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.