Abstract

The SARS-CoV-2 (COVID-19) pandemic has caused millions of deaths worldwide. Early risk assessment of COVID-19 cases can help direct early treatment measures that have been shown to improve the prognosis of severe cases. Currently, circulating miRNAs have not been evaluated as canonical COVID-19 biomarkers, and identifying biomarkers that have a causal relationship with COVID-19 is imperative. To bridge these gaps, we aim to examine the causal effects of miRNAs on COVID-19 severity in this study using two-sample Mendelian randomization approaches. Multiple studies with available GWAS summary statistics data were retrieved. Using circulating miRNA expression data as exposure, and severe COVID-19 cases as outcomes, we identified ten unique miRNAs that showed causality across three phenotype groups of COVID-19. Using expression data from an independent study, we validated and identified two high-confidence miRNAs, namely, hsa-miR-30a-3p and hsa-miR-139-5p, which have putative causal effects on developing cases of severe COVID-19. Using existing literature and publicly available databases, the potential causative roles of these miRNAs were investigated. This study provides a novel way of utilizing miRNA eQTL data to help us identify potential miRNA biomarkers to make better and early diagnoses and risk assessments of severe COVID-19 cases.

Highlights

  • Published: 11 December 2021COVID-19, a disease caused by the SARS-CoV-2 virus, has grown into a worldwide pandemic that has infected more than 200 million people and caused more than 4.4 million deaths since December 2019

  • Using summary statistics from genomewide association studies (GWAS), we identified multiple putative causal miRNAs that can contribute to the severity of COVID-19

  • By analyzing three phenotype phenotype groups with different COVID-19 severities, we identified ten mature miRNAs causally groups with different COVID-19 severities, we identified ten mature miRNAs causally associated with COVID-19 severity and hospitalization

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Summary

Introduction

Published: 11 December 2021COVID-19, a disease caused by the SARS-CoV-2 virus, has grown into a worldwide pandemic that has infected more than 200 million people and caused more than 4.4 million deaths since December 2019. Most infected cases of COVID-19 are asymptomatic or show mild symptoms, such as fever, cough, shortness of breath and muscle ache [1]. A small subset of the cases may develop more severe and critical disease courses, with dyspnea and hypoxemia as the most common symptoms [2,3]. Evidence has shown that early diagnosis and antiviral treatment of such cases can alleviate severe symptoms and improve prognosis [4,5]. The most common and accessible biomarkers for COVID-19 are from blood samples, such as hemoglobin and lymphocyte counts [7]. Biomarkers based on these signatures, such as a high neutrophil-tolymphocyte ratio, can be suggestive of disease severity. Many protein-based biomarkers, such as C-reactive protein (CRP) and cytokines targeting inflammatory factors, Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations

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