Effects of host genetic variations on response to, susceptibility and severity of respiratory infections

Ghafouri‐Fard, Soudeh; Noroozi, Rezvan; Vafaee, Reza; Branicki, Wojciech; Pośpiech, Ewelina; Pyrć, Krzysztof; Łabaj, Paweł P.; Omrani, Mir Davood; Sanak, Marek

doi:10.1016/j.biopha.2020.110296

Cited by 51 publications

(42 citation statements)

References 29 publications

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“…It has yet to be determined if host genomics or confounding factors (e.g., access to healthcare, environment) also play a role. Several studies though suggest that higher susceptibility to COVID-19 is associated with genetic variants, including those in the ACE1, ACE2, TMPRSS2, GSTT1 genes [60][61][62] . Interestingly, several important ACE2 variants on the X-linked locus were identified in male as hemizygous, which may explain the higher mortality in male 63 .…”

Section: Summary Of Clinical Implications Of Pharmacogenomics For Covmentioning

confidence: 99%

Pharmacogenomics of COVID-19 therapies

et al. 2020

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A new global pandemic of coronavirus disease 2019 (COVID-19) has resulted in high mortality and morbidity. Currently numerous drugs are under expedited investigations without well-established safety or efficacy data. Pharmacogenomics may allow individualization of these drugs thereby improving efficacy and safety. In this review, we summarized the pharmacogenomic literature available for COVID-19 drug therapies including hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir/ritonavir, darunavir/cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib, and corticosteroids. We searched PubMed, reviewed the Pharmacogenomics Knowledgebase (PharmGKB ®) website, Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, the U.S. Food and Drug Administration (FDA) pharmacogenomics information in the product labeling, and the FDA pharmacogenomics association table. We found several drug-gene variant pairs that may alter the pharmacokinetics of hydroxychloroquine/chloroquine (CYP2C8, CYP2D6, SLCO1A2, and SLCO1B1); azithromycin (ABCB1); ribavirin (SLC29A1, SLC28A2, and SLC28A3); and lopinavir/ritonavir (SLCO1B1, ABCC2, CYP3A). We also identified other variants, that are associated with adverse effects, most notable in hydroxychloroquine/chloroquine (G6PD; hemolysis), ribavirin (ITPA; hemolysis), and interferon β-1b (IRF6; liver toxicity). We also describe the complexity of the risk for QT prolongation in this setting because of additive effects of combining more than one QT-prolonging drug (i.e., hydroxychloroquine/chloroquine and azithromycin), increased concentrations of the drugs due to genetic variants, along with the risk of also combining therapy with potent inhibitors. In conclusion, although direct evidence in COVID-19 patients is lacking, we identified potential actionable genetic markers in COVID-19 therapies. Clinical studies in COVID-19 patients are deemed warranted to assess potential roles of these markers.

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Section: Summary Of Clinical Implications Of Pharmacogenomics For Covmentioning

confidence: 99%

Pharmacogenomics of COVID-19 therapies

et al. 2020

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“…Iran has been among the first countries experienced epidemic of this viral infection [2]. The clinical manifestations of COVID-19 is quite wide, including asymptomatic infection, minor upper respiratory tract disease, and severe extensive pneumonia leading to respiratory distress and even demise [3][4][5]. Disease severity is influenced by a number of population specific parameters [6] between two groups.…”

Section: Introductionmentioning

confidence: 99%

Clinical and demographic characteristics of patients with COVID-19 infection: Statistics from a single hospital in Iran

Samsami

Mehravaran

Tabarsi

et al. 2021

HAB

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Coronavirus disease 2019 (COVID-19) has caused a global pandemic in early 2020. This infectious disorder has a heterogeneous course ranging from asymptomatic disorder to a critical situation needing intensive cares. In the current study, we present a report of affected patients admitted in a single hospital in Iran. Eighty-two hospitalized patients with COVID-19 were assessed. Demographic, clinical, and paraclinical parameters were gathered and statistically analyzed. The median age (IQR) of the patients was 57.32 (45.75, 70) years. At primary evaluation, fever was present in 45.12% of the affected individuals. The most common clinical symptoms were dyspnea (81.71%) and cough (65.85%). Totally, 12 (14.63%) and 14 (17.07%) of patients had low and high WBC counts, respectively. Lymphopenia was detected in 36 (43.9%) of patients, while 6 (7.32%) of patients had lymphocytosis. High levels of Il-6 were detected in 4 (4.88%) of patients. CRP levels were elevated in 69 (84.1%) of patients. The median (IQR) of hospitalization was 7 (5, 9) days. Totally, 26 patients (31%) were hospitalized in ICU. All patients were discharged with good health conditions except for one patient who died. The current study shows the heterogeneous clinical manifestations and paraclinical parameters of COVID-19 patients.

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“…This could be explained by the suppression of the ACE2 shedding barrier and the production of soluble form of ACE2 in the presence of a high viral load, which enables infection. Other polymorphisms with effects on COVID-19 progression were also observed in non-coding sequences for cathepsin L, monocyte chemoattractant protein-1 (CCL2), and neutrophil elastase genes, enhancing virus infection and inflammation ( Ghafouri-Fard et al., 2020 ; Vargas-Alarcón et al., 2020 ).…”

Section: Predicting the Future: The Genotype As An Indicator Of Suscementioning

confidence: 99%

Perspectives and Challenges in the Fight Against COVID-19: The Role of Genetic Variability

Guilger-Casagrande

Barros

Antunes

et al. 2021

Front. Cell. Infect. Microbiol.

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In the last year, the advent of the COVID-19 pandemic brought a new consideration for the multidisciplinary sciences. The unknown mechanisms of infection used by SARS-CoV-2 and the absence of effective antiviral pharmacological therapy, diagnosis methods, and vaccines evoked scientific efforts on the COVID-19 outcome. In general, COVID-19 clinical features are a result of local and systemic inflammatory processes that are enhanced by some preexistent comorbidities, such as diabetes, obesity, cardiovascular, and pulmonary diseases, and biological factors, like gender and age. However, the discrepancies in COVID-19 clinical signs observed among those patients lead to investigations about the critical factors that deeply influence disease severity and death. Herein, we present the viral infection mechanisms and its consequences after blocking the angiotensin-converting enzyme 2 (ACE2) axis in different tissues and the progression of inflammatory and immunological reactions, especially the influence of genetic features on those differential clinical responses. Furthermore, we discuss the role of genotype as an essential indicator of COVID-19 susceptibility, considering the expression profiles, polymorphisms, gene identification, and epigenetic modifications of viral entry factors and their recognition, as well as the infection effects on cell signaling molecule expression, which amplifies disease severity.

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Effects of host genetic variations on response to, susceptibility and severity of respiratory infections

Cited by 51 publications

References 29 publications

Pharmacogenomics of COVID-19 therapies

Pharmacogenomics of COVID-19 therapies

Clinical and demographic characteristics of patients with COVID-19 infection: Statistics from a single hospital in Iran

Perspectives and Challenges in the Fight Against COVID-19: The Role of Genetic Variability

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