PreVitaCOV RCT: Low-Dose Prednisolone Yields Modest, Transient Fatigue Benefit in Post-COVID Syndrome

The PreVitaCOV trial randomized 323 adults with confirmed SARS-CoV-2 infection at least 12 weeks prior and ongoing symptoms into four arms: low-dose prednisolone, B vitamins, both, or placebo for 28 days. Primary outcomes tracked changes in fatigue, dyspnea, cognition, anxiety and depression. Prednisolone recipients showed greater fatigue relief than non-recipients, while B vitamins conferred no detectable benefit. All regimens were well tolerated with high retention. The absolute between-group difference remained below the threshold set for meaningful daily-life improvement.

Contextual analysis reveals alignment with broader post-COVID literature indicating low-grade inflammation as a plausible driver yet also highlighting heterogeneity in symptom clusters. Prior observational data from NEJM and JAMA have similarly noted transient steroid responses without durable functional gains, underscoring that surrogate fatigue scales do not equate to objective capacity measures. The general-practice setting strengthens external validity but limits biomarker-guided stratification.

Next steps require longer-duration or tapered regimens, subgroup identification via pending blood analyses, and trials powered for objective endpoints such as six-minute walk distance. Larger adaptive platform studies could test combination immunomodulation in inflammatory phenotypes while monitoring adverse-event accumulation beyond four weeks.