Exosomal miRNAs affect poor outcomes in elderly people with SARS-CoV-2

Elderly people and patients with comorbidities are at higher risk of COVID-19 infection, resulting in severe complications and high mortality. However, the underlying mechanisms are unclear. Researchers from the Chinese Academy of Medical Sciences Research Unit of Extracellular RNA investigated whether miRNAs in serum exosomes can exert antiviral functions and affect the response to COVID-19 in the elderly and people with diabetes.

First, the researchers identified four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) through high-throughput sequencing and quantitative real-time PCR analysis, that are remarkably decreased in the elderly and diabetic groups. They further demonstrated that these miRNAs, either in the exosome or in the free form, can directly inhibit S protein expression and SARS-CoV-2 replication. Serum exosomes from young people can inhibit SARS-CoV-2 replication and S protein expression, while the inhibitory effect is markedly decreased in the elderly and diabetic patients. Moreover, three out of the four circulating miRNAs are significantly increased in the serum of healthy volunteers after 8-weeks’ continuous physical exercise. Serum exosomes isolated from these volunteers also showed stronger inhibitory effects on S protein expression and SARS-CoV-2 replication.

This study demonstrates for the first time that circulating exosomal miRNAs can directly inhibit SARS-CoV-2 replication and may provide a possible explanation for the difference in response to COVID-19 between young people and the elderly or people with comorbidities.

The inhibitory effects of circulating exosomes on SARS-CoV-2 replication
were decreased in elderly people and diabetic patients

Fig. 3

a Diagrams of the collection of exosomes from serum in young, elderly and diabetic groups and the measurement of the biological activities of exosomes in inhibiting S protein expression and SARS-CoV-2 replication. b Efficacy of exosomes collected from young, elderly and diabetic groups in inhibiting the replication of SARS-CoV-2. cde Cytometric analysis (c), fluorescence images (d) and western blot (e) of GFP-S protein-overexpressing HEK293T cells after treatment with PBS and serum exosomes collected from the young, elderly and diabetic groups. Data are shown as means ± SEMs. Statistical significance was assessed using one-way ANOVA coupled with Bonferroni’s post hoc test (bce). *P < 0.05; **P < 0.01; ***P < 0.001

Wang Y, Zhu X, Jiang XM, Guo J, Fu Z, Zhou Z, Yang P, Guo H, Guo X, Liang G, Zeng P, Xiao G, Ma J, Yin X, Zhang LK, Yan C, Zhang CY. (2021) Decreased inhibition of exosomal miRNAs on SARS-CoV-2 replication underlies poor outcomes in elderly people and diabetic patients. Signal Transduct Target Ther 6(1):300.[article]

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