Immunoadsorption versus sham treatment for Post-COVID syndrome : a randomised sham-controlled crossover trial

Abstract

Background: Post-Covid syndrome is a debilitating condition which may be caused and/or aggravated by autoantibodies. The current study aimed to determine whether autoantibody depletion by immunoadsorption is effective to reduce the symptom burden of patients with post-Covid syndrome. Methods: IAMPOCO was a randomised, patient-blinded, sham-controlled crossover trial of immunoadsorption with tryptophan adsorbers versus sham treatment in patients with post-Covid syndrome at a tertiary academic care centre. The primary outcome was the difference in change in symptom severity before and after the respective therapies. Secondary outcomes included treatment safety, prevalence of autoantibodies against G protein-coupled receptors (adrenergic and muscarinergic receptors), and the influence of treatment on autoantibody levels. Findings: 40 patients with post-Covid syndrome and a symptom severity of at least 2 on the Post-Covid-19 Functional Scale were included and randomised to a treatment sequence. There was no difference in change in symptom severity between immunoadsorption and sham; odds ratio in Post-Covid-19 Functional Scale, OR = 1.17 (95% CI, 0.41–3.36; p = 0.771), mean difference in MFI-20 2.4 (95% CI, −3.7–8.5; p = 0.437), in CFS 0.09 (95% CI, −4.5 to 4.7; p = 0.970), in Bell-Scale −2.6 (95% CI, −6.9 to 1.8; p = 0.246), in MoCA score −0.01 (95% CI, −1.2 to 1.1, p = 0.993) and in Handgrip-strength deviation from individual normal value 1.3 (−0.83 to 3.5, p = 0.234). 34 adverse events occurred, 10 during or after sham treatment and 24 during or after immunoadsorption. Autoantibodies against G protein-coupled receptors were depleted by immunoadsorption but not sham treatment. Interpretation: Immunoadsorption was not effective in reducing symptom burden in post-Covid syndrome. Funding: Ministry of Health, state of Rhineland-Palatinate; Mainz University Medical Centre; DIAMED Medical Technology. Trial Registration: ClinicalTrials.gov, number NCT05841498.