Neurological vs Psychiatric Outcomes After COVID-19: Which Risks Last Longer?

Following COVID-19 infection, the risk for developing neurological disorders remains high after 2 years, while the risk for psychiatric disorders subsides earlier. These are the findings of a study published in Lancet Psychiatry.

Researchers analyzed outcome data in a multinational, retrospective cohort study. They obtained data from the TriNetX electronic health records network between January 20, 2020 and April 13, 2022. A total of 1,284,437 patients diagnosed with COVID-19 were included compared with an equal number of patients diagnosed with other respiratory infections in the comparison cohort. In both cohorts, there were 185,748 children, 856,588 adults aged 18 to 64 years, and 242,101 adults aged 65 years and older, respectively. In the study sample, the mean age was 42.5 years, and 57.8% were women.

Researchers also stratified patients into subgroups of Alpha, Delta, and Omicron depending on when they were first diagnosed with COVID-19 and what was the dominant strain at the time of diagnosis in the United States.

They analyzed 2-year risk trajectories for individual outcomes after COVID-19 infection, calculating hazard ratios (HRs) after 6 months, risk horizons, and time to equal incidence, contrasting these outcome trajectories with the comparison cohort.

Within the first 6 months after COVID-19 infection, patients with COVID-19 demonstrated a higher risk for:

• insomnia (HR, 1.13; 95% CI, 1.10-1.16; P <.0001),
• cognitive deficits (HR, 1.36; 95% CI, 1.33-1.39; P <.0001),
• epilepsy or seizures (HR, 1.14; 95% CI, 1.09-1.19; P <.0001),
• dementia (HR, 1.33; 95% CI, 1.26-1.41; P <.0001),
• psychotic disorder (HR, 1.27; 95% CI, 1.18-1.37; P <.0001),
• mood disorder (HR, 1.08; 95% CI, 1.06-1.1; P <.0001),
• anxiety disorder (HR, 1.13; 95% CI, 1.11-1.15; P <.0001),
• ischemic stroke (HR, 1.11; 95% CI, 1.06-1.17; P <.0001),
• intracranial hemorrhage (HR, 1.09; 95% CI, 1.01-1.18; P =.020), and
• myoneural junction or muscle disease (HR, 1.89; 95% CI, 1.76-2.04; P <.0001).

Patients were less likely to develop Guillain-Barré syndrome, parkinsonism, encephalitis, or nerve, nerve root, or plexus disorders. Children with COVID-19 were less likely to develop mood or anxiety disorders, but they were more likely to develop encephalitis and nerve, nerve root, or plexus disorders compared with older age groups and compared with individuals with other respiratory diseases.

Risk horizons indicate when the risk for a certain outcome returns to baseline levels. Mood disorders, anxiety disorders, ischemic stroke, and insomnia all had shorter risk horizon durations which returned to baseline after 43, 58, 66 and 90 days, respectively. Myoneural junction or muscle diseases and intracranial hemorrhaging demonstrated longer risk horizons of 497 and 506 days, respectively, while risk horizons for the remaining outcomes were never reached.

Time to equal incidence reflects the point when incidence of outcomes is the same in the both the COVID-19 cohort and the comparison cohort. Times to equal incidence of anxiety disorders, mood disorders, intracranial hemorrhage, and ischemic stroke occurred after 417, 457, 658, and 712 days, respectively, but the other outcomes never reached time to equal incidence.

Researchers noted that 6-month risk profiles were similar before the Alpha variant compared with immediately after its emergence. When the Delta variant emerged, the 6-month risks for anxiety disorders, insomnia, cognitive deficit, epilepsy or seizures, and ischemic strokes were significantly higher, while dementia risk was lower. The death rate also increased. With the Omicron variant, risks for neurological and psychiatric outcomes remained similar, while the death rate was lower before the emergence of the variant.

Researchers noted different risk trajectories among post-COVID-19 neurological and psychiatric outcomes.

“The risk of cognitive deficit, dementia, psychotic disorder, and epilepsy or seizures remained increased at 2 years after a COVID-19 diagnosis, while the risks of other diagnoses (notably, mood and anxiety disorders) subsided early and showed no overall excess over the 2-year follow-up,” the researchers stated.

They concluded that “The possible mechanisms underlying neurological and psychiatric consequences of COVID-19 remain to be determined in longitudinal and multifaceted studies.”

Several study limitations warrant mention, the researchers acknowledge. Asymptomatic or self-diagnosed COVID-19 cases were not included in the electronic health records, nor was infection severity for either COVID-19 or other respiratory infections considered. Data about mortality after hospital discharge was incomplete. Additionally, the researchers only analyzed outcomes of individuals from the beginning of the pandemic during the 2-year follow-up, so the possibility of different variants and vaccination status may have resulted in different outcomes. Children and adolescents were categorized together.