Impact of long COVID phenotypes on quality of life following symptomatic omicron infection in Brazil: a machine learning analysis

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BACKGROUND: This study aimed to identify phenotypes of long COVID symptoms in adults following Omicron infection and assess their association with health-related quality of life (HRQoL). METHODS: We analyzed three prospective observational studies in Brazil, enrolling adult patients who sought care for symptomatic Omicron infection between December 2021 and March 2023. The infection was confirmed by either an antigen test or reverse transcriptase polymerase chain reaction. Long COVID symptoms were assessed three months after enrollment through structured interviews. Phenotypes of Long COVID-19 were identified using a machine learning-based clustering approach. Exploratory analyses were conducted to examine predisposing factors and health-related quality of life utilities, measured by EQ-5D-3 L, associated with each phenotype. RESULTS: A total of 2,989 patients were analyzed (39% women, median age 41 years, and 96% had completed the primary series of COVID-19 vaccination). Long COVID symptoms at three months were reported by 1,155 (38.6%) patients. Three phenotypes were identified: cluster 1 (n = 459 [39.7%]), characterized by a median of three symptoms (IQR, 2-5) with memory loss (80.4%), concentration problems (38.3%) and fatigue (35.7%) being most common; cluster 2 (n = 549 [47.5%]), characterized by a median of two symptoms (IQR, 1-4) with fatigue (43.7%), other symptoms (42.3%), and cough (20.6%) being most common; and cluster 3 (n = 147, 12.7%), characterized by a higher number of symptoms (median, 8; IQR, 7-10), with fatigue (89.9%), memory loss (88.4%), and anxiety (64.6%) as the most common. The mean EQ-5D-3 L utility at 3 months was 0.75 for cluster 1, 0.73 for cluster 2, and 0.59 for cluster 3 (p < 0.001). After adjusted regression analysis, cluster 3 was independently associated with the lowest EQ-5D-3 L utilities (mean difference, -0.21; 95%CI, -0.24 to -0.18; p < 0.001). CONCLUSIONS: Distinct phenotypic presentations of Long COVID following Omicron infection in Brazil were identified, with significant differences in quality of life. CLINICAL TRIAL NUMBER: Not applicable.

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