Your new experience awaits. Try the new design now and help us make it even better

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  WellsAnne Marie WellsSummer  RolinSummer RolinBarbara  Robles-RamamurthyBarbara Robles-RamamurthyGabriela  Gibson-LopezGabriela Gibson-LopezMartin  GorosMartin GorosJonathan A  GelfondJonathan A GelfondStephen  GelfondStephen GelfondPhilip  E BalfanzPhilip E BalfanzMelissa  DeuterMelissa DeuterDon  McGearyDon McGearyMonica  Verduzco GutierrezMonica Verduzco Gutierrez*
  • The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

The final, formatted version of the article will be published soon.

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

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.