scholarly journals Immunogenetic Factors Associated with Severe Respiratory Illness Caused by Zoonotic H1N1 and H5N1 Influenza Viruses

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Jennifer Juno ◽  
Keith R. Fowke ◽  
Yoav Keynan

Following the 2009 H1N1 pandemic and ongoing sporadic avian-to-human transmission of H5N1 viruses, an emphasis has been placed on better understanding the determinants and pathogenesis of severe influenza infections. Much of the current literature has focused on viral genetics and its impact on host immunity as well as novel risk factors for severe infection (particularly within the H1N1 pandemic). An understanding of the host genetic determinants of susceptibility and severe respiratory illness, however, is currently lacking. By better defining the role of genetic variability in influenza infection and identifying key polymorphisms that impair the host immune response or correlate with protection, we will be able to better identify at-risk populations and new targets for therapeutic interventions and vaccines. This paper will summarize known immunogenetic factors associated with susceptibility or severity of both pH1N1 and H5N1 infections and will also identify genetic pathways and polymorphisms of high relevance for future study.

2000 ◽  
Vol 74 (22) ◽  
pp. 10807-10810 ◽  
Author(s):  
Jacqueline M. Katz ◽  
Xiuhua Lu ◽  
Terrence M. Tumpey ◽  
Catherine B. Smith ◽  
Michael W. Shaw ◽  
...  

ABSTRACT Highly pathogenic avian influenza A H5N1 viruses caused an outbreak of human respiratory illness in Hong Kong. Of 15 human H5N1 isolates characterized, nine displayed a high-, five a low-, and one an intermediate-pathogenicity phenotype in the BALB/c mouse model. Sequence analysis determined that five specific amino acids in four proteins correlated with pathogenicity in mice. Alone or in combination, these specific residues are the likely determinants of virulence of human H5N1 influenza viruses in this model.


2021 ◽  
pp. 1-3
Author(s):  
Malek Michael Bouhairie ◽  
◽  
Racha Seblani ◽  

Background: COVID-19 has emerged as a global health pandemic emergency with a massive effect on public health globally. In addition to its effects on respiratory tract, COVID-19 disease had been linked to many gastrointestinal symptoms. Rarely, it has been associated with intestinal ischemia due to the resultant hypercoagulable state. Case Summary: We report a case of a young lady previously healthy, who presented with severe abdominal pain associated with tenesmus and mucoïdbloody diarrhea, diagnosed to have ischemic colitis post covid19 infection. One of the port of entry of coronavirus 2 (SARS-CoV-2), to cause infection, is via an angiotensin-converting enzyme2 (ACE2). View that these ACE 2 receptors are highly expressed at the level of gastrointestinal tract, a variety of symptoms will occur. Recently, coagulopathy due to COVID-19 has emerged as a major component of the disease. The resultant ischemia has been reported to be associated with a hypercoagulable state. Lately, few cases were described worldwide of intestinal ischemia due to COVID-19 infection, mainly occuring in patients presenting with severe respiratory illness. Our patient did not complain of severe COVID-19 infection in the context of dyspnea or respiratory distress and did not have any features of shock requiring a vasopressor therapy. Treatment for ischemic colitis mainly involves supportive care with bowel rest. Conclusion: New datas concerning covid 19 infection are emerging. Ischemic colitis is a new aspect of manifestation of the infection, which can take place without necessarily being linked to a severe infection with covid 19 as in our case.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1358-1358 ◽  
Author(s):  
A.J. Gerard Jansen ◽  
Hui Zhi Low ◽  
Judith van den Brand ◽  
Debbie van Riel ◽  
Albert Osterhaus ◽  
...  

Abstract Thrombocytopenia is a common and sometimes life-threatening symptom in patients with influenza, which indicates that platelets may play a significant role during virus infection. However, the mechanisms underlying influenza associated thrombocytopenia are still unclear to date. In this study, the relationship between platelets and influenza infection was studied in vivo and in vitro. In the period 2009-2012 we randomly measured viral load and platelet count in laboratory-confirmed influenza patients (A/H1N1 subtype; n=85) presented at the emergency department of Erasmus MC. In a cross-sectional study we found, after excluding patients with HIV infection, chemotherapy treatment and immediate referral to the ICU, that a high viral load was significantly correlated with a low platelet count at presentation (n=36; Spearman correlation coefficient 0.341; P=0.042). To study this relationship further we inoculated ferrets (n=120) with an H3N2 (n=30), pandemic H1N1 (n=30), or H5N1 influenza A virus (n=30) and measured platelet counts in six ferrets per time point at day 0, 1, 2, 3 and 4 after infection. Thrombocytopenia was seen at day 3 in all ferrets compared to the control animals (n=30). The decrease in platelet counts was significant in the H5N1 infected ferrets (p<0.05). For the sialidase and influenza virus inhibitor oseltamivir, we have previously shown that it functions as an inhibitor of platelet degradation. Interestingly, thrombocytopenia in ferrets could also be inhibited by oral administration of oseltamivir. However, these results were not statistically significant. Finally, we studied the interaction between platelets and influenza viruses by electron microscopy. In a platelet suspension incubated for 1 minute with influenza virus we observed platelets with virus containing vacuoles, suggesting that the platelets had rapidly phagocytosed the viruses. Characteristics of these platelets incubated with influenza virus were measured including membrane expression of the GPIb-IX-V complex, CD62P, and surface glycans sialic acid and GlcNac using flowcytometry and functional capacity employing aggregometry using collagen, thrombin and ADP as agonists. However, no effect was seen in expression of GPIba and GPIX, P-selectin expression and surface expression of sialic acid and GlcNAc after incubation with influenza virus. Also no effect was seen on functional capacity of these platelets. Our study shows that influenza virus is significantly correlated with a lower platelet count. Phagocytosis of influenza virus by platelets may play an important role in the occurrence of thrombocytopenia during influenza infection and may be a mechanism of virus clearance during infection. Disclosures Osterhaus: Viroclinics Biosciences: Other: chief scientific officer and hold certificates of shares.


2020 ◽  
Vol 118 (1) ◽  
pp. e2015794118
Author(s):  
Stephanie L. Sarbanes ◽  
Vincent A. Blomen ◽  
Eric Lam ◽  
Søren Heissel ◽  
Joseph M. Luna ◽  
...  

The journey from plasma membrane to nuclear pore is a critical step in the lifecycle of DNA viruses, many of which must successfully deposit their genomes into the nucleus for replication. Viral capsids navigate this vast distance through the coordinated hijacking of a number of cellular host factors, many of which remain unknown. We performed a gene-trap screen in haploid cells to identify host factors for adenovirus (AdV), a DNA virus that can cause severe respiratory illness in immune-compromised individuals. This work identified Mindbomb 1 (MIB1), an E3 ubiquitin ligase involved in neurodevelopment, as critical for AdV infectivity. In the absence of MIB1, we observed that viral capsids successfully traffic to the proximity of the nucleus but ultimately fail to deposit their genomes within. The capacity of MIB1 to promote AdV infection was dependent on its ubiquitination activity, suggesting that MIB1 may mediate proteasomal degradation of one or more negative regulators of AdV infection. Employing complementary proteomic approaches to characterize proteins proximal to MIB1 upon AdV infection and differentially ubiquitinated in the presence or absence of MIB1, we observed an intersection between MIB1 and ribonucleoproteins (RNPs) largely unexplored in mammalian cells. This work uncovers yet another way that viruses utilize host cell machinery for their own replication, highlighting a potential target for therapeutic interventions that counter AdV infection.


MedAlliance ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 90-92

The review analyzed data on the risks of influenza infection and severe course in tobacco smokers compared with non-smokers. The incidence of influenza in the Russian Federation in 2018 amounted to 26.33 per 100 000 people, and was 24% lower than the incidence in 2017 (34.86 per 100 000) due to the fact that in recent years the coverage of the population with preventive vaccinations has been significantly increased against the flu. Meta-analyzes shows that current smokers are more likely to get the flu than non-smokers. It is noted that smoking may increase the risk of hospitalization in smokers (OR 1.32–2.18 in various meta-analyzes) and former smokers after infection with the influenza virus. Tobacco has been found to increase the risk of death from influenza among older people. At the same time, there is a study of risk factors for severe outcomes in patients hospitalized with the 2009 H1N1 pandemic flu, in which smoking was not a risk factor for severe outcomes. During the influenza epidemic, smokers and former smokers should be given the flu shot and be informed of the risk of hospitalization, and they are also strongly advised to stop smoking.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 914-914
Author(s):  
A. Boteanu ◽  
A. García Fernández ◽  
N. De la Torre ◽  
M. Pavia Pascual ◽  
O. Sanchez Pernaute ◽  
...  

Background:Patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 may be at risk to develop a severe course of COVID-19 due to the immune dysregulation or the influence of immunomodulating drugs on the course of the infection. For a better understanding of SARS-CoV-2 infections in patients with IRD and due to the high incidence of COVID-19 in Madrid from the beginning of this pandemic infection in Spain, the Society of Rheumatology from Madrid (SORCOM) established a registry (REUMA-COVID SORCOM) shortly after the beginning of the pandemic in Spain.Objectives:To determine factors associated with severity of infection with SARS-CoV-2 in patients with inflammatory rheumatic diseases in MadridMethods:The REUMA-COVID SORCOM registry is a multicenter, retrospective, observational cohort study conducted in Madrid, a SORCOM initiative. All rheumatology departments from Madrid were invited to participate. The study includes patients with IRD presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and November 10, 2020. We consider severe infection death or need of hospitalization. Inclusion criteria was having an IRD and at least 1 of the following 4 criteria: (1) a biologically confirmed COVID-19 diagnosis based on a positive result of a SARS-CoV-2 polymerase chain reaction (PCR) test on a nasopharyngeal swab; (2) Detection of IgM or IgG anti SARS-CoV2 in a symptomatic or asymptomatic patients (3)typical thoracic computed tomography (CT) abnormalities (ground-glass opacities) in epidemic areas; (4) COVID19–typical symptoms in an epidemic zone of COVID-19.Results:As of November 10, 2020, 417 patients with IRD were included in the REUMA-COVID SORCOM registry. 5 patients were discharged for incomplete data. Of 412 patients (mean age 57 years, 87.4% Caucasian race, 66.3% female) 174 need hospitalization (42.2%) and 33 patients died (18.4% mortality in hospitalized patients). 82.3% had comorbidities. 234 (56.8%) patients were classified as inflammatory arthropathy, 133 (32.3%) had connective tissue diseases (CTD). 41.1% of the patients had a large history of IRD (> 10 years). 10.4% of patients had previously pulmonary involvement. The study includes 143 patients taking Methotrexate, 89 patients taking anti-TNFα therapy and 27 Rituximab. In the univariant analysis, no differences were seen in the severity of COVID-19 infection in patients taking methotrexate. 63% of the all patients taking Rituximab included in the registry need hospitalization and 22% of them died. Hypertension, COPD or cardiovascular disease was associated with hospitalization.Independent factors associated with COVID-19 hospitalization in the multivariate analysis was: age (>62 years), male sex, IMC >30, previous cardiovascular comorbidities and the IRD disease duration (> 10 years). Independent factors associated with COVID-19 related death was: age (> 62 years), having a CTD diagnose, pulmonary involvement before infection and chronical GC treatment.Conclusion:Patients with IRD represent a population of particular interest in the pandemic context because the baseline immunological alteration and the treated with immunosuppressants agents they receive, comorbidities and the well-known risk of severe infection. Older age, male sex, cardiovascular comorbidities were factors associated with high risk of hospitalization in IRD patients. CTD diseases, previously pulmonary involvement and chronical GC treatment with more than 10mg/day were associated with high risk of death. Neither anti TNF-α treatment nor Methotrexate were risk factor for hospitalization or death COVID-19 related in IRD patients.Disclosure of Interests:None declared


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