Symptom-based phenotypes and health-related quality of life in Spanish patients with long COVID: a latent class analysis

Long COVID presents with heterogeneous, fluctuating symptoms that markedly reduce health-related quality of life (HRQol). This study aimed to identify symptom-based subgroups of patients with Long COVID using Latent Class Analysis (LCA) and to compare health-related quality of life across the identified classes. A cross-sectional study was conducted in Salamanca, Spain. Adults with Long COVID per WHO criteria were recruited from primary care and a specialized post-COVID unit. Sociodemographic, clinical, and symptom data ( ad hoc checklist) were collected; HRQoL was assessed using the SF-36. Latent Class Analysis identified symptom-based groups; model selection was based on BIC, entropy, and interpretability. Classes were compared on sociodemographic, clinical, and HRQoL variables. A total of 304 participants were included in the analysis (68.1% women; mean age 52.7 ± 11.9 years). Four classes were identified: Class 1 (28.9%) high multisystem symptom burden; Class 2 (20.1%) low symptom burden; Class 3 (25.3%) moderate neuropsychiatric and sleep-related symptoms; and Class 4 (25.7%) moderate physical-respiratory symptoms. HRQoL differed across classes in all SF-36 domains ( p < 0.001). Class 1 had the lowest scores [physical functioning 34.97 (95% CI: 32.56–37.38); vitality 28.98 (27.21–30.75); social functioning 26.31 (23.27–29.34); mental health 38.14 (35.61–40.67)], whilst Class 2 had the highest scores [52.36 (50.84–53.88); 46.85 (44.47–49.23); 47.07 (44.41–49.72); and 50.04 (48.04–52.04), respectively]. PCS and MCS scores were also lower in Class 1 [30.73 (28.50–32.96) and 35.07 (31.93–38.22), respectively] and higher in Class 2 [48.49 (46.32–50.65) and 48.49 (45.76–51.23), respectively]. Classes 3 and 4 showed intermediate patterns of quality of life, with lower scores in Class 3 compared with Class 4 in terms of social functioning, emotional role and mental health. LCA identified four distinct latent classes based on symptoms, which differ in symptom burden and predominant symptom patterns, and are associated with differences in health-related quality of life. These findings provide a better understanding of the clinical heterogeneity of long COVID. However, the classes are exploratory and sample-specific. The results need to be replicated in independent cohorts and in longitudinal studies. Clinical trial registration Clinicaltrials.gov , Identifier NCT05819840.