Diabetics are more susceptible to SARS-CoV-2 infection, a study with laboratory-generated mini-rion suggests

Posted in ‘Cell metabolism’


The results of this international investigation, led by a team from Spain, were verified in patient samples, confirming that diabetes in the kidney provides an increased number of ‘gateways’ for the virus that causes COVID-19. .

Nuria Monserrat, from IBEC, at the Centre, with a group of researchers.
Nuria Monserrat, from IBEC, at the Centre, with a group of researchers.IBEC

An international team led by ICREA research professor Nuria Montserrat at the Institute of Bioengineering of Catalonia (IBEC) has Developed mini-kidneys that simulate the organs of patients in the early stages of diabetes and show that they are more susceptible to infection by SARS-CoV-2, which causes the disease COVID-19.

in work, the results of which are published in the journal cell metabolismhas collaborated with, among others, researchers from the University of Florida, the Life Sciences Institute of the University of British Columbia in Canada, the Karolinska Institutet and Karolinska University Hospital in Sweden, as well as Spanish researchers from the CIMA Clinic and the University of Navarra. , Hospital Clinic in Barcelona, ​​Hospital de la Santa Creu i Sant Pau in Barcelona and the University of Barcelona.

Two years ago, with the outbreak of the pandemic, thousands of scientists and doctors around the world began working to understand How Covid-19 evolved and how it relates to other diseases, During this whole time, Various studies have indicated that people with diabetes were more likely to develop severe COVID, as well as the fact that more than 20% of patients hospitalized for the disease suffered severe kidney injury. However, till date, The causal factor was unknown. Because of which this happened.

As Nuria Monserrat tells EL Mundo, “Studies on how to make organoids of diabetes began before the pandemic. We spent more than a year and a half trying to understand whether we could study pathologies of systemic origin, such as diabetes.” Can take advantage of organoid technology to do this in the kidney.”

When the study began on the prognosis of COVID in patients with type 2 diabetes, “a call came in from the COVID-19 Fund of the Carlos III Institute of Health and we were able to launch. A joint project to test whether type 2 diabetes or diabetes in organs underpins the prognosis of COVID, but above all if there was more infection in diabetic organs, Taking advantage of the prior knowledge we had with organoids and what we knew at the time”, Monserratt recalls.

In parallel, in June 2020, the Monserrat team requested assistance from the BBVA Foundation for the SARS-CoV-2 and Covid-19 scientific research teams, Organoids defective for other receptors described to date, by genetic engineering Entry Gate for the virus. The aim was to demonstrate that the ACE2 receptor has an essential role for SARS-CoV-2 infection in the kidney.,

Detail of the proximal tubular structure (magenta) within the renal organ
Detail of a proximal tubular structure (magenta) within the kidney after SARS-CoV-2 infection, showing ACE2-positive cells (green) and SARS-CoV-2-infected cells (red).IBEC

To create mini-rions with similar cellular characteristics and similar metabolic changes found in the kidney of a diabetic person in the early stages of the disease, the researchers grew these organoids in the laboratory from pluripotent human stem cells, which were . Subjected to culture conditions in the laboratory to reproduce the diabetic environment.

Then, using various molecular biology techniques, such as gene editing, observed that in diabetic mini-rion, it was the abundance of the ACE2 receptor that determined susceptibility to viral infection.Establishing a causal relationship between diabetes and the presence of one of the determined receptors in SARS-CoV-2 infection.

Furthermore, employing RNA sequencing, Researchers have identified that diabetic mini-kidneys have a metabolic signature that may explain why they become more infected.

To verify whether the results obtained from the laboratory mini-kidneys were also observed in the parent organ, the researchers analyzed kidney cells from patients with diabetes and individuals without it. The data showed that kidney cells from diabetic patients presented more ACE2 receptors, similar to mini-kidneys, and suffered susceptibility to SARS-CoV-2 infection. To delve into the mechanisms that explain such observations, the researchers used a compound that regulates the metabolic state of cells and found that the treatment significantly reduced viral infection.

“To be able to treat these cells with a compound that controls this discrepancy and, in doing so, also reduces the number of viruses, is a good message. Because we can only get the virus by closing the doors or removing them.” Not to think of attacking ACE2 is out of the way; we also modify cell metabolism, we can reduce virus infection,” Monserrat concludes.

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