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COVID: Severe infection causes cognitive decline equivalent to 20 years of aging

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Research on the effects of COVID-19 is becoming more numerous, and the results are more and more alarming. Indeed, there is growing evidence that COVID-19 can cause long-term cognitive and mental health problems. Patients who have recovered from the infection report symptoms such as fatigue, brain fog, sleep disturbances, and anxiety several months after infection. Recently, a team of researchers demonstrated that a severe infection would have the same impact in terms of cognitive impairment as harmful deterioration mechanisms occurring in people aged 50 to 70, with a loss equivalent to 10 IQ points.

Although even mild cases can lead to persistent cognitive symptoms, one third to three quarters of hospitalized patients still report having cognitive symptoms after three to six months. Recently, the direct effects of this disease associated with the loss of gray matter have also been demonstrated. The exact long-term neurological effects of COVID are still being studied in recovered patients. Brain fog is one of the most common symptoms in people with long-term COVID. According to a recent study from the University of Cambridge, seven in 10 patients with the disease experience problems with concentration and memory within a few months of onset, and many of them perform worse than their peers on cognitive tests.

Indeed, Dr Muzaffer Kaser, Research Fellow in the Department of Psychiatry at the University of Cambridge and Consultant Psychiatrist for the NHS Foundation in Cambridgeshire and Peterborough, said in a statement: “There is strong evidence that when people say they have cognitive difficulties after COVID, they are not necessarily the result of anxiety or depression. The effects are measurable – something alarming is happening.” Understanding the neurological disorders caused by this disease, especially in the long term, is a public health issue. As Dr Lucy Check, a researcher in the Department of Psychology at the University of Cambridge, points out: “The long COVID has received very little political or medical attention. There is an urgent need to take this form of the disease more seriously, and cognitive problems are an important part of that. When politicians talk about “living with COVID” – meaning full infection – they ignore it. The impact on the working population can be enormous.”

To better understand these chronic disorders and be able to actually treat them, research is increasing. Recently, a team from the University of Cambridge was also able to find preliminary evidence of a possible link between severe COVID-19 and persistent cognitive impairment. The study is published in eClinicalMedicine.

Preliminary data for an unprecedented comparison

In an effort to determine the impact of severe COVID infections, the authors conducted detailed cognitive assessments of 46 people receiving intensive care for COVID-19 at Addenbrooke’s Hospital in the UK between March 10, 2020 and July 31, 2020, including 16 in mechanical ventilation. These scores 6 months after infection took into account anxiety, depression, and post-traumatic stress disorder, among others. They were carried out using the Cognitron platform. The latter measures various aspects of mental ability such as memory, attention, and thinking. Scores (response time) for specific tests were compiled and then compared with control data sets set for similar age groups. This is the first time such a thorough assessment and comparison of the consequences of severe COVID-19 has been carried out.

As a result, people who contracted COVID-19 had longer response times than control data from people who did not contract the disease, as well as much less accurate responses. The effect was greatest in those who required mechanical ventilation.

In particular, cured patients performed particularly poorly on tasks such as verbal reasoning by analogy, confirming the oft-reported problem of difficulty finding words. They also showed lower processing speed, consistent with previous observations post-COVID-19 in, among other things, decreased attention, complex problem solving, and working memory.

Taking into account these results, the authors considered, on the one hand, that cognitive deficit after a severe course of COVID-19 is more associated with the severity of the acute disease, and, on the other hand, persists in the chronic phase for a long time. Patients, if recovering, then very slowly.

As a result, researchers are trying to understand what causes these chronic disorders. They suggest that a set of concomitant factors may be the cause. They list, in particular, insufficient supply of oxygen or blood to the brain, blockage of large or small blood vessels due to the formation of blood clots and microscopic bleeding. Recent evidence suggests that the most important mechanism may be damage caused by the body’s inflammatory response and the immune system.

Irreversible cognitive decline?

Comparing patients with 66,008 members of the general public, the researchers calculated that the magnitude of cognitive loss was, on average, similar to that seen in 20s, between ages 50 and 70, equivalent to a loss of 10 IQ points. Professor David Menon, from the Department of Anesthesia at the University of Cambridge, lead author of the study, said in a statement: “Cognitive impairment is common across a wide range of neurological disorders, including dementia and even natural aging, but the patterns we observed — COVID-19 Fingerprint Cognitive Impairment — differed from all this”.

In addition, the team found no significant difference in levels of cognitive impairment between those who completed testing six months after admission to the hospital and those who were tested 10 months later, although there were signs of improvement. Indeed, patients’ performance and reaction times began to improve over time, but the researchers say any cognitive recovery was gradual at best and likely depended on a number of factors, including the severity of the disease and its neurological or psychological consequences.

Unfortunately, Professor Menon explains: “We followed some patients up to ten months after their acute infection, so we could see a very slow improvement. While it’s not statistically significant, at least it’s moving in the right direction, it’s highly likely that some of these people will never fully recover.”

Further studies are needed to confirm this association, to determine whether cognitive impairment is related to the clinical features of the acute phase or mental health status at the time of assessment, and to quantify the rate of recovery. This is what Prof. Menon and Prof. Ed Bullmore from the Cambridge Department of Psychiatry are trying to achieve with the COVID-19 Clinical Neuroscience Research (COVID-CNS) workgroups. The latter are aimed at identifying biomarkers associated with neurological disorders caused by COVID-19 and associated changes in neuroimaging.

The public health stakes are high when we know that the number of people suffering from acute or mild cognitive impairment months after infection is increasing, whether they have been hospitalized or not.

eClinicalMedicine

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