Gene expression profiling of SARS-CoV-2 infections reveal distinct primary lung cell and systemic immune infection responses that identify pathways relevant in COVID-19 disease

Abstract To identify key gene expression pathways altered with infection of the novel coronavirus SARS-CoV-2, we performed the largest comparative genomic and transcriptomic analysis to date. We compared the novel pandemic coronavirus SARS-CoV-2 with SARS-CoV and MERS-CoV, as well as influenza A strains H1N1, H3N2 and H5N1. Phylogenetic analysis confirms that SARS-CoV-2 is closely related to SARS-CoV at the level of the viral genome. RNAseq analyses demonstrate that human lung epithelial cell responses to SARS-CoV-2 infection are distinct. Extensive Gene Expression Omnibus literature screening and drug predictive analyses show that SARS-CoV-2 infection response pathways are closely related to those of SARS-CoV and respiratory syncytial virus infections. We validated SARS-CoV-2 infection response genes as disease-associated using Kaplan–Meier survival estimates in lung disease patient data. We also analysed COVID-19 patient peripheral blood samples, which identified signalling pathway concordance between the primary lung cell and blood cell infection responses.

Download Full-text

Influenza Viral Infection is a High-Risk Factor for Developing Coronavirus Disease 2019 (COVID-19)

10.20944/preprints202003.0307.v1 ◽

2020 ◽

Author(s):

Lei Zhang ◽

Youwei Zhang

Keyword(s):

Gene Expression ◽

Risk Factor ◽

High Risk ◽

Viral Infection ◽

Respiratory System ◽

Influenza A ◽

Target Cells ◽

High Risk Factor ◽

Syncytial Virus ◽

Influenza Viral Infection

Coronavirus disease 2019 (COVID-19) is caused by infection with the 2019 novel coronavirus 2 (2019-nCoV, now referred to as SARS-CoV-2). COVID-19 has become a global pandemic since its outbreak at the end of Dec 2019. COVID-19 could lead to severe acute respiratory disease, especially to those who have reduced immunity. Binding of the viral Spike protein (S) to its receptor ACE2 (Angiotensin Converting Enzyme 2) on the surface of target cells has been proven to be key for virus entry and infection. Although ACE2 expression in the respiratory system is necessary for pneumonia infection by SARS-CoV-2, the regulation of ACE2 gene expression remains poorly investigated, especially for patients that are in pre-pathological conditions. Here, by analyzing The Gene Expression Omnibus (GEO) database, we investigated the expression regulation of ACE2 in various kinds of primary epithelial cells from the respiratory system after influenza A or respiratory Syncytial Virus (RSV) infection. Our analyses reveal that infection of influenza A, RSV or influenza vaccines greatly increased ACE2 expression, suggesting that influenza viral infection could represent a high risk factor for developing COVID-19. We also found that the regulatory effect of influenza A virus on ACE2 expression is associated with activation of the interferon beta-induced pathway and viral RNA-activated host response. Together, our data provide a theoretical framework for clinical classification for SARS-CoV-2 infection susceptibility and could be used for future prevention and therapy treatment for COVID-19.

Download Full-text

COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve out- come in severe cases

10.21203/rs.3.rs-29392/v1 ◽

2020 ◽

Author(s):

Sorin Draghici ◽

Tuan-Minh Nguyen ◽

Larry A. Sonna ◽

Cordelia Ziraldo ◽

Radu Vanciu ◽

...

Keyword(s):

Gene Expression ◽

Influenza A ◽

Immune Modulation ◽

Clinical Results ◽

Current Management ◽

All Cause Mortality ◽

Syncytial Virus ◽

Approved Drugs ◽

Fda Approved Drugs ◽

Disease Pathways

Abstract Current management efforts of COVID-19 include: early diagnosis, use of antivirals, and immune modulation. After the initial viral phase of the illness, identification of the patients developing cytokine storm syndrome is critical.1, 2 Treatment of hyper- inflammation in these patients using existing, approved therapies with proven safety profiles could address the immediate need to reduce the rising mortality.3 The identification of existing drugs that could modulate the immune response is an immediate need. Here we show that an analysis of the changes in the gene expression, path- ways and putative mechanisms between SARS-CoV2, influenza A, and respiratory syncytial virus can be used to identify FDA-approved drugs that could be repurposed to help COVID-19 patients with severe symptoms related to hyper-inflammation. An important finding is that drugs in the same class may not achieve similar effects. An independent clinical study evaluated 213 subjects, 81 (38%) and 132 (62%) in pre-and post-methylprednisolone groups, respectively. Thirty-day all-cause mortality occurred at a significantly lower rate in the post-methylprednisolone group compared to pre-methylprednisolone group (29.6% vs. 16.6%, p=0.027). Clinical results con- firmed the in silico prediction that methylprednisolone could improve outcomes in severe cases of COVID-19. These findings are important for any future pandemic regardless of the virus.

Download Full-text

Viral co-infections are associated with dysregulation of HLA family gene expression.

10.31219/osf.io/v7bf6 ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Gene Expression ◽

Influenza A ◽

Microarray Dataset ◽

Human Coronavirus ◽

Significant Differential Expression ◽

A Cell ◽

Family Gene ◽

Coronavirus Infection ◽

Syncytial Virus ◽

One Year

Co-infection is a process by which a cell or organism already infected with a virus is then infected with a second, different virus (1, 2). The human coronavirus SARS-CoV-2 has resulted in the death of nearly 200,000 Americans in less than one year (3, 4); the upcoming influenza could potentially pose a problem with respect to co-infection with Influenza and SARS-CoV-2; significant co-infection in patients with SARS-CoV-2 has been reported (5). We mined a published microarray dataset (6) to discover genes associated with viral co-infection in patients with a coronavirus infection. We found that genes of the HLA family, particularly HLA-DRB and HLA-A, were significantly differentially expressed in the blood of patients with human coronavirus infections, including HCoV-229E, HCoV OC43, HCoV NL63, and HCoV HKU1. Different viral co-infections, including Influenza A, Human Rhinovirus, Enterovirus, and Respiratory Syncytial Virus A co-infections were also associated with significant differential expression of HLA family genes in patient blood. Perturbation of HLA family gene expression appears to be a general feature of viral co-infection in humans.

Download Full-text

Analytical performances of the AMPLIQUICK® Respiratory Triplex assay for simultaneous detection and differentiation of SARS-CoV-2, influenza A/B and respiratory syncytial viruses in respiratory specimens

PLoS ONE ◽

10.1371/journal.pone.0262258 ◽

2022 ◽

Vol 17 (1) ◽

pp. e0262258

Author(s):

Ralph-Sydney Mboumba Bouassa ◽

Serge Tonen-Wolyec ◽

David Veyer ◽

Hélène Péré ◽

Laurent Bélec

Keyword(s):

Influenza A ◽

Viral Infections ◽

Simultaneous Detection ◽

Influenza B ◽

The Novel ◽

Perfect Agreement ◽

Qualitative Detection ◽

High Concordance ◽

Syncytial Virus ◽

Respiratory Specimens

Although patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A, influenza B and respiratory syncytial virus (RSV) show comparable or very similar manifestations, the therapeutic approaches of these respiratory viral infections are different, which requires an accurate diagnosis. Recently, the novel multiplex real-time reverse transcription-polymerase chain reaction assay AMPLIQUICK® Respiratory Triplex (BioSynex SA, Illkirch-Graffenstaden, France) allows simultaneous detection and differentiation of SARS-CoV-2, influenza A, influenza B, and RSV in respiratory tract samples. We herein evaluated the performance of the AMPLIQUICK® Respiratory Triplex for the detection of the four viruses in respiratory specimens, using Allplex™ Respiratory Panel 1 and 2019-nCoV assays (Seegene, Seoul, Korea) as reference comparator assays. A total of 359 archived predetermined respiratory samples, including 83, 145, 19 and 95 positive specimens for SARS-CoV-2, influenza A, influenza B and RSV respectively, were included. The AMPLIQUICK® Respiratory Triplex showed high concordance with the reference assays, with an overall agreement for SARS-CoV-2, influenza A, influenza B, and RSV at 97.6%, 98.8%, 98.3% and 100.0%, respectively, and high κ values ranging from 0.93 to 1.00, indicating an almost perfect agreement between assays. Furthermore, high correlations of cycle threshold (Ct) values were observed for positive samples of the four viruses between the AMPLIQUICK® Respiratory Triplex and comparator assays, with an overall high agreement between Ct values assessed by Bland-Altman analyses. In conclusion, these observations demonstrate that the multiplex AMPLIQUICK® Respiratory Triplex is a reliable assay for the qualitative detection and differentiation of SARS-CoV-2, influenza A, influenza B, and RSV in respiratory specimens, which may prove useful for streamlining diagnostics during the winter influenza-seasons.

Download Full-text

COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve outcome in severe cases

10.1101/2020.05.06.20076687 ◽

2020 ◽

Author(s):

Sorin Draghici ◽

Tuan-Minh Nguyen ◽

Larry A Sonna ◽

Cordelia Ziraldo ◽

Radu L Vanciu ◽

...

Keyword(s):

Gene Expression ◽

Influenza A ◽

Immune Modulation ◽

Composite Endpoint ◽

Clinical Results ◽

Methyl Prednisolone ◽

Expression Pathways ◽

Syncytial Virus ◽

Using Data ◽

Approved Drugs

Background. Current management efforts of COVID-19 include: early diagnosis, use of antivirals and immune modulation. After the initial viral phase of the illness, identification of the patients developing cytokine storm syndrome is critical. Treatment of this hyper-inflammation in these patients using existing, approved therapies with proven safety profiles could address the immediate need to reduce the rising mortality. Methods. Using data from an A549 cell line, primary human bronchial epithelial (NBHE), as well as from COVID-19-infected lung, we compare the changes in the gene expression, pathways and mechanisms between SARS-CoV2, influenza A, and respiratory syncytial virus. Results. We identified FDA-approved drugs that could be repurposed to help COVID-19 patients with severe symptoms related to hyper-inflammation. An important finding is that drugs in the same class will not achieve similar effects. For instance methylprednisolone and prednisolone were predicted to be effective in reverting many of the changes triggered by COVID-19, while other closely related steroids, such as prednisone or dexamethasone, were not. An independent clinical study evaluated 213 subjects, 81 (38%) and 132 (62%) in pre-and post-methylprednisolone groups, respectively. The composite end point was composed of escalation to intensive care units, need for mechanical ventilation, and death. The composite endpoint occurred at a significantly lower rate in post-methylprednisolone group compared to pre-methylprednisolone group (34.9% vs. 54.3%, p=0.005). Conclusion. Clinical results confirmed the efficacy of the in silico prediction that indicated methyl- prednisolone could improve outcomes in severe COVID-19. These findings are important for any future pandemic regardless of the virus.

Download Full-text

The Virome of Acute Respiratory Diseases in Individuals at Risk of Zoonotic Infections

Viruses ◽

10.3390/v12090960 ◽

2020 ◽

Vol 12 (9) ◽

pp. 960

Author(s):

Nguyen Thi Kha Tu ◽

Nguyen Thi Thu Hong ◽

Nguyen Thi Han Ny ◽

Tran My Phuc ◽

Pham Thi Thanh Tam ◽

...

Keyword(s):

At Risk ◽

Influenza A ◽

Respiratory Diseases ◽

Respiratory Pathogens ◽

The Novel ◽

Rt Pcr ◽

Pcr Screening ◽

Zoonotic Infections ◽

Acute Respiratory Diseases ◽

Syncytial Virus

The ongoing coronavirus disease 2019 (COVID-19) pandemic emphasizes the need to actively study the virome of unexplained respiratory diseases. We performed viral metagenomic next-generation sequencing (mNGS) analysis of 91 nasal-throat swabs from individuals working with animals and with acute respiratory diseases. Fifteen virus RT-PCR-positive samples were included as controls, while the other 76 samples were RT-PCR negative for a wide panel of respiratory pathogens. Eukaryotic viruses detected by mNGS were then screened by PCR (using primers based on mNGS-derived contigs) in all samples to compare viral detection by mNGS versus PCR and assess the utility of mNGS in routine diagnostics. mNGS identified expected human rhinoviruses, enteroviruses, influenza A virus, coronavirus OC43, and respiratory syncytial virus (RSV) A in 13 of 15 (86.7%) positive control samples. Additionally, rotavirus, torque teno virus, human papillomavirus, human betaherpesvirus 7, cyclovirus, vientovirus, gemycircularvirus, and statovirus were identified through mNGS. Notably, complete genomes of novel cyclovirus, gemycircularvirus, and statovirus were genetically characterized. Using PCR screening, the novel cyclovirus was additionally detected in 5 and the novel gemycircularvirus in 12 of the remaining samples included for mNGS analysis. Our studies therefore provide pioneering data of the virome of acute-respiratory diseases from individuals at risk of zoonotic infections. The mNGS protocol/pipeline applied here is sensitive for the detection of a variety of viruses, including novel ones. More frequent detections of the novel viruses by PCR than by mNGS on the same samples suggests that PCR remains the most sensitive diagnostic test for viruses whose genomes are known. The detection of novel viruses expands our understanding of the respiratory virome of animal-exposed humans and warrant further studies.

Download Full-text