A study of over 1.25 million people diagnosed with COVID-19 suggests an elevated risk of developing some neurological and psychiatric conditions for two years after COVID-19 infection compared to other respiratory infections.
The increased risk of some neurological and psychiatric conditions (such as dementia, psychosis, 'brain fog' and seizures) is still higher two years after COVID-19 compared to other respiratory infections, suggests an observational study funded by MQ of more than 1.25 million patient health records published in The Lancet Psychiatry journal. The increased risk of depression and anxiety in adults lasts less than two months before returning to rates comparable to those after other respiratory infections.
In another recent paper published in Brain Communications by the same researchers, they found support for the hypothesis that brain fog, or cognitive decline, is associated with damaged small blood vessels in the brain, caused by COVID-19.
Since the COVID-19 pandemic began, there has been growing evidence that survivors might be at increased risk of neurological and psychiatric conditions. A previous study reported that COVID-19 survivors are at increased risk of several neurological and mental health conditions in the first six months after infection. However, until now, there have been no large-scale data examining the risks of these diagnoses over a longer time period. This study was also the first large-scale study to look at the risk of neurological and mental health conditions after COVID-19 in children and to assess how the risks change with the emergence of new variants.
Professor Paul Harrison, lead author of the study, from the University of Oxford, UK, says:
In addition to confirming previous findings that COVID-19 can increase the risk for some neurological and psychiatric conditions in the first six months after infection, this study suggests that some of these increased risks can last for at least two years. The results have important implications for patients and health services as it suggests new cases of neurological conditions linked to COVID-19 infection are likely to occur for a considerable time after the pandemic has subsided. Our work also highlights the need for more research to understand why this happens after COVID-19, and what can be done to prevent or treat these conditions.
The study analysed data on 14 neurological and psychiatric diagnoses gathered from electronic health records, mostly from the US, over a two-year period. Of those 1,284,437 people had a confirmed SARS-CoV-2 infection on or after January 20, 2020 and were included in the study: 185,748 children (aged under 18 years), 856,588 adults between 18 and 64 years old, and 242,101 adults over 65. These individuals were matched to an equal number of patients with another respiratory infection to act as a control group.
Records from COVID-19 patients infected during different pandemic waves were also compared to investigate differences in the impact of the alpha, delta, and omicron variants on the risk of neurological and psychiatric diagnoses. People who had a first diagnosis of COVID-19 within the period when a particular variant was dominant (alpha: 47,675 people, delta: 44,835 people, omicron: 39,845 people) were compared with a control group of the same number of individuals who had a first diagnosis of COVID-19 in the period just before the emergence of that variant.
The study found that, in adults, the risk of having a depression or anxiety diagnosis initially increased post-SARS-CoV-2 infection but returned to the same as with other respiratory infections after a relatively short time (depression at 43 days, anxiety at 58 days.) After the initial increase, the risks for a depression or anxiety diagnosis dropped to below that of the control group, meaning that after two years, there was no difference in the overall incidence of depression and anxiety between the COVID-19 group and the other respiratory infections group (in adults aged 18-64 in both groups, within two years post infection, there were approximately 1,100 cases of depression per 10,000 people and about 1,800 cases of anxiety per 10,000 people).
However, the risk of diagnosis of some other neurological and mental health conditions was still higher after COVID-19 than for other respiratory infections at the end of the two-year follow-up. Adults aged 18-64 who had COVID-19 up to two years previously had a higher risk of cognitive deficit, or ‘brain fog’ (640 cases per 10,000 people), and muscle disease (44 cases per 10,000), compared to those who had other respiratory infections up to two years previously (550 cases per 10,000 people of ‘brain fog’ and 32 cases per 10,000 of muscle disease). In adults aged 65 and over who had COVID-19 up to two years previously, there was a higher occurrence of ‘brain fog’ (1,540 cases per 10,000 people), dementia (450 cases per 10,000 people) and psychotic disorder (85 cases per 10,000 people) compared to those who previously had a different respiratory infection (1,230 cases per 10,000 for ‘brain fog’, 330 cases per 10,000 for dementia and 60 cases per 10,000 for psychotic disorder.)
The likelihood of most neurological and psychiatric diagnoses after COVID-19 was lower in children than in adults, and they were not at greater risk of anxiety or depression than children who had other respiratory infections. However, like adults, children were more likely to be diagnosed with some conditions, including seizures (260 cases per 10,000 children for the COVID-19 group; 130 cases per 10,000 for the control group) and psychotic disorders (18 cases per 10,000 children for the COVID-19 group; 6 cases per 10,000 for the control group), over the two years following COVID-19.
Little change was observed in the risks of neurological and psychiatric diagnoses six months post COVID-19 just before and just after the emergence of the alpha variant. However, the emergence of the delta variant was associated with significantly higher six-month risks of anxiety (10% increased risk), insomnia (19% increased risk), cognitive deficit (38% increased risk), epilepsy or seizures (26% increased risk), and ischaemic strokes (27% increased risk) but a lower risk of dementia (40% decreased risk) when compared to those diagnosed with COVID-19 just before the delta wave. The risks during the omicron wave were similar to those when delta was the dominant variant.
Our findings shed new light on the longer-term mental and brain health consequences for people following COVID-19 infection. It is good news that the higher risk of depression and anxiety diagnoses after COVID-19 is relatively short-lived and there is no increase in the risk of these diagnoses in children. However, it is worrying that some other conditions, such as dementia and seizures, continue to be more frequently diagnosed after COVID-19, even two years later.
Says Dr Max Taquet from the University of Oxford, who led the analyses. “The emergence of the delta variant was associated with an increase in risk for several conditions; however, it’s important to note that the overall risk of these conditions is still low. With omicron as the dominant variant, although we see much milder symptoms directly after infection, similar rates of neurological and psychiatric diagnoses are observed as with delta, suggesting that the burden on the healthcare system may continue even with variants that are less severe in other respects.”
In a separate study it was found that a particular type of anticonvulsant medication, called phenytoin, reduces the risk of cognitive defects by 22-27% in people with COVID-19 infection, provided it was administered at the right time.
According to that research, also funded by MQ, this might indicate that brain fog is, at least in part, due to damage to small blood vessels in the brain. Maxime Taquet, lead author of that study, says
These findings shed new light on the possible causes of brain fog, and how it might be prevented in the future. We are definitely not suggesting that people should start taking phenytoin if they have COVID. The goal of this study was to identify possible mechanisms, not possible treatments.
The researchers are calling for their study findings to inform healthcare clinics and public health policy:
- This study suggests that an increase in the number of new COVID-19 cases is likely to lead to a relatively short-lived increase in the number of mood and anxiety conditions, meaning mental health practitioners need to be prepared and well-resourced after a COVID-19 wave.
- Additionally, the sustained increased risk for some neurological and psychiatric diagnoses over two years post-COVID-19 indicates that patients and clinicians must remain alert to the possibility of these delayed conditions.
- Healthcare centres should be well supported to diagnose and treat these neurological and mental health conditions since new cases are likely to occur for a considerable time after the pandemic has subsided.
The authors caution that there are some important limitations to consider, including that the study may underrepresent self-diagnosed and asymptomatic cases of COVID-19 as these are unlikely to be recorded in electronic health records. Additionally, they did not look at the severity or length of each condition after diagnosis or whether these are similar after COVID-19 than after other respiratory infections.
This research was funded by the National Institute for Health and Care Research (NIHR), MQ and the Wolfson Foundation.
