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Just over a third of people who overcome the coronavirus are diagnosed with a psychiatric or neurological disorder six months on, research suggests.
Early in the outbreak, experts warned the pandemic could have a "profound" and "pervasive" impact on people's mental health for some time. It is also increasingly coming to light the respiratory virus can impact the brain, with recent research revealing abnormal cells in the vital organ post-infection.
To learn more, scientists from the University of Oxford analysed the health records of more than 236,000 people with the coronavirus.
Results – published in The Lancet Psychiatry – estimate 34% were later diagnosed with one of 14 neurological or psychiatric conditions, including anxiety, mood disorders, strokes or even dementia.
The risk of these subsequent diagnoses was up to 44% higher in coronavirus survivors than those who had overcome flu or another respiratory infection, suggesting the pandemic is having a "specific impact".
Although unclear, the coronavirus may directly affect the brain, trigger an exaggerated immune response that damages the vital organ or simply cause stress that has mental health consequences, like the "cabin fever" that comes with quarantining.
"These are real-world data from a large number of patients," said lead author Professor Paul Harrison.
"They confirm the high rates of psychiatric diagnoses after COVID-19 [the disease caused by the coronavirus] and show 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."
While previous studies have flagged similar risks, the scientists felt large-scale data were lacking.
They therefore analysed the electronic health records of more than 236,000 coronavirus patients from the US database TriNetX.
The participants were made up of people over 10 years old, who had caught the infection after 20 January 2020 and were alive on 13 December.
They were compared against more than 105,000 flu patients and over 236,000 with any respiratory tract infection.
Overall, an estimated 34% of those who overcame the coronavirus later endured a neurological or psychiatric condition. For more than one in 10 (13%), this was their first diagnosis of its kind.
Anxiety was the most common condition, affecting just under one in five (17%). This was followed by mood disorders (14%), substance misuse (7%) and insomnia (5%).
Neurological disorders were less common. Nevertheless, around one in 50 (2.1%) were estimated to endure an ischaemic stroke; when a blood clot blocks oxygen reaching the brain.
Dementia (0.7%) and brain bleeds (0.6%) also occurred.
While 34% of the overall coronavirus patients endured a psychiatric or neurological disorder, this rose to 38% in those admitted to hospital, 46% in intensive care and 62% with delirium during their infection.
Watch: How coronavirus affects the brain in severe cases
Overall, the coronavirus patients were 44% more likely to endure a neurological or psychiatric disorder than those who overcame flu. They were also 16% more at risk than the patients who had any respiratory infection.
"Our results indicate brain diseases and psychiatric disorders are more common after COVID-19 than after flu or other respiratory infections, even when patients are matched for other risk factors," said co-author Dr Max Taquet.
The scientists took into account the participants' age, sex, ethnicity and underlying health.
"We now need to see what happens beyond six months," said Dr Taquet.
"The study cannot reveal the mechanisms involved, but does point to the need for urgent research to identify these, with a view to preventing or treating them."
The study did not link the coronavirus to Guillain-Barré syndrome; a nerve condition flagged as a potential risk earlier in the pandemic.
The coronavirus was also not linked to the onset of Parkinson's-like symptoms. So-called Parkinsonism was observed in survivors of the 1918 Spanish flu pandemic and may be a "delayed outcome" of the existing outbreak, emerging beyond the six-month study, wrote the Oxford scientists.
Dr Jonathan Rogers from University College London – who was not involved in the research – added, however: "From the outbreak start in Wuhan, China, we can say with growing confidence delayed neuropsychiatric sequelae such as post-encephalitic Parkinsonism do not occur after COVID-19 – unless the delay exceeds one year."
The scientists acknowledged the electronic health records they analysed may not be completely accurate and up to date.
Mild or asymptomatic coronavirus cases may also not seek medical care and could therefore be unaccounted for in the records.
The severity of the patients' psychiatric and neurological diagnoses is also unknown. A family history of these disorders may also be lacking from the health data, particularly if "different providers were involved in managing records", wrote Dr Rogers.
Supposedly newfound "psychoses" may be "exacerbations of pre-existing conditions unknown to the health-care provider", he added.
Nevertheless, the results could aid service planning for coronavirus survivors.
"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," said Professor Harrison.
"As a result, health care systems need to be resourced to deal with the anticipated need, both within primary and secondary care services."
Dr Rogers concluded: "[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 the impact of COVID-19 could be with us for many years."
Dr Musa Sami, from the University of Nottingham, added: "What is important for the public to remember is most patients who develop COVID-19 will not develop these complications.
"Those experiencing psychological or neurological symptoms should seek medical attention and remember effective treatments are available for many of these conditions."
Watch: How vaccines are reducing COVID infection