19 was distinct from all of these.

While it is now well established that people who have recovered from severe COVID-19 illness can have a broad spectrum of symptoms of poor mental health depression, anxiety, post-traumatic stress, low motivation, fatigue, low mood, and disturbed sleep the team found that acute illness severity was better at predicting the cognitive deficits.

The patients scores and reaction times began to improve over time, but the researchers say that any recovery in cognitive faculties was at best gradual and likely to be influenced by a number of factors including illness severity and its neurological or psychological impacts.

Professor Menon added: We followed some patients up as late as ten months after their acute infection, so were able to see a very slow improvement. While this was not statistically significant, it is at least heading in the right direction, but it is very possible that some of these individuals will never fully recover.

There are several factors that could cause the cognitive deficits, say the researchers.Direct viral infection is possible, but unlikely to be a major cause; instead, it is more likely that a combination of factors contribute, including inadequate oxygen or blood supply to the brain, blockage of large or small blood vessels due to clotting, and microscopic bleeds. However, emerging evidence suggests that the most important mechanism may be damage caused by the bodys own inflammatory response and immune system.

While this study looked at hospitalised cases, the team say that even those patients not sick enough to be admitted may also have tell-tale signs of mild impairment.

Professor Adam Hampshire from the Department of Brain Sciences at Imperial College London, the studys first author, said: Around 40,000 people have been through intensive care with COVID-19 in England alone and many more will have been very sick, but not admitted to hospital. This means there is a large number of people out there still experiencing problems with cognition many months later. We urgently need to look at what can be done to help these people.

Professor Menon and Professor Ed Bullmore from Cambridges Department of Psychiatry are co-leading working groups as part of theCOVID-19 Clinical Neuroscience Study (COVID-CNS)that aim to identify biomarkers that relate to neurological impairments as a result of COVID-19, and the neuroimaging changes that are associated with these.

Funding: The research was funded by the NIHR BioResource, NIHR Cambridge Biomedical Research Centre and the Addenbrookes Charitable Trust.

Author: Craig BrierleySource: University of CambridgeContact: Craig Brierley University of CambridgeImage: The image is in the public domain

Original Research: Open access.Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort by Hampshire, A et al. eClinicalMedicine

Abstract

Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort

Preliminary evidence has highlighted a possible association between severe COVID-19 and persistentcognitive deficits. Further research is required to confirm this association, determine whether cognitive deficits relate to clinical features from the acute phase or to mental health status at the point of assessment, and quantify rate of recovery.

46 individuals who received critical care for COVID-19 at Addenbrookes hospital between 10th March 2020 and 31st July 2020 (16 mechanically ventilated) underwent detailed computerised cognitive assessment alongside scales measuring anxiety, depression and post-traumatic stress disorder under supervised conditions at a mean follow up of 6.0 ( 2.1) months following acute illness.

Patient and matched control (N=460) performances were transformed into standard deviation from expected scores, accounting for age and demographic factors usingN=66,008 normative datasets. Global accuracy and response time composites were calculated (G_SScore & G_RT). Linear modelling predicted composite score deficits from acute severity, mental-health status at assessment, and time from hospital admission.

The pattern of deficits across tasks was qualitatively compared with normal age-related decline, and early-stagedementia.

COVID-19 survivors were less accurate (G_SScore=-0.53SDs) and slower (G_RT=+0.89SDs) in their responses than expected compared to their matched controls. Acute illness, but not chronic mental health, significantly predicted cognitive deviation from expected scores (G_SScore (p=0.0037) and G_RT (p=0.0366)).

The most prominent task associations with COVID-19 were for higher cognition and processing speed, which was qualitatively distinct from the profiles of normal aging and dementia and similar in magnitude to the effects of aging between 50 and 70 years of age. A trend towards reduced deficits with time from illness (r=0.15) did not reach statistical significance.

Cognitive deficits after severe COVID-19 relate most strongly to acute illness severity, persist long into the chronic phase, and recover slowly if at all, with a characteristic profile highlighting higher cognitive functions and processing speed.

This work was funded by theNational Institute for Health Research(NIHR) CambridgeBiomedical ResearchCentre (BRC), NIHR Cambridge Clinical Research Facility (BRC-1215-20014), the Addenbrookes Charities Trust and NIHR COVID-19 BioResource RG9402. AH is funded by theUKDementia Research Institute Care Research and Technology Centre and Imperial College London Biomedical Research Centre. ETB and DKM are supported byNIHRSenior Investigator awards.JBR is supported by theWellcome Trust(220258) and Medical Research Council (SUAG/051 G101400). VFJN is funded by an Academy of Medical Sciences/ The Health Foundation Clinician Scientist Fellowship. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

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