Higher Risk of Psychiatric and Neurologic Comorbidities Following Severe COVID-19 Infection

Individuals with prior COVID-19 infections face an increased risk of developing psychiatric and neurologic comorbidities such as dementia, parkinsonism, anxiety, and psychosis, according to a study published in Parkinsonism & Related Disorders. Notably, the risk of these complications appears to be higher in patients who experienced severe COVID-19.

Proposed mechanisms for this association include direct damage to the basal ganglia, hypoxic brain injury, unmasking of pre-existing subclinical parkinsonism, or viral spread to the brain via the olfactory route. However, existing literature provides mixed findings, with some studies suggesting an increased risk of PD following COVID-19 and others finding no such association.

In this study, researchers aimed to investigate the incidence of PD following COVID-19 infection compared to individuals without prior COVID-19 infection. Using an extensive healthcare research network encompassing over 100 million patients in the US, researchers sought to shed light on the relationship between COVID-19 and the risk of developing PD, considering a time horizon of up to 2.5 years.

The study included data from 27,614,510 patients, with 2,036,930 having a positive COVID-19 diagnosis and 25,577,580 without. To address potential biases, researchers employed propensity score matching based on age, sex, and smoking history and collected various clinical data, including patient demographics, comorbid conditions, medication use, encounter details, laboratory results, and new-onset PD diagnoses up to 2 years following the index event. After propensity score matching, age, sex, and smoking history differences became non-significant, resulting in 2,036,930 patients in each cohort.

The analysis revealed significantly increased odds of new-onset PD in the COVID-19 cohort at 3, 6, 9, and 12 months following the index event. The peak odds ratio of 1.25 (95% CI 1.15–1.39) was observed at six months post-COVID-19 infection. However, beyond 12 months, the risk of PD diagnosis in the COVID-19 group decreased, and at 24 months, it was significantly lower than in the non-COVID-19 group, with an odds ratio of 0.92 (95% CI 0.87–0.98).

Findings suggest that individuals with COVID-19 are at an elevated risk of developing PD during the first year after infection. This risk decreases over time, indicating a complex relationship between COVID-19 pathophysiology and PD development. Several factors could contribute to this trend, including acute exacerbation of pre-existing subclinical parkinsonism, alterations in dopaminergic expression, hypoxic injury to the basal ganglia, and COVID-19-induced neurodegeneration.

Notably, the study underscores the need for further research to highlight the relationship between COVID-19 and PD, including pathological and biochemical investigations. It also raises questions about the potential impact of COVID-19 vaccination on PD risk.

"The study's limitations, including the use of healthcare diagnosis codes and the potential for missed COVID-19 infections early in the pandemic, should be considered in interpreting the results," said researchers.

Reference

Wang AS, Perez JA, Gunzler SA. Frequency of Parkinson disease following COVID-19 infection: A two-year retrospective cohort study. Parkinsonism & Related Disorders. 2023;111:105433-105433. doi:10.1016/j.parkreldis.2023.105433