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Front Immunol ; 12: 728896, 2021.
Article in English | MEDLINE | ID: covidwho-1456291


A purified spike (S) glycoprotein of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) coronavirus was used to study its effects on THP-1 macrophages, peripheral blood mononuclear cells (PBMCs), and HUVEC cells. The S protein mediates the entry of SARS-CoV-2 into cells through binding to the angiotensin-converting enzyme 2 (ACE2) receptors. We measured the viability, intracellular cytokine release, oxidative stress, proinflammatory markers, and THP-1-like macrophage polarization. We observed an increase in apoptosis, ROS generation, MCP-1, and intracellular calcium expression in the THP-1 macrophages. Stimulation with the S protein polarizes the THP-1 macrophages towards proinflammatory futures with an increase in the TNFα and MHC-II M1-like phenotype markers. Treating the cells with an ACE inhibitor, perindopril, at 100 µM reduced apoptosis, ROS, and MHC-II expression induced by S protein. We analyzed the sensitivity of the HUVEC cells after the exposure to a conditioned media (CM) of THP-1 macrophages stimulated with the S protein. The CM induced endothelial cell apoptosis and MCP-1 expression. Treatment with perindopril reduced these effects. However, the direct stimulation of the HUVEC cells with the S protein, slightly increased HIF1α and MCP-1 expression, which was significantly increased by the ACE inhibitor treatment. The S protein stimulation induced ROS generation and changed the mitogenic responses of the PBMCs through the upregulation of TNFα and interleukin (IL)-17 cytokine expression. These effects were reduced by the perindopril (100 µM) treatment. Proteomic analysis of the S protein stimulated THP-1 macrophages with or without perindopril (100 µM) exposed more than 400 differentially regulated proteins. Our results provide a mechanistic analysis suggesting that the blood and vascular components could be activated directly through S protein systemically present in the circulation and that the activation of the local renin angiotensin system may be partially involved in this process. Graphical: Suggested pathways that might be involved at least in part in S protein inducing activation of inflammatory markers (red narrow) and angiotensin-converting enzyme inhibitor (ACEi) modulation of this process (green narrow).

Angiotensin-Converting Enzyme Inhibitors/pharmacology , Apoptosis/drug effects , COVID-19/immunology , Macrophages/immunology , Oxidative Stress/drug effects , Perindopril/pharmacology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , COVID-19/drug therapy , COVID-19/physiopathology , COVID-19/virology , Cell Line , Humans , Macrophages/drug effects , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/immunology , Pyroptosis/drug effects , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
J Infect Public Health ; 14(9): 1268-1273, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1370602


INTRODUCTION: Healthcare workers (HCWs) in Saudi Arabia are a unique population who have had exposures to the Middle East Respiratory Syndrome coronavirus (MERS-CoV) and Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It follows that HCWs from this country could have pre-existingMERS-CoV antibodies that may either protect from coronavirus disease 2019 (COVID-19) infection or cause false SARS-CoV-2 seropositive results. In this article, we report the seroprevalence of MERS-CoV and SARS-CoV-2 among high-risk healthcare workers in Riyadh city, Saudi Arabia. METHODS: This is a cross-sectional study enrolling 420 high-risk HCWs who are physically in contact with COVID-19 patients in three tertiary hospitals in Riyadh city. The participants were recruited between the 1st of July to the end of December 2020. A 3 ml of the venous blood samples were collected and tested for the presence of IgG antibodies against the spike proteins of SARS-CoV-2 and MERS-CoV using enzyme-linked immunosorbent assay (ELISA). RESULTS: The overall prevalence of SARS-CoV-2 in high-risk HCWs was 14.8% based on SARS-CoV-2 IgG testing while only 7.4% were positive by Polymerase Chain Reaction (PCR) for viral RNA. Most of the SARS-CoV-2 seropositive HCWs had symptoms and the most frequent symptoms were body aches, fever, cough, loss of smell and taste, and headache. The seroprevalence of MERS-CoV IgG was 1% (4 participants) and only one participant had dual seropositivity against MERS-CoV and SARS-CoV-2. Three MERS-CoV positive samples (75%) turned to be negative after using in-house ELISA and none of the MERS-CoV seropositive samples had detectable neutralization activity. CONCLUSION: Our SARS-CoV-2 seroprevalence results were higher than reported regional seroprevalence studies. This finding was expected and similar to other international findings that targeted high-risk HCWs. Our results provide evidence that the SARS-CoV-2- seropositivity in Saudi Arabia similar to other countries was due to exposure to SARS-CoV-2 rather than MERS-CoV antibody.

COVID-19 , Middle East Respiratory Syndrome Coronavirus , Antibodies, Viral , Cross-Sectional Studies , Health Personnel , Humans , SARS-CoV-2 , Seroepidemiologic Studies
CJC Open ; 3(8): 1060-1074, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1184887


In the current COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 uses angiotensin-converting enzyme-2 (ACE-2) receptors for cell entry, leading to ACE-2 dysfunction and downregulation, which disturb the balance between the classical and counter-regulatory renin-angiotensin system (RAS) in favor of the classical RAS. RAS dysregulation is one of the major characteristics of several cardiovascular diseases; thus, adjustment of this system is the main therapeutic target. RAS inhibitors-particularly angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs)-are commonly used for treatment of hypertension and cardiovascular disease. Patients with cardiovascular diseases are the group most commonly seen among those with COVID-19 comorbidity. At the beginning of this pandemic, a dilemma occurred regarding the use of ACEIs and ARBs, potentially aggravating cardiovascular and pulmonary dysfunction in COVID-19 patients. Urgent clinical trials from different countries and hospitals reported that there is no association between RAS inhibitor treatment and COVID-19 infection or comorbidity complication. Nevertheless, the disturbance of the RAS that is associated with COVID-19 infection and the potential treatment targeting this area have yet to be resolved. In this review, the link between the dysregulation of classical RAS and counter-regulatory RAS activities in COVID-19 patients with cardiovascular metabolic diseases is investigated. In addition, the latest findings based on ACEI and ARB administration and ACE-2 availability in relation to COVID-19, which may provide a better understanding of the RAS contribution to COVID-19 pathology, are discussed, as they are of the utmost importance amid the current pandemic.

Dans l'actuelle pandémie de la COVID-19, le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) utilise les récepteurs de l'enzyme de conversion de l'angiotensine 2 (ECA-2) pour entrer dans les cellules, s'ensuit le dysfonctionnement et la régulation à la baisse de l'ECA-2, qui perturbent l'équilibre entre le système rénine-angiotensine (SRA) traditionnel et le SRA contre-régulateur en faveur du SRA traditionnel. La dysrégulation du SRA est l'une des caractéristiques principales des maladies cardiovasculaires. Par conséquent, l'ajustement de ce système est l'objectif thérapeutique principal. Les inhibiteurs du SRA, particulièrement les inhibiteurs de l'ECA (IECA) et les antagonistes des récepteurs de type 1 de l'angiotensine II (ARA), sont communément utilisés pour traiter l'hypertension et les maladies cardiovasculaires. Les patients atteints de maladies cardiovasculaires représentent le groupe le plus fréquemment observé parmi les patients atteints de comorbidités associées à la COVID-19. Au début de la pandémie, un dilemme à propos de l'utilisation des IECA et des ARA s'est posé, puisqu'ils aggravaient potentiellement la dysfonction cardiovasculaire et pulmonaire chez les patients atteints de la COVID-19. Des essais cliniques urgents issus de différents pays et hôpitaux ont montré qu'il n'y avait pas d'association entre le traitement par inhibiteurs du SRA et les complications liées à l'infection par la COVID-19 ou aux comorbidités. Néanmoins, la perturbation du SRA qui est associée à l'infection par la COVID-19 et le traitement potentiel dans ce champ restent à résoudre. Dans la présente revue, le lien entre la dysrégulation du SRA traditionnel et les activités contre-régulatrices du SRA chez les patients atteints de la COVID-19 qui ont des maladies cardiovasculaires métaboliques est étudié. De plus, nous nous penchons sur les plus récentes conclusions fondées sur l'administration des IECA et des ARA et la disponibilité de l'ECA2 en relation avec la COVID-19 pour offrir une meilleure compréhension de la contribution du SRA à la pathologie de la COVID-19, puisqu'ils sont de la plus haute importance dans le contexte de l'actuelle pandémie.

Genomics ; 113(4): 1733-1741, 2021 07.
Article in English | MEDLINE | ID: covidwho-1171554


Interferon-induced membrane proteins (IFITM) 3 gene variants are known risk factor for severe viral diseases. We examined whether IFITM3 variant may underlie the heterogeneous clinical outcomes of SARS-CoV-2 infection-induced COVID-19 in large Arab population. We genotyped 880 Saudi patients; 93.8% were PCR-confirmed SARS-CoV-2 infection, encompassing most COVID-19 phenotypes. Mortality at 90 days was 9.1%. IFITM3-SNP, rs12252-G allele was associated with hospital admission (OR = 1.65 [95% CI; 1.01-2.70], P = 0.04]) and mortality (OR = 2.2 [95% CI; 1.16-4.20], P = 0.01). Patients less than 60 years old had a lower survival probability if they harbor this allele (log-rank test P = 0.002). Plasma levels of IFNγ were significantly lower in a subset of patients with AG/GG genotypes than patients with AA genotype (P = 0.00016). Early identification of these individuals at higher risk of death may inform precision public health response.

COVID-19/genetics , Genetic Predisposition to Disease , Membrane Proteins/genetics , RNA-Binding Proteins/genetics , SARS-CoV-2/genetics , Adult , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/virology , Female , Genetic Association Studies , Genotype , Humans , Interferons/genetics , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , SARS-CoV-2/pathogenicity