A multifactorial score including autophagy for prognosis and care of COVID-19 patients

Domdom, Marie Angela; Brest, Patrick; Grosjean, Iris; Roméo, Barnabé; Landi, Maria Teresa; Gal, Jocelyn; Klionsky, Daniel J.; Hofman, Paul; Mograbi, Baharia

doi:10.1080/15548627.2020.1844433

Cited by 12 publications

(10 citation statements)

References 54 publications

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“…The current knowledge and our work confirm these findings in COVID-19 [41,43,45,57,58]. Autophagy genes have recently been proposed as susceptibility factors in COVID-19 [46]. Our results are the first report on the potential involvement of variants in an autophagy gene in determining susceptibility for severe COVID-19 phenotype.…”

Section: Discussionsupporting

confidence: 89%

“…In conclusion, C9orf72 intermediate alleles >10 repeat units are over-represented in hospitalized COVID-19 patients with severe pneumonia and related to MV and NIV requirements independently of age, suggesting that they could represent a risk factor contributing to the occurrence of severe COVID-19 forms. Autophagy may be involved in the COVID-19 clinical phenotype and a polygenic model also related to genes involved in the autophagy machinery has been recently proposed to explain COVID-19 risk assessment and guide precision medical care [46]. This is the first report describing the association of severe forms of COVID-19 with variants in a gene involved in autophagy.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic background contributes to susceptibility to autoimmune and infectious diseases in humans and genetic variants associated with those diseases are often found in genes involved in immune response and inflammation, including genes related to the autophagy pathways [44,45]. Furthermore, a multifactorial risk score for COVID-19 severity based on a polygenic model and including autophagy genes has been recently proposed [46].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

C9orf72 Intermediate Repeats Confer Genetic Risk for Severe COVID-19 Pneumonia Independently of Age

Zanella

Zacchi

Piva

et al. 2021

IJMS

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A cytokine storm, autoimmune features and dysfunctions of myeloid cells significantly contribute to severe coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Genetic background of the host seems to be partly responsible for severe phenotype and genes related to innate immune response seem critical host determinants. The C9orf72 gene has a role in vesicular trafficking, autophagy regulation and lysosome functions, is highly expressed in myeloid cells and is involved in immune functions, regulating the lysosomal degradation of mediators of innate immunity. A large non-coding hexanucleotide repeat expansion (HRE) in this gene is the main genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), both characterized by neuroinflammation and high systemic levels of proinflammatory cytokines, while HREs of intermediate length, although rare, are more frequent in autoimmune disorders. C9orf72 full mutation results in haploinsufficiency and intermediate HREs seem to modulate gene expression as well and impair autophagy. Herein, we sought to explore whether intermediate HREs in C9orf72 may be a risk factor for severe COVID-19. Although we found intermediate HREs in only a small portion of 240 patients with severe COVID-19 pneumonia, the magnitude of risk for requiring non-invasive or mechanical ventilation conferred by harboring intermediate repeats >10 units in at least one C9orf72 allele was more than twice respect to having shorter expansions, when adjusted for age (odds ratio (OR) 2.36; 95% confidence interval (CI) 1.04–5.37, p = 0.040). The association between intermediate repeats >10 units and more severe clinical outcome (p = 0.025) was also validated in an independent cohort of 201 SARS-CoV-2 infected patients. These data suggest that C9orf72 HREs >10 units may influence the pathogenic process driving more severe COVID-19 phenotypes.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

C9orf72 Intermediate Repeats Confer Genetic Risk for Severe COVID-19 Pneumonia Independently of Age

Zanella

Zacchi

Piva

et al. 2021

IJMS

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“…Dysfunction of autophagy contributes to a variety of diseases, including neurodegenerative disorders [16], infectious diseases [17], diabetes [18]. Particularly, the association of autophagy and tumorigenesis has been gradually veri ed in various malignancies [19].…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Prognostic Value of Autophagy-related Genes Correlated With Metastasis in Uveal Melanoma Patients

Sun

Wang

Chen

et al. 2021

Preprint

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Half of the patients with primary uveal melanoma will develop progressive metastasis, leading to high mortality rate. Autophagy has been demonstrated to engage in metastasis in multiple tumors. Detection, diagnosis and treatment at the early-stage of uveal melanoma may help prevent potential tumor progression and optimize the prognosis. The purpose of our study was to discover autophagy-related genes (ARGs) correlated with uveal melanoma metastasis and determine their prognostic values. We analyzed the gene expression profiles and the clinical data from the Gene Expression Omnibus (GEO) database in uveal melanoma. A total of 14 and 16 differentially expressed ARGs were identified to be related to uveal melanoma metastasis from GSE22138 and GSE27831 sets. The two datasets shared three common genes including RAF1, CDKN1A and WIPI1 that occupied the core positions in the Protein-Protein Interactions (PPI) Network of ARGs. Following that, TCGA was introduced for survival analysis of the three genes. The survival analysis showed that high expression of RAF1 was related to favorable prognosis of uveal melanoma, whereas high expression of CDKN1A and WIPI1 suggested poor prognosis. Then a three-ARG based prognostic risk score model was constructed to predict survival outcomes. Univariate and multivariate Cox regression analyses indicated that the risk score can be considered as an independent prognostic factor for uveal melanoma, exhibiting good accuracy and sensitivity. In summary, we established an autophagy-related prognostic model based on uveal melanoma metastasis, which may contribute to the detection of early metastasis and prediction of prognosis, thereby prolonging survival through early personalized intervention.

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“…Autophagy has been widely discussed and studied in SARS-CoV-2 infection, and its regulation provides the possibility to produce effective therapies [ 11 , 12 ]. Evidence shows that coronaviruses form double-membrane vesicles via autophagy during infection, which can be used as RNA replication platforms to enhance virus replication efficiency [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Construction of an autophagy interaction network based on competitive endogenous RNA reveals the key pathways and central genes of SARS-CoV-2 infection in vivo

Chen

Wang

et al. 2021

Microbial Pathogenesis

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As of April 1, 2021, more than 2.8 million people have died of SARS-CoV-2 infection. In addition, the mutation of virus strains that have accompanied the pandemic has brought more severe challenges to pandemic control. Host microRNAs (miRNAs) are widely involved in a variety of biological processes of coronavirus infection, including autophagy in SARS-CoV-2 infection. However, the mechanisms underlying miRNAs involved in autophagy in SARS-CoV-2 infection have not been fully elucidated. In this study, the miRNA and messenger RNA (mRNA) expression profiles of patients with SARS-CoV-2 infection were investigated based on raw data from Gene Expression Omnibus (GEO) datasets, and potential novel biomarkers of autophagy were revealed by bioinformatics analyses. We identified 32 differentially expressed miRNAs and 332 differentially expressed mRNAs in patients with SARS-CoV-2 infection. Cytokine receptor related pathways were the most enriched pathways for differentially expressed miRNAs identified by pathway analysis. Most importantly, an autophagy interaction network, which was associated with the pathological processes of SARS-CoV-2 infection, especially with the cytokine storm, was constructed. In this network, hsa-miR-340–3p, hsa-miR-652–3p, hsa-miR-4772–5p, hsa-miR-192–5p, TP53INP2, and CCR2 may be biomarkers that predict changes in mild SARS-CoV-2 infection. Some molecules, including hsa-miR-1291 and CXCR4, were considered potential targets to predict the emergence of severe symptoms in SARS-CoV-2 infection. To our knowledge, this study provided the first profile analysis of an autophagy interaction network in SARS-CoV-2 infection and revealed several novel autophagy-related biomarkers for understanding the pathogenesis of SARS-CoV-2 infection in vivo.

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A multifactorial score including autophagy for prognosis and care of COVID-19 patients

Cited by 12 publications

References 54 publications

C9orf72 Intermediate Repeats Confer Genetic Risk for Severe COVID-19 Pneumonia Independently of Age

C9orf72 Intermediate Repeats Confer Genetic Risk for Severe COVID-19 Pneumonia Independently of Age

WITHDRAWN: Prognostic Value of Autophagy-related Genes Correlated With Metastasis in Uveal Melanoma Patients

Construction of an autophagy interaction network based on competitive endogenous RNA reveals the key pathways and central genes of SARS-CoV-2 infection in vivo

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