Identification of PBMC-based molecular signature associational with COVID-19 disease severity

Abstract

The longevity of COVID-19 as a global pandemic, and the devastating effects it has had on certain subsets of individuals thus far has highlighted the importance of identifying blood-based biomarkers associated with disease severity. We employed computational and transcriptome analyses of publicly available datasets from PBMCs from 126 patients with COVID-19 admitted to ICU (n=50), COVID-19 not admitted to ICU (n=50), non-COVID-19 admitted to ICU (n=16) and non-COVID-19 not admitted to ICU (n=10), and utilized the Gencode V33 assembly to analyze protein coding mRNA and long noncoding RNA (lncRNA) transcriptomes in the context of disease severity. Our data identified several aberrantly expressed mRNA and lncRNA based biomarkers associated with SARS-CoV-2 severity, which in turn significantly affected canonical, upstream, and disease functions in each group of patients. Immune, interferon, and antiviral responses were severely suppressed in COVID-19 admitted to ICU versus COVID-19 who were not admitted to ICU. Our data suggests a possible therapeutic approach for severe COVID-19 through administration of interferon therapy. Delving further into these biomarkers, roles and their implications on the onset and disease severity of COVID-19 could play a crucial role in patient stratification and identifying varied therapeutic options with diverse clinical implications.

Co-Regulation of Protein Coding Genes by Transcription Factor and Long Non-Coding RNA in SARS-CoV-2 Infected Cells: An In Silico Analysis

“…Differential expression of lncRNA in PBMC between severe and mildly affected COVID-19 patients has also been reported. It has been observed that increased level of LINC02207, LINC01127 was associated with the severe COVID-19 group, whereas LINC02084, LINC02446, LINC00861, LINC01871, and ANKRD44-AS1 were associated with the mild COVID-19 group [38]. PVT1 was downregulated in severe COVID-19 patients compared with non-severity [37].…”

“…Expressions of hundreds of lncRNAs including uncharacterized novel transcripts have been identified in SARS-CoV-2 infected cells [32][33][34][35], BALF from the COVID-19 patients [35,36], and PBMC from COVID-19 patients [36][37][38][39]). In most of the studies, reanalyses of expression data for lncRNA from published transcriptomic data, except in two studies [33,37] were carried out.…”

“…Direct evidence that lncRNA is involved in the pathogenesis of COVID-19 is not available. Bioinformatics analysis with interacting partners of deregulated lncRNA in SARS-CoV-2 infected cells and comparison with experimental evidence for other viral infections inferred possible relevance of deregulated lncRNA in COVID-19 [32][33][34][35][36][37][38][39]. In the present study, in silico analysis revealed further that lncRNA interacting PCGs (i) interacted with SARS-CoV-2 coded proteins, (ii) deregulated SARS-CoV-2 infected cells, (iii) were modulated by interferon treatment, and (iv) modulated SARS-CoV-2 infection identified in a CRISPR screen.…”

Tangled quest of post-COVID-19 infection-caused neuropathology and what 3P nano-bio-medicine can solve?

“…LncRNAs have roles in viral transformation, viral latency maintenance, viral replication promotion, and viral-gene expression augmentation [ 96 ] ; implicate in modulating host cell immunity and/or inflammation, host cell energy/ metabolism, host cell cycle, and apoptosis; and thus negatively impact the normal physiological activities of host cells [ 97 ]. Multiple lncRNAs were differentially expressed during SARS-CoV-2 infection, which are considered potential disease biomarkers [ 98 ]. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and lncRNA X-inactive specific transcript (XIST) have been reported to play a key role during the SARS-CoV-2 inflammatory immune response [ 99 ].…”

SnoRNAs and miRNAs Networks Underlying COVID-19 Disease Severity

“…Recent research has suggested that a unique non-coding RNA signature can aid in identifying the likelihood of developing specific disease outcomes [2]. Alterations of miRNA levels in the blood have been described in multiple inflammatory and infectious diseases, including SARS-related coronaviruses [3][4][5][6][7][8][9]. MiRNAs are endogenous small non-coding RNAs, around 22 nucleotides, that bind specific messenger RNAs (mRNAs) through complementary base-pairing [10].…”