Among Brazilian adults after symptomatic Omicron infection, a high-symptom phenotype was linked to markedly worse quality of life at 3 months.
Evidence
This machine learning clustering analysis of three prospective observational studies in 2,989 adults in Brazil identified three long COVID symptom phenotypes and compared EQ-5D-3L utilities across them.
Caveat
This was an observational clustering study based on symptoms reported 3 months after infection, so the phenotypes do not establish causes of long COVID or quality-of-life differences.
Simplified
BACKGROUND: This study aimed to identify phenotypes of 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 , 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.
Key numbers
1,155
Prevalence
Patients reporting persistent symptoms out of 2,989 screened.
0.59
Quality of Life Score
Mean utility score for 3.
3
Symptomatic
Distinct identified in the study.
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22 authors work at Hospital Moinhos de Vento, which received grants for the studies in this analysis; 2 of them also received research grants, and 6 other authors work for Pfizer.
