Immunological assessment of SARS-CoV-2 in IENIMINI cohort individuals with influenza like symptoms.

The COVID19 pandemic caused by the SARS-CoV-2 virus causes enormous concerns
and problems all over the world. Although the virus causes mild influenza like
symptoms in the majority of the cases, some people are suffering from severe
courses of the virus, often resulting in death.(7) For several groups of
patients the risk of a more severe course of an infection appears to be
increased, and indeed some patients may have a higher risk for falling ill
after exposure than others. Patients with IMIDs might be part of these risk
groups because they are more susceptible for infections than the general
population.(5, 6) Their potential treatment with immunosuppressive medication
might further increase this risk. To monitor possible differences in
susceptibility and course of disease in SARS-CoV-2 infections between patients
with IMIDs with or without immunosuppressive medication, compared to patients
without IMIDs and immunosuppressive medication, the IENIMINI cohort was started
in March 2020, at the beginning of the epidemic in the Netherlands. Two groups
were included in this cohort, patients with an IMID with or without
immunosuppressants and patients without an IMID and healthy (potential) kidney
donors who served as control group. We approached patients with IMIDs from the
pulmonology, rheumatology, gastroenterology and nephrology departments from the
Leiden University Medical Center (LUMC). We included patients with
fibromyalgia, patients who are in follow up for familial colon cancer (Familial
Adenomatous Polyposis (FAP) or Lynch syndrome) and potential healthy kidney
donors in the non-IMID control group. For a complete list of included diagnoses
see appendix A.

Out of 8670 patients who were approached, 3174 signed informed consent and
agreed to participate in a prospective study using questionnaires to monitor
potential infections, outcomes, and the relation with underlying disease and
treatment. In addition, they agreed to be approached for further investigations
regarding COVID19. All participants received two-monthly paper questionnaires
or weekly online questionnaires where they had to register flu-like symptoms
that might indicate infection with SARS-CoV-2 as they experienced them. In
addition, questions about potential exposure to infected individuals, COVID19
testing, use or discontinuation of medication were completed. This prospective
inventory of potential infection is currently ongoing. Preliminary results of
this cohort showed 836 out of 3172 (4 patients withdrew their consent before
they completed a single questionnaire) patients experienced flu-like symptoms
in March-June 2020. Of these, 544 were patients with IMID and 292 were
controls.

The first evaluation of the IENIMINI cohort shows us that patients with an
autoimmune or autoinflammatory disorder (IMID) are not experiencing more
influenza like (COVID19 like) symptoms than control persons. Also there does
not seem worse outcomes for patients with an IMID. This has been confirmed by
other (inter)national reports. With this study we want to evaluate what the
seroprevalence is of COVID19 in patients with an IMID and control persons who
experienced influenza like symptoms in March-November 2020. Besides we want to
evaluate if there is a difference in immune response between participants with
mild and severe symptoms.

Primary objective:
To evaluate, in a cohort of non-tested individuals who reported flu-like
symptoms during the COVID19 epidemic in the Netherlands (March-November), the
seroprevalence of COVID19 in patients with an IMID, with or without
immunosuppressive medication, and patients without an IMID (controls).

Secondary objective:
To evaluate the difference in antibody response to COVID19 between:
- Patients with a severe course of COVID19-like symptoms and patients with only
mild symptoms.

Severe course is in this study defined as: having had fever and more than 7
executive days of illness.

This study is an observational follow-up study of the IENIMINI cohort. The
IENIMINI cohort consists of two groups: patients with an IMID with or without
immunosuppressants and a control group with patients without an IMID and
without immunosuppressants. All patients completed questionnaires about
influenza like symptoms as they experienced them in March-November 2020. After
informed consent, diagnosis and prescribed medication were confirmed from their
medical records. Continued use or temporary discontinuation of medication were
inventoried through the questionnaires. All patients who reported an illness
episode with flu-like symptoms, possibly due to COVID19 infection during March
until November 2020 are eligible for this study. In conclusion, in total
(2x500)= 1000 participants of the IENIMINI cohort will be asked to participate
in this new study. All participants of the IENIMINI cohort have agreed to be
approached for a follow up study when they gave informed consent for the
IENIMINI cohort study. If a participant agrees to participate, the participant
will be asked to withdraw blood by using a fingerstick test which will be send
to them by Sanquin.

As this study is observational, there is no interference with standard
treatment of the IMID disease. Only one assessment needs to be done. Total time
investment for this follow-up study will be approximately 20 minutes. There are
no immediate benefits. Patients will be informed if a SARS-CoV-2 antibody
response is found, with the connotation that there is currently insufficient
evidence that this is of any (lasting) benefit.