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.
Highlights
A novel disease has been spreading in a pandemic manner since the end of 2019. This disease was named COVID-19, as it was found to be associated with the zoonotic Severe Acute Respiratory Syndrome Corona Virus type 2 (SARS-CoV-2)
The results show n = 85 in mild cases and n = 171 in severe cases in both orientations, while the sense orientation is higher in abundance
The mapping of the plasma-derived small RNAs reads against the SARS-CoV-2 genome resulted in the identification of SARS-CoV-2 derived sequences
Summary
A novel disease has been spreading in a pandemic manner since the end of 2019. This disease was named COVID-19 (coronavirus disease 2019), as it was found to be associated with the zoonotic Severe Acute Respiratory Syndrome Corona Virus type 2 (SARS-CoV-2).SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA betacoronavirus of the family Coronaviridae. A novel disease has been spreading in a pandemic manner since the end of 2019 This disease was named COVID-19 (coronavirus disease 2019), as it was found to be associated with the zoonotic Severe Acute Respiratory Syndrome Corona Virus type 2 (SARS-CoV-2). The case fatality ratio of SARS-CoV-2 is approximately 100 times higher than the common influenza infection (case fatality ratio: 0.01–0.04 deaths per 100 positive cases, [2]). It ranges between 1 and 5 per 100 cases, depending on local medicinal standards (MERS: 34.4, SARS; 9.5 [3]) and vulnerability, e.g., Trisomy 21 [4]. This high rate is mainly driven by the lack of effective treatment of severe cases
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