Host genomics of COVID-19: Evidence point towards Alpha 1 antitrypsin deficiency as a putative risk factor for higher mortality rate

Dutta, Atanu Kumar; Goswami, Kalyan

doi:10.1016/j.mehy.2021.110485

Cited by 16 publications

(12 citation statements)

References 11 publications

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“…As discussed previously, AATD patients are at increased risk of poor outcomes associated with COVID-19 infection [10][11][12][13]. In light of this, we hypothesized that during the current pandemic, the reduced exposure of self-infusion may outweigh the benefits of current therapy for AATD patients.…”

Section: Discussionmentioning

confidence: 89%

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Assessment of Patient Perspectives and Barriers to Self-Infusion of Augmentation Therapy for Alpha-1 Antitrypsin Deficiency During the COVID-19 Pandemic

et al. 2022

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Introduction Alpha-1 antitrypsin (AAT) deficiency is an autosomal co-dominant genetic condition that predisposes individuals to pulmonary and hepatic disease, and in severe cases is treated with augmentation by intravenous infusion. Our aim was to assess patient reluctance to transition to self-administered augmentation of alpha-1-antitrypsin, during the pandemic of SARS-CoV-2. Methods A phone questionnaire was administered to 22 patients with severe alpha-1-antitrypsin deficiency who were currently receiving AAT augmentation therapy. Inclusion criteria included patients 18 years old, diagnosed with AATD, and receiving intravenous AAT protein augmentation therapy. Information was gathered regarding demographics, perspectives on transitioning to self-administered treatment, and anxiety and depression prevalence. Results were collected anonymously using REDCap. Joint and marginal statistical analysis was done to quantify links between participants’ willingness to transition to self-infusion and correlations with sex, age, years of therapy, anxiety, and depression. Results Of 22 patients, 14 were male and eight were female. Ages ranged from 36 to 79 years, with an average of 62.5. Genotypes were ZZ (14), MZ (3), and SZ (2) among others. Average length of intravenous augmentation was 9.5 years. The majority, 16 participants, were aware self-infusion was an option. Eight participants were willing to consider transitioning to self-infusion if trained and educated. Eight patients reported that fear of COVID-19 transmission influenced their decision-making. Above-normal anxiety, and depression scores, were found in four, and six patients, respectively. Neither sex, age, years of treatment, anxiety, or depression were found to be associated with willingness to consider self-infusion therapy. Conclusions Although there are many reasons AATD patients may benefit from AAT self-infusion, including decreased exposure to SARS-CoV-2, the majority preferred home nurse-infused therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s41030-022-00182-z.

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Section: Discussionmentioning

confidence: 89%

“…In addition, weekly infusions can significantly interrupt a patient and their family's daily activities and lifestyle choices, compounding anxiety. One of the most recent stressors for AATD patients is that their condition places them at extremely high risk of poor outcomes associated with SARS-CoV-2 infection (COVID-19) [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Patient Perspectives and Barriers to Self-Infusion of Augmentation Therapy for Alpha-1 Antitrypsin Deficiency During the COVID-19 Pandemic

et al. 2022

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“…In addition to immune cells, it is important to understand the role that some crucial genes and the signaling pathways they are involved in play in COVID-19 disease, unlike traditional statistical tests that can only detect genes by differential expression and always produce thousands genes, supervised machine learning methods focus on genes that influence the decision making on whether it is expression spectrum of healthy people, patients with mild COVID-19 or patients with severe COVID-19, through which we obtained 360 informative genes. Some of them are reported as potential biomarkers or important pathological genes, for example S100A8 and the calprotectin production pathway it is involved in was reported to serve as biomarkers distinguishing between mild and severe disease states[25, 26], FPR1 was reported to be a candidate surface and druggable targets FPR1 for drug delivery[27], defective Bcl-6+ TFH cell generation and dysregulated humoral immune induction early in COVID-19 disease was identified and reported as well[28], these findings along with others[29-32] validates that our gene lists do contains meaningful genes. However, there are genes in the list which have not been studies in depth, such as SLC25A37, FAM151B, PYGL, and TKT.…”

Section: Discussionmentioning

confidence: 96%

AImmune: a new blood-based machine learning approach to improving immune profiling analysis on COVID-19 patients

Zhang

Han

2021

Preprint

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A massive number of transcriptomic profiles of blood samples from COVID-19 patients has been produced since pandemic COVID-19 begins, however, these big data from primary studies have not been well integrated by machine learning approaches. Taking advantage of modern machine learning arthrograms, we integrated and collected single cell RNA-seq (scRNA-seq) data from three independent studies, identified genes potentially available for interpretation of severity, and developed a high-performance deep learning-based deconvolution model AImmune that can predict the proportion of seven different immune cells from the bulk RNA-seq results of human peripheral mononuclear cells. This novel approach which can be used for clinical blood testing of COVID-19 on the ground that previous research shows that mRNA alternations in blood-derived PBMCs may serve as a severity indicator. Assessed on real-world data sets, the AImmune model outperformed the most recognized immune profiling model CIBERSORTx. The presented study showed the results obtained by the true scRNA-seq route can be consistently reproduced through the new approach AImmune, indicating a potential replacing the costly scRNA-seq technique for the analysis of circulating blood cells for both clinical and research purposes.

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“…α1-Antitrypsin, the most widely present serine protease inhibitor in plasma, is reported to hinder SARS-CoV-2 viral infection by inhibition of TMPRSS2, disintegrin, and metalloproteinase 17 (ADAM17) activity [ 79 , 80 ]. Reduced ADAM17 activity helps to control the release of inflammatory mediators, and consequently ‘cytokine storm,’ a characteristic feature of COVID-19 that enhances the probability of vascular hyperpermeability, multi-organ failure, as well as mortality [ 81 ].…”

Section: Peptides As Drugs Against Covid-19mentioning

confidence: 99%

Antimicrobial peptides: A plausible approach for COVID-19 treatment

Rani

Kapoor

Gulati

et al. 2022

Expert Opinion on Drug Discovery

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Introduction Coronavirus disease 2019 (COVID-19), which emerged as a major public health threat, has affected >400 million people globally leading to >5 million mortalities to date. Treatments of COVID-19 are still to be developed as the available therapeutic approaches are not able to combat the virus causing the disease (severe acute respiratory syndrome coronavirus-2; SARS-CoV-2) satisfactorily. However, antiviral peptides (AVPs) have demonstrated prophylactic and therapeutic effects against many coronaviruses (CoVs). Areas covered This review critically discusses various types of AVPs evaluated for the treatment of COVID-19 along with their mechanisms of action. Furthermore, the peptides inhibiting the entry of the virus by targeting its binding to angiotensin-converting enzyme 2 (ACE2) or integrins, fusion mechanism as well as activation of proteolytic enzymes (cathepsin L, transmembrane serine protease 2 (TMPRSS2), or furin) are also discussed. Expert opinion Although extensively investigated, successful treatment of COVID-19 is still a challenge due to emergence of virus mutants. Antiviral peptides are anticipated to be blockbuster drugs for the management of this serious infection because of their formulation and therapeutic advantages. Although they may act on different pathways, AVPs having a multi-targeted approach are considered to have the upper hand in the management of this infection.

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Host genomics of COVID-19: Evidence point towards Alpha 1 antitrypsin deficiency as a putative risk factor for higher mortality rate

Cited by 16 publications

References 11 publications

Assessment of Patient Perspectives and Barriers to Self-Infusion of Augmentation Therapy for Alpha-1 Antitrypsin Deficiency During the COVID-19 Pandemic

Assessment of Patient Perspectives and Barriers to Self-Infusion of Augmentation Therapy for Alpha-1 Antitrypsin Deficiency During the COVID-19 Pandemic

AImmune: a new blood-based machine learning approach to improving immune profiling analysis on COVID-19 patients

Antimicrobial peptides: A plausible approach for COVID-19 treatment

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