#16,953
Between vaccines, acquired immunity, and better medical treatments we have reduced the risks of dying from acute COVID infection, but we continue to see evidence of lingering, often debilitating, `Long-COVID' illness in many patients.
More than two years ago (April 2020), in JAMA: Neurologic Manifestations Of Patients With Severe Coronavirus Disease, we saw the first major report on the neurological impact of COVID-19, one which found that more than 1/3rd of a study group (n=214) hospitalized in Wuhan, China showed signs of neurological involvement.
Findings that led some researchers over the summer of 2020 to wonder - Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms by Emily A. Troyer, Jordan N. Kohn, and Suzi Hong.
Within months it became apparent that COVID can affect many other parts of the body, manifesting in a wide range of post-covid symptoms.
In recent weeks, we've looked at a number of new studies that serve to remind us that COVID is more than just a `flu-like' illness.
MMWR: Post–COVID-19 Symptoms and Conditions Among Children and Adolescents
More Evidence On The Long-term Impact of SARS-CoV-2 Infection
BMJ: Prognosis and Persistence of Smell and Taste Dysfunction in Patients with Covid-19
Today we can add another; a comprehensive review of the neurological and psychiatric impact of COVID infection on more than 1 million patients. I've reproduced the Abstract below, which is followed by a press release from Oxford University.
Maxime Taquet, PhD Rebecca Sillett, BA Lena Zhu, BS Jacob Mendel, MMath Isabella Camplisson, BS Quentin Dercon, MScOpen Access Published:August 17, 2022 DOI:https://doi.org/10.1016/S2215-0366(22)00260-7
Summary
Background
COVID-19 is associated with increased risks of neurological and psychiatric sequelae in the weeks and months thereafter. How long these risks remain, whether they affect children and adults similarly, and whether SARS-CoV-2 variants differ in their risk profiles remains unclear.
Methods
In this analysis of 2-year retrospective cohort studies, we extracted data from the TriNetX electronic health records network, an international network of de-identified data from health-care records of approximately 89 million patients collected from hospital, primary care, and specialist providers (mostly from the USA, but also from Australia, the UK, Spain, Bulgaria, India, Malaysia, and Taiwan). A cohort of patients of any age with COVID-19 diagnosed between Jan 20, 2020, and April 13, 2022, was identified and propensity-score matched (1:1) to a contemporaneous cohort of patients with any other respiratory infection.
Matching was done on the basis of demographic factors, risk factors for COVID-19 and severe COVID-19 illness, and vaccination status. Analyses were stratified by age group (age <18 years [children], 18–64 years [adults], and ≥65 years [older adults]) and date of diagnosis. We assessed the risks of 14 neurological and psychiatric diagnoses after SARS-CoV-2 infection and compared these risks with the matched comparator cohort. The 2-year risk trajectories were represented by time-varying hazard ratios (HRs) and summarised using the 6-month constant HRs (representing the risks in the earlier phase of follow-up, which have not yet been well characterised in children), the risk horizon for each outcome (ie, the time at which the HR returns to 1), and the time to equal incidence in the two cohorts. We also estimated how many people died after a neurological or psychiatric diagnosis during follow-up in each age group. Finally, we compared matched cohorts of patients diagnosed with COVID-19 directly before and after the emergence of the alpha (B.1.1.7), delta (B.1.617.2), and omicron (B.1.1.529) variants.
Findings
We identified 1 487 712 patients with a recorded diagnosis of COVID-19 during the study period, of whom 1 284 437 (185 748 children, 856 588 adults, and 242 101 older adults; overall mean age 42·5 years [SD 21·9]; 741 806 [57·8%] were female and 542 192 [42·2%] were male) were adequately matched with an equal number of patients with another respiratory infection.
The risk trajectories of outcomes after SARS-CoV-2 infection in the whole cohort differed substantially. While most outcomes had HRs significantly greater than 1 after 6 months (with the exception of encephalitis; Guillain-Barré syndrome; nerve, nerve root, and plexus disorder; and parkinsonism), their risk horizons and time to equal incidence varied greatly. Risks of the common psychiatric disorders returned to baseline after 1–2 months (mood disorders at 43 days, anxiety disorders at 58 days) and subsequently reached an equal overall incidence to the matched comparison group (mood disorders at 457 days, anxiety disorders at 417 days).
By contrast, risks of cognitive deficit (known as brain fog), dementia, psychotic disorders, and epilepsy or seizures were still increased at the end of the 2-year follow-up period. Post-COVID-19 risk trajectories differed in children compared with adults: in the 6 months after SARS-CoV-2 infection, children were not at an increased risk of mood (HR 1·02 [95% CI 0·94–1·10) or anxiety (1·00 [0·94–1·06]) disorders, but did have an increased risk of cognitive deficit, insomnia, intracranial haemorrhage, ischaemic stroke, nerve, nerve root, and plexus disorders, psychotic disorders, and epilepsy or seizures (HRs ranging from 1·20 [1·09–1·33] to 2·16 [1·46–3·19]). Unlike adults, cognitive deficit in children had a finite risk horizon (75 days) and a finite time to equal incidence (491 days).
A sizeable proportion of older adults who received a neurological or psychiatric diagnosis, in either cohort, subsequently died, especially those diagnosed with dementia or epilepsy or seizures. Risk profiles were similar just before versus just after the emergence of the alpha variant (n=47 675 in each cohort). Just after (vs just before) the emergence of the delta variant (n=44 835 in each cohort), increased risks of ischaemic stroke, epilepsy or seizures, cognitive deficit, insomnia, and anxiety disorders were observed, compounded by an increased death rate. With omicron (n=39 845 in each cohort), there was a lower death rate than just before emergence of the variant, but the risks of neurological and psychiatric outcomes remained similar.
Interpretation
This analysis of 2-year retrospective cohort studies of individuals diagnosed with COVID-19 showed that the increased incidence of mood and anxiety disorders was transient, with no overall excess of these diagnoses compared with other respiratory infections. In contrast, the increased risk of psychotic disorder, cognitive deficit, dementia, and epilepsy or seizures persisted throughout. The differing trajectories suggest a different pathogenesis for these outcomes.
Children have a more benign overall profile of psychiatric risk than do adults and older adults, but their sustained higher risk of some diagnoses is of concern. The fact that neurological and psychiatric outcomes were similar during the delta and omicron waves indicates that the burden on the health-care system might continue even with variants that are less severe in other respects. Our findings are relevant to understanding individual-level and population-level risks of neurological and psychiatric disorders after SARS-CoV-2 infection and can help inform our responses to them.
Increased risk of some neurological and psychiatric disorders remains two years after COVID-19 infection
CORONA VIRUS MEDICAL SCIENCES MENTAL HEALTH
New diagnoses of disorders including psychosis, dementia, seizures and ‘brain fog’ remain commoner two years after COVID-19 than after other respiratory infections, whereas the increased risks of depression and anxiety after COVID-19 are short-lived and there is no overall excess of cases.
Published in The Lancet Psychiatry, the new study from the University of Oxford and the National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre investigated neurological and psychiatric diagnoses in over 1.25 million people following diagnosed COVID-19 infection, using data from the US-based TriNetX electronic health record network.
The study reports on 14 neurological and psychiatric diagnoses over a 2-year period and compares their frequency with a matched group of people recovering from other respiratory infections. It also reports data in children and older adults separately, and compares data across three waves of the pandemic. To our knowledge, these are the first robust data addressing these important questions.
Confirming previous studies, many of the disorders are more common after COVID-19. Notably, the increased risk of anxiety and depression subsides within two months of COVID-19 and, over the whole 2-year period, are no more likely to occur than after other respiratory infections. In contrast, diagnoses of many neurological disorders (such as dementia and seizures), as well as psychotic disorders and ‘brain fog’, continue to be made more often after COVID-19 throughout the 2 years.
Results in children (under 18) showed similarities and differences to adults. The likelihood of most diagnoses after COVID-19 was lower 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 recovering from COVID-19 were more likely to be diagnosed with some conditions, including seizures and psychotic disorders.
More neurological and psychiatric disorders were seen during the delta variant wave than with the prior alpha variant. The omicron wave is associated with similar neurological and psychiatric risks as delta.
The study has several limitations. It is not known how severe, or how long-lasting, the disorders are. Nor is it clear when they began, since problems may be present for some time before a diagnosis is made. Unrecorded cases of COVID-19 and unrecorded vaccinations introduce some uncertainty into the results.
Professor Paul Harrison, Department of Psychiatry, University of Oxford, and Theme Lead, NIHR Oxford Health Biomedical Research Centre, who headed the study, said: ‘It is good news that the excess of depression and anxiety diagnoses after COVID-19 is short-lived, and that it is not observed in children. However, it is worrying that some other disorders, such as dementia and seizures, continue to be more likely diagnosed after COVID-19, even two years later. It also appears that omicron, although less severe in the acute illness, is followed by comparable rates of these diagnoses.’
Dr Max Taquet, NIHR Academic Clinical Fellow, University of Oxford, who led the analyses, said: 'The findings shed new light on the longer-term mental and brain health consequences for people following COVID-19 infection. 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.’
Although the degree of impairment can vary widely, and many of these impacts may lessen or resolve over time, we've seen studies suggesting that as many as 1 in 5 adults (20%) experience some type of `Long-COVID' sequelae.
And there is other research which suggest this number may be higher. Any way you figure it, there are likely tens of millions of Americans dealing with some form of `Long-COVID', and globally that number likely reaches into the hundreds of millions.
The burden on public health in the years ahead could be enormous, particularly given that at least one study (see Outcomes of SARS-CoV-2 Reinfection) strongly suggests that repeated COVID infections may lead to increasingly worse outcomes.
All of which makes COVID infection still something you really, really, should try to avoid if at all possible.
