Obesity and diabetes are established comorbidities for COVID-19 . Adipose tissue demonstrates high expression of ACE2 which SARS- CoV-2 exploits to enter host cells . This makes adipose tissue a reservoir for SARS-CoV-2 viruses and thus increases the integral viral load . Acute viral infection results in ACE2 downregulation . This relative deficiency can lead to disturbances in other systems controlled by ACE2, including the renin-angiotensin system . This will be further increased in the case of pre-conditions with already compromised functioning of these systems, such as in patients with obesity and diabetes. Here, we propose that interactions of virally-induced ACE2 deficiency with obesity and/or diabetes leads to a synergistic further impairment of endothelial and gut barrier function . The appearance of bacteria and/or their products in the lungs of obese and diabetic patients promotes interactions between viral and bacterial pathogens, resulting in a more severe lung injury in COVID-19.