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1.
Am J Reprod Immunol ; 86(6): e13494, 2021 12.
Article in English | MEDLINE | ID: covidwho-1360445

ABSTRACT

INTRODUCTION: Oogenesis, the process of egg production by the ovary, involves a complex differentiation program leading to the production of functional oocytes. This process comprises a sequential pathway of steps that are finely regulated. The question related to SARS-CoV-2 infection and fertility has been evoked for several reasons, including the mechanism of molecular mimicry, which may contribute to female infertility by leading to the generation of deleterious autoantibodies, possibly contributing to the onset of an autoimmune disease in infected patients. OBJECTIVE: The immunological potential of the peptides shared between SARS-CoV-2 spike glycoprotein and oogenesis-related proteins; Thus we planned a systematic study to improve our understanding of the possible effects of SARS-CoV-2 infection on female fertility using the angle of molecular mimicry as a starting point. METHODS: A library of 82 human proteins linked to oogenesis was assembled at random from UniProtKB database using oogenesis, uterine receptivity, decidualization, and placentation as a key words. For the analyses, an artificial polyprotein was built by joining the 82 a sequences of the oogenesis-associated proteins. These were analyzed by searching the Immune Epitope DataBase for immunoreactive SARS-CoV-2 spike glycoprotein epitopes hosting the shared pentapeptides. RESULTS: SARS-CoV-2 spike glycoprotein was found to share 41 minimal immune determinants, that is, pentapeptides, with 27 human proteins that relate to oogenesis, uterine receptivity, decidualization, and placentation. All the shared pentapeptides that we identified, with the exception of four, are also present in SARS-CoV-2 spike glycoprotein-derived epitopes that have been experimentally validated as immunoreactive.

2.
Autoimmun Rev ; 20(4): 102792, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1086776

ABSTRACT

Autoimmunity may be generated by a variety of factors by creating a hyper-stimulated state of the immune system. It had been established long ago that viruses are a substantial component of environmental factors that contribute to the production of autoimmune antibodies, as well as autoimmune diseases. Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) are viruses that withhold these autoimmune abilities. In a similar manner, SARS-CoV-2 may be counted to similar manifestations, as numerous records demonstrating the likelihood of COVID-19 patients to develop multiple types of autoantibodies and autoimmune diseases. In this review, we focused on the association between COVID-19 and the immune system concerning the tendency of patients to develop over 15 separate types of autoantibodies and above 10 distinct autoimmune diseases. An additional autoimmunity manifestation may be one of the common initial symptoms in COVID-19 patients, anosmia, the complete loss of the ability to sense smell, and other olfactory alterations. We summarize current knowledge on principal mechanisms that may contribute to the development of autoimmunity in the disease: the ability of SARS-CoV-2 to hyper-stimulate the immune system, induce excessive neutrophil extracellular traps formation with neutrophil-associated cytokine responses and the molecular resemblance between self-components of the host and the virus. Additionally, we will examine COVID-19 potential risk on the new-onsets of autoimmune diseases, such as antiphospholipid syndrome, Guillain-Barré syndrome, Kawasaki disease and numerous others. It is of great importance to recognize those autoimmune manifestations of COVID-19 in order to properly cope with their outcomes in the ongoing pandemic and the long-term post-pandemic period. Lastly, an effective vaccine against SARS-CoV-2 may be the best solution in dealing with the ongoing pandemic. We will discuss the new messenger RNA vaccination strategy with an emphasis on autoimmunity implications.


Subject(s)
Autoimmune Diseases , COVID-19 , Epstein-Barr Virus Infections , Autoimmunity , COVID-19 Vaccines , Herpesvirus 4, Human , Humans , SARS-CoV-2
3.
Front Pharmacol ; 11: 870, 2020.
Article in English | MEDLINE | ID: covidwho-615558

ABSTRACT

There is an urgent need for new therapeutic strategies to contain the spread of the novel coronavirus disease 2019 (COVID-19) and to curtail its most severe complications. Severely ill patients experience pathologic manifestations of acute respiratory distress syndrome (ARDS), and clinical reports demonstrate striking neutrophilia, elevated levels of multiple cytokines, and an exaggerated inflammatory response in fatal COVID-19. Mechanical respirator devices are the most widely applied therapy for ARDS in COVID-19, yet mechanical ventilation achieves strikingly poor survival. Many patients, who recover, experience impaired cognition or physical disability. In this review, we argue the need to develop therapies aimed at inhibiting neutrophil recruitment, activation, degranulation, and neutrophil extracellular trap (NET) release. Moreover, we suggest that currently available pharmacologic approaches should be tested as treatments for ARDS in COVID-19. In our view, targeting host-mediated immunopathology holds promise to alleviate progressive pathologic complications of ARDS and reduce morbidities and mortalities in severely ill patients with COVID-19.

4.
Autophagy ; 16(12): 2260-2266, 2020 12.
Article in English | MEDLINE | ID: covidwho-593676

ABSTRACT

During the last week of December 2019, Wuhan (China) was confronted with the first case of respiratory tract disease 2019 (coronavirus disease 2019, COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the rapid outbreak of the transmission (~3.64 million positive cases and high mortality as of 5 May 2020), the world is looking for immediate and better therapeutic options. Still, much information is not known, including origin of the disease, complete genomic characterization, mechanism of transmission dynamics, extent of spread, possible genetic predisposition, clinical and biological diagnosis, complete details of disease-induced pathogenicity, and possible therapeutic options. Although several known drugs are already under clinical evaluation with many in repositioning strategies, much attention has been paid to the aminoquinoline derivates, chloroquine (CQ) and hydroxychloroquine (HCQ). These molecules are known regulators of endosomes/lysosomes, which are subcellular organelles central to autophagy processes. By elevating the pH of acidic endosomes/lysosomes, CQ/HCQ inhibit the autophagic process. In this short perspective, we discuss the roles of CQ/HCQ in the treatment of COVID-19 patients and propose new ways of possible treatment for SARS-CoV-2 infection based on the molecules that selectivity target autophagy.Abbreviation: ACE2: angiotensin I converting enzyme 2; CoV: coronavirus; CQ: chloroquine; ER: endoplasmic reticulum; HCQ: hydroxychloroquine; MERS-CoV: Middle East respiratory syndrome coronavirus; SARS-CoV: severe acute respiratory syndrome coronavirus; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.


Subject(s)
Autophagy/physiology , COVID-19/immunology , Chloroquine/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Autophagy/drug effects , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Chloroquine/therapeutic use , Endosomes/drug effects , Endosomes/metabolism , Humans , Hydrogen-Ion Concentration/drug effects , Hydroxychloroquine/pharmacology , Hydroxychloroquine/therapeutic use , Immunity, Innate/physiology , Lysosomes/drug effects , Lysosomes/metabolism , Molecular Targeted Therapy/methods , Molecular Targeted Therapy/trends , SARS-CoV-2/pathogenicity , Severity of Illness Index
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