COVID-ASTER Obesity and COVID-19: AdipoSe TissuE Responses to SARS-CoV-2 infection

We hypothesize that obesity is a major amplifier of organ inflammation and
injury accounting for the severe respiratory failure and death in SARS-CoV-2
infected patients. The rationale for this hypothesis is based on our clinical
observations that most of the SARS-CoV-2 infected patients admitted to the ICU
with respiratory failure had central obesity, extensive visceral fat and a Body
Mass Index (BMI) of 25 kg/m2 or higher (mean 30 kg/m2). Recent findings from
the UK, in the largest cohort study to date, confirm that the likelihood of
hospital death due to SARS-CoV-2 is associated with obesity severity1.
Circulating adipose tissue (AT)-derived mediators including leptin are known to
be associated with BMI and are known to have immunomodulating properties which
may prime obese individuals to infection resulting in an exaggerated response.
We therefore postulate that excess adipose tissue, its distribution and
secreted mediators play an important role in the type of immune response and
subsequently in the progression towards respiratory insufficiency in patients
with SARS-CoV-2.

Objective: To investigate the adipose tissue response upon ex vivo SARS-CoV-2
infection, more specifically to answer the following questions:
1. Is adipose tissue permissive to direct SARS-CoV-2 infection?
2. Are adipose tissue-derived factors released in response to SARS-CoV-2
infection?
3. What is the response of adipose tissue-derived factors on endothelial and
epithelial cell behaviour?

Study design: Small visceral and subcutaneous adipose tissue samples collected
from obese (BMI 40 and higher, intervention group) and lean (BMI 25 or lower,
control group) patients undergoing surgery will be infected with SARS-CoV-2
virus ex vivo.

Patients who have given informed consent for participation in this study will
undergo surgery. The bariatric surgery procedure will be performed normally, no
modifications are necessary. After introduction of the laparoscopic
instruments, a small piece of omental fat of 2 cm3 will be collected by
diathermia and taken out of the patient by one of the trocarts. After this, the
bariatric procedure will be continued and performed as it normally would. At
the end of the operation, the location in the omentum where the fat tissue was
harvested will be checked for bleeding complications. In patients undergoing
abdominal surgery (Control group), after the abdomen is opened by laparotomy or
the instruments are placed in laparoscopic procedure a piece of omental fat of
2 cm3 will be collected by diathermia and taken out of the patient by one of
the trocarts or the laparotomy. After the omental fat is taken out of the
patient it will be immediately placed into Dulbecco*s modified Eagle*s medium
(DMEM) containing 10% fetal bovine serum and antibiotics. Samples will then
immediately be transferred to the UMCG BSL3 laboratory for subsequent
SARS-CoV-2 infection experiments.

Collection of visceral and subcutaneous fat tissue:. This can induce bleeding
which can be resolved immediately during the operation. In the worst-case
scenario, bleeding can occur post-operatively and patients have to be
reoperated by laparoscopy. The chance of bleeding after finishing the operation
is very small.