Find out why older people and people with diabetes are more vulnerable to covid-19

The research was funded by grants from the Chinese Science and Technology Major Project of China, National Basic Research Program of China (program 973), National Natural Science Foundation of China, Training Program from the Major Research Plan of the National Natural Science Foundation of China. , the Natural Science Foundation of Jiangsu Province, and the Basic Research Fund for Central Universities.

Titled “Decreased Exosomal MiRNA Inhibition on SARS-CoV-2 Replication Underlies Poor Outcomes in Elderly and Diabetic Patients,” the research was published in Signal Transduction and Targeted Therapy last week. .

Serum exosomes (the main vector of circulating RNAs) containing these young miRNAs could strongly inhibit the replication of SARS-CoV-2, but this inhibitory effect was attenuated in older patients and diabetics.

Clinical data from around the world has shown that the elderly and patients with co-morbidities have higher risks of developing serious complications and higher death rates from covid-19. However, there is a lack of scientific explanation for this phenomenon.

Using high-throughput sequencing and bioinformatics analysis, the group identified four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) that are markedly decreased in elderly and diabetic groups. These miRNAs are either in exosomes or in free form that can directly inhibit S protein expression and SARS-CoV-2 replication. This phenomenon is markedly reduced in elderly and diabetic patients.

In addition, three of the four circulating miRNAs increased significantly in the serum of healthy volunteers after eight weeks of continuous physical exercise. Serum exosomes isolated from these volunteers also showed stronger inhibitory effects on S protein expression and SARS-CoV-2 replication, the authors said.

“This study demonstrates for the first time that our own endogenous miRNAs could directly inhibit the SARS-CoV-2 virus. This is not surprising since the group’s previous studies have already shown that about 89% of viruses that infect humans could be targeted by human miRNAs, ”the authors said. The study provides strong evidence to support the theory that miRNAs, especially extracellular miRNAs, could function as “RNA defense” and protect cells against foreign nucleic acids, they added.

Classical immunology indicates that the mammalian immune system is based on proteins and that immune protection is provided by antibodies, cytokines, interferons, etc. Studies by the Zhang group indicate that miRNAs are an important part of the endogenous RNA-based immune system to fight viral infection.

“Older people have multiple factors that could increase their risk for covid-19, including poor organ function, diabetes, poor fitness and immunity, and so on. Age can also lead to genetic damage with less repair potential and in this study the effect of these important protectors miRNA is attenuated, ”said Dr. Anoop Misra, President of the Fortis-C Center of Excellence. DOC for diabetes, metabolic diseases and endocrinology.