Post-COVID Complaints in children Study (POCOS)

The pandemic novel coronavirus (SARS-COV-2) causes the disease COVID-19,
ranging from mild flu like symptoms to severe and potentially fatal acute
respiratory distress and cardiogenic shock syndrome. In adults who recovered
from COVID-19, long-term sequela (long-COVID/post-COVID/Post-Acute Sequelae of
COVID-19 (PASC)) are frequently reported, causing mild to severe long term
morbidity. In adults, post-COVID is a well-documented multisystem disease that
describes the 10% of COVID-19 infected with long-term sequelae persisting for
more than 12 weeks. Far less is known about these long-term sequelae in
children, as only recently this disease has started to garner scientific
literary attention. In children, the first cohort studies show long term
sequelae in 12-42% of patients. A Dutch survey among pediatricians showed 89
children with long term complaints, resulting in severe limitations in daily
life in 36%.

We aim to describe the clinical characteristics and immune response in children
seeking care for post-COVID complaints. Moreover, in a subset of children we
evaluate the effect of the reinfection on clinical and inflammatory outcomes in
children with Post-COVID syndrome.

A mixed-method multi-centre international prospective cohort study, with a
feasibility phase and a definitive design phase comprehending 2 possible
trajectories:
- Trajectory 1: One study visit to the outpatient clinic and evaluations of
quality of life and symptoms (through digital questionnaires sent by email) at
6 and 12 months.
- Trajectory 2: In addition to the trajectory 1, the subgroup of children
participating in the evaluation of SARS-CoV2 virus re-infections for Post-COVID
syndrome will receive follow-up study visits (or home self-tests) at 3, 6 and 9
months. Moreover, the children also receive extra evaluation moments
(self-testing at home) in case of complaints that fit a possible corona
infection

The results from this study will benefit the target group, i.e. children with
post-COVID syndrome, with possible long-term morbidity, leading to early
detection and hopefully treatment.
The study visit will be combined with routine standard of care visits to the
outpatient clinic or planned in another moment according to the patient*s
convenience. Caregivers and/or children will be asked for consent to have data
from these outpatient visits retrieved from the hospital file and registered at
the study CRF. The procedures which are solely part of research are
immunological evaluation, exhaled breath analysis, microbiome analysis, fatigue
questionnaires, the neurocognitive questionaires and evaluation tests (Emma
Tool box) and an odour identification test.
The exhaled breath and the odour identification test do not provide extra
burden to the patient. The administration of the tests included in the Emma
toolbox require 30 minutes and could be tiresome for the children. For this
purpose we propose the mixed-method design such that after the inclusion of the
first 20 patients there will be a re-evaluation to optimize the study
procedures according to the expertise acquired in this first (feasibility)
phase.
The collection of a nasal and throat swabs provide a minimal burden to the
children. Children have reported an itchy feeling and tearing eyes, and in rare
circumstances local bleeding might occur.
All children and/or their caregivers will be asked for consent to have
additional blood collected for immunological evaluation. Blood withdrawal is
standard care in these patients, so the collection of the blood sample for
immunological evaluation will be combined with a blood sample collection for
routine clinical care.
The expected required time-investment of the children and their caregivers
exclusively for the study is approximately 2 hours, depending on the age and
willingness of the child. Both the clinical disease-course and the capacity to
recover are different in children when compared to adults and we therefore
cannot deduce long-term sequelae from adults COVID studies.
Children participating in the reinfection sub-set longitudinal portion of the
study will have three additional study visits (home visits or self-sampling) at
3, 6 and 9 months after inclusion. During these visits blood is drawn and
questionnaires are administered. Moreover, the children also receive extra
evaluation moments (self-testing at home) in the event of complaints that match
a possible corona infection. The estimated extra time for the complete
reinfection sub-study will be of 2 hours, including all planned study visits.
Participants participating in the extension of trajectory 2, will be followed
up for additional 6 months. During these months, participants will continue
collecting NP/OP swabs. One additional blood collection and questionnaire is
implemeted at april 2024.