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1.
J Mol Cell Cardiol ; 164: 13-16, 2022 03.
Article in English | MEDLINE | ID: covidwho-1527886

ABSTRACT

Aged males disproportionately succumb to increased COVID-19 severity, hospitalization, and mortality compared to females. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) facilitate SARS-CoV-2 viral entry and may have sexually dimorphic regulation. As viral load dictates disease severity, we investigated the expression, protein levels, and activity of ACE2 and TMPRSS2. Our data reveal that aged males have elevated ACE2 in both mice and humans across organs. We report the first comparative study comprehensively investigating the impact of sex and age in murine and human levels of ACE2 and TMPRSS2, to begin to elucidate the sex bias in COVID-19 severity.


Subject(s)
Aging/metabolism , Angiotensin-Converting Enzyme 2/biosynthesis , COVID-19/epidemiology , Gene Expression Regulation, Enzymologic , Receptors, Virus/biosynthesis , SARS-CoV-2/physiology , Sex Characteristics , Aging/genetics , Angiotensin-Converting Enzyme 2/genetics , Animals , Disease Susceptibility , Female , Heart/virology , Humans , Intestine, Small/enzymology , Intestine, Small/virology , Kidney/enzymology , Kidney/virology , Lung/enzymology , Lung/virology , Male , Mice , Mice, Inbred C57BL , Middle Aged , Myocardium/enzymology , Organ Specificity , Receptors, Virus/genetics , Serine Endopeptidases/biosynthesis , Serine Endopeptidases/genetics , Young Adult
3.
Int J Biol Sci ; 17(8): 1925-1939, 2021.
Article in English | MEDLINE | ID: covidwho-1266906

ABSTRACT

Background: Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) allow entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells and play essential roles in cancer therapy. However, the functions of ACE2 and TMPRSS2 in kidney cancer remain unclear, especially as kidneys are targets for SARS-CoV-2 infection. Methods: UCSC Xena project, the Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases (GSE30589 and GSE59185) were searched for gene expression in human tissues, gene expression data, and clinical information. Several bioinformatics methods were utilized to analyze the correlation between ACE2 and TMPRSS2 with respect to the prognosis of kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP). Results: ACE2 expression was significantly upregulated in tumor tissue, while its downregulation was associated with low survival in KIRC and KIRP patients. TMPRSS2 was downregulated in KIRC and KIRP, and its expression was not correlated with patient survival. According to clinical risk factor-based prediction models, ACE2 exhibits predictive accuracy for kidney cancer prognosis and is correlated with metabolism and immune infiltration. In an animal model, ACE2 expression was remarkably downregulated in SARS-CoV-2-infected cells compared to in the control. Conclusion: ACE2 expression is highly correlated with various metabolic pathways and is involved in immune infiltration.it plays a crucial role than TMPRSS2 in diagnosing and prognosis of kidney cancer patients. The overlap in ACE2 expression between kidney cancer and SARS-CoV-2 infection suggests that patients with KIRC or KIRP are at high risk of developing serious symptoms.


Subject(s)
Angiotensin-Converting Enzyme 2/biosynthesis , COVID-19/complications , Carcinoma, Renal Cell/complications , Kidney Neoplasms/complications , Receptors, Virus/biosynthesis , SARS-CoV-2 , Adult , Aged , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/physiology , Animals , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/mortality , Chlorocebus aethiops , Down-Regulation , Drug Resistance, Neoplasm , Female , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/immunology , Kidney Neoplasms/metabolism , Kidney Neoplasms/mortality , Lymphocytes, Tumor-Infiltrating/immunology , Male , Middle Aged , Models, Animal , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Organ Specificity , Prognosis , Proportional Hazards Models , Receptors, Virus/genetics , Renin-Angiotensin System/physiology , Serine Endopeptidases/biosynthesis , Serine Endopeptidases/genetics , Serine Endopeptidases/physiology , Tissue Array Analysis , Vero Cells
5.
Eur Rev Med Pharmacol Sci ; 25(5): 2409-2414, 2021 03.
Article in English | MEDLINE | ID: covidwho-1148418

ABSTRACT

The COVID-19 (Corona Virus Disease 2019) outbreak, which seriously affected people's lives across the world, has not been effectively controlled. Previous studies have demonstrated that SARS-COV-2 (Severe acute respiratory syndrome coronavirus 2) infecting host cells mainly rely on binding to receptor proteins, namely ACE2 and TMPRSS2. COVID-19 transmission is faster than the severe acute respiratory syndrome (SARS) pneumonia outbreak in 2002. This is mainly attributed to the different pathways of virus-infected host cells, coupled with patients' atypical clinical characteristics. SARS-CoV-2 is mainly transmitted through respiratory droplets and contact, infecting lung tissues before damaging other body organs, such as the liver, brain, kidney and heart. The present study identified potential target genes for SARS-COV-2 receptors, ACE2 and TMPRSS2, in normal human lung tissue. The findings provide novel insights that will guide future drug development approaches for treatment of COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/genetics , Receptors, Virus/genetics , Serine Endopeptidases/genetics , Angiotensin-Converting Enzyme 2/biosynthesis , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , COVID-19/virology , Correlation of Data , Gene Expression , Humans , Receptors, Virus/biosynthesis , Receptors, Virus/metabolism , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Serine Endopeptidases/biosynthesis , Serine Endopeptidases/metabolism
6.
Immun Inflamm Dis ; 9(2): 331-339, 2021 06.
Article in English | MEDLINE | ID: covidwho-1074323

ABSTRACT

Coronavirus disease 2019 (COVID-19), can present with a wide spectrum of severity. Elderly patients with cardiac, pulmonary and metabolic comorbidities are more likely to develop the severe manifestations of COVID-19, which are observed in less than 5% of the pediatric patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to induce an immune impairment and dysregulation, finally resulting in the massive release of inflammatory mediators, strongly contributing to the pulmonary and systemic manifestations in COVID-19. In children, the immune dysregulation following SARS-CoV-2 can also be responsible of a severe disease phenotype defined as multisystem inflammatory syndrome in children. As the immune system undergoes a complex process of maturation from birth to adult age, differences in the immune and inflammatory response could have a significant impact in determining the spectrum of severity of COVID-19. Indeed, children show a higher ability to respond to viral infections and a reduced baseline pro-inflammatory state compared with elderly patients. Age and comorbidities contribute to disease severity through immune-mediated mechanisms, since they are associated with a chronic increase of pro-inflammatory mediators, and cause an enhanced susceptibility to develop an immune dysregulation following SARS-CoV-2 infection. Also the expression of ACE2, the receptor of SARS-CoV-2, varies with age, and is linked to the immune and inflammatory response through a complex, and not completely elucidated, network. This paper reviews the peculiar immunopathogenic aspects of COVID-19, with a focus on the differences between adult and pediatric patients.


Subject(s)
Age Factors , Aging/immunology , COVID-19/immunology , SARS-CoV-2 , Adaptive Immunity , Adolescent , Adult , Age of Onset , Aged , Angiotensin-Converting Enzyme 2/biosynthesis , COVID-19/etiology , Child , Child, Preschool , Comorbidity , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Humans , Immunity, Innate , Infant , Inflammation/immunology , Lymphocyte Subsets/immunology , Male , Middle Aged , Receptors, Virus/biosynthesis , Severity of Illness Index , Systemic Inflammatory Response Syndrome/etiology , Systemic Inflammatory Response Syndrome/immunology , Young Adult
7.
Am J Physiol Lung Cell Mol Physiol ; 320(1): L152-L157, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-1054733

ABSTRACT

The COVID-19 pandemic is associated with severe pneumonia and acute respiratory distress syndrome leading to death in susceptible individuals. For those who recover, post-COVID-19 complications may include development of pulmonary fibrosis. Factors contributing to disease severity or development of complications are not known. Using computational analysis with experimental data, we report that idiopathic pulmonary fibrosis (IPF)- and chronic obstructive pulmonary disease (COPD)-derived lung fibroblasts express higher levels of angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 entry and part of the renin-angiotensin system that is antifibrotic and anti-inflammatory. In preclinical models, we found that chronic exposure to cigarette smoke, a risk factor for both COPD and IPF and potentially for SARS-CoV-2 infection, significantly increased pulmonary ACE2 protein expression. Further studies are needed to understand the functional implications of ACE2 on lung fibroblasts, a cell type that thus far has received relatively little attention in the context of COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/biosynthesis , COVID-19/pathology , Fibroblasts/metabolism , Idiopathic Pulmonary Fibrosis/pathology , Pulmonary Disease, Chronic Obstructive/pathology , Adult , Animals , Female , Gene Expression Regulation/drug effects , Humans , Male , Mice , Mice, Inbred C57BL , Middle Aged , Receptors, Virus/biosynthesis , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/virology , SARS-CoV-2/metabolism , Smoke/adverse effects
8.
Genes (Basel) ; 12(1)2020 12 25.
Article in English | MEDLINE | ID: covidwho-1021948

ABSTRACT

The human serine protease serine 2 TMPRSS2 is involved in the priming of proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a possible target for COVID-19 therapy. The TMPRSS2 gene may be co-expressed with SARS-CoV-2 cell receptor genes angiotensin-converting enzyme 2 (ACE2) and Basigin (BSG), but only TMPRSS2 demonstrates tissue-specific expression in alveolar cells according to single-cell RNA sequencing data. Our analysis of the structural variability of the TMPRSS2 gene based on genome-wide data from 76 human populations demonstrates that a functionally significant missense mutation in exon 6/7 in the TMPRSS2 gene is found in many human populations at relatively high frequencies, with region-specific distribution patterns. The frequency of the missense mutation encoded by rs12329760, which has previously been found to be associated with prostate cancer, ranged between 10% and 63% and was significantly higher in populations of Asian origin compared with European populations. In addition to single-nucleotide polymorphisms, two copy number variants were detected in the TMPRSS2 gene. A number of microRNAs have been predicted to regulate TMPRSS2 and BSG expression levels, but none of them is enriched in lung or respiratory tract cells. Several well-studied drugs can downregulate the expression of TMPRSS2 in human cells, including acetaminophen (paracetamol) and curcumin. Thus, the interactions of TMPRSS2 with SARS-CoV-2, together with its structural variability, gene-gene interactions, expression regulation profiles, and pharmacogenomic properties, characterize this gene as a potential target for COVID-19 therapy.


Subject(s)
COVID-19/drug therapy , COVID-19/therapy , Gene Expression Regulation, Enzymologic/drug effects , Molecular Targeted Therapy , SARS-CoV-2/physiology , Serine Endopeptidases/genetics , Acetaminophen/pharmacology , Acetaminophen/therapeutic use , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/biosynthesis , Angiotensin-Converting Enzyme 2/genetics , Asia/epidemiology , Basigin/biosynthesis , Basigin/genetics , Basigin/physiology , COVID-19/ethnology , COVID-19/genetics , Curcumin/pharmacology , Curcumin/therapeutic use , Europe/epidemiology , Exons/genetics , Gene Frequency , Genetic Predisposition to Disease , Genetic Variation , Humans , MicroRNAs/genetics , Mutation, Missense , Pharmacogenomic Testing , Protein Interaction Mapping , Receptors, Virus/antagonists & inhibitors , Receptors, Virus/biosynthesis , Receptors, Virus/genetics , Serine Endopeptidases/biosynthesis , Serine Endopeptidases/physiology , Single-Cell Analysis , Spike Glycoprotein, Coronavirus/metabolism
9.
Genes (Basel) ; 12(1)2020 12 24.
Article in English | MEDLINE | ID: covidwho-1016121

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein D614G mutation became the predominant globally circulating variant after its emergence in the early coronavirus disease 2019 (COVID-19) pandemic. Studies showed that this mutation results in an open conformation of the S glycoprotein receptor-binding domain (RBD), and increased angiotensin 1-converting enzyme 2 (ACE2) binding and fusion, which result in an increase in SARS-CoV-2 transmissibility and infectivity. Dynamic tracking of SARS-CoV-2 showed that the D614G variant became predominant after emergence in Europe and North America, but not in China. The current absence of selective pressures from antiviral treatment suggests that the driving force for viral evolution could be variations in human population genetics. Results show that ACE2 expression is higher in Asian populations than that in European, North American, and African populations. This supports the idea that lower ACE2 expression is a driving force in the positive selection for the D614G mutation. This study suggests that the dynamics of the SARS-CoV-2 D614G mutation during the early-to-mid pandemic is associated with enhanced transmission efficiency in populations with lower ACE2 expression. Understanding the role that human genetic diversity plays in the adaptive evolution of SARS-CoV-2 may have an important impact on public health and measures to control the pandemic.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/genetics , Mutation, Missense , Pandemics , Point Mutation , Receptors, Virus/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Africa/epidemiology , Alleles , Amino Acid Substitution , Angiotensin-Converting Enzyme 2/biosynthesis , Binding Sites , COVID-19/ethnology , COVID-19/transmission , COVID-19/virology , China/epidemiology , Europe/epidemiology , Evolution, Molecular , Gene Expression , Genetic Predisposition to Disease , Genetic Variation , Humans , North America/epidemiology , Protein Binding , Protein Conformation , Protein Domains , Receptors, Virus/biosynthesis , SARS-CoV-2/isolation & purification , Selection, Genetic
10.
Sci Rep ; 10(1): 22401, 2020 12 28.
Article in English | MEDLINE | ID: covidwho-997946

ABSTRACT

The severity of COVID-19 lung disease is higher in the elderly and people with pre-existing co-morbidities. People who were born preterm may be at greater risk for COVID-19 because their early exposure to oxygen (hyperoxia) at birth increases the severity of respiratory viral infections. Hyperoxia at birth increases the severity of influenza A virus infections in adult mice by reducing the number of alveolar epithelial type 2 (AT2) cells. Since AT2 cells express the SARS-CoV-2 receptors angiotensin converting enzyme (ACE2) and transmembrane protease/serine subfamily member 2 (TMPRSS2), their expression should decline as AT2 cells are depleted by hyperoxia. Instead, ACE2 was detected in airway Club cells and endothelial cells at birth, and then AT2 cells at one year of age. Neonatal hyperoxia stimulated expression of ACE2 in Club cells and in AT2 cells by 2 months of age. It also stimulated expression of TMPRSS2 in the lung. Increased expression of SARS-CoV-2 receptors was blocked by mitoTEMPO, a mitochondrial superoxide scavenger that reduced oxidative stress and DNA damage seen in oxygen-exposed mice. Our finding that hyperoxia enhances the age-dependent expression of SARS-CoV-2 receptors in mice helps explain why COVID-19 lung disease is greater in the elderly and people with pre-existing co-morbidities.


Subject(s)
Alveolar Epithelial Cells/metabolism , Angiotensin-Converting Enzyme 2/biosynthesis , COVID-19/pathology , Hyperoxia/pathology , Receptors, Virus/biosynthesis , Serine Endopeptidases/biosynthesis , Aging , Animals , Humans , Infant, Newborn , Mice , Mice, Inbred C57BL , SARS-CoV-2/metabolism , Severity of Illness Index
11.
PLoS One ; 15(10): e0240647, 2020.
Article in English | MEDLINE | ID: covidwho-895060

ABSTRACT

The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. The small intestine expressed higher levels of ACE2 mRNA than any other organ. By immunohistochemistry, duodenum, kidney and testis showed strong signals, whereas the signal was weak in the respiratory tract. Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Gene ontology analysis suggested that, besides its classical role in the renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene as well as a new putative short form of ACE2. These include several interferon-stimulated response elements sites for STAT1, IRF8, and IRF9. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung.


Subject(s)
Betacoronavirus/physiology , Computational Biology , Coronavirus Infections/virology , Pandemics , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/virology , Receptors, Virus/physiology , Aging/metabolism , Angiotensin-Converting Enzyme 2 , Binding Sites , COVID-19 , Carrier Proteins/biosynthesis , Carrier Proteins/genetics , Female , Gene Expression Regulation, Enzymologic , Gene Ontology , Humans , Interferons/physiology , Lung/metabolism , Male , Metalloproteases/biosynthesis , Metalloproteases/genetics , Neovascularization, Physiologic/physiology , Organ Specificity , Peptidyl-Dipeptidase A/biosynthesis , Peptidyl-Dipeptidase A/genetics , Promoter Regions, Genetic , RNA, Messenger/biosynthesis , Receptors, Virus/biosynthesis , Receptors, Virus/genetics , Renin-Angiotensin System/physiology , SARS-CoV-2 , Sex Characteristics , Single-Cell Analysis , Transcription Factors/metabolism , Transcription Initiation Site , Virus Attachment
13.
Neurologia (Engl Ed) ; 35(9): 628-632, 2020.
Article in English, Spanish | MEDLINE | ID: covidwho-747866

ABSTRACT

INTRODUCTION: In recent months, doubts have arisen among patients, general practitioners, and neurologists as to whether some drugs commonly used in patients with headaches and neuralgia may favour or complicate the disease caused by SARS-CoV-2. MATERIAL AND METHODS: We collected information on the opinions of scientific societies and medicines agencies (American, European, and Spanish) to clarify doubts regarding the use of drugs such as lisinopril, candesartan, ibuprofen, corticosteroids, carbamazepine, and monoclonal antibodies targeting the calcitonin gene-related peptide in the context of the COVID-19 pandemic. RESULTS: We make recommendations about the use of standard headache treatments in the context of the COVID-19 pandemic, based on the current scientific evidence. CONCLUSIONS: At present, there is no robust scientific argument to formally contraindicate any of the standard treatments employed for headaches and neuralgias.


Subject(s)
Analgesics/adverse effects , Coronavirus Infections/complications , Headache/drug therapy , Neuralgia/drug therapy , Pneumonia, Viral/complications , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Analgesics/pharmacology , Analgesics/therapeutic use , Angiotensin-Converting Enzyme 2 , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Anticonvulsants/adverse effects , Anticonvulsants/therapeutic use , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , Antiviral Agents/pharmacology , Benzimidazoles/adverse effects , Benzimidazoles/therapeutic use , Betacoronavirus , Biphenyl Compounds , COVID-19 , Calcitonin Gene-Related Peptide Receptor Antagonists/adverse effects , Calcitonin Gene-Related Peptide Receptor Antagonists/therapeutic use , Carbamazepine/adverse effects , Carbamazepine/therapeutic use , Coronavirus Infections/drug therapy , Disease Susceptibility/chemically induced , Drug Interactions , Enzyme Induction/drug effects , Headache/complications , Headache/prevention & control , Humans , Ibuprofen/adverse effects , Ibuprofen/pharmacology , Ibuprofen/therapeutic use , Lisinopril/adverse effects , Lisinopril/therapeutic use , Neuralgia/complications , Pandemics , Peptidyl-Dipeptidase A/biosynthesis , Peptidyl-Dipeptidase A/genetics , Receptors, Virus/biosynthesis , Receptors, Virus/genetics , Risk Factors , SARS-CoV-2 , Tetrazoles/adverse effects , Tetrazoles/therapeutic use
14.
Med Hypotheses ; 143: 110117, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-652869

ABSTRACT

With rapid spread of severe acute respiratory syndrome- corona virus-2 (SARS-COV-2) globally, some new aspects of the disease have been reported. Recently, it has been reported the incidence of Kawasaki-like disease among children with COVID-19. Since, children had been known to be less severely affected by the virus in part due to the higher concentration of Angiotensin converting enzyme (ACE)-2 receptor, this presentation has emerged concerns regarding the infection of children with SARS-COV2. ACE2 has anti-inflammatory, anti-fibrotic and anti-proliferative characteristics through converting angiotensin (Ag)-II to Ang (1-7). ACE2 receptor is downregulated by the SARS-COV through the spike protein of SARS-CoV (SARS-S) via a process that is tightly coupled with Tumor necrosis factor (TNF)-α production. TNF-α plays a key role in aneurysmal formation of coronary arteries in Kawasaki disease (KD). Affected children by COVID-19 with genetically-susceptible to KD might have genetically under-expression of ACE2 receptor that might further decrease the expression of ACE2 due to the downregulation of the receptor by the virus in these patients. It appears that TNF- α might be the cause and the consequence of the ACE2 receptor downregulation which results in arterial walls aneurysm. Conclusion: Genetically under-expression of ACE2 receptor in children with genetically-susceptible to KD who are infected with SARS-CoV-2 possibly further downregulates the ACE2 expression by TNF-α and leads to surge of inflammation including TNF-α and progression to Kawasaki-like disease.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/complications , Models, Immunological , Mucocutaneous Lymph Node Syndrome/etiology , Pandemics , Pneumonia, Viral/complications , Angiotensin-Converting Enzyme 2 , Asia/epidemiology , COVID-19 , Child , Coronary Vessels/immunology , Coronary Vessels/pathology , Coronavirus Infections/epidemiology , Coronavirus Infections/genetics , Cytokine Release Syndrome/etiology , Disease Progression , Endothelium, Vascular/virology , Genetic Predisposition to Disease , Humans , Inflammation , Macrophage Activation , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/genetics , Mucocutaneous Lymph Node Syndrome/immunology , Netherlands/epidemiology , Peptidyl-Dipeptidase A/biosynthesis , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/genetics , Receptors, Virus/biosynthesis , Receptors, Virus/genetics , Receptors, Virus/physiology , SARS-CoV-2 , Seasons , Spike Glycoprotein, Coronavirus/physiology , Tumor Necrosis Factor-alpha/physiology , United States/epidemiology
15.
Headache ; 60(8): 1558-1568, 2020 09.
Article in English | MEDLINE | ID: covidwho-638748

ABSTRACT

OBJECTIVE: To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. BACKGROUND: The use of non-steroidal anti-inflammatory drugs and corticosteroids in patients during the COVID-19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID-19 pandemic. METHODS: A detailed search of the scientific and popular literature was performed. RESULTS: There is limited literature pertaining to the safety of non-steroidal anti-inflammatory drugs and corticosteroids during the COVID-19 pandemic. To date, there are no clear scientific data that preclude the use of non-steroidal anti-inflammatory drugs in the general population who may acquire COVID-19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. CONCLUSION: Scientific information regarding the COVID-19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non-steroidal anti-inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID-19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.


Subject(s)
Adrenal Cortex Hormones/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , COVID-19/epidemiology , Headache/drug therapy , Pandemics , SARS-CoV-2/drug effects , Adrenal Cortex Hormones/therapeutic use , Angiotensin-Converting Enzyme 2/biosynthesis , Angiotensin-Converting Enzyme 2/genetics , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , COVID-19/etiology , COVID-19/prevention & control , Contraindications, Drug , Disease Susceptibility/chemically induced , Dogs , Humans , Hypernatremia/chemically induced , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Mass Media , Models, Animal , Neutrophils/drug effects , Practice Guidelines as Topic , Pulmonary Edema/chemically induced , Rats , Receptors, Virus/biosynthesis , Receptors, Virus/genetics , Risk Assessment , SARS-CoV-2/growth & development , SARS-CoV-2/physiology , Up-Regulation/drug effects , Virus Shedding/drug effects
16.
Med Hypotheses ; 144: 110005, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-599137

ABSTRACT

Cytokine storm, multiorgan failure, and particularly acute respiratory distress syndrome (ARDS) is the leading cause of mortality and morbidity in patients with COVID-19. A fulminant ARDS kills the majority of COVID-19 victims. Pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone), is a novel anti-fibrotic agent with trivial adverse effects. Pirfenidone is approved for the treatment of Idiopathic Pulmonary Fibrosis (IPF) for patients with mild to moderate disease. Pirfenidone could inhibit apoptosis, downregulate ACE receptors expression, decrease inflammation by several mechanisms and ameliorate oxidative stress and hence protect pneumocytes and other cells from COVID-19 invasion and cytokine storm simultaneously. Based on the pirfenidone mechanism of action and the known pathophysiology of COVID-19, I believe that pirfenidone has the potential for the treatment of COVID-19 patients.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Drug Repositioning , Pyridones/therapeutic use , Alveolar Epithelial Cells/drug effects , Angiotensin-Converting Enzyme 2/biosynthesis , Angiotensin-Converting Enzyme 2/genetics , Animals , Anti-Inflammatory Agents/pharmacology , Apoptosis/drug effects , COVID-19/complications , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/prevention & control , Disease Models, Animal , Down-Regulation/drug effects , Humans , Lipid Peroxidation/drug effects , Oxidative Stress/drug effects , Pyridones/pharmacology , Receptors, Virus/biosynthesis , Receptors, Virus/genetics
17.
Med Hypotheses ; 144: 109987, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-592474

ABSTRACT

In 2019, a new coronavirus (SARS CoV2) infecting humans has emerged in Wuhan, China which caused an unprecedented pandemic involving at least 185 countries infecting 2.5 million people till date. This virus is transmitted directly or indirectly through the upper aerodigestive tract. As it is evident from the recent studies that SARS-CoV-2 requires host enzyme Furin to activate receptor binding domain of its S protein and host Angiotensin Convertase Enzyme 2 (ACE2) is required as binding receptor, facilitating the entry of virus into the host cell. Evidence from literature shows that oral cancer tissues as well as paracarcinoma tissue exhibit higher expression of both Furin and ACE2, giving rise to the hypothesis that patients with oral cancer have higher chances of SARS CoV2 infection. It is also hypothesised that there will be increased severity of disease due to facilitated entry of the virus into the cells. Therefore, we suggest oral cancer patients require extra attention during COVID-19 pandemic and re-evaluation of current treatment paradigms in oral oncology is also needed.


Subject(s)
Angiotensin-Converting Enzyme 2/physiology , COVID-19/virology , Furin/metabolism , Mouth Neoplasms/virology , Neoplasm Proteins/metabolism , Receptors, Virus/physiology , SARS-CoV-2/physiology , Virus Internalization , Angiotensin-Converting Enzyme 2/biosynthesis , Angiotensin-Converting Enzyme 2/genetics , COVID-19/epidemiology , COVID-19/prevention & control , Disease Susceptibility , Furin/genetics , Gene Expression Regulation, Neoplastic , Humans , Models, Biological , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Neoplasm Proteins/genetics , Pandemics , Protein Binding , Receptors, Virus/biosynthesis , Receptors, Virus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Up-Regulation
18.
Biochem Biophys Res Commun ; 528(3): 413-419, 2020 07 30.
Article in English | MEDLINE | ID: covidwho-436643

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a worldwide pandemic. It has a high transmission rate among humans, and is a threat to global public health. However, there are no effective prophylactics or therapeutics available. It is necessary to identify vulnerable and susceptible groups for adequate protection and care against this disease. Recent studies have reported that COVID-19 has angiotensin-converting enzyme 2 (ACE2) as a functional receptor, which may lead to the development of severe cerebrovascular diseases (CVD), including strokes, in patients with risk factors for CVD such as diabetes and smoking. Thus, the World Health Organization (WHO) advised caution against COVID-19 for smokers and patients with underlying clinical symptoms, including cardiovascular diseases. Here, we observed ACE2 expression in the brain of rat middle cerebral artery occlusion (MCAO) model and evaluated the effects of cigarette smoke extract (CSE) and diabetes on ACE2 expression in vessels. We showed that the levels of ACE2 expression was increased in the cortex penumbra after ischemic injuries. CSE treatment significantly elevated ACE2 expression in human brain vessels. We found that ACE2 expression was upregulated in primary cultured human blood vessels with diabetes compared to healthy controls. This study demonstrates that ACE2 expression is increased in ischemic brains and vessels exposed to diabetes or smoking, makes them vulnerable to COVID-19 infection.


Subject(s)
Betacoronavirus/metabolism , Brain Ischemia/virology , Brain/blood supply , Diabetes Mellitus , Peptidyl-Dipeptidase A/biosynthesis , Receptors, Virus/biosynthesis , Smokers , Stroke/virology , Up-Regulation , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/pathogenicity , Brain/drug effects , Brain Ischemia/genetics , Brain Ischemia/metabolism , COVID-19 , Coronavirus Infections/genetics , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Diabetes Mellitus/genetics , Diabetes Mellitus/metabolism , Disease Models, Animal , Disease Susceptibility , Infarction, Middle Cerebral Artery/complications , Male , Mice , Mice, Inbred C57BL , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , Rats , Rats, Sprague-Dawley , Receptors, Virus/genetics , SARS-CoV-2 , Smoke/adverse effects , Stroke/genetics , Stroke/metabolism , Up-Regulation/drug effects
19.
J Hematol Oncol ; 13(1): 43, 2020 05 04.
Article in English | MEDLINE | ID: covidwho-165275

ABSTRACT

The novel coronavirus (2019-nCoV) is an emerging causative agent that was first described in late December 2019 and causes a severe respiratory infection in humans. Notably, many of affected patients of COVID-19 were people with malignancies. Moreover, cancer has been identified as an individual risk factor for COVID-19. In addition, the expression of angiotensin converting enzyme 2 (ACE2), the receptor of COVID-19, were aberrantly expressed in many tumors. However, a systematic analysis of ACE2 aberration remained to be elucidated in human cancers. Here, we analyzed genetic alteration, RNA expression, and DNA methylation of ACE2 across over 30 tumors. Notably, overexpression of ACE2 have been observed in including colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), pancreatic adenocarcinoma (PAAD), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD), and lung adenocarcinoma (LUAD). In addition, hypo DNA methylation of ACE2 has also been identified in most of these ACE2 highly expressed tumors. Conclusively, our study for the first time curated both genetic and epigenetic variations of ACE2 in human malignancies. Notably, because our study is a bioinformatics assay, further functional and clinical validation is warranted.


Subject(s)
Betacoronavirus , Coronavirus Infections , Neoplasms/enzymology , Pandemics , Peptidyl-Dipeptidase A , Pneumonia, Viral , Receptors, Virus , Angiotensin-Converting Enzyme 2 , COVID-19 , Coronavirus Infections/enzymology , Coronavirus Infections/etiology , Coronavirus Infections/virology , DNA Methylation , DNA, Neoplasm/metabolism , Humans , Neoplasms/complications , Peptidyl-Dipeptidase A/biosynthesis , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/enzymology , Pneumonia, Viral/etiology , Pneumonia, Viral/virology , RNA/biosynthesis , Receptors, Coronavirus , Receptors, Virus/biosynthesis , Receptors, Virus/genetics , SARS-CoV-2
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