Research identifies a new way in which Covid-19 enters human cells
13.11.2023
Published in Cell Press, the study by the University of Padua and Human Technopole, RAGE engagement by SARS-CoV-2 enables monocyte infection and underlies COVID-19 severity identifies how SARS-CoV-2 binds the Receptor for Advanced Glycation Endproducts (the RAGE receptor) and how this interaction drives an innate immune response. The publication is the result of the collaboration between researchers coordinated by Prof. Antonella Viola at the Department of Biomedical Sciences at the University of Padua and researchers from Human Technopole coordinated by Prof. Giuseppe Testa, with the support of the European Institute of Oncology and the University of Milan. The study demonstrates how the RAGE receptor found on the surface of specific human immune cells penetrates them and pathologically alters their function. This study also shows how the involvement of RAGE determines the degree of severity with which COVID-19 can manifest.
The study took data from patients hospitalized for COVID-19 during the first phase of the pandemic at the Complex Operative Unit for Infectious Diseases and Tropical Diseases in Padua, led by Dr Anna Maria Cattelan. The research team in Padua isolated and characterized the immune cells from the blood of COVID-19 patients at three different time points during and after the infection, i.e. on admission, at discharge and one month after release.
The analysis then continued in Milan, where researchers used technologies to analyze what happens inside a single cell by looking at the expression of all 20,000 genes encoded by its DNA. The amount of data observed for each patient is comparable to the amount of information in a 140-megapixel image, a resolution at the frontier of the possibilities of commonly available cameras. Images captured over different points of hospitalization amplified the amount of data and provided insight to each patients’ response to the SARS-CoV-2 virus.
The analysis showed that the RAGE receptor induces specific alterations in gene regulation, enhancing the inflammatory effect of the virus and contributing to disease exacerbation. Identifying this new mode of interaction between the virus and human cells is crucial for developing targeted therapeutic strategies, mainly to protect individuals at risk of severe complications, such as the elderly or frail individuals. This discovery could lay the foundations for a more targeted and effective approach to counteracting the spread of the virus in these vulnerable groups. For instance, by comparing the characteristic molecular responses detected in the study with those collected in some global databases, scientists also found that the drug Baricitinib, already approved by AIFA in 2021 for the treatment of COVID-19, could potentially reverse the identified harmful effects.
