Host transcriptomic profiling of COVID-19 patients with mild, moderate, and severe clinical outcomes

Jain, Ruchi; Ramaswamy, Sathishkumar; Harilal, Divinlal; Uddin, Mohammed; Loney, Tom; Nowotny, Norbert; Suwaidi, Hanan Al; Varghese, Rupa; Deesi, Zulfa; Alkhajeh, Abdulmajeed; Khansaheb, Hamda; Alsheikh‐Ali, Alawi A.; Tayoun, Ahmad Abou

doi:10.1016/j.csbj.2020.12.016

Cited by 78 publications

(91 citation statements)

References 35 publications

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“…Recent reports further indicate a link between increased expression of interferon-related genes and higher viral load in severe COVID-19 patients 45-47 . Also, we found overexpression of other genes such as ACE2, STAT1 44 , and TMPRSS13 48 (Figure 5A and Table S8) that are elevated in critical COVID-19 disease.…”

Section: Resultsmentioning

confidence: 85%

“…Also, we found overexpression of other genes such as ACE2, STAT1 44 , and TMPRSS13 48 (Figure 5A and Table S8) that are elevated in critical COVID-19 disease.…”

Section: The N Mutant (R203k/g204r) Induces Overexpression Of Interferon Related Genes In Transfected Host Cellsmentioning

confidence: 85%

“…We found a robust overexpression of interferon-related genes in the N-mutant compared to N-control transfected cells (Figure 5A-B) after adjusting for fold change (Figure S13D). Indeed, strong overexpression of interferon and chemokine related genes (Table S8) were reported in critical COVID-19 patients 43,44 . Recent reports further indicate a link between increased expression of interferon-related genes and higher viral load in severe COVID-19 patients [45][46][47] .…”

Section: The N Mutant (R203k/g204r) Induces Overexpression Of Interferon Related Genes In Transfected Host Cellsmentioning

confidence: 97%

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Saudi Arabian SARS-CoV-2 genomes implicate a mutant Nucleocapsid protein in modulating host interactions and increased viral load in COVID-19 patients

Mourier

Shuaib

Hala

et al. 2021

Preprint

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Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. The availability of patient hospital records is crucial for linking the genomic sequence information to virus function during the course of infections. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. From the assembled sequences, we estimate the SARS-CoV-2 effective population size and infection rate and outline the epidemiological dynamics of import and transmission events during this period in Saudi Arabia. We show that two consecutive mutations (R203K/G204R) in the SARS-CoV-2 nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein by mass-spectrometry analysis. Furthermore, analysis of the host cell transcriptome suggests that the mutant N protein results in dysregulated interferon response genes. We provide crucial information in linking the R203K/G204R mutations in the N protein as a major modulator of host-virus interactions and increased viral load and underline the potential of the nucleocapsid protein as a drug target during infection.

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Section: Resultsmentioning

confidence: 85%

“…Also, we found overexpression of other genes such as ACE2, STAT1 44 , and TMPRSS13 48 (Figure 5A and Table S8) that are elevated in critical COVID-19 disease.…”

Section: The N Mutant (R203k/g204r) Induces Overexpression Of Interferon Related Genes In Transfected Host Cellsmentioning

confidence: 85%

Section: The N Mutant (R203k/g204r) Induces Overexpression Of Interferon Related Genes In Transfected Host Cellsmentioning

confidence: 97%

See 1 more Smart Citation

Saudi Arabian SARS-CoV-2 genomes implicate a mutant Nucleocapsid protein in modulating host interactions and increased viral load in COVID-19 patients

Mourier

Shuaib

Hala

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Several studies have implicated CCR5 variation and expression to be associated with COVID-19 severity (Gómez et al, 2020; Hubacek et al, 2021; Kasela et al, 2021), while others have not (Bernas et al, 2021). TNFSF15 is a third immune response protein in the XCR1 RR subnetwork that shows elevated expression in patients with severe COVID-19 (Jain et al, 2021). We recognize that the involvement of these immune-related proteins does not require an effect mediated through ACE2; however, their protein evolutionary correlations suggest that ACE2 may be part of a signaling network (perhaps modulated through XCR1) that is contributory.…”

Section: Resultsmentioning

confidence: 99%

Evolutionary Inference Predicts Novel ACE2 Protein Interactions Relevant to COVID-19 Pathologies

Cheng

Werren

2021

Preprint

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Angiotensin-converting enzyme 2 (ACE2) is the human cell receptor that the coronavirus SARS-CoV-2 binds to and uses to enter and infect human cells. COVID-19, the pandemic disease caused by the coronavirus, involves diverse pathologies beyond those of a respiratory disease, including micro-thrombosis (micro-clotting), cytokine storms, and inflammatory responses affecting many organ systems. Longer-term chronic illness can persist for many months, often well after the pathogen is no longer detected. A better understanding of the proteins that ACE2 interacts with can reveal information relevant to these disease manifestations and possible avenues for treatment. We have undertaken a different approach to predict candidate ACE2 interacting proteins which uses evolutionary inference to identify a set of mammalian proteins that "coevolve" with ACE2. The approach, called evolutionary rate correlation (ERC), detects proteins that show highly correlated evolutionary rates during mammalian evolution. Such proteins are candidates for biological interactions with the ACE2 receptor. The approach has uncovered a number of key ACE2 protein interactions of potential relevance to COVID-19 pathologies. Some proteins have previously been reported to be associated with severe COVID-19, but are not currently known to interact directly with ACE2, while additional predicted novel interactors with ACE2 are of potential relevance to the disease. Using reciprocal rankings of protein ERCs, we have identified strongly interconnected ACE2 associated protein networks relevant to COVID-19 pathologies. ACE2 has clear connections to coagulation pathway proteins, such as coagulation factor V and fibrinogen components FGG, FGB, and FGA, the latter possibly mediated through ACE2 connections to Clusterin (which clears misfolded extracellular proteins) and GPR141 (whose functions are relatively unknown). Additionally, ACE2 has connections to proteins involved in cytokine signaling and immune response (e.g. IFNAR2, XCR1, and TLR8), and to Androgen Receptor (AR). The ERC prescreening approach has also elucidated possible functions for previously uncharacterized proteins and possible additional functions for well-characterized ones. Suggested validation approaches for ERC predicted ACE2 interacting proteins are discussed. We propose that ACE2 has novel protein interactions that are disrupted during SARS-CoV-2 infection, contributing to the spectrum of COVID-19 pathologies.

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“…SARS-CoV-2-induced cellular perturbations, cytokine storm, and IFNs-I inhibition cause serious clinical outcomes such as ARDS, thromboinflammation, MODS, and death in patients with severe/critical COVID-19 [82] , [83] , [84] . Reduction of ACE2 following the virus entry and also ADAM17 activity can underlie the increase of blood pressure, elevated permeability of pulmonary vessels, acute lung injury (ALI), fibrotic and thrombotic responses.…”

Section: Sars-cov-2 and Clinical Outcomesmentioning

confidence: 99%

Cytokine storm in the pathophysiology of COVID-19: Possible functional disturbances of miRNAs

Aslani

Mortazavi-Jahromi

Mirshafiey

2021

International Immunopharmacology

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SARS-CoV-2, as the causative agent of COVID-19, is an enveloped positives-sense single-stranded RNA virus that belongs to the Beta-CoVs sub-family. A sophisticated hyper-inflammatory reaction named cytokine storm is occurred in patients with severe/critical COVID-19, following an imbalance in immune-inflammatory processes and inhibition of antiviral responses by SARS-CoV-2, which leads to pulmonary failure, ARDS, and death. The miRNAs are small non-coding RNAs with an average length of 22 nucleotides which play various roles as one of the main modulators of genes expression and maintenance of immune system homeostasis. Recent evidence has shown that Homo sapiens (hsa)-miRNAs have the potential to work in three pivotal areas including targeting the virus genome, regulating the inflammatory signaling pathways, and reinforcing the production/signaling of IFNs-I. However, it seems that several SARS-CoV-2-induced interfering agents such as viral (v)-miRNAs, cytokine content, competing endogenous RNAs (ceRNAs), etc. preclude efficient function of hsa-miRNAs in severe/critical COVID-19. This subsequently leads to increased virus replication, intense inflammatory processes, and secondary complications development. In this review article, we provide an overview of hsa-miRNAs roles in viral genome targeting, inflammatory pathways modulation, and IFNs responses amplification in severe/critical COVID-19 accompanied by probable interventional factors and their function. Identification and monitoring of these interventional elements can help us in designing the miRNAs-based therapy for the reduction of complications/mortality rate in patients with severe/critical forms of the disease.

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Host transcriptomic profiling of COVID-19 patients with mild, moderate, and severe clinical outcomes

Cited by 78 publications

References 35 publications

Saudi Arabian SARS-CoV-2 genomes implicate a mutant Nucleocapsid protein in modulating host interactions and increased viral load in COVID-19 patients

Saudi Arabian SARS-CoV-2 genomes implicate a mutant Nucleocapsid protein in modulating host interactions and increased viral load in COVID-19 patients

Evolutionary Inference Predicts Novel ACE2 Protein Interactions Relevant to COVID-19 Pathologies

Cytokine storm in the pathophysiology of COVID-19: Possible functional disturbances of miRNAs

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