Abstract
(1) Background: The coronavirus (COVID-19) pandemic is still a major global health problem, despite the development of several vaccines and diagnostic assays. Moreover, the broad symptoms, from none to severe pneumonia, and the various responses to vaccines and the assays, make infection control challenging. Therefore, there is an urgent need to develop non-invasive biomarkers to quickly determine the infection severity. Circulating RNAs have been proven to be potential biomarkers for a variety of diseases, including infectious ones. This study aimed to develop a genetic network related to cytokines, with clinical validation for early infection severity prediction. (2) Methods: Extensive analyses of in silico data have established a novel IL11RA molecular network (IL11RNA mRNA, LncRNAs RP11-773H22.4 and hsa-miR-4257). We used different databases to confirm its validity. The differential expression within the retrieved network was clinically validated using quantitative RT-PCR, along with routine assessment diagnostic markers (CRP, LDH, D-dimmer, procalcitonin, Ferritin), in100 infected subjects (mild and severe cases) and 100 healthy volunteers. (3) Results: IL11RNA mRNA and LncRNA RP11-773H22.4, and the IL11RA protein, were significantly upregulated, and there was concomitant downregulation of hsa-miR-4257, in infected patients, compared to the healthy controls, in concordance with the infection severity. (4) Conclusion: The in-silico data and clinical validation led to the identification of a potential RNA/protein signature network for novel predictive biomarkers, which is in agreement with ferritin and procalcitonin for determination of COVID-19 severity.
Highlights
IntroductionHuman coronaviruses are newly recognized airborne viruses (family coronaviridae, genus Betacoronavirus) of zoonotic origin
Human coronaviruses are newly recognized airborne viruses of zoonotic origin
We first reviewed the currently available literature on the pathophysiology and molecular signaling pathways involved in the cytokine storm related to the pathogenesis and severity of COVID-19, focusing on the Kyoto Encyclopedia of Genes and Genomes (KEGG) map pathways database, and on cytokine-related pathways
Summary
Human coronaviruses are newly recognized airborne viruses (family coronaviridae, genus Betacoronavirus) of zoonotic origin They are positive-stranded RNA viruses with nucleocapsids, and are considered some of the largest RNA viruses, having about 26 to 32 kilobases of RNA. They mainly cause severe acute respiratory syndrome (SARS) [1]. The first coronavirus outbreak appeared in China in 2003, along with four other countries [2] This newly identified coronavirus was called SARS-CoV-1. At the end of 2019 in Wuhan, Hubei, China, a novel third coronavirus outbreak was reported, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Before the 6 June 2021, there were over 172.5 million cases reported, and over 3.5 million deaths globally [6]
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