Can Alpha-1 Antitrypsin Levels be Used to Predict the Prognosis of COVID-19 Therapy?

Aras-Atik, Elif; Özdemir, Nesligül; Demirkan, Kutay

doi:10.4274/tjps.galenos.2020.20727

Cited by 3 publications

(2 citation statements)

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“…According to different data, the percentage of comorbid conditions varies from 32% to 46–50% [ 131 ]. The percentage of unfavorable outcomes in comorbid patients is up to 67% [ 132 ].…”

Section: Role Of Proteinases In the Development Of Coronavirus Infec...mentioning

confidence: 99%

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Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection

Акбашева

Spirina

Dyakov

et al. 2022

Biochem. Moscow Suppl. Ser. B

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The SARS-CoV-2 pandemic had stimulated the emergence of numerous publications on the α 1 -proteinase inhibitor (α 1 -PI, α 1 -antitrypsin), especially when it was found that the regions of high mortality corresponded to the regions with deficient α 1 -PI alleles. By analogy with the data obtained in the last century, when the first cause of the genetic deficiency of α 1 -antitrypsin leading to elastase activation in pulmonary emphysema was proven, it can be supposed that proteolysis hyperactivation in COVID-19 may be associated with the impaired functions of α 1 -PI. The purpose of this review was to systematize the scientific data and critical directions for translational studies on the role of α 1 -PI in SARS-CoV-2-induced proteolysis hyperactivation as a diagnostic marker and a therapeutic target. This review describes the proteinase-dependent stages of viral infection: the reception and penetration of the virus into a cell and the imbalance of the plasma aldosterone–angiotensin–renin, kinin, and blood clotting systems. The role of ACE2, TMPRSS, ADAM17, furin, cathepsins, trypsin- and elastase-like serine proteinases in the virus tropism, the activation of proteolytic cascades in blood, and the COVID-19-dependent complications is considered. The scientific reports on α 1 -PI involvement in the SARS-CoV-2-induced inflammation, the relationship with the severity of infection and comorbidities were analyzed. Particular attention is paid to the acquired α 1 -PI deficiency in assessing the state of patients with proteolysis overactivation and chronic non-inflammatory diseases, which are accompanied by the risk factors for comorbidity progression and the long-term consequences of COVID-19. Essential data on the search and application of protease inhibitor drugs in the therapy for bronchopulmonary and cardiovascular pathologies were analyzed. The evidence of antiviral, anti-inflammatory, anticoagulant, and anti-apoptotic effects of α 1 -PI, as well as the prominent data and prospects for its application as a targeted drug in the SARS-CoV-2 acquired pneumonia and related disorders, are presented.

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“…According to different data, the percentage of comorbid conditions varies from 32% to 46–50% [ 131 ]. The percentage of unfavorable outcomes in comorbid patients is up to 67% [ 132 ].…”

Section: Role Of Proteinases In the Development Of Coronavirus Infec...mentioning

confidence: 99%

“…Until now, not a single biomarker has been found that could provide an accurate forecast for COVID-19 [ 132 ]. About 30 laboratory indicators discussed in literature are associated with the risk of the severe form of this disease [ 1 ].…”

Section: Role Of Proteinases In the Development Of Coronavirus Infec...mentioning

confidence: 99%

Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection

Акбашева

Spirina

Dyakov

et al. 2022

Biochem. Moscow Suppl. Ser. B

View full text Add to dashboard Cite

show abstract

Proteolysis and deficiency of α1-proteinase inhibitor in SARS-CoV-2 infection

et al. 2022

View full text Add to dashboard Cite

The SARS-CoV-2 pandemia had stimulated the numerous publications emergence on the α1-proteinase inhibitor (α1-PI, α1-antitrypsin), primarily when it was found that high mortality in some regions corresponded to the regions with deficient α1-PI alleles. By analogy with the last century's data, when the root cause of the α1-antitrypsin, genetic deficiency leading to the elastase activation in pulmonary emphysema, was proven. It is evident that proteolysis hyperactivation in COVID-19 may be associated with α1-PI impaired functions. The purpose of this review is to systematize scientific data, critical directions for translational studies on the role of α1-PI in SARS-CoV-2-induced proteolysis hyperactivation as a diagnostic marker and a target in therapy. This review describes the proteinase-dependent stages of a viral infection: the reception and virus penetration into the cell, the plasma aldosterone-angiotensin-renin, kinins, blood clotting systems imbalance. The ACE2, TMPRSS, ADAM17, furin, cathepsins, trypsin- and elastase-like serine proteinases role in the virus tropism, proteolytic cascades activation in blood, and the COVID-19-dependent complications is presented. The analysis of scientific reports on the α1-PI implementation in the SARS-CoV-2-induced inflammation, the links with the infection severity, and comorbidities were carried out. Particular attention is paid to the acquired α1-PI deficiency in assessing the patients with the proteolysis overactivation and chronic non-inflammatory diseases that are accompanied by the risk factors for the comorbidities progression, and the long-term consequences of COVID-19 initiation. Analyzed data on the search and proteases inhibitory drugs usage in the bronchopulmonary cardiovascular pathologies therapy are essential. It becomes evident the antiviral, anti-inflammatory, anticoagulant, anti-apoptotic effect of α1-PI. The prominent data and prospects for its application as a targeted drug in the SARS-CoV-2 acquired pneumonia and related disorders are presented.

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SARS-CoV2 Infection and Comorbidities, Role in Oncogenesis

Spirina

Masunova

Masunov

et al. 2022

Asian Pac J Cancer Prev

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The widespread infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) significantly impacts major human diseases. It is undoubtedly evident that cancer patients are more susceptible to the infection and at a higher risk of severe COVID-19 than the general population. Moreover, the rise in cancers incidence is waiting in the Globe as a long-term effect of post-COVID-19 complications. Multiple mostly unknown mechanisms participate and determine the oncogenic impact of virus-induced transformation. Imbalance in oncogenesis is considered critical in cancer development. Modified immunogenicity and metabolic features emerge as pivotal in COVID-19 pathogenesis and the organism system's response. The molecular mechanisms of the onset of the metabolic disorder have not yet been fully elucidated. The pathology is complicated, multifactorial, and emerging in various processes. Preventive anticancer therapy taking into account the change in metabolic processes, helps them respond better to anti-COVID-19 treatment than relying only on antiviral drugs. The modified therapeutic algorithm was provided to reduce the likelihood of post-acute complications in patients with preexisting pathologies and the onset of other chronic pathologies and cancers.

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Can Alpha-1 Antitrypsin Levels be Used to Predict the Prognosis of COVID-19 Therapy?

Cited by 3 publications

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Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection

Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection

Proteolysis and deficiency of α1-proteinase inhibitor in SARS-CoV-2 infection

SARS-CoV2 Infection and Comorbidities, Role in Oncogenesis

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