AUTHOR=Wells Anne Marie , Rolin Summer , Robles-Ramamurthy Barbara , Gibson-Lopez Gabriela , Goros Martin , Gelfond Jonathan A. , Gelfond Stephen , Balfanz Philip , Deuter Melissa , McGeary Donald , Verduzco-Gutierrez Monica 

TITLE=Neuropsychiatric symptoms cluster as primary drivers of Long COVID complexity: a South Texas retrospective cohort study

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1612489

DOI=10.3389/fneur.2025.1612489

ISSN=1664-2295

ABSTRACT=Long COVID, previously known as Post-Acute Sequelae of SARS-CoV-2 (PASC), refers to prolonged symptoms or diagnosable conditions following COVID-19 infection. The neuropsychiatric profile of Long COVID patients remains ambiguous. This study aimed to assess neuropsychiatric symptoms in a retrospective cohort of Long COVID patients (N = 162) at a Rehabilitation Medicine clinic in South Texas. Clinical data from patient records were used to calculate a Symptom Score, and screening tools for stress/PTSD (PCL-5), depression (PHQ-9), anxiety (GAD-7), and quality of life (SWL) were employed to evaluate if Long COVID duration and severity could predict neuropsychiatric outcomes. The majority were female (71%) and Hispanics (53%) who presented for treatment of Long COVID symptoms during the study period, including fatigue (93%), coughing/shortness of breath (81%), fever (67%), anosmia (58%), ageusia (54%), and weight loss (56%). A minority of participants were hospitalized (N = 49) or required ventilator support (N = 5) during acute infection. There was a high burden of neuropsychiatric symptoms, including subjective cognitive impairment (79%), headache (74%), and insomnia (58%). Symptom Score (median = 9, IQR [8,11]) was significantly correlated with increased depression (PHQ-9; p < 0.05), anxiety (GAD-7; p < 0.05) and elevated stress/PTSD (PCL-5; p < 0.05) symptoms. Long COVID patients taking stimulants or mood stabilizers had higher GAD-7 (p < 0.031, p < 0.035) and PHQ-9 (p < 0.034, p < 0.009) scores but not PCL-5 scores. Importantly, duration of Long COVID symptomatology also did not predict PCL-5 scores. No patient factors (e.g., sex, age, BMI, ethnicity) mediated Symptom Score. Nonetheless, historically marginalized groups, such as women and Hispanics, have been disproportionately affected by COVID-19. This study is the first to utilize validated screening tools to determine the presence and severity of neuropsychiatric symptoms in Long COVID patients. These findings may guide clinical management and future research on Long COVID, especially in historically excluded populations.