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Severe Cases of COVID-19 Are Associated with Changes in Circulating Small RNA

21 Pages Posted: 17 May 2021

See all articles by Claudius Grehl

Claudius Grehl

Martin Luther University of Halle-Wittenberg - Institute of Computer Science

Christoph Schultheiß

Martin-Luther-University Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology

Katrin Hoffmann

Martin Luther University of Halle-Wittenberg - Institute of Human Genetics

Mascha Binder

Martin-Luther-University Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology

Thomas Altmann

Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) - Department of Molecular Genetics, Heterosis

Ivo Grosse

Martin Luther University of Halle-Wittenberg - Institute of Computer Science

Markus Kuhlmann

Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) - Department of Molecular Genetics, Heterosis

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Abstract

RNA-interference is described as an evolutionary conserved host defense mechanism against viral infection. Up to now, the relevance of this mechanism for SARS-CoV-2-directed immune responses remains elusive.

Here, we used high throughput sequencing to profile the plasma of active and convalescent COVID-19 patients for the presence of small circulating RNAs. The presence 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 target search revealed candidate genes associated with ageusia and long COVID symptoms. These virus-derived small RNAs are detectable also after recovery from the disease.

The additional analysis of circulating human miRNAs revealed differentially abundant miRNAs discriminating mild from severe cases. 29 miRNAs are reduced or absent in severe cases. Several of these are associated with the Interferon JAK-STAT response (e.g. hsa-miRNA4516, hsa-miR-320 b, c and d, hsa-miR-126-3p).

Funding Statement: This project was partially funded by the German Research Foundation (CRC 841, to MB) as well as by the Martin-Luther-University Halle (Saale) and Leibniz Institute of Plant Genetics and Crop Plant Research, Gatersleben, Germany.

Declaration of Interests: The authors have no conflict of interests.

Ethics Approval Statement: Blood collection was performed under institutional review board approvals numbers 2020- 039 and 11/17.

Keywords: SARS-CoV-2, COVID-19, long COVID, small RNA, circulating-miRNA

Suggested Citation

Grehl, Claudius and Schultheiß, Christoph and Hoffmann, Katrin and Binder, Mascha and Altmann, Thomas and Grosse, Ivo and Kuhlmann, Markus, Severe Cases of COVID-19 Are Associated with Changes in Circulating Small RNA. Available at SSRN: https://ssrn.com/abstract=3844793 or http://dx.doi.org/10.2139/ssrn.3844793

Claudius Grehl

Martin Luther University of Halle-Wittenberg - Institute of Computer Science ( email )

Emil-Abderhalden-Str. 7
Halle an der Saale
06099 Halle (Saale), DE Sachsen-Anhalt 06099
Germany

Christoph Schultheiß

Martin-Luther-University Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology ( email )

Germany

Katrin Hoffmann

Martin Luther University of Halle-Wittenberg - Institute of Human Genetics ( email )

Emil-Abderhalden-Str. 7
Halle an der Saale
06099 Halle (Saale), DE Sachsen-Anhalt 06099
Germany

Mascha Binder

Martin-Luther-University Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology ( email )

Germany

Thomas Altmann

Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) - Department of Molecular Genetics, Heterosis ( email )

Seeland
Germany

Ivo Grosse

Martin Luther University of Halle-Wittenberg - Institute of Computer Science ( email )

Emil-Abderhalden-Str. 7
Halle an der Saale
06099 Halle (Saale), DE Sachsen-Anhalt 06099
Germany

Markus Kuhlmann (Contact Author)

Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) - Department of Molecular Genetics, Heterosis ( email )

Seeland
Germany