COVID-19 serology, virology, and host factors among healthcare workers

The majority of people infected with SARS-CoV-2 have mild disease. At the start
of the epidemic, initial surveillance of SARS-CoV-2 was directed at persons
that present at the hospital, who have serious SARS-CoV-2 symptoms that require
admission. Patients with more severe symptoms are thought to be at increased
risk of transmitting SARS-CoV-2 to other individuals. Transmission of
SARS-CoV-2 during mild disease course is considered rare, provided social
distancing is adequately applied. However, for healthcare workers, social
distancing may not be possible, as physical proximity to admitted patients is
often required. As such, there is concern to contract and spread SARS-CoV-2 to
vulnerable patients in the hospital, illustrating the need for additional
information on symptom severity, and the potential to infect others. In
addition, it remains unclear to what extent healthcare workers generate
antibodies against SARS-CoV-2, and whether this prevents re-infection.
Importantly, recent studies indicated that people who experience mild disease
may develop a less potent antibody response to SARS-CoV-2. For these reasons,
reliable assessment of antibody generation in the blood of healthcare workers
is urgent. To investigate which health care workers are vulnerable to
infection, we will additionally map host and virological factors related to
SARS-CoV-2.

In this study, we therefore aim to establish the kinetics of the humoral immune
response against SARS-CoV-2, and relate this to the viral characteristics,
microbiome and host factors of healthcare workers.

A single center, longitudinal, observational, investigator initiated study

We aim to include 75 SARS-CoV-2 positive healthcare workers for follow up.
Based on the current prevalence among tested healthcare workers of 10%, we
expect to include a total of 750 healthcare workers in the study.

All included individuals will be healthcare workers with symptoms associated
with SARS CoV-2 who are tested according to the regular procedure in the UMCU
for healthcare workers. One nose-throat swab at day 0 (visit 0) and one after
symptoms have resolved (visit 2) will be performed (standard of care). In
asymptomatic healthcare workers a control nose-throat swab is performed after 5
days. If the SARS-CoV-2 PCR at visit 2 is positive, the PCR test will be
repeated weekly until negative. During this study, healthcare workers will be
asked to visit the UMC Utrecht test location two additional times (4 visits
total). The nose brush (for isolation of nasal epithelial cells) will only be
performed for SARSCoV-
2 positive patients. All visits that include a nose throat swab are standard of
care (visit 0 and 2). The testing of blood at any timepoint is not standard of
care. At visit 3, three weeks after the first symptoms have occurred, only
blood tests are performed (no swab is done). If symptoms persist, timepoint X
can be delayed to a maximum of three months.
If the SARS-CoV-2 PCR is positive at visit 2, the test will be repeated weekly
until the participant is SARS-CoV-2 PCR negative. Retesting when the PCR is
positive with a CT value < 32 is standard of care for healthcare workers,
retesting after a PCR with a CT value > 32 is additional.

Visit 0: COVID test healthcare worker with symptoms (standard of care)
- Nose-throat swab (for SARS-CoV-2 testing)*

Visit 1: blood test and nose brush
- Inclusion: sign PIF
- Questionnaire
- Symptom diary (day 1 - day 21)
- 4 blood tubes (2 serum, 2 heparin)
- Nose brush (nasal epithelial cells, the nose brush is only performed if
SARS-CoV-2 PCR is positive)
This material will be collected by a physician and medical students
specifically allocated to this project.

Visit 2: control nose-throat swab after resolution of symptoms**
- Nose-throat swab (for SARS-CoV-2 testing)*

Visit 3: blood test after 3 weeks
- 4 blood tubes (2 serum, 2 heparin)
* This swab is part of the regular procedure for healthcare workers of the
UMCU. The swab is repeated until the PCR is negative.
** In asymptomatic healthcare workers a control nose-throat swab is performed
after 5 days.
If SARS-CoV-2 negative participants become SARS-CoV-2 positive during follow-up
the participant will be transferred to the SARS-CoV-2 positive study group. The
questionnaire and symptom diary will be sent again, a nose brush will be
performed and visit 3 will be postponed to 3 weeks after onset of their first
SARS-CoV-2 symptoms.