Detection of SARS-CoV-2 Derived Small RNAs and Changes in Circulating Small RNAs Associated with COVID-19

Abstract

Cleavage of double-stranded RNA is described as an evolutionary conserved host defense mechanism against viral infection. Small RNAs are the product and triggers of post transcriptional gene silencing events. Up until now, the relevance of this mechanism for SARS-CoV-2-directed immune responses remains elusive. Herein, we used high throughput sequencing to profile the plasma of active and convalescent COVID-19 patients for the presence of small circulating RNAs. The existence of SARS-CoV-2 derived small RNAs in plasma samples of mild and severe COVID-19 cases is described. Clusters of high siRNA abundance were discovered, homologous to the nsp2 3’-end and nsp4 virus sequence. Four virus-derived small RNA sequences have the size of human miRNAs, and a target search revealed candidate genes associated with ageusia and long COVID symptoms. These virus-derived small RNAs were detectable also after recovery from the disease. The additional analysis of circulating human miRNAs revealed differentially abundant miRNAs, discriminating mild from severe cases. A total of 29 miRNAs were reduced or absent in severe cases. Several of these are associated with JAK-STAT response and cytokine storm.

Gene Network Analysis of the Transcriptome Impact of SARS-CoV-2 Interacting MicroRNAs in COVID-19 Disease

“…Upon abstract collection, 44 research papers (23 in silico [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ] and 21 experimental studies [ 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]) met the inclusion criteria and were used for downstream analysis. The entire workflow of the current study is depicted in Figure 1 .…”

The role of microRNAs in solving COVID-19 puzzle from infection to therapeutics: A mini-review

“…Another investigation in which plasma samples from COVID-19 patients were examined using high throughput sequencing approach to detect small circulating RNAs buttressed that four small virus-derived RNAs similar in size to human miRNAs are linked with COVID-19 symptoms and ageusia. These virus-derived tiny RNAs might represent promising biomarkers since they present abundantly even in recovered COVID-19 patients ( Grehl et al, 2021 ). In this same study, 20 miRNAs displayed lower abundance in severe cases of COVID-19, while 11 miRNAs were upregulated.…”

“…In this same study, 20 miRNAs displayed lower abundance in severe cases of COVID-19, while 11 miRNAs were upregulated. Among these differentially expressed miRNAs, hsa-miR-320a-3p, hsa-miR-629-5p, hsa-miR-29a-3p, hsa-miR-342-3p, hsa-miR-185-5p, and hsa-miR-4516 were the most representative ones because of their possible association with severe states of COVID-19 and their potential application in molecular diagnostics ( Grehl et al, 2021 ).…”

Viral and Host Small RNA Response to SARS-CoV-2 Infection

“…It has been reported that the N protein of SARS-CoV-2 may act as a viral suppressor of RNAi [9]. Several publications have reported results of small RNAs and SARS-CoV-2-infection related studies, and potential vsmRNAs have been identified [10][11][12][13][14][15][16][17][18][19]. However, a consensus has not been reached yet.…”