Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to major post-acute sequelae. It is estimated that over 60 million people worldwide are affected by this multisystemic condition, here referred to as post-COVID. Affective symptoms such as fatigue and depressed mood are particularly prevalent in patients with post-COVID and pose significant individual and socioeconomic burdens. This stands in stark contrast to the currently limited number of available therapeutic options. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation modality that has been demonstrated to be both safe and effective in treating various neuropsychiatric disorders, including depression. However, whether rTMS also has an effect on post-COVID associated affective symptoms remains to be elucidated.

The overall objective of this randomized, double-blinded study is twofold: First, the investigators will examine the effect of rTMS on post-COVID associated affective symptoms. 52 individuals with post-COVID will be randomized to either receive 20 sessions of rTMS or sham treatment. A detailed psychopathological assessment of the study participants will be performed before and after the completion of rTMS/sham treatment. Secondly, the investigators will perform detailed characterization of the immune system before and after rTMS/sham treatment.

The individual burden and socioeconomic costs of post-COVID-associated neuropsychiatric symptoms are enormous, however, treatment options are limited. The investigators believe that the current proposal will address this key gap in the literature by testing whether rTMS, which constitutes a novel treatment with little side effects, could alleviate these debilitating symptoms. If proven effective, this study could pave the way for a completely new way in which post-COVID conditions are treated.

Inclusion:

• Informed Consent as documented by signature
• Age between 18-65 years
• Proof of past COVID-19 infection by polymerase chain reaction (PCR) test or serology
• Negative COVID- 19 PCR test at the time of inclusion
• Affective symptoms (≥ 15 points on the Montgomery- Åsberg Depression Rating Scale) lasting for more than 12 weeks since COVID-19 infection
• No psychiatric history prior to the COVID-19 infection
• No major somatic comorbidities or substance use disorder

Exclusion:

• Contraindications to the rTMS treatment e.g. cochlear implants and metallic devices close to the TMS coil, a history of strokes, head injuries or seizures/epilepsy
• Epileptiform potentials in the electroencephalogram (EEG)
• Previous rTMS prior to the study
• Known severe hypersensitivity or severe adverse reaction to rTMS
• Women who are pregnant or breastfeeding
• Intention to become pregnant during the course of the study
• Psychiatric history prior to the COVID-19 infection
• Major somatic comorbidities e.g. renal failure, hepatic dysfunction, heart failure, cardiovascular disease.
• If the participant took antidepressants before the beginning of the study, there needs to be a washout period. The antidepressant has to be stopped for at least 3 weeks before commencing the study.
• The following drugs are not allowed during the study: any antidepressants, any antipsychotics, any drugs that lower the seizure threshold
• Known or suspected non-compliance, drug or alcohol abuse
• Inability to follow the procedures of the study, e.g. due to language problems
• Participation in another study with investigational treatment within the 30 days preceding and during the present study
• Enrolment of the investigator, his/her family members, employees and other dependent persons