COVID-19 long-term sequelae: Omicron versus Alpha and Delta variants

BACKGROUND: The study aimed to assess the association between three predominant SARS-CoV-2 variants (Alpha, Delta, and Omicron) and the risk of developing long COVID (persistence of physical, medical, and cognitive symptoms more than 4 weeks after infection), post-COVID-19 syndrome (symptoms extending beyond 12 weeks), and viral persistence (testing positive beyond 4 weeks despite clinical resolution). METHODS: Retrospective study of 325 patients hospitalized for COVID-19 with genomic sequencing information. For each SARS-CoV-2 variant, sample characteristics, frequency of symptoms, and long-term sequelae were compared using Chi-squared test, Fisher’s exact test, Kruskal-Wallis test, and Dunn's test as appropriate. Odds ratios (OR) were calculated using logistic regression models to assess the association of risk factors and sequelae. RESULTS: The adjusted model showed that the Omicron (vs Alpha) variant (OR, 0.30; 95% CI 0.16–0.56), admission to ICU (OR, 1.14; 95% CI 1.05–1.23), and being treated with antiviral or immunomodulatory drugs (OR, 2.01; 95% CI 1.23–3.27) predicted long COVID and post-COVID-19 syndrome. Viral persistence showed no difference between variants. CONCLUSIONS: The Omicron variant was associated with significantly lower odds of developing long-term sequelae from COVID-19 compared with previous variants, while severity of illness indicators increased the risk. Vaccination status, age, sex, and comorbidities were not found to predict sequelae development. This information has implications for both health managers and clinicians when deciding on the appropriate clinical management and subsequent outpatient follow-up of these patients. More studies with non-hospitalized patients are still necessary.