scholarly journals Human genetic factors associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Cleo Anastassopoulou ◽  
Zoi Gkizarioti ◽  
George P. Patrinos ◽  
Athanasios Tsakris
Keyword(s):  
Disease Severity ◽  
Genetic Factors ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Severe Pneumonia ◽  
Cell Surface Receptor ◽  
Main Body ◽  
Susceptibility To Infection ◽  
Novel Coronavirus

Abstract Background The emergence of the novel coronavirus in Wuhan, Hubei Province, China, in December 2019 marked the synchronization of the world to a peculiar clock that is counting infected cases and deaths instead of hours and minutes. The pandemic, highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has indeed caused considerable morbidity and mortality and drastically changed our everyday lives. As we continue to become acquainted with the seventh coronavirus known to infect our species, a number of its characteristics keep surprising us. Among those is the wide spectrum of clinical manifestations of the resulting coronavirus disease 2019 (COVID-19), which ranges from asymptomatic or mildly symptomatic infections to severe pneumonia, respiratory failure, and death. Main body Data, now from patient populations, are beginning to accumulate on human genetic factors that may contribute to the observed diversified disease severity. Therefore, we deemed it prudent to review the associations between specific human genetic variants and clinical disease severity or susceptibility to infection that have been reported in the literature to date (at the time of writing this article in early August 2020 with updates in mid-September). With this work, we hope (i) to assist the fast-paced biomedical research efforts to combat the virus by critically summarizing current knowledge on the potential role of host genetics, and (ii) to help guide current genetics and genomics research towards candidate gene variants that warrant further investigation in larger studies. We found that determinants of differing severity of COVID-19 predominantly include components of the immune response to the virus, while determinants of differing susceptibility to SARS-CoV-2 mostly entail genes related to the initial stages of infection (i.e., binding of the cell surface receptor and entry). Conclusion Elucidating the genetic determinants of COVID-19 severity and susceptibility to SARS-CoV-2 infection would allow for the stratification of individuals according to risk so that those at high risk would be prioritized for immunization, for example, if or when safe and effective vaccines are developed. Our enhanced understanding of the underlying biological mechanisms could also guide personalized therapeutics. Such knowledge is already beginning to provide clues that help explain, at least in part, current epidemiologic observations regarding the typically more severe or benign disease course in older males and children, respectively.

scholarly journals Coronavirus Disease-2019 (COVID-19): An Updated Review

Drug Research ◽  
2020 ◽  
Vol 70 (09) ◽  
pp. 389-400 ◽  
Author(s):  
Mithun Rudrapal ◽  
Shubham J. Khairnar ◽  
Laxmikant B. Borse ◽  
Anil G. Jadhav
Keyword(s):  
Current Knowledge ◽  
Clinical Manifestations ◽  
Multiple Organ ◽  
Therapeutic Interventions ◽  
Disease Epidemiology ◽  
Host Immune Responses ◽  
Treatment Regimens ◽  
Prophylactic Measures ◽  
Precautionary Measures ◽  
Novel Coronavirus

AbstractThe current outbreak of novel Coronavirus Disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major pandemic situation and a catastrophe for humans. COVID-19 is a severe infectious disease particularly of the respiratory system characterized by fatal complications such as severe acute respiratory distress syndrome (SARS), pneumonia, cardiac arrhythmia, kidney failure/ multiple organ failure and even death. Since its discovery, the SARS-CoV-2 has spread across 213 countries or territories, causing more than 8.5 million people with a rising death toll over 5.5 million people (as of June 2020, WHO). In fact, the current looming crisis of COVID-19 has become an increasingly serious concern to public health. It has affected lives of millions of people with severe impact on health systems and economies globally. Since there are no specific drugs and/or vaccines available so far, combating COVID-19 remains to be a major challenging task. Therefore, development of potential and effective treatment regimens (prophylactic/therapeutic) is urgently required which could resolve the issue. In this review, we summarize the current knowledge about the coronavirus, disease epidemiology, clinical manifestations and risk factors, replication of the virus, pathophysiology and host immune responses of SARS-CoV-2 infection. The therapeutic interventions and prophylactic measures along with precautionary measures are the frontline approaches that could be undertaken in order to control and prevent the spread of the deadly and highly contagious COVID-19 are also detailed herein.

scholarly journals Diagnostic SARS-CoV-2 Cycle Threshold Value Predicts Disease Severity, Survival, and Six-Month Sequelae in COVID-19 Symptomatic Patients

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 281
Author(s):  
Mattia Trunfio ◽  
Francesco Venuti ◽  
Francesca Alladio ◽  
Bianca Maria Longo ◽  
Elisa Burdino ◽  
...  
Keyword(s):  
Disease Severity ◽  
Clinical Manifestations ◽  
Signs And Symptoms ◽  
Predictive Marker ◽  
Threshold Value ◽  
Nasopharyngeal Swab ◽  
Cycle Threshold ◽  
Composite Scale ◽  
Group B ◽  
Novel Coronavirus

To date, there is no severe acute respiratory syndrome coronavirus 2-(SARS-CoV-2)-specific prognostic biomarker available. We assessed whether SARS-CoV-2 cycle threshold (Ct) value at diagnosis could predict novel CoronaVirus Disease 2019 (COVID-19) severity, clinical manifestations, and six-month sequelae. Hospitalized and outpatient cases were randomly sampled from the diagnoses of March 2020 and data collected at 6 months by interview and from the regional database for COVID-19 emergency. Patients were stratified according to their RNA-dependent-RNA-polymerase Ct in the nasopharyngeal swab at diagnosis as follows: Group A ≤ 20.0, 20.0 < group B ≤ 28.0, and Group C > 28.0. Disease severity was classified according to a composite scale evaluating hospital admission, worst oxygen support required, and survival. Two hundred patients were included, 27.5% in Groups A and B both, 45.0% in Group C; 90% of patients were symptomatic and 63.7% were hospitalized. The median time from COVID-19 onset to swab collection was five days. Lethality, disease severity, type, and number of signs and symptoms, as well as six-month sequelae distributed inversely among the groups with respect to SARS-CoV-2 Ct. After controlling for confounding, SARS-CoV-2 Ct at diagnosis was still associated with COVID-19-related death (p = 0.023), disease severity (p = 0.023), number of signs and symptoms (p < 0.01), and presence of six-month sequelae (p < 0.01). Early quantification of SARS-CoV-2 may be a useful predictive marker to inform differential strategies of clinical management and resource allocation.

scholarly journals Coronavirus Disease 2019 (COVID-19): Pathogenesis, Immune Responses, and Treatment Options

2020 ◽  
Author(s):  
Nandini Eswaran ◽  
Shwetha Krishna
Keyword(s):  
Immune Responses ◽  
Immune Evasion ◽  
Defense Mechanisms ◽  
Current Knowledge ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Evolutionary Process ◽  
Effective Vaccine ◽  
Novel Coronavirus

Background: The emergence and the spread of the novel coronavirus or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating impact on the economy and has become a pressing issue globally. Due to the significant increase in the number of confirmed cases and death tolls worldwide, and certain countries reporting second waves, there is an immediate need for an effective vaccine or other therapeutic intervention to control the spread of the disease. Improving our understanding on the host’s anti-viral immune response on SARS-CoV-2 infection, the potential immune evasion mechanisms adopted by the virus, and the speculated role of antibody dependent enhancement (ADE) in coronavirus disease 2019 (COVID-19) pathogenesis will aid in identifying and designing effective therapeutics. Aim: This review aims to provide an in-depth view of the current knowledge available on the range of host defense mechanisms activated by SARS-CoV-2 infection and various immune evasion mechanisms utilized by the virus. In addition, it also highlights the postulated role of ADE in viral pathogenesis and covers the different preventive and therapeutic options available for the treatment of COVID-19 based on current literature. Discussion: The ongoing COVID-19 pandemic serves as a timely reminder on the constant evolutionary process the virus undergoes to emerge as a novel strain and to spread undetected within the population. Similar to other infectious diseases, the host defence mechanism is triggered, and it plays a central role in dampening viral replication by recruiting immune cells and activating anti-viral mechanisms to control the spread of infection by SARS-CoV-2. However, the virus has adopted different immune evasion mechanisms to circumvent host surveillance to successfully establish infection. Hence, understanding the host’s immune responses triggered by SARS-CoV-2 infection is critical for identifying and designing novel and effective therapeutics. Currently, over 70% of the population are either asymptomatic or they showcase mild to moderate symptoms and reasons for why some people can mount immune responses more quickly than others are unknown. However, a growing body of research speculates that the ADE mechanism may facilitate the SARS-CoV-2 entry and can contribute to severe clinical manifestations. With the constant rise in the number of confirmed cases, there is an immediate need for an effective vaccine to mitigate the spread of the virus. Presently, there is no treatment for COVID-19 although several vaccine candidates are in clinical trials. Therefore, preventive measures like social distancing, isolation, and travel restrictions, may be the key to controlling the rapid spread of COVID-19.

scholarly journals Practices in Handling Clinical Samples in a COVID-19 Laboratory - An Experience from Chennai, India

2021 ◽  
Vol 10 (39) ◽  
pp. 3508-3510
Author(s):  
Saramma Mini Jacob ◽  
Kanagasabai Sivasangeetha ◽  
Durairaj Anitha ◽  
Singaram Kaplana
Keyword(s):  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Gastrointestinal Symptoms ◽  
World Health ◽  
Clinical Samples ◽  
The Novel ◽  
Global Pandemic ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Respiratory Droplets

In early January 2020, China had started raising concerns of a new contagious disease caused by new strains of coronavirus, Severe Acute Respiratory SyndromeCoronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) on March 11, 2020, had declared the novel coronavirus (COVID-19) outbreak a global pandemic. COVID-19 was transmitted from person to person through respiratory droplets generated when an infected person coughs, sneezes, breathing or through contact with a surface that has been contaminated 1 and through aerosols-airborne microdroplets.2 The clinical manifestations of COVID-19 represents a wide spectrum of disease ranging from mild to severe respiratory syndrome influenza-like illness with mainly lower respiratory tract symptoms, complicated by pneumonia and Acute Respiratory Distress Syndrome (ARDS), high fever, and headache. In many cases, loss of taste and smell and severe gastrointestinal symptoms were reported, as are cardiac problems, with the latter being perhaps secondary to a cytokine storm such as is seen in the more severely affected patients. 3 WHO COVID-19 dashboard on June 25th 2021 showed 179, 686, 071 confirmed cases worldwide.

Cystic Fibrosis: Pathophysiology of Lung Disease

2019 ◽  
Vol 40 (06) ◽  
pp. 715-726 ◽  
Author(s):  
Christelle Bergeron ◽  
André M. Cantin
Keyword(s):  
Cystic Fibrosis ◽  
Mucociliary Clearance ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Cftr Gene ◽  
Susceptibility To Infection ◽  
Life Threatening ◽  
Cftr Protein ◽  
And Function

AbstractCystic fibrosis (CF) is a common, life-threatening, multisystemic, autosomal recessive disorder. In the last few years, giant steps have been made with regard to the understanding of CF pathophysiology, allowing the scientific community to propose mechanisms that cause the myriad of CF clinical manifestations. Following the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989, the structure and function of the CFTR protein were described. Since then, more than 2,000 variants of the CFTR gene and their impact on the amount and function of the CFTR protein have been reported. The role of the CFTR protein as an ion channel transporting chloride and bicarbonate and its repercussions on different epithelial cell-lined organs and mucus are now better understood. Mechanisms behind susceptibility to infection in CF have also been proposed and include abnormalities in the composition, volume and acidity of the airway surface liquid, changes in the submucosal gland's anatomy and function, and deficiencies in the mucociliary clearance system. Numerous hypotheses explaining the excessive inflammatory response in CF are also debated and involve impaired mucociliary clearance, persistent hypoxia, lipid abnormalities, protease and antiprotease disproportion, and oxidant and antioxidant imbalance. The purpose of this review is to summarize our current knowledge of CF pathophysiology, including significant historic discoveries and most recent breakthroughs, and to improve understanding and awareness of this fatal disease.

scholarly journals Correlation of tumor necrosis factor-α -308G>A polymorphism with susceptibility, clinical manifestations and severity in Behçet syndrome: evidences from an Italian genetic case-control study

2019 ◽  
Author(s):  
Maria Carmela Padula ◽  
Pietro Leccese ◽  
Nancy Lascaro ◽  
Rosa Paola Radice ◽  
Antonina Rita Limongi ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Disease Severity ◽  
Tumor Necrosis ◽  
Wide Spectrum ◽  
Direct Sequencing ◽  
Clinical Manifestations ◽  
Genotype Distribution ◽  
Behçet Syndrome ◽  
Behcet Syndrome ◽  
Necrosis Factor

Abstract Background The tumor necrosis factor (TNF)α is a multifunctional proinflammatory cytokine, implicated in a variety of diseases, including Behçet syndrome (BS), a rare vasculitis with a wide spectrum of clinical manifestations. The aim of the present study was to investigate the association between a functional drug-response TNFα gene polymorphism (at the positions of -308; rs1800629) and both disease susceptibility and clinical manifestations in a cohort of Italian BS patients compared with healthy controls (HC).Methods We recruited 130 Italian patients with BS consecutively seen at Rheumatology Institute of Lucania (Italy) and 100 ethnically, age and gender matched HC. Demographic and clinical features were retrieved by medical records. Specific primer pairs were designed for TNFα coverage. Genomic DNA isolation, primer-specific PCR amplification and direct sequencing were performed for genotyping our group of patients and controls. In silico analysis was downstream performed using Mutation Surveyor software (SoftGenetics, USA) and NCBI-BlastN on line tool for the query-subject similarity analysis.Results The genotype distribution of BS patients and HC underlined a higher percentage of wild-type GG genotype in BS patients group vs HC (106/130 patients, 81.5% vs 91/100 HC, 91%; p<0.05), while the heterozygous genotype (GA) was identified in 24/130 patients (18.5%) vs 9/100 HC (9%) (p<0.05). GA genotype was significantly associated with the disease (OR=2.29, 95% CI 1.01-5.18). No significant association was recognized between the SNP and the BS clinical manifestations, as well as with disease severity (Krause's index).Conclusions We found statistically significant higher frequency of TNFα rs1800629 GA genotype in patients than in controls. No significant association was recognized between the polymorphism and the clinical parameters, as well as between the SNP and the disease severity. Our data need to be confirmed in larger cohort of patients and matched controls.

scholarly journals Viral Toxin NS1 Implication in Dengue Pathogenesis Making It a Pivotal Target in Development of Efficient Vaccine

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 946
Author(s):  
Grégorie Lebeau ◽  
Alisé Lagrave ◽  
Eva Ogire ◽  
Lauriane Grondin ◽  
Soundary Seriacaroupin ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Current Knowledge ◽  
Nonstructural Protein ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Public Health Problem ◽  
Severe Dengue ◽  
Global Public Health ◽  
Dengue Disease ◽  
Nonstructural Protein 1

The mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often fatal. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of four genetically related but antigenically distinct serotypes DENV-1–DENV-4. The growing burden of the four DENV serotypes has intensified both basic and applied research to better understand dengue physiopathology. Research has shown that the secreted soluble hexameric form of DENV nonstructural protein-1 (sNS1) plays a significant role in the pathogenesis of severe dengue. Here, we provide an overview of the current knowledge about the role of sNS1 in the immunopathogenesis of dengue disease. We discuss the potential use of sNS1 in future vaccine development and its potential to improve dengue vaccine efficiency, particularly against severe dengue illness.

scholarly journals Common variants at 21q22.3 locus influence MX1 gene expression and susceptibility to severe COVID-19

2020 ◽  
Author(s):  
Immacolata Andolfo ◽  
Roberta Russo ◽  
Alessandro Vito Lasorsa ◽  
Sueva Cantalupo ◽  
Barbara Eleni Rosato ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Study Data ◽  
Chromosome 21 ◽  
Type I ◽  
Nucleotide Polymorphisms ◽  
Common Variants

AbstractThe COVID-19 disease, caused by the SARS-Cov-2, presents a heterogeneous clinical spectrum. The risk factors do not fully explain the wide spectrum of disease manifestations, so it is possible that genetic factors could account for novel insights into its pathogenesis.In our previous study, we hypothesized that common variants on chromosome 21, near TMPRSS2 and MX1 genes, may be genetic risk factors associated to the different clinical manifestations of COVID-19. Here, we performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms (SNPs) within TMPRSS2 and near MX1 gene show suggestive associations (P≤1×10−5) with severe COVID-19. All five SNPs replicated the association in two independent cohorts of Asian subjects while two and one out of the 5 SNPs replicated in African and Italian populations, respectively (P≤0.05). The minor alleles of these five SNPs correlated with a reduced risk of developing severe COVID-19 and increased level of MX1 expression in blood.Our findings provide further evidence that host genetic factors can contribute to determine the different clinical presentations of COVID-19 and that MX1, an antiviral effector of type I and III interferon pathway, may be a potential therapeutic target.

scholarly journals Viral Toxin ns1 as Pivotal Target in Development of Efficient Dengue Vaccine

2021 ◽  
Author(s):  
Grégorie Lebeau ◽  
Alisé Lagrave ◽  
Eva Ogire ◽  
Lauriane Grondin ◽  
Soundary Seriacaroupin ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Nonstructural Protein ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Public Health Problem ◽  
Severe Dengue ◽  
Global Public Health ◽  
Dengue Vaccine ◽  
Dengue Disease ◽  
Nonstructural Protein 1

Mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often associated to fatality. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of the four related antigenically distinct serotypes, DENV-1 to DENV-4. The growing burden that represents the four DENV serotypes has intensified both basic and applied researches to better understand the dengue physiopathology. It has been proposed a significant role for the secreted soluble DENV nonstructural protein 1 (sNS1) glycoprotein in the pathogenesis of severe dengue. Here, we provided an overview on current knowledge about the role of sNS1 in the immunopathogenesis of dengue disease. The reasons for the consideration of sNS1 in the design of future dengue vaccine candidates will be discussed.

scholarly journals Evaluation of Risk Factors for Exacerbations in Children with Adenoviral Pneumonia

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Na Xu ◽  
Peng Chen ◽  
Ying Wang
Keyword(s):  
Risk Factors ◽  
Disease Severity ◽  
Clinical Manifestations ◽  
Severe Pneumonia ◽  
Clinical Implications ◽  
Laboratory Findings ◽  
Severe Group ◽  
Adenovirus Pneumonia ◽  
The Difference ◽  
D Dimer

Purpose. The aim of this work was to analyze clinical features and laboratory findings of children with adenovirus pneumonia and guide clinical diagnosis, treatment, and assessment of disease severity. Material and Methods. Retrospective analysis of clinical data of 285 children with adenoviral pneumonia who were hospitalized in Wuhan Children’s Hospital from December 2018 to October 2019. According to the assessment criteria for severe pneumonia, it was divided into the severe group (92 cases) and the nonsevere group (193 cases). Collected clinical manifestations, complications, and laboratory test indicators in two groups of children and conducted all statistical analyses. Results. The risk of fever and wheezing was significantly higher in the severe group than in the nonsevere group. The difference was statistically significant (P<0.05). The risk of complications in the severe group was significantly higher than that in the nonsevere group. The difference was statistically significant (P<0.05). The levels of AST, LDH-L, PCT, ferritin, and D-dimer in the severe group were significantly higher than those in the nonsevere group. The difference was statistically significant (P<0.05). Conclusion. Children with severe adenovirus pneumonia have severe clinical manifestations and many complications. AST, LDH-L, PCT, ferritin, and D-dimer levels have important clinical implications for assessing disease severity.

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