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New observational study finds ‘measurable’, if limited, cognitive decline in people with persistent symptoms of COVID-19. Image credit: Mel Karlberg/Stocksy.
  • Cognitive and memory impairment can occur in people after infection with SARS-CoV-2, the virus that causes COVID-19, and this effect is greater in people with long COVID.
  • Those who received at least two vaccinations and had fewer repeat infections, and those who were infected with later variants of SARS-CoV-2 had lower measures of cognitive decline.
  • There are still a number of questions remaining about ‘brain fog’ in people who have long COVID.

People who had an infection with SARS-CoV-2, the virus that causes COVID-19, showed measurable cognitive impairment compared with those who have not had COVID-19, a new study from Imperial College of London in the United Kingdom shows.

While the cognitive and memory deficits were small for people who had mild infections or did not go on to develop long COVID, the effect of more severe infections that resulted in admission to intensive care units was associated with a more pronounced effect.

The researchers found that vaccination had a protective effect, however.

The study, published in The New England Journal of Medicine, used a multiple regression analysis to focus on the results of 112,964 adults in England.

Study participants who had recovered from COVID-19 and whose symptoms resolved in less than 4 weeks or at least 12 weeks had small cognitive deficits compared with those in the “no–COVID-19 group,” who had not ever been infected with the SARS-CoV-2 virus, or had unconfirmed infection.

People who had symptoms occurring over 12 weeks after recovery from the initial infection — such as chronic fatigue, respiratory difficulty, or neurological issues — had greater cognitive deficits, as did people who had become infected with early variants of the SARS-CoV-2 virus.

Even though the researchers did not attach a “long COVID” diagnosis to these participants, such persistent symptoms are common in people with this post-viral condition.

“By using an innovative cognitive test which has also been completed by people who did not have COVID-19, this important and well-conducted study provides the first accurate quantification of the scale of cognitive deficits in people who had COVID-19,” Dr. Maxime Taquet, NIHR Academic Clinical Fellow in Psychiatry, University of Oxford, who was not involved with the study, commented.

Dr. Taquet added that the disparity was the most obvious at the extremes:

“The risk of having more severe cognitive problems was almost twice as high in those who had COVID-19 compared to those who did not, and three times as high in those who were hospitalised with COVID-19. A few key questions remain open: Do these cognitive problems persist or improve in the years after infection? What is their biological explanation? How does it affect people’s everyday life and their ability to work?”

The mental and psychological effects of COVID-19 have been the focus of study since evidence emerged they were linked to SARS-CoV-2 infections in 2020.

Long COVID has been associated with longer periods of anxiety, poor memory, or struggles with concentration or thinking, but this study did not draw any significant conclusions about the neurocognitive impact of long COVID.

The authors emphasize that further study is required here.

“We focused on symptoms that had persisted for at least 12 weeks, and we did not depend on a diagnosis of long Covid, which may require clinical assessment,” the study authors wrote. “In the absence of baseline cognitive data before infection, we could not assess cognitive change, and the observational nature of the data means that we could not infer causality.”

Dr. Scott Kaiser, MD, a board-certified geriatrician and director of Geriatric Cognitive Health for the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in the study, told Medical News Today that it helps fill out some of the ongoing uncertainty around “brain fog.”

“This study reinforces the idea that the experience of cognitive impairment following COVID is quite frequent and is striking in the extent to which this impairment may persists for many months following infection, even in cases that were not that severe,” Dr. Kaiser said.

“As far as the true long-term consequences it’s just too soon to tell. While it appears that most cases gradually resolve — even if it takes several months — it’s unclear if a subset of people may continue to have lingering symptoms across an even longer time horizon. Similarly, it remains unknown whether this could actually increase one’s ultimate risk of a major neurocognitive disorder — dementia — later in life.”

– Dr. Scott Kaiser

The study found that participants who had received two or more vaccinations and had minimal repeat infections of COVID-19 had less cognitive decline.

Similarly, those who were infected with later variants of SARS-CoV-2 had better cognitive abilities than those who were infected during the alpha stage of the pandemic.

The authors of the study also note that the delta variant occurred in “a highly vaccinated population.”

Dr. Kaiser advised that anyone experiencing brain fog should reach out to a medical professional and seek guidance, given that at this stage in the pandemic there are more resources available and better opportunities to understand what long-term effects the SARS-CoV-2 virus has on cognition.

“Because this is all a relatively new phenomena the overall understanding continues to evolve. There are many potential pathways — reduced oxygen delivery, reduced blood flow, an attack by the immune system on healthy brain cells or an actual invasion of infectious cells into the brain, or inflammation affecting brain cells — and a combination of multiple factors may be at play,” Dr. Kaiser said.

“Additional factors associated with having COVID may indirectly contribute as well — increased stress and anxiety, depressed mood, changes in diet, medications, decreased physical activity, poor sleep quality, or even social isolation and feelings of loneliness,” he added.

”And while it’s possible that certain cases have very different causes, overall, there does appear to be a clear physiologic pathway by which infection with the virus induces an inflammatory response which actually causes inflammation in the brain — neuroinflammation — which can, in turn, can cause cognitive dysfunction.”

– Dr. Scott Kaiser