ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy

Asselta, Rosanna; Paraboschi, Elvezia Maria; Mantovani, Alberto; Duga, Stefano

doi:10.18632/aging.103415

Cited by 333 publications

(385 citation statements)

References 30 publications

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“…Instead androgens have an immune suppressive effect which may explain the greater susceptibility to infectious diseases observed in men, but a minor incidence of asthma in boys than girls [20]. X-chromosome inactivation in women causes an imbalance of genes involved in immune response, such as CD40L and TLR7, and ACE2 that exert a protective function in pathologies like hypertension, cardiovascular diseases and acute respiratory distress syndrome, which are concurrent conditions representing a major risk of worse prognosis in COVID-19 [7,21]. ACE2 expression is higher in young people than in elderly individuals and higher in women than in men [22].…”

Section: Analysis Of Infection Incidence In Exponential Virus Spreadingmentioning

confidence: 99%

Age and gender distribution of COVID-19 infected cases in Italian population

Arisi

Mantuano

2020

Preprint

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Since the SARS-CoV-2 epidemic started, it became clear that the impact of the infection incidence and fatality rate were closely related to the population structure. Our analysis was devoted to the distribution of the infected cases in the Italian population stratified by age and sex in order to define the differences in gender impact of COVID-19 in each age class. Data on infected cases were extracted from the Italian EpiCentro (ISS) web site from March 12 to May 20, 2020. Data were pooled in ten years’ groups. Odds ratio (OR) men versus women was evaluated by the Fisher exact test. Logistic regression was used to investigate the combined effect of age and sex on infection incidence. Statistical analysis, performed by R-Bioconductor, highlights differences in age-dependent susceptibility to infection between men and women. In elderly class (50+ ) generally man result more infected than women, with the exception of the oldest women (90+). In age classes <50 OR was about 1.0, while an intriguing exception is the age group 20-29 in which the ratio was unbalanced in favour of men. This analysis supports a strong influence of biological sex and environmental factors related to age in COVID-19 infection by SARS-Cov-2.

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Section: Analysis Of Infection Incidence In Exponential Virus Spreadingmentioning

confidence: 99%

Age and gender distribution of COVID-19 infected cases in Italian population

Arisi

Mantuano

2020

Preprint

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“…Contemporary studies on the large number of samples have analyzed the genomic variations present among populations worldwide (Cao et al, 2020;Stawiski et al, 2020). It was unanimously shown that a polymorphism rs2285666 present in ACE2, varied significantly among European and Asians (Asselta et al, 2020;Cao et al, 2020). The expression experiments have suggested that the alternate allele (TT-plus strand or AAminus strand) of rs2285666 elevated the expression of this gene upto 50%, hence may play a role in SARS-CoV-2 susceptibility (Wu et al, 2017;Asselta et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Genetic Association of ACE2 rs2285666 Polymorphism With COVID-19 Spatial Distribution in India

et al. 2020

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Studies on host-pathogen interaction have identified human ACE2 as a host cell receptor responsible for mediating infection by coronavirus (COVID-19). Subsequent studies have shown striking difference of allele frequency among Europeans and Asians for a polymorphism rs2285666, present in ACE2. It has been revealed that the alternate allele (TT-plus strand or AA-minus strand) of rs2285666 elevate the expression level of this gene upto 50%, hence may play a significant role in SARS-CoV-2 susceptibility. Therefore, we have first looked the phylogenetic structure of rs2285666 derived haplotypes in worldwide populations and compared the spatial frequency of this particular allele with respect to the COVID-19 infection as well as case-fatality rate in India. For the first time, we ascertained a significant positive correlation for alternate allele (T or A) of rs2285666, with the lower infection as well as case-fatality rate among Indian populations. We trust that this information will be useful to understand the role of ACE2 in COVID-19 susceptibility.

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“…Numerous demographic, clinical, genetic, and behavioral factors have been identified to influence susceptibility to SARS-CoV-2 infection and, among those infected, the severity of the disease, including the risk of death. Those factors include age, sex [3], genetic loci of certain cytokines/chemokines and the ABO blood system group [4,5], smoking history [6], obesity and underlying comorbidities such diabetes, hypertension, lung diseases [7,8], and cancer [9][10][11]. Among cancer patients, those with malignancies of hematological origin have been reported as particularly vulnerable to COVID-19 [12].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 genomic and quasispecies analyses in cancer patients reveal relaxed intrahost virus evolution

Siqueira

Goes

Alves

et al. 2020

Preprint

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Numerous factors have been identified to influence susceptibility to SARS-CoV-2 infection and disease severity. Cancer patients are more prone to clinically evolve to more severe COVID-19 conditions, but the determinants of such a more severe outcome remain largely unknown. We have determined the full-length SARS-CoV-2 genomic sequences of cancer patients and healthcare workers (HCW; non-cancer controls) by deep sequencing and investigated the within-host viral quasispecies of each infection, quantifying intrahost genetic diversity. Naso- and oropharyngeal SARS-CoV-2+ swabs from 57 cancer patients and 14 healthcare workers (HCW) from the Brazilian Cancer Institute were collected in April–May 2020. Complete genome amplification using ARTIC network V3 multiplex primers was performed followed by next-generation sequencing. Assemblies were conducted in Geneious R11, where consensus sequences were extracted and intrahost single nucleotide variants (iSNVs) were identified. Maximum likelihood phylogenetic analysis was performed using PhyMLv.3.0 and lineages were classified using Pangolin and CoV-GLUE. Phylogenetic analysis showed that all but one strain belonged to clade B1.1. Four genetically linked mutations known as the globally dominant SARS-CoV-2 haplotype (C241T, C3037T, C14408T and A23403G) were found in the majority of consensus sequences. SNV signatures of previously characterized Brazilian genomes were also observed in most samples. Another 85 SNVs were found at a lower frequency (1.4-19.7%). Cancer patients displayed a significantly higher intrahost viral genetic diversity compared to HCW (p = 0.009). Intrahost genetic diversity in cancer patients was independent of SARS-CoV-2 Ct values, and was not associated with disease severity, use of corticosteroids, or use of antivirals, characteristics that could influence viral diversity. Such a feature may explain, at least in part, the more adverse outcomes to which cancer/COVID-19 patients experience.Author SummaryCancer patients are more prone to clinically evolve to more severe COVID-19 conditions, but the determinants of such a more severe outcome remain largely unknown. In this study, phylogenetic and variation analysis of SARS-CoV-2 genomes from cancer patients and non-cancer healthcare workers at the Brazilian National Cancer Institute were characterized by deep sequencing. Viral genomes showed signatures characteristic of Brazilian viruses, consistent with the hypothesis of local, community transmission rather than virus importation from abroad. Despite most genomes in patients and healthcare workers belonging to the same lineage, intrahost variability was higher in cancer patients when compared to non-cancer counterparts. The intrahost genomic diversity analysis presented in our study highlights the relaxed evolution of SARS-CoV-2 in a vulnerable population of cancer patients. The high number of minor variations can result in the selection of immune escape variants, resistance to potential drugs, and/or increased pathogenicity. The impact of this higher intrahost variability over time warrants further investigation.

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ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy

Cited by 333 publications

References 30 publications

Age and gender distribution of COVID-19 infected cases in Italian population

Age and gender distribution of COVID-19 infected cases in Italian population

Genetic Association of ACE2 rs2285666 Polymorphism With COVID-19 Spatial Distribution in India

SARS-CoV-2 genomic and quasispecies analyses in cancer patients reveal relaxed intrahost virus evolution

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