Neurobiological Underpinnings of Neuropsychological Consequences in Long COVID

Research Objectives Describe the standardized evaluation of the psychopathological and neurocognitive function of long COVID NP patients and their evolution over time; Compare the immunological profile and the cortisol awakening response (CAR) of long COVID NP patients to those of COVID-19 survivors without persistent complaints and healthy uninfected controls; Explore the cross-sectional and longitudinal association between long COVID NP symptoms and immunological and cortisol measures. Methodology Recruitment and study population Inclusion criteria - patients: All patients 18-70 years referred to the University Psychiatric Hospital (Campus UZA and Campus Duffel) for psychological and/or cognitive complaints at least \>4 weeks following a confirmed diagnosis of COVID-19 infection with a positive PCR test or an antibodies test will be invited to participate in the study. The sample size of the patients is estimated on 50 participants. The patients have to be examined by their treating physician before enrollment to make sure other medical causes for their complaints are excluded. A positive score on at least two domains (psychological /cognitive) is necessary during the screening phase. Inclusion criteria - controls: Two control groups, one of 30 healthy uninfected controls (Cb), another of 50 COVID-19 survivors without persistent complaints (Ca), matched on age, sex and education with the patient group will be included. The participants for Ca will be recruited in UZA and by advertising. The healthy controls (Cb) will be recruited by mailing within the hospital and by advertising. A positive score on maximum one domain (psychological / cognitive) is allowed in the absence of a psychiatric diagnosis (confirmed by the MINI) and when the complaint causes significant distress (which is investigated during the screening phase). Exclusion criteria for each subgroup: * HPA subgroup: Participant is pregnant or breastfeeding / Participant receives hormonal replacement therapy (contraception is allowed) /Participant is treated with cortisol \<4 weeks ago * Neurocognitive assessment: IQ \< 90 (screened with Raven Standard Progressive Matrices (Short Form) (RSPM-SF) / Participant takes sedative medication: benzodiazepines (Larger than the equivalent of diazepam 10mg per day, Last administration \<8 hours prior to the neurocognitive test), new sedative antipsychotics/antidepressants (\<4 weeks), other medication from DRUID class III (\<4 weeks), last administration \<8 hours prior to the neurocognitive tests, or causing significant sedation / Severe substance abuse (alcohol + drugs) / Pre-existing neurological diseases causing cognitive problems. Study design This is a longitudinal study, which will be organized into three work packages (WP1, WP2 and WP3). Enrollment will continue for an estimated period of 24 months, depending on the time course of the epidemic curve. Last-patient-in is expected no later than November 1st, 2023. Patients will be referred mainly by the University Hospital of Antwerp (UZA) and enrolled at first visit to the University Psychiatric Hospital (UPCD), where follow-up will also take place at 3, 6 and 12 months. Patients can also be referred by the Flemish long COVID patient support group. WP1 includes a blood withdrawal and psychometric questionnaires and is part of every visit. WP2 includes cortisol measurement in saliva and takes place on the baseline visit for every participant and on the third visit for patients. Finally, WP3 includes a neurocognitive assessment at baseline for patients and Ca controls and on the third visit for patients.