Methylprednisolone in Patients with Cognitive Deficits in Post-COVID-19 Syndrome (PCS)

Around 10-40% of mild COVID-19 patients experience persisting or new symptoms known as post-COVID-19 syndrome (PCS). Neurological symptoms, particularly cognitive deficits and fatigue, are common in PCS, with a higher prevalence in female patients (Boesl et al., 2021; Ceban et al., 2022). The underlying causes of PCS remain unclear, but some evidence suggests autoimmune mechanisms may play a role. Currently, there are no proven treatments for PCS, leading to a need for effective therapies. This randomized controlled trial (RCT) aims to investigate the impact of methylprednisolone, a generally well-tolerated and affordable drug, on cognitive deficits in PCS patients with suspected autoimmune involvement. The objective is to demonstrate improvement in memory satisfaction as measured by the Multifactorial Memory Questionnaire (MMQ) in patients with post-COVID-19 syndrome treated with Methylprednisolone compared with placebo. Methylprednisolone is a well-known immunosuppressant used for multiple diseases of (suspected) autoimmune etiology. This is a two-arm, double-blind, randomized, placebo-controlled trial evaluating the effects of Methylprednisolone versus placebo in patients with post-COVID-19 syndrome (PCS) and cognitive deficits. The study spans 52 weeks, and participants will be stratified based on age, sex, and cognitive screening using the Montreal Cognitive Assessment Scale (MoCA). They will be randomly assigned in a 1:1 ratio to receive either Methylprednisolone (including a tapering phase) or placebo for 6 weeks, followed by an additional 6 weeks of open treatment phase with Methylprednisolone after a 6-weeks treatment pause. During the study, follow-up visits will be conducted as outpatient visits in weeks 8 and 20, with a final telephone follow-up after 52 weeks. The screening and baseline examinations will involve recording of medical history, checking inclusion and exclusion criteria, and conducting clinical examinations. The intervention group will receive approximately 1mg/kg body weight oral Methylprednisolone once daily for 6 weeks, with dosage reduction after week 4. The other group will receive a matching placebo once daily for 6 weeks, following the same titration regimen to maintain blinding. The starting dose for both interventions will be Methylprednisolone at approximately 1 mg/kg body weight or matching placebo once per day. Throughout the treatment phase, all participants will undergo safety and monitoring examinations. This clinical trial is of significant importance as it has the potential to benefit individuals with post-COVID-19 syndrome (PCS) by exploring the effects of Methylprednisolone on cognitive impairment and fatigue. Additionally, it may provide crucial insights into PCS's pathophysiological processes, leading to the development of more effective therapies and improved patient outcomes.