ORIGINAL RESEARCH article
Front. Neurol.
Sec. Neurorehabilitation
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1612489
Neuropsychiatric Symptoms Cluster as Primary Drivers of Long COVID Complexity: A South Texas Retrospective Cohort Study
Provisionally accepted
Anne Marie Wells
Summer Rolin
Barbara Robles-RamamurthyGabriela Gibson-LopezMartin GorosJonathan A GelfondStephen GelfondPhilip E BalfanzMelissa Deuter
Don McGeary
Monica Verduzco Gutierrez*- The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
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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.
Keywords: Long Covid, PTSD, stress, Depression, Anxiety, PCL-5, GAD-7, PHQ-9
Received: 15 Apr 2025; Accepted: 07 Jul 2025.
Copyright: © 2025 Wells, Rolin, Robles-Ramamurthy, Gibson-Lopez, Goros, Gelfond, Gelfond, Balfanz, Deuter, McGeary and Verduzco Gutierrez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Monica Verduzco Gutierrez, The University of Texas Health Science Center at San Antonio, San Antonio, 78229, Texas, United States
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