Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility

Cell Discovery, Год журнала: 2020, Номер 6(1)

Опубликована: Ноя. 10, 2020

Abstract The COVID-19 pandemic has accounted for millions of infections and hundreds thousand deaths worldwide in a short-time period. patients demonstrate great diversity clinical laboratory manifestations disease severity. Nonetheless, little is known about the host genetic contribution to observed interindividual phenotypic variability. Here, we report first study Chinese population by deeply sequencing analyzing 332 categorized varying levels severity from Shenzhen Third People’s Hospital. Upon total 22.2 million variants, conducted both single-variant gene-based association tests among five groups including asymptomatic, mild, moderate, severe, critical ill after correction potential confounding factors. Pedigree analysis suggested monogenic effect loss function variants GOLGA3 DPP7 critically asymptomatic demonstration. Genome-wide suggests most significant gene locus associated with were located TMEM189–UBE2V1 that involved IL-1 signaling pathway. p.Val197Met missense variant affects stability TMPRSS2 protein displays decreasing allele frequency severe compared mild general population. We identified HLA-A*11:01, B*51:01, C*14:02 alleles significantly predispose worst outcome patients. This initial genomic provides insights into difference patient highlighted genes may help guide targeted efforts containing outbreak. Limitations advantages also reviewed future international on elucidating architecture host–pathogen interaction other infectious complex diseases.

Язык: Английский

---

SARS-CoV-2 tropism, entry, replication, and propagation: Considerations for drug discovery and development

PLoS Pathogens, Год журнала: 2021, Номер 17(2), С. e1009225 - e1009225

Опубликована: Фев. 17, 2021

Since the initial report of novel Coronavirus Disease 2019 (COVID-19) emanating from Wuhan, China, Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has spread globally. While effects SARS-CoV-2 infection are not completely understood, there appears to be a wide spectrum disease ranging mild symptoms severe respiratory distress, hospitalization, and mortality. There no Food Drug Administration (FDA)-approved treatments for COVID-19 aside remdesivir; early efforts identify efficacious therapeutics have mainly focused on drug repurposing screens compounds with antiviral activity against in cellular systems. These yielded intriguing hits, but use nonhuman immortalized cell lines derived non-pulmonary or gastrointestinal origins poses any number questions predicting physiological pathological relevance these potential interventions. our knowledge this virus continues evolve, current understanding key molecular interactions involved is discussed order provide framework developing most appropriate vitro toolbox support future discovery efforts.

Язык: Английский

---

Cathepsin L in COVID-19: From Pharmacological Evidences to Genetics

Frontiers in Cellular and Infection Microbiology, Год журнала: 2020, Номер 10

Опубликована: Дек. 8, 2020

The coronavirus disease 2019 (COVID-19) pandemics is a challenge without precedent for the modern science. Acute Respiratory Discomfort Syndrome (ARDS) most common immunopathological event in SARS-CoV-2, SARS-CoV, and MERS-CoV infections. Fast lung deterioration results of cytokine storm determined by robust immunological response leading to ARDS multiple organ failure. Here, we show cysteine protease Cathepsin L (CatL) involvement with severe acute respiratory syndrome 2 (SARS-CoV-2) COVID-19 from different points view. CatL lysosomal enzyme that participates numerous physiological processes, including apoptosis, antigen processing, extracellular matrix remodeling. implicated pathological conditions like invasion metastasis tumors, inflammatory status, atherosclerosis, renal disease, diabetes, bone diseases, viral infection, other diseases. expression up-regulated during chronic inflammation involved degrading matrix, an important process SARS-CoV-2 enter host cells. In addition, probably processing spike protein. As its inhibition detrimental infection possibly exit cells late stages could have been considered valuable therapeutic target. Therefore, describe here some drugs already market potential inhibiting capacity be used treat patients. discuss possible role genetics etiology spreading disease.

Язык: Английский

---

ACE2 and TMPRSS2 polymorphisms in various diseases with special reference to its impact on COVID-19 disease

Microbial Pathogenesis, Год журнала: 2020, Номер 150, С. 104621 - 104621

Опубликована: Дек. 2, 2020

Язык: Английский

---

COVID-19: Understanding Inter-Individual Variability and Implications for Precision Medicine

Mayo Clinic Proceedings, Год журнала: 2020, Номер 96(2), С. 446 - 463

Опубликована: Дек. 3, 2020

Язык: Английский

---

Genetic susceptibility of COVID-19: a systematic review of current evidence

European journal of medical research, Год журнала: 2021, Номер 26(1)

Опубликована: Май 20, 2021

While COVID-19 pandemic continues to spread worldwide, researchers have linked patterns of traits poor disease outcomes. Risk factors for include asthma, elderly age, being pregnant, having any underlying diseases such as cardiovascular disease, diabetes, obesity, and experiencing lifelong systemic racism. Recently, connections certain genes also been found, although the susceptibility has not yet established. We aimed investigate available evidence genetic COVID-19.

Язык: Английский

---

Genetic Determinants of Antibody-Mediated Immune Responses to Infectious Diseases Agents: A Genome-Wide and HLA Association Study

Open Forum Infectious Diseases, Год журнала: 2020, Номер 7(11)

Опубликована: Сен. 24, 2020

Abstract Background Infectious diseases are causally related to a large array of noncommunicable (NCDs). Identifying genetic determinants infections and antibody-mediated immune responses may shed light on this relationship provide therapeutic targets for drug vaccine development. Methods We used the UK biobank cohort up 10 000 serological measurements infectious genome-wide genotyping. data 13 pathogens define 46 phenotypes: 15 seropositivity case–control phenotypes 31 quantitative antibody measurement phenotypes. For each these, we performed association studies (GWAS) using fastGWA linear mixed model package human leukocyte antigen (HLA) classical allele amino acid residue associations analyses Lasso regression variable selection. Results included total 8735 individuals phenotypes, an average (range) 4286 (276–8555) samples per analysis. Fourteen GWAS yielded significant (P < 5 ×10-8) locus at major histocompatibility complex (MHC) chromosome 6. Outside MHC, found 60 loci, multiple associated with Epstein-Barr virus (EBV)–related NCDs (eg, RASA3, MED12L, IRF4). FUT2 was also identified as important gene polyomaviridae. HLA analysis highlighted importance DRB1*09:01, DQB1*02:01, DQA1*01:02, DQA1*03:01 in EBV serologies DRB1*15:01 Conclusions have variants response infections, many which biologically plausible or targets. This help prioritize future research

Язык: Английский

---

COVID-19 and human reproduction: A pandemic that packs a serious punch

Systems Biology in Reproductive Medicine, Год журнала: 2021, Номер 67(1), С. 3 - 23

Опубликована: Янв. 2, 2021

The COVID-19 pandemic has led to a worldwide health emergency that impacted 188 countries at last count. rapid community transmission and relatively high mortality rates with in modern times are unique features of this flu have resulted an unparalleled global crisis. SARS-CoV-2, being respiratory virus, mainly affects the lungs, but is capable infecting other vital organs, such as brain, heart kidney. Emerging evidence suggests virus also targets male female reproductive organs express its main receptor ACE2, although it yet unclear if any implications for human fertility. Furthermore, professional bodies recommended discontinuing fertility services during been affected. Although increased safety measures helped mitigate propagation number countries, seems there no predictable timeline containment goal likely remain elusive until effective vaccine becomes available widely distributed across globe. In parallel, research on reproduction postponed obvious reasons, while diagnostic tests detect or antibodies against importance support public policies, social distancing our obligation wear masks spaces. This review aims provide overview critical ethics issues continuously emerging field medicine tragically unfolds.

Язык: Английский

---

The Role of Immunogenetics in COVID-19

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(5), С. 2636 - 2636

Опубликована: Март 5, 2021

Coronavirus disease 2019 (COVID-19) is induced by SARS-CoV-2 and may arise as a variety of clinical manifestations, ranging from an asymptomatic condition to life-threatening associated with cytokine storm, multiorgan respiratory failure. The molecular mechanism behind such variability still under investigation. Several pieces experimental evidence suggest that genetic variants influencing the onset, maintenance resolution immune response be fundamental in predicting evolution disease. identification system reactivity function COVID-19 help elaboration personalized therapeutic strategies. In frenetic look for universally shared treatment plans, those are common other diseases/models also addressing future research terms drug repurposing. this paper, we discuss most recent updates about role immunogenetics determining susceptibility history infection. We propose narrative review available data, speculating lessons have learnt viral infections immunosenescence, discussing what kind aspects should deepened order improve our knowledge how host impacts outcome patients.

Язык: Английский

---

Molecular Mechanisms Related to Responses to Oxidative Stress and Antioxidative Therapies in COVID-19: A Systematic Review

Antioxidants, Год журнала: 2022, Номер 11(8), С. 1609 - 1609

Опубликована: Авг. 19, 2022

The coronavirus disease (COVID-19) pandemic is a leading global health and economic challenge. What defines the disease's progression not entirely understood, but there are strong indications that oxidative stress defense against reactive oxygen species crucial players. A big influx of immune cells to site infection marked by increase in nitrogen species. Our article aims highlight critical role emergence severity COVID-19 and, more importantly, shed light on underlying molecular genetic mechanisms. We have reviewed available literature clinical trials extract relevant variants within pathway associated with anti-oxidative therapies currently evaluated for treatment, particular glutathione N-acetylcysteine.

Язык: Английский

---