The largest study to date, published in The Lancet Psychiatry, suggests that there is a link between Covid-19 infection and subsequent brain conditions.

For the past year, experts have grown progressively concerned that Covid-19 could increase the risk of developing a neurological or psychiatric disorder. However, there have been no previous large-scale studies examining these risks in the six months after Covid-19 infection.

This paper has revealed such concerns to be well-founded, as one third of patients were found to develop a neurological or psychiatric disorder after contracting Covid-19.

Researchers studied the electronic health records of more than 230,000 Covid-19 patients in the USA. They discovered that 34% of them received a neurological or psychiatric diagnosis within six months of infection with the SARS-CoV-2 virus.

The most common diagnoses were anxiety disorders (occurring in 17% of patients), mood disorders (14%), substance misuse disorders (7%), and insomnia (5%). The risk of developing a neurological disorder was lower but still significant, including strokes (occurring in 2% of patients), dementia (0.7%) and brain haemorrhage (0.6%).

Who was most at risk of developing a brain condition?

The risk of developing a neurological or psychiatric condition was greatest in patients who had severe Covid-19.

Compared to the overall 34% incidence, a neurological or psychiatric diagnosis occurred in 38% of those who had been admitted to hospital, 46% of those in intensive care, and 62% in those who had delirium (encephalopathy) during their Covid-19 infection.

This gradient of risk applied to individual disorders too. For example, 2.7% of people needing intensive care and 3.6% of people with encephalopathy had a brain haemorrhage (compared to 0.3% in people without hospitalisation); 6.9% and 9.4% had ischaemic stroke (compared to 1.3% without hospitalisation); 1.7% and 4.7% developed dementia (0.4% without hospitalisation); and 2.8% and 7% were diagnosed with a psychotic disorder (0.9% without hospitalisation).

How does this compare to other respiratory illnesses?

The study was observational, so the researchers also looked at people who experienced flu and other respiratory tract infections over the same time frame. This was done in order to determine whether these neurological and mental health complications were linked specifically to Covid-19.

After accounting for biological characteristics - such as age, sex, ethnicity and existing health conditions - there was overall a 44% greater risk of neurological and mental health diagnoses after Covid-19 than after flu, and a 16% greater risk after Covid-19 than with respiratory tract infections.

As a result, the authors say that Covid-19 does lead to a greater risk of neurological and psychiatric disorders than these other health conditions.

It is worth nothing, however, that this was not seen for all conditions; there was no clear evidence that Covid-19 is associated with Parkinson’s or Guillain-Barré syndrome.

Professor Paul Harrison, lead author of the study, from the University of Oxford, UK, said: "These are real-world data from a large number of patients. They confirm the high rates of psychiatric diagnoses after Covid-19, and show that serious disorders affecting the nervous system (such as stroke and dementia) occur too. While the latter are much rarer, they are significant, especially in those who had severe Covid-19."

"Although the individual risks for most disorders are small, the effect across the whole population may be substantial for health and social care systems due to the scale of the pandemic and that many of these conditions are chronic. As a result, health care systems need to be resourced to deal with the anticipated need, both within primary and secondary care services."

Were there any limitations of the study?

The authors note several limitations to their study. Firstly, the completeness and accuracy of the electronic health records is not known. Secondly, many people with Covid-19 have mild or no symptoms and do not present for health care, therefore, the people studied here are likely to have been more severely affected than in the general population. Thirdly, the severity and course of the neurological and psychiatric disorders is not known.

Writing in a linked Comment article, Dr Jonathan Rogers (from University College London), who was not involved in the study, said: "[This] study points us towards the future, both in its methods and implications. Researchers need to be able to observe and anticipate the neurological and psychiatric outcomes of future emerging health threats by use of massive, international, real-world clinical data. Selection biases will remain an issue, not necessarily mitigated by sample size, and thus the onus should be on countries with public health-care systems to enable truly comprehensive national data to be available for research. Sadly, many of the disorders identified in this study tend to be chronic or recurrent, so we can anticipate that the impact of Covid-19 could be with us for many years."