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Brain Fog May Persist 2 Years After COVID, Anxiety, and Depression Resolve: Study

Adults who had COVID-19 were found to be more at risk of longer term neurological and psychiatric disorders compared with those who experienced other respiratory conditions, a study found.

Although increased incidence of mood and anxiety disorders following SARS-CoV-2 infection was transient, researchers found that elevated risk of some other disorders could persist for up to two years.

Specialists at the University of Oxford said although many neurological and psychiatric conditions were known to be linked to COVID, they believed their findings were the first robust evidence to show that these disorders could persist longer than 12 months. The findings also had important implications for health services as well as patients, they said.

The study, published in The Lancet Psychiatry, was based on anonymised electronic health records stored on the TriNetX analytics database of almost 1.3 million people diagnosed with COVID between January 2020 and April 2022 who were matched with an equal number of people who had another respiratory infection. Most of the records were of patients in the US, but also included data from Australia, the UK, and several other countries. Both cohorts comprised children, adults, and older adults, with females accounting for almost 58% in both groups.

Researchers compared both groups for incidence of 14 neurological and psychiatric disorders over two years.

The analysis confirmed previous findings that many of the disorders were more common in COVID patients six months after their diagnosis than among patients who had another respiratory condition.

However, several differences were observed. The hazard ratio for people infected with SARS-CoV-2 returned to baseline for mood disorders after 43 days, and for anxiety after 58 days. Dr Max Taquet PhD, academic clinical fellow in psychiatry at the University of Oxford, who led the investigation, told a Science Media Centre briefing that it was "very reassuring" that "two years after infection, the number of people diagnosed with depression or an anxiety disorder were the same, whether people had COVID-19 or whether they had another recent infection".

In contrast, risks of cognitive deficit, commonly referred to as 'brain fog', dementia, psychotic disorders, and epilepsy or seizures remained higher for those in the COVID group throughout the two-year follow-up period.

Findings Were Mixed for Children

Results in children showed similarities and differences to adults. The likelihood of most diagnoses after COVID was lower among those under the age of 18 than in adults, and they did not share a greater risk of anxiety or mood disorders compared with the group who had other respiratory infections. However, like adults, children recovering from COVID were more likely to be diagnosed with some conditions. Children were found to be at 2-fold increased risk of epilepsy/seizures and at 3-fold increased risk of psychotic disorder, even though this was rare, the researchers stressed.

More neurological and psychiatric disorders were seen when the Delta variant of SARS-CoV-2 was dominant, compared with the original Alpha 'wild type' variant, the researchers found. Those risks were compounded by an elevated risk of mortality seen just after Delta emerged. Despite Omicron leading to milder acute illness and fewer deaths than Delta, the researchers wrote: "The comparable risks seen after the emergence of Omicron indicate that the neurological and psychiatric burden of COVID-19 might continue even with variants that lead to otherwise less severe disease."

Health Service Burden

Dr Taquet said: "The results have implications for patients and health services and highlight the need for more research to understand why this happens after COVID-19, and what can be done to prevent these disorders from occurring, or treat them when they do."

The authors note several limitations in their investigation, including uncertainty over how severe or long-lasting disorders could be, or when they began.

In an assessment of the findings for the Science Media Centre, Dr Rachel Sumner, senior research fellow at Cardiff Metropolitan University, said the findings were "concerning for those that work in frontline roles, who are exposed to COVID infection repeatedly, with very little ability to keep themselves safe from it". Meanwhile, "patients that experience COVID and go on to develop some of these disorders will continue to have delay in diagnosis and treatment with healthcare systems that are struggling to deal with both COVID infections and backlogs of patient waiting lists", she added.

Paul Garner, professor in evidence synthesis in global health at the Liverpool School of Tropical Medicine, urged caution when interpreting "the reported small increases in dementia and psychosis", which he believed were "more likely to be related to the societal upheaval we have been living through rather than being a direct effect of the virus". Instead, the research "reassures us that mood and anxiety problems appear to return to normal levels quite quickly".

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