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HGNC Genes

SARS-CoV-2 proteins

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ORF1ab (1)


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SARS-CoV-2 Proteins
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    Transcriptome analysis of PBMCs reveals distinct immune response in the asymptomatic and re-detectable positive COVID-19 MESHD patients

    Authors: Jiaqi Zhang; Dongzi Lin; Kui Li; Xiangming Ding; Lin Li; Yuntao Liu; Dongdong Liu; Jing Lin; Xiangyun Teng; Yizhe Li; Ming Liu; Xiaodan Wang; Dan He; Yaling Shi; Dawei Wang; Jianhua Xu

    doi:10.1101/2021.03.16.21251286 Date: 2021-03-24 Source: medRxiv

    The existence of asymptomatic and re-detectable positive COVID-19 MESHD patients presents the disease control challenges of COVID-19 MESHD. Most studies on immune response of COVID-19 MESHD have focused on the moderately or severely symptomatic patients, however little is known about the immune response in asymptomatic and re-detectable positive patients. Here we performed a comprehensive analysis of the transcriptomic profiles of PBMCs from 48 COVID-19 MESHD patients which include 8 asymptomatic, 13 symptomatic, 15 recovering and 12 RP MESHD patients. Our analysis revealed a down-regulation of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, we observed a lower expression of the cytokines and chemokines in the PBMC of asymptomatic and symptomatic patients. In contrast, the cytokines and chemokines level in the RP patients are higher than the recovering. GSEA analysis showed the enrichment of TNFa HGNC/ NF-{kappa}B HGNC and influenza infection MESHD in the RP MESHD patients compared with the recovering patients, indicating a flu-like, hyper-inflammatory immune response in the PBMC of RP MESHD patients. Thus our findings could extend our understanding of host immune response during the progression COVID-19 MESHD disease and help the clinical management and the immunotherapy development for COVID-19 MESHD.

    Pediatric nasal epithelial cells are less permissive to SARS-CoV-2 replication compared to adult cells

    Authors: Yanshan Zhu; Keng Yih Chew; Anjana C. Karawita; Ayaho Yamamoto; Larisa L. Labzin; Tejasri Yarlagadda; Alexander A. Khromykh; Claudia J. Stocks; Yao Xia; Tobias R. Kollmann; David Martino; Anthony Kicic; Helle Bielefeldt-Ohmann; Asha C. Bowen; Peter D. Sly; Kirsten M. Spann; Kirsty R. Short

    doi:10.1101/2021.03.08.434300 Date: 2021-03-08 Source: bioRxiv

    Rationale: Young children (typically those <10 years old) are less susceptible to SARS-CoV-2 infection MESHD and symptoms compared to adults. However, the mechanisms that underlie these age-dependent differences remain to be determined and could inform future therapeutics for adults. Objective: To contrast the infection dynamics of SARS-CoV-2 in primary nasal epithelial cells from adults and children. Methods: Viral replication was quantified by plaque assay. The cellular transcriptome of infected and uninfected cells was assessed by RNA-seq. ACE2 HGNC and TMPRSS2 HGNC protein expression were quantified by Western Blot Measurements and Main Results: We report significantly higher SARS-CoV-2 replication in adult compared to pediatric nasal epithelial cells. This was restricted to SARS-CoV-2 infection MESHD, as the same phenomenon was not observed with influenza virus infection MESHD. The differentiational SARS-CoV-2 replication dynamics were associated with an elevated type I and III interferon response, and a more pronounced inflammatory response in pediatric cells. No significant difference between the two age groups was observed in the protein levels of ACE2 HGNC and TMPRSS2 HGNC. Conclusions: Our data suggest that the innate immune response of pediatric nasal epithelial cells, and not differential receptor expression, may contribute to the reported reduced SARS-COV-2 infection MESHD and symptoms reported amongst children.

    Human nasal and lung tissues infected ex vivo with SARS-CoV-2 provide insights into differential tissue-specific and virus-specific innate immune responses in the upper and lower respiratory tract

    Authors: Or Alfi; Arkadi Yakirevich; Ori Wald; Ori Wandel; Uzi Izhar; Esther Oiknine-Djian; Yuval Nevo; Sharona Elgavish; Elad Dagan; Ory Madgar; Gilad Feinmesser; Eli Pikarsky; Michal Bronstein; Olesya Vorontsov; Wayne Jonas; John Ives; Joan Walter; Zichria Zakay-Rones; Menachem Oberbaum; Amos Panet; Dana G Wolf

    doi:10.1101/2021.03.08.434404 Date: 2021-03-08 Source: bioRxiv

    The nasal-mucosa constitutes the primary entry site for respiratory viruses including SARS-CoV-2. While the imbalanced innate immune response of end-stage COVID-19 MESHD has been extensively studied, the earliest stages of SARS-CoV-2 infection MESHD at the mucosal entry site have remained unexplored. Here we employed SARS-CoV-2 and influenza virus infection MESHD in native multi-cell-type human nasal turbinate and lung tissues ex vivo, coupled with genome-wide transcriptional analysis, to investigate viral susceptibility and early patterns of local-mucosal innate immune response in the authentic milieu of the human respiratory tract. SARS-CoV-2 productively infected the nasal turbinate tissues, predominantly targeting respiratory epithelial cells, with rapid increase in tissue-associated viral sub-genomic mRNA, and secretion of infectious viral progeny. Importantly, SARS-CoV-2 infection MESHD triggered robust antiviral and inflammatory innate immune responses in the nasal mucosa. The upregulation of interferon stimulated genes, cytokines and chemokines, related to interferon signaling and immune-cell activation pathways, was broader than that triggered by influenza virus infection MESHD. Conversely, lung tissues exhibited a restricted innate immune response to SARS-CoV-2, with a conspicuous lack of type I and III interferon upregulation, contrasting with their vigorous innate immune response to influenza virus. Our findings reveal differential tissue-specific innate immune responses in the upper and lower respiratory tract, that are distinct to SARS-CoV-2. The studies shed light on the role of the nasal-mucosa in active viral transmission and immune defense, implying a window of opportunity for early interventions, whereas the restricted innate immune response in early- SARS-CoV-2-infected lung MESHD tissues could underlie the unique uncontrolled late-phase lung damage of advanced COVID-19 MESHD.

    Differential Cytokine Signatures of SARS-CoV-2 and Influenza Infection Highlight Key Differences in Pathobiology

    Authors: Andrew H Karaba; Weiqiang Zhou; Leon L Hsieh; Alexis Figueroa; Guido Massaccesi; Richard E Rothman; Katherine ZJ Fenstermacher; Lauren Sauer; Kathryn Shaw-Saliba; Paul W Blair; Sherry Leung; Russell Wesson; Nada Alachkar; Ramy El-Diwany; Hongkai Ji; Andrea L Cox

    doi:10.1101/2021.01.29.21250317 Date: 2021-02-01 Source: medRxiv

    Background: Several inflammatory cytokines are upregulated in severe COVID-19 MESHD. We compared cytokines in COVID-19 MESHD versus influenza in order to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19 MESHD, we examined the relationship of BMI to cytokines associated with severe disease. Methods: Thirty-seven cytokines and chemokines were measured in plasma from 145 patients with COVID-19 MESHD, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was utilized to determine the cytokines most important in distinguishing severe COVID-19 MESHD and influenza. Mediation analysis was utilized to identify cytokines that mediate the effect of BMI on disease severity. Results: IL-18 HGNC, IL-1{beta HGNC}, IL-6 HGNC, and TNF HGNC- were significantly increased in COVID-19 MESHD versus influenza patients while GM-CSF HGNC, IFN-{gamma}, IFN-{lambda}1, IL-10 HGNC, IL-15 HGNC, and MCP-2 HGNC were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18 HGNC, IL-6 HGNC, and TNF HGNC- were elevated in severe COVID-19 MESHD, but not severe influenza. Random forest analysis identified high IL-6 HGNC and low IFN-{lambda}1 HGNC levels as the most distinct between severe COVID-19 MESHD and severe influenza. Finally, IL-1RA HGNC was identified as a potential mediator of the effects of BMI on COVID-19 MESHD severity. Conclusions: These findings point to activation of fundamentally different innate immune pathways in SARS-CoV-2 and influenza infection MESHD, and emphasize drivers of severe COVID-19 MESHD to focus both mechanistic and therapeutic investigations.

    Vaccination Against Influenza Among Lebanese Health Care Workers in the Era HGNC of Coronavirus Disease 2019 MESHD 

    Authors: Dalal Youssef; Linda Abou Abass; Janet Youssef; Atika Berry

    doi:10.21203/rs.3.rs-150253/v1 Date: 2021-01-18 Source: ResearchSquare

    Background: Health care workers (HCWs) are at increased risk of i nfluenza infection. MESHD Hence, the rationale for immunization to protect them and their patients particularly during the co-circulation of influenza and coronavirus disease 2019 MESHD ( COVID-19 MESHD). This study aims to assess knowledge, attitudes, and practices among HCWs towards the influenza vaccine and to identify the determinants of their willingness to vaccinate. Methods: Using an online survey, a cross-sectional study, was conducted in Lebanon between 14th and 28th October 2020 among HCWs. Descriptive statistics were reported using frequency and percentages for categorical variables. Multivariable logistic regression was carried out to identify the factors associated with influenza vaccine uptake. Adjusted odds ratio and their 95% confidence intervals were reported.   Results: A total of 560 HCWs participated in the survey of which 72.9% were females. The majority were nurses (63.2%), married (66.1%) and aged between 30-49 years (53.9%). Nearly half of them had a good level of knowledge (≥80%).  As perceived by HCWs, the availability of a sufficient quantity of vaccine will be the biggest challenge. Benefits of vaccination in enhancing patient safety, and avoiding c o-infection MESHDby influenza and COVID-19 MESHD were well-acknowledged by HCWs. 32.1% of HCWs have received the influenza vaccine during the last year and 80.2% were willing to vaccinate for the current year. The influenza uptake was higher among HCWs who have received influenza vaccine in the past season (OR = 6.812, CI (3.045-15.239)), having a fair health status (OR = 3.117, CI (1.345-7.220)), good knowledge (OR=3.305, CI (1.155-9.457)), positive attitude (OR=2.305, CI (0.921-5.571)), low perception of barriers (OR= 4.130, CI (1.827-9.334)) and high perception of benefits (OR=6.264, CI (2.919-13.442) and was lower in single and divorced (OR=0.527, CI (0.284-0.978)). ConclusionAddressing misconceptions unveiled in this study through adapted training, along with economic interventions are needed to improve influenza vaccination coverage among HCWs.

    A Novel Multiplex PCR Based Detection Assay Using Saliva or Nasopharyngeal Samples for SARS-Cov-2, Influenza A and B: Clinical Validation and Utility for Mass Surveillance.

    Authors: Nikhil Shri Sahajpal; Ashis K Mondal; Sudha Ananth; Allan Njau; Pankaj Ahluwalia; Eesha Oza; Ted Ross; Vamsi Kota; Arvind Kothandaraman; Sadanand Fulzele; Madhuri Hegde; Alka Chaubey; Amyn M Rojiani; Ravindra Kolhe

    doi:10.1101/2021.01.13.21249629 Date: 2021-01-15 Source: medRxiv

    BackgroundThe COVID-19 pandemic MESHD has resulted in a significant diversion of human and material resources to COVID-19 MESHD diagnostics, to the extent that testing of viral pathogens normally contributing to seasonal respiratory tract infections have been markedly neglected. The global health burden due to influenza viruses MESHD and co-infection MESHD in COVID-19 MESHD patients remains undocumented but clearly pose serious public health consequences. To address these clinical and technical challenges, we have optimized and validated a highly sensitive RT-PCR based multiplex assay for the detection of SARS-CoV-2, Influenza A and B viruses in a single test. MethodsThis study evaluated clinical specimens (n=1411) that included 1019 saliva and 392 nasopharyngeal swab (NPS) samples collected in either healthcare or community setting. Samples were tested using two assays: FDA-EUA approved SARS-CoV-2 assay that targets N and ORF1ab PROTEIN gene, and the PKamp RT-PCR based assay that targets SARS-CoV-2, Influenza viruses A and B. The limit of detection (LoD) studies was conducted as per the FDA guidelines using SARS-CoV-2 and Influenza A and B reference control materials. ResultsOf the 1019 saliva samples, 17.0% (174/1019) tested positive for SARS-CoV-2 using either assay. The detection rate for SARS-CoV-2 was higher with our multiplex assay compared to SARS-specific assay [91.9% (160/174) vs. 87.9% (153/174)], respectively. Of the 392 NPS samples, 10.4% (41/392) tested positive for SARS-CoV-2 using either assay. The detection rate for SARS-CoV-2 was higher with our multiplex assay compared to SARS-specific assay [97.5% (40/41) vs. 92.1% (39/41)], respectively. The Ct values for SARS-CoV-2 were comparable between the two assays, whereas the Ct values of the housekeeping gene was significantly lower with multiplex assay compared to SARS-specific assay. The LoD was established as 60 copies/ml for SARS-CoV-2 and 180 copies/ml for Influenza A and B viruses for both saliva and NPS samples. ConclusionThis study presents clinical validation of a multiplex PCR assay for testing SARS-CoV-2, Influenza A and B viruses, using NPS and saliva samples, and demonstrates the feasibility of implementing the assay without disrupting the existing laboratory workflow. This novel assay uses the same instruments, sample types, supplies, and laboratory personnel as needed for the testing of SARS-CoV-2 virus.

    Increased lethality in Influenza and SARS-CoV-2 co-infection MESHD is prevented by influenza immunity but not SARS-CoV-2 immunity MESHD

    Authors: Hagit Achdout; Einat B. Vitner; Boaz Politi; Sharon Melamed; Yfat Yahalom-Ronen; Hadas Tamir; Noam Erez; Roy Avraham; Lilach Cherry; Efi Makdasi; Didi Gur; Moshe Aftalion; Yaron Vagima; Nir Paran; Tomer Israely

    doi:10.21203/rs.3.rs-136702/v1 Date: 2020-12-27 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause for the ongoing COVID-19 pandemic MESHD1. The continued spread of SARS-CoV-2 along with the imminent flu season increase the probability of influenza-SARS-CoV-2 dual infection which might result in a severe disease. In this study, we examined the disease outcome of influenza A virus (IAV) and SARS-CoV-2 co-infection MESHD in K18- hACE2 HGNC mice. Our data indicates that IAV-infected MESHD mice are more susceptible to develop severe disease upon co-infection MESHD with SARS-CoV-2 two days post influenza infection. This co-infection MESHD results in severe morbidity and nearly uniform fatality as compared to the non-fatal influenza disease MESHD, or the partial fatality of SARS-CoV-2 alone. Co-infection MESHD was associated with elevated influenza viral load in respiratory organs. Remarkably, prior immunity to influenza, but not to SARS-CoV-2, prevented the severe disease and mortality. These data provide an experimental support that flu intervention by prior vaccination may be valuable in reducing the risk of sever Flu - SARS-CoV-2 comorbidity, and highlight the importance of vaccination.

    Disruption of nasal bacteria enhances protective immune responses to influenza A virus and SARS-CoV-2 infection MESHD in mice

    Authors: Minami Nagai; Miyu Moriyama; Takeshi Ichinohe; Chiara Cosma; Filippo Navaglia; Stefania Moz; Nicole Contran; Carlo-Federico Zambon; Anna Maria Cattelan; Mario Plebani; Liam Crawford; Andrew Bosworth; Tim Plant; Alan McNally

    doi:10.1101/2020.12.25.424300 Date: 2020-12-27 Source: bioRxiv

    Gut microbiota plays a critical role in the induction of adaptive immune responses to influenza virus infection MESHD. However, the role of nasal bacteria in the induction of the virus-specific adaptive immunity is less clear. Here we demonstrate that while intranasal administration of influenza virus hemagglutinin vaccine alone was insufficient to induce the vaccine-specific antibody responses, disruption of nasal bacteria by lysozyme or addition of culturable oral bacteria from a healthy human volunteer rescued inability of the nasal bacteria to generate antibody responses to intranasally administered the split-virus vaccine. Myd88 HGNC-depdnent signaling in the hematopoietic compartment was required for adjuvant activity of intranasally administered oral bacteria. In addition, we found that the oral bacteria-combined intranasal vaccine induced protective antibody response to influenza virus and SARS-CoV-2 infection MESHD. Our findings here have identified a previously unappreciated role for nasal bacteria in the induction of the virus-specific adaptive immune responses.

    Comparison of Hospitalized Patients with Severe Pneumonia MESHD Caused by COVID-19 MESHD and Highly Pathogenic Avian Influenza (H7N9): A Retrospective Study from A Designated Hospital

    Authors: Binbin Gu; Lin Yao; XinYun Zhu; Pei-jun Tang; Cheng Chen

    doi:10.21203/rs.3.rs-135753/v1 Date: 2020-12-24 Source: ResearchSquare

    Background: Considerable attention has been focused on clinical features of Coronavirus Disease 2019 MESHD ( COVID-19 MESHD), it is also important for clinicians to differentiate it from influenza virus infections MESHD.Methods: The clinical data of 23 cases of H7N9 and 23 cases of COVID-19 MESHD with severe pneumonia MESHD were collected. The comparisons were performed with the t test, Mann-Whitney U test, Fisher exact test or the chi-squared test, and multivariable logistic regression analysis.Results: All of the cases were under the circumstance of sufficient medical staff and medical supplies. Radiologically, severe COVID-19 MESHD patients had less consolidation and pleural effusion MESHD, but more crazy-paving pattern than severe H7N9 patients (p<0.05). Clinically, compared to severe H7N9, severe COVID-19 MESHD patients were more inclined to surfer to relative better disease severity score, less secondary bacterial infection MESHD, a shorter time to beginning absorption on CT, but a longer duration of viral shedding from the admission (p<0.05). Although more severe H7N9 patients needed non-invasive respiratory support, these two groups ultimately yielded comparable mortality. Based on multiple logistic regression analysis, severe COVID-19 MESHD infection was associated with a lower risk of the presence of severe ARDS (OR 0.964, 95% [CI] 0.931-0.998, p=0.040), but exhibited longer duration of viral shedding (OR 0.734, 95% [CI] 0.550-0.980, p=0.036) than severe H7N9 infection.Conclusion: Although the conditions of severe H7N9 patients seemed to be more critical than those of severe COVID-19 MESHD patients, the relatively lower mortality of these two severe cases is to be expected in context of sufficient medical supplies.

    Disruption of Nasal Bacteria Enhances Protective Immune Responses to Influenza A Virus and SARS-CoV-2 Infection MESHD

    Authors: Minami Nagai; Miyu Moriyama; Takeshi Ichinohe

    doi:10.21203/rs.3.rs-129105/v1 Date: 2020-12-15 Source: ResearchSquare

    Background: Gut microbiota and these microbial-derived products play a critical role in the induction of adaptive immune responses to influenza virus infection MESHD. However, the role of nasal bacteria in the induction of the virus-specific adaptive immunity is less clear. Here, we examine whether nasal bacteria critically regulates the generation of influenza virus specific adaptive immune response after infection or intranasal vaccination. Results: We demonstrated that disruption of nasal bacteria by topical mucosal application of antibiotic enhances the virus-specific antibody responses to influenza virus infection MESHD. Although intranasal administration of hemagglutinin (HA) vaccine alone was insufficient to induce the HA-specific antibody responses, disruption of nasal bacteria by lysozyme or addition of culturable oral bacteria from a healthy human volunteer rescued inability of the nasal bacteria to generate antibody responses to intranasally administered split-virus vaccines. Myd88-depdnent signaling in the hematopoietic compartment was required for adjuvant activity of intranasally administered oral bacteria. In addition, we found that the oral bacteria-combined intranasal vaccine induced protective antibody response to influenza virus and SARS-CoV-2 infection MESHD.Conclusion: We show for the first time that disruption of nasal bacteria enhances protective immune responses to influenza virus and SARS-CoV-2 infection MESHD. Our findings here have identified a previously unappreciated role for nasal bacteria in the induction of the virus-specific adaptive immune responses.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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