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.
Long Covid