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1.
J Korean Med Sci ; 37(8): e65, 2022 Feb 28.
Article in English | MEDLINE | ID: covidwho-1714983

ABSTRACT

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2) are key proteins mediating viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although gene expressions of ACE2 and TMPRSS2 have been analyzed in various organs and diseases, their soluble forms have been less studied, particularly in asthma. Therefore, we aimed to measure circulating ACE2 and TMPRSS2 in the serum of asthmatics and examine their relationship with clinical characteristics. METHODS: Clinical data and serum samples of 400 participants were obtained from an asthma cohort. The soluble ACE2 (sACE2) and soluble TMPRSS2 (sTMPRSS2) level was measured by enzyme-linked immunosorbent assay, and the values underwent a natural log transformation. Associations between sACE2 and TMPRSS2 levels and various clinical variables were analyzed. RESULTS: The patients younger than 70 years old, those with eosinophilic asthma (eosinophils ≥ 200 cells/µL), and inhaled corticosteroids (ICS) non-users were associated with higher levels of sACE2. Blood eosinophils and fractionated exhaled nitric oxide levels were positively correlated with serum ACE2. In contrast, lower levels of sTMPRSS2 were noted in patients below 70 years and those with eosinophilic asthma, while no association was noted between ICS use and sTMPRSS2. The level of sTMPRSS2 also differed according to sex, smoking history, coexisting hypertension, and forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio. The proportion of sputum neutrophils was positively correlated with sTMPRSS2, while the FEV1/FVC ratio reported a negative correlation with sTMPRSS2. CONCLUSION: The levels of ACE2 and TMPRSS2 were differently expressed according to age, ICS use, and several inflammatory markers. These findings suggest variable susceptibility and prognosis of SARS-CoV-2 infection among asthmatic patients.


Subject(s)
Angiotensin-Converting Enzyme 2/blood , Asthma/complications , COVID-19/etiology , SARS-CoV-2 , Serine Endopeptidases/blood , Adrenal Cortex Hormones/therapeutic use , Adult , Age Factors , Aged , Asthma/blood , Asthma/drug therapy , Female , Humans , Male , Middle Aged
2.
Nutrients ; 13(4)2021 Apr 14.
Article in English | MEDLINE | ID: covidwho-1187014

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for one of the worst pandemics in modern history. Several prevention and treatment strategies have been designed and evaluated in recent months either through the repurposing of existing treatments or the development of new drugs and vaccines. In this study, we show that L-carnitine tartrate supplementation in humans and rodents led to significant decreases of key host dependency factors, notably angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and Furin, which are responsible for viral attachment, viral spike S-protein cleavage, and priming for viral fusion and entry. Interestingly, pre-treatment of Calu-3, human lung epithelial cells, with L-carnitine tartrate led to a significant and dose-dependent inhibition of the infection by SARS-CoV-2. Infection inhibition coincided with a significant decrease in ACE2 mRNA expression levels. These data suggest that L-carnitine tartrate should be tested with appropriate trials in humans for the possibility to limit SARS-CoV-2 infection.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/drug therapy , Carnitine/administration & dosage , Tartrates/administration & dosage , Adult , Aged , Angiotensin-Converting Enzyme 2/blood , Animals , COVID-19/metabolism , Carnitine/pharmacology , Cell Line , Cell Survival/drug effects , Female , Furin/blood , Furin/metabolism , Humans , Inflammation/metabolism , Male , Middle Aged , Rats , SARS-CoV-2 , Serine Endopeptidases/blood , Serine Endopeptidases/metabolism , Tartrates/pharmacology , Young Adult
3.
J Thromb Haemost ; 19(1): 46-50, 2021 01.
Article in English | MEDLINE | ID: covidwho-894786

ABSTRACT

There is an urgent need to understand the underlying mechanisms contributing to thrombotic and inflammatory complications during COVID-19. Data from independent groups have identified that platelets are hyperreactive during COVID-19. Platelet hyperreactivity is accompanied by changes in platelet gene expression, and enhanced interactions between platelets and leukocytes. In some patients, SARS-CoV-2 mRNA has been detected in platelets. Together, this suggests that SARS-CoV-2 may interact with platelets. However, controversy remains on which receptors mediate SARS-CoV-2 platelet interactions. Most, but not all, transcriptomic and proteomic analyses fail to observe the putative SARS-CoV-2 receptor, angiotensin converting enzyme-2, or the cellular serine protease necessary for viral entry, TMPRSS2, on platelets and megakaryocytes. Interestingly, platelets express other known SARS-CoV-2 receptors, which induce similar patterns of activation to those observed when platelets are incubated with SARS-CoV-2. This article explores these findings and discusses ongoing areas of controversy and uncertainty with regard to SARS-CoV-2 platelet interactions.


Subject(s)
Angiotensin-Converting Enzyme 2/blood , Blood Platelets/virology , COVID-19/blood , COVID-19/virology , Receptors, Virus/blood , SARS-CoV-2/physiology , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/physiology , COVID-19/complications , Host Microbial Interactions/genetics , Host Microbial Interactions/physiology , Humans , Megakaryocytes/virology , Models, Biological , Platelet Activation , RNA, Viral/blood , RNA, Viral/genetics , Receptors, Virus/physiology , SARS-CoV-2/genetics , Serine Endopeptidases/blood , Serine Endopeptidases/physiology , Thrombosis/blood , Thrombosis/etiology , Thrombosis/virology , Virus Internalization
4.
J Endocrinol Invest ; 44(5): 951-956, 2021 May.
Article in English | MEDLINE | ID: covidwho-763952

ABSTRACT

BACKGROUND: The recent emergence of COVID-19 poses a global health emergency. One of the most frequently reported data is sex-related severity and mortality: according to the last available analysis on 239,709 patients in Italy, lethality is 17.7% in men and 10.8% in women, with 59% of total deaths being men. Interestingly, the infection rate is lower in males than in females, with 45.8% and 54.2% of positive cases, respectively, suggesting that gender-related factor may worsen disease evolution. A tentative hypothesis to explain these findings is the role of angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 involved in viral infection. PURPOSE: In this review, we summarize the available evidence pointing to gender-related differences in ACE2 and TMPRSS2 expression, from both genetic and endocrine points of view. RESULTS: Altogether, available evidence points toward two not-mutually exclusive mechanisms in gender susceptibility to COVID-19 by sex hormonal regulation of ACE2 and TMPRSS2. On one hand, ACE2 expression could be increased in women, either by estrogens or constitutively by X chromosome inactivation escape or by reduced methylation, providing a larger reservoir of ACE2 to maintain the fundamental equilibrium of RAS regulatory axis. On the other, low levels of androgens in women may keep at low levels TMPRSS2 expression, representing a further protective factor for the development of COVID-19 infection, despite the increased expression of ACE2, which represents the Trojan horse for SARS-CoV-2 entry. CONCLUSIONS: Both mechanisms consistently point to the role of sex hormones and sex chromosomes in the differential severity and lethality of COVID-19 in men and women.


Subject(s)
COVID-19/epidemiology , COVID-19/genetics , Chromosomes, Human, X/genetics , Genetic Predisposition to Disease/epidemiology , Gonadal Steroid Hormones , Angiotensin-Converting Enzyme 2/blood , Angiotensin-Converting Enzyme 2/genetics , Female , Humans , Male , Serine Endopeptidases/blood , Serine Endopeptidases/genetics , Sex Characteristics , Sex Factors
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