Text version
How long do COVID-associated psychiatric disorders last? Are some age groups more likely to be affected for long periods of time? A prospective cohort study would help address these questions, but previous studies have looked only about 10 months out. Keeping track of a really large cohort beyond that is difficult. So, instead, let’s turn to a retrospective view of an affected cohort with an unaffected comparison group.
Hi! Jim Phelps here for the Psychopharmacology Institute. COVID-19 is known to be associated with many neurologic and psychiatric sequelae, but important clinical questions remain. These include the duration of increased risk and differences in susceptibility by age, if any. To address these questions, Dr. Maxime Taquet and colleagues looked at de-identified records from 89 million patients from 8 countries around the world, of whom 1.5 million had documented COVID-19. Think of all the psychiatric and neurologic disorders you’ve heard are associated with COVID and imagine what happens to them months, years, and 2 years later.
Well, here’s the good news. Mood and anxiety symptoms revert to their baselines relatively quickly, within 2 months, whereas rates of psychosis and cognitive impairment are still elevated at 2 years. I thought this outcome a little ho-hum until I looked at the details. Take psychosis, for example. The authors are looking at new-onset cases, not exacerbations or recurrences. Their results suggest that after COVID-19 infection, the odds of becoming psychotic are elevated relative to the comparison cohort who had a non-COVID respiratory infection. Furthermore, this elevated risk continued for 2 years, with no suggestion that the risk decreases with time. That’s pretty alarming.
For all of the illnesses studied, which included neurologic disorders such as Guillain-Barre and epilepsy, the risk of acquiring a new diagnosis is shown as a hazard ratio, which was greater than, equal to, or less than in the comparison group. As a key aspect of this study, these hazard ratios are shown over time out to 2 years. That’s how we see that the risk of developing psychosis is sustained. The hazard ratio is 1.5 in the first month, meaning a 50% increase in the probability of a new diagnosis among those with COVID-19 relative to the comparison group. The hazard ratio for psychosis is still elevated relative to the comparison group, although lower at 1.1 after a year. The hazard ratio is still at 1.1 at 2 years. By contrast, for both mood and anxiety disorders, hazard ratios are increased in the first month after diagnosis, to roughly 1.5 and 1.6 respectively, but these rapidly fall to 1.0 or no difference from the comparison group by 2 months.
Now, let’s look at cognitive impairment. What do the hazard ratios look like over time? Well, first, let’s see how this was measured. All of the other outcomes, such as a mood disorder, anxiety disorder, or psychosis, were based on a single diagnostic code. For cognitive impairment, however, the authors stitched together several ICD-10 codes, trying to capture what’s often described as brain fog. Using this composite measure, the hazard ratio for brain fog was 1.6 in the first month—that is, brain fog is 60% more likely than in the group that had a non-COVID respiratory infection. This likelihood of cognitive impairment decreases to a hazard ratio of only 1.1 by 1 year and slowly declines from there, to nearly 1.0 at 2 years.
For children less than 18 years of age, the picture was quite different. Mood and anxiety diagnoses were not elevated at all. Encephalitis, epilepsy, and several other neurologic disorders showed increased hazard ratios. For psychosis, however, the risk for the exposed group is double relative to that of the comparison group, with a hazard ratio of 2.0.
The authors point out that knowing the risk trajectory over time supports clinical guidance. For example, if no anxiety disorder has been diagnosed within 2 months of COVID, then the risk thereof is not likely to be greater than after a non-COVID respiratory infection. By contrast, vigilance for psychosis should remain increased for at least 2 years.
For more on all this, Figure 1 in the article, which is linked here, presents hazard ratios over time for all of the diagnoses considered. The patterns are interesting.
Abstract
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.
Funding: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, The Wolfson Foundation, and MQ Mental Health Research.
Download PDF and other files
Reference
Taquet, M., Sillett, R., Zhu, L., Mendel, J., Camplisson, I., Dercon, Q., & Harrison, P. J. (2022).
The Lancet Psychiatry, 9
(10), 815-827.
