Prednisolone for post-COVID-19 syndrome: effect below the threshold for clinical relevance

What was studied

PreVitaCOV was a randomised, double-blind, placebo-controlled phase 3 trial with a 2 × 2 factorial design at three university sites in Germany. Participants were adults with persistent symptoms after documented SARS-CoV-2 infection ≥12 weeks previously. Of 323 randomised participants, 310 patients had evaluable outcome data.

Participants received once-daily oral prednisolone, B vitamins, their combination, or placebo for 28 days. Prednisolone doses were 20 mg on days 1–5 and 5 mg on days 6–28. The vitamin regimen comprised thiamine nitrate 100 mg, pyridoxine hydrochloride 50 mg, and cyanocobalamin 500 μg.

The primary outcome was change in overall symptom severity to day 28 using a customised Patient-Reported Outcomes Measurement Information System (PROMIS) total T-score. A change of ≥3 points was considered clinically meaningful. Main effects of prednisolone and B vitamins were assessed using a prespecified factorial analysis.

Results

The adjusted mean difference between participants receiving prednisolone and those not receiving it was −1.4 points (95% confidence interval: −2.5 to −0.4; p = 0.008). The effect was driven primarily by the change in the fatigue subscore: −6.4 points; p < 0.001.

B vitamins showed no statistically significant or clinically meaningful difference compared with no B vitamins: −0.1 points (95% confidence interval: −1.2 to +1.0; p = 0.85). Adverse events were equally distributed between groups, with no study-drug-related serious adverse events.

Clinical relevance

The short-term prednisolone effect did not reach the prespecified threshold for clinical relevance. The authors call for further research to confirm efficacy, establish the optimal dose and treatment duration, and balance benefits against longer-term adverse effects.