Risk trajectories of post-COVID neurological and psychiatric outcomes

In a recent study published in The Lancet Psychiatry, researchers examined the evolution of incidence or relative risk of neuropsychiatric diagnoses for two years in patients who had recovered from coronavirus disease 2019 (COVID-19).

Study: Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients. Image Credit: Drazen Zigic/Shutterstock

Background

There is a lack of studies evaluating the neurological and psychiatric outcomes of COVID-19 for a prolonged time elapse following the index severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since increased risks of neurological and psychiatric sequelae persist in both children and adults, albeit with different risk profiles; so, it is crucial to investigate these aspects too.

About the study

In the present study, researchers assessed the risks of 14 neurological and psychiatric outcomes of COVID-19 up to two years in a cohort comprising 1284437 patients. They extracted the study data from an international network, the TriNetX electronic health records network, for all patients (of any age) with COVID-19 diagnosed between January 20, 2020, and April 13, 2022.

They also created a control cohort comprised of patients with any other respiratory infection, propensity-score matched 1:1 based on demographic factors, COVID-19 risk factors, severity, and vaccination status. The team stratified the study population based on age and date of COVID-19 diagnosis. There were COVID-19 patients under 18 years [children], 18 to 64 years [adults], and 65 years and above [older adults].

The researchers presented the two-year risk trajectories using time-varying hazard ratios (HRs), summarized using the six-month constant HRs. The study findings represented the risks in the earlier phase of follow-up, the risk horizon for each outcome (i.e., the time in which the HR returned to one), and the time to the equal incidence in both the study cohorts.

Further, they estimated the number of deaths after a neurological or psychiatric diagnosis during the follow-up in each age group. Lastly, the team compared the study cohorts diagnosed with COVID-19 before and after the emergence of the Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529) SARS-CoV-2 variants of concern (VOCs).

Study findings

The study analyses covered 1284437 individuals, with 185748 children, 856588 adults, and 242101 older adults. Their average was 42.5 years, and 57.8% of them were females. The authors noted that the risks of post-COVID-19 neurological and psychiatric outcomes followed different trajectories for different age groups.

Children were not at an increased risk of mood or anxiety disorders over six months follow-up, and the risk of cognitive deficit among them was transient; however, they shared adults’ risk of several other diagnoses and were at risk of epilepsy or seizures. In adults, the risk of cognitive deficit, dementia, psychotic disorder, and epilepsy or seizures remained elevated throughout the study duration.

Likewise, most neurological and psychiatric outcomes of COVID-19 had HRs significantly greater than one after six months of follow-up; the risk horizons and time to equal incidence varied greatly. The risks of the common psychiatric disorders, such as mood and anxiety disorders) returned to normal within one to two months and eventually attained an equal overall incidence to the control group.

Conversely, the risks of cognitive deficit (brain fog), dementia, psychotic disorders, and seizures remained elevated throughout the two-year study period. The older adults in both the study cohorts with a neurological or psychiatric diagnosis subsequently died, especially those diagnosed with dementia or seizures.

Notably, the emergence of the Omicron VOC had no substantial effect on the neurological and psychiatric outcomes of COVID-19. Accordingly, these outcomes remained the same as observed after the emergence of the Delta VOC, albeit with a significantly lower death rate.

Conclusions

Overall, the two-year retrospective cohort study of individuals diagnosed with COVID-19 demonstrated that risk trajectories of all 14 post-COVID-19 neurological and psychiatric outcomes varied, indicating the involvement of different pathogenesis behind each outcome.

Since some of the neurological and psychiatric post-COVID-19 outcomes, including cognitive deficit, dementia, psychotic disorders, and epilepsy, tend to persist for as long as two years, public health officials should enhance service provision to diagnose and manage these and research to understand the mechanisms. More importantly, policies should aim at controlling COVID-19 in pediatric populations; although they had different risk profiles, they showed similar risk profiles as adults for several neuropsychiatric diagnoses.

Furthermore, since neurological and psychiatric outcomes remained similar regardless of the SARS-CoV-2 VOCs involved, the burden on the healthcare system might not ease even with the emergence of less severe variants.

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