Genetic predisposition models to COVID-19 infection

Darbeheshti, Farzaneh; Rezaei, Nima

doi:10.1016/j.mehy.2020.109818

Cited by 57 publications

(37 citation statements)

References 10 publications

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“…Most probably there is highly penetrant dominant trait in X-linked ACE2 gene that affected our family cluster but further analyses are needed. 37 In the present study, COVID-19 cases in the large family cluster…”

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confidence: 57%

Determining host factors contributing to disease severity in a family cluster of 29 hospitalized SARS‐CoV‐2 patients: Could genetic factors be relevant in the clinical course of COVID‐19?

İkitimur

Uysal

Cengiz

et al. 2020

Journal of Medical Virology

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In this study, we report a large family cluster consisting of 29 genetically related patients hospitalized with coronavirus disease-2019 (COVID-19). We sought to determine the clinical characteristics relevant to the clinical course of COVID-19 by comparing the family cluster to unrelated patients with SARS-CoV-2 infection so that the presence of potential determinants of disease severity, other than traditional risk factors previously reported, could be investigated. Twenty-nine patient files were investigated in group 1 and group 2 was created with 52 consecutive patients with COVID-19 having age and gender compatibility. The virus was detected for diagnosis. The clinical, laboratory and imaging features of all patients were retrospectively screened. Disease course was assessed using records regarding outcome from patient files retrospectively. Groups were compared with respect to baseline characteristics, disease severity on presentation, and disease course. There was no difference between the two groups in terms of comorbidity and smoking history. In terms of inhospital treatment, use differed not significantly between two groups. We found that all 29 patients in the group 1 had severe pneumonia, 18 patients had severe pneumonia. Hospitalization rates, length of hospital stay, and transferred to intensive care unit were found to be statistically significantly higher in the group 1. In the present study, COVID-19 cases in the large family cluster were shown to have more severe disease and worse clinical course compared with consecutive patients with COVID-19 presenting to the same time. We believe further studies into potential genetic mechanisms of host susceptibility to COVID-19 should include such family clusters.

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confidence: 57%

Determining host factors contributing to disease severity in a family cluster of 29 hospitalized SARS‐CoV‐2 patients: Could genetic factors be relevant in the clinical course of COVID‐19?

İkitimur

Uysal

Cengiz

et al. 2020

Journal of Medical Virology

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“…For example, smoking is more prevalent in men than women although the limited evidence linking smoking and severity of COVID‐19 is weak 13 . Genetic predisposition has also been evoked as a susceptibility factor to COVID‐19 113 …”

Section: Methodsmentioning

confidence: 99%

Why does COVID‐19 kill more elderly men than women? Is there a role for testosterone?

Papadopoulos

Samplaski

2020

Andrology

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Background Recent epidemiological data indicate that there may be a gender predisposition to COVID‐19, with men predisposed to being most severely affected, and older men accounting for most deaths. Objectives Provide a review of the research literature, propose hypotheses and therapies based on the potential link between testosterone (T) and COVID‐19 induced mortality in elderly men. Materials and Methods A search of publications in academic electronic databases, and government and public health organization web sites on T, aging, inflammation, severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS‐CoV‐2) infection, and COVID‐19 disease state and outcomes was performed. Results The link between T, the immune system and male aging is well‐established, as is the progressive decline in T levels with aging. In women, T levels drop before menopause and variably increase with advanced age. Elevated IL‐6 is a characteristic biomarker of patients infected with COVID‐19 and has been linked to the development of the acute respiratory distress syndrome (ARDS). Thus far, half of the admitted COVID‐19 patients developed ARDS, half of these patients died, and elderly male patients have been more likely to develop ARDS and die. Low T is associated with ARDS. These data suggest that low T levels may exacerbate the severity of COVID‐19 infection in elderly men. It may also stand to reason that normal T levels may offer some protection against COVID‐19. SARS‐CoV‐2 binds to the angiotensin‐converting enzyme 2, present in high levels in the testis. Conclusion At present, it is not known whether low T levels in aging hypogonadal males create a permissive environment for severe responses to COVID‐19 infection or if the virus inhibits androgen formation. Given the preponderance of COVID‐19 related mortality in elderly males, additional testing for gonadal function and treatment with T may be merited.

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“…To maximize the statistical power given the relatively small hospitalized sample size and for accurate detection of extremely rare variants, we conducted deep whole genome sequencing (average 46×) for the patients. Given a fixed samples size, this protocol facilitates the estimation of genetic effects of rare and loss of function variants in addition to the common variants that may be potentially contributing to the COVID-19 clinical variability 34 . Based on the 22.2 million variation detected from the patients, we investigated host factors by conducting both single variant and gene-based genome-wide association study (GWAS) and by evaluating the difference of allele frequency of the protein truncating variants and HLA alleles among the patient groups.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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

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Genetic predisposition models to COVID-19 infection

Cited by 57 publications

References 10 publications

Determining host factors contributing to disease severity in a family cluster of 29 hospitalized SARS‐CoV‐2 patients: Could genetic factors be relevant in the clinical course of COVID‐19?

Determining host factors contributing to disease severity in a family cluster of 29 hospitalized SARS‐CoV‐2 patients: Could genetic factors be relevant in the clinical course of COVID‐19?

Why does COVID‐19 kill more elderly men than women? Is there a role for testosterone?

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

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