Factors associated with the presence and intensity of ongoing symptoms in Long COVID

Identification of modifiable factors associated with symptom intensity among people seeking care for Post-Acute Sequelae of SARS-CoV-2 infection (PASC) could help guide the development of comprehensive, whole-person care pathways to alleviate symptoms irrespective of potential underlying pathophysiologies. We aimed to better define the key contributors to PASC, and sought the factors associated with PASC symptom presence and intensity.

In this cross-sectional study, 249 patients presenting for PASC care at a dedicated Post-COVID-19 clinic completed a standardized screening assessment prior to initial visit and evaluation by a general internist or nurse practitioner. We measured 46 symptoms based on the WHO's Global COVID-19 Clinical Platform Case Report Form for Post COVID Condition and performed a factor analysis and item response theory based 2-parameter logistic model to develop a population-based t-score to measure PASC symptom presence and intensity (PASC-SPI). A multivariable linear regression analysis was used to assess factors associated with PASC-SPI, accounting for demographics, comorbidities, COVID-19 infection duration and severity, and mental health.

Greater PASC-SPI was associated with greater symptoms of anxiety, a longer duration of COVID-19 infection, and hypercholesterolemia. Lower PASC-SPI was associated with older age, self-reported 1-3 units of alcohol per week, and self-reported clinician confirmation of COVID-19 diagnosis. Symptoms of anxiety accounted for a considerably higher proportion of variation in PASC-SPI than other variables.

Symptoms of anxiety were the strongest correlate of PASC-SPI, highlighting it as both a potential neuroinflammatory marker of PASC and a modifiable component of the illness. This emphasizes the need for comprehensive, whole person treatment strategies that integrate evidence-based interventions to address the multifaceted nature of PASC.