Latent class analysis of post-acute sequelae of SARS-CoV-2 infection

Symptoms post-SARS-CoV-2 infection may persist for months and cause significant impairment and impact to quality of life. Acute symptoms of SARS-CoV-2 infection are well studied, yet data on clusters of symptoms over time, or post-acute sequelae of SARS-CoV-2 infection (PASC), are limited. We aim to characterize PASC phenotypes by identifying symptom clusters over a six-month period following infection in individuals vaccinated (boosted and not) and those unvaccinated. Subjects with ≥1 self-reported symptom and positive RT-PCR for SARS-CoV-2 at CVS Health US test sites were recruited between January and April 2022. Patient-reported outcomes symptoms, health-related quality of life (HRQoL), work productivity and activity impairment (WPAI) were captured at 1 month, 3 months, and 6 months post-acute infection. Phenotypes of PASC were determined based on subject matter knowledge and balanced consideration of statistical criteria (lower AIC, lower BIC, and adequate entropy) and interpretability. Generalized estimation equation approach was used to investigate relationship between QoL, WPAI and number of symptoms and identified phenotypes, and relationship between phenotypes and vaccination status as well. LCA identified three phenotypes that are primarily differentiated by number of symptoms. These three phenotypes remained consistent across time periods. Subjects with more symptoms were associated with lower HRQoL, and worse WPAI scores. Vaccinated individuals were more likely to be in the low symptom burden latent classes at all time points compared to unvaccinated individuals.