sElective Serotonin reuPtake inhibitoRs In posT-covid After COVID-19

Overview

Fatigue, cognitive problems, post-exertional malaise (PEM) and postural orthostatic tachycardia syndrome (POTS) are common and debilitating symptoms after COVID-19. The pathophysiology of post-COVID is not well understood and there is no established biomedical treatment. Treatment options for post-COVID are thus much needed. A promising candidate intervention is fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), that may reduce post-COVID symptoms because of its regulatory effect on the (neuro) immune system, the hypothalamic-pituitary-adrenal (HPA) axis and the tryptophan system. The investigators will randomize 160 participants to either fluvoxamine or placebo for 12 weeks. The investigators will use advanced functional neuroimaging techniques during cognitive challenge (optional substudy) and plasma biomarkers (inflammatory markers, cortisol, serotonin, IDO-2 activity), to facilitate identifying potential mechanistic pathways of post -COVID treatment.

In this randomized placebo-controlled trial, the investigators will study the effectiveness of fluvoxamine in reducing fatigue severity (primary outcome), cognitive problems, PEM and POTS after 12 weeks of treatment in 160 post-COVID patients. Moreover, the investigators will study treatment-emergent changes in plasma biomarkers, including blood-based neuro)inflammatory markers, cortisol, serotonin, aryl hydrocarbon receptor -indoleamine 2,3-dioxygenase-2 (IDO-2) and kynurenine pathway (KP) metabolites for potential mechanistic pathways of post-COVID treatment. Numerous studies have indicated involvement of brain dysfunction in post COVID, which also relate to the degree of symptom severity (e.g. fatigue / cognitive problems). In an optional neuro-imaging sub-study, the investigators will use functional neuroimaging techniques with and without cognitive challenge to gain a better understanding of the brain functioning and structure in long COVID during fluvoxamine treatment versus placebo. Objectives: * To determine if fluvoxamine treatment (50 mg to 200 mg daily dosing) results in lower levels of fatigue severity than placebo after 12 weeks of treatment (primary). * To determine if fluvoxamine treatment results in lower levels of PEM and POTS and a better cognitive functioning and health-related quality of life (HRQL) than placebo. * To determine if changes in symptoms, i.e. fatigue severity, PEM, POTS, cognitive symptoms, are related to changes in biomarkers, i.e., (neuro)inflammation markers, cortisol, serotonin and IDO-2 -KP metabolites. * To determine if biomarkers, i.e., (neuro)inflammation markers, cortisol, serotonin and IDO-2- KP metabolites, change from baseline to week 12 in participants who received fluvoxamine. Optional Neuro-imaging sub-study: -To determine which changes occur on functional brain imaging, brain metabolites and neuroinflammation during cognitive challenge and to determine if this brain response to cognitive challenge changes after fluvoxamine treatment versus placebo.