Mayo Clin Proc. 2026 Mar 16:S0025-6196(26)18429-8. doi: 10.1016/j.mayocp.2026.02.018. Online ahead of print.
ABSTRACT
OBJECTIVES: To assess the impact of COVID-19 vaccination on distinct clinical definitions and phenotypes of post-COVID syndrome (PCS) and identify risk factors for PCS despite vaccination.
METHODS: Data were drawn from the German National Pandemic Cohort Network (NAPKON), including adult COVID-19 patients with known vaccination status recruited between December 2, 2020, and February 13, 2023. PCS prevalence was assessed using 3 clinical definitions: the broad WHO definition (any sequelae at 3 months), symptom clusters (Fatigue, Respiratory, Cognitive), and a symptom-based PCS score reflecting clinical severity. Multivariable logistic regression was employed to estimate the protective effect of vaccination.
RESULTS: Among 756 patients, 26% were fully vaccinated (≥2 doses) before infection. Vaccination was associated with a significantly reduced risk of PCS according to the WHO definition (OR 0.555, 95% CI 0.339-0.906), the PCS score (OR 0.536, 95% CI 0.335-0.856), the Respiratory Cluster (OR 0.508, 95% CI 0.295-0.875), and the Cognitive Cluster (OR 0.443, 95% CI 0.213-0.923). In contrast, no protective association was observed for the Fatigue Cluster (OR 0.917, 95% CI 0.554-1.519). The favorable association with vaccination was particularly observed in patients with mild acute symptoms, regardless of hospitalization. The protective effect of vaccination persisted at 12-month follow-up, although fatigue remained unaffected.
CONCLUSION: Findings indicate that broader PCS definitions may mask clinically relevant heterogeneity and support the need for differentiated, phenotype-oriented definitions that reflect clinical presentations of PCS, including differential responses to vaccination. Such refined clinical definitions may facilitate exploration of whether these phenotypes reflect distinct underlying pathophysiological mechanisms.
PMID:41850429 | DOI:10.1016/j.mayocp.2026.02.018