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2.
Artigo em Inglês | MEDLINE | ID: mdl-34501738

RESUMO

BACKGROUND: Tocilizumab is an anti-IL-6 therapy widely adopted in the management of the so-called "cytokine storm" related to SARS-CoV-2 virus infection, but its effectiveness, use in relation to concomitant corticosteroid therapy and safety were unproven despite widespread use in numerous studies, mostly open label at the start of the pandemic. METHODS: We performed a systematic review and meta-analysis of case-control studies utilising tocilizumab in COVID-19 on different databases (PubMed/MEDLINE/Scopus) and preprint servers (medRxiv and SSRN) from inception until 20 July 2020 (PROSPERO CRD42020195690). Subgroup analyses and meta-regressions were performed. The impact of tocilizumab and concomitant corticosteroid therapy or tocilizumab alone versus standard of care (SOC) on the death rate, need for mechanical ventilation, ICU admission and bacterial infections were assessed. RESULTS: Thirty-nine studies with 15,531 patients (3657 cases versus 11,874 controls) were identified. Unadjusted estimates (n = 28) failed to demonstrate a protective effect of tocilizumab on survival (OR 0.74 ([95%CI 0.55-1.01], p = 0.057), mechanical ventilation prevention (OR 2.21 [95%CI 0.53-9.23], p = 0.277) or prevention of ICU admission (OR 3.79 [95%CI 0.38-37.34], p = 0.254). Considering studies with adjusted, estimated, tocilizumab use was associated with mortality rate reduction (HR 0.50 ([95%CI 0.38-0.64], p < 0.001) and prevention of ICU admission (OR 0.16 ([95%CI 0.06-0.43], p < 0.001). Tocilizumab with concomitant steroid use versus SOC was protective with an OR of 0.49 ([95%CI 0.36-0.65], p < 0.05) as was tocilizumab alone versus SOC with an OR of 0.59 ([95%CI 0.34-1.00], p < 0.001). Risk of infection increased (2.36 [95%CI 1.001-5.54], p = 0.050; based on unadjusted estimates). CONCLUSION: Despite the heterogeneity of included studies and large number of preprint articles, our findings from the first eight of the pandemic in over 15,000 COVID-19 cases suggested an incremental efficacy of tocilizumab in severe COVID-19 that were confirmed by subsequent meta-analyses of large randomized trials of tocilizumab. This suggests that analysis of case-control studies and pre-print server data in the early stages of a pandemic appeared robust for supporting incremental benefits and lack of major therapeutic toxicity of tocilizumab for severe COVID-19.


Assuntos
COVID-19 , Pandemias , Anticorpos Monoclonais Humanizados , COVID-19/tratamento farmacológico , Humanos , SARS-CoV-2 , Padrão de Cuidado , Resultado do Tratamento
3.
Lupus ; : 9612033211045922, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34569385
4.
Autoimmun Rev ; 20(11): 102945, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34509655

RESUMO

Notwithstanding the fact that the 12th international congress of autoimmunity (AUTO12) was held virtual this year, the number of the abstracts submitted and those presented crossed the thousand marks. Leading investigators and researchers from all over the world presented the latest developments of their research in the domain of autoimmunity and its correlation with various diseases. In terms of mechanisms of autoimmunity, an update on the mechanisms behind the association of autoimmunity with systemic diseases focusing on hyperstimulation was presented during AUTO12. In addition, a new mechanism of ASIA syndrome caused by an intrauterine contraceptive device was revealed demonstrating a complete resolution of symptoms following device removal. In regard to the correlation between autoimmunity and neurogenerative diseases, the loss of structural protein integrity as the trigger of immunological response was shown. Schizophrenia as well, and its correlation to pro-inflammatory cytokines was also addressed. Furthermore, and as it was said AUTO12 virtual due to COVID-19 pandemic, various works were dedicated to SARS-CoV-2 infection and COVID-19 in terms of autoimmune mechanisms involved in the pathogenesis, treatment and complications of COVID-19. For instance, the correlation between autoimmunity and the severity of COVID-19 was viewed. Moreover, the presence and association of autoantibodies in COVID-19 was also demonstrated, as well as the clinical outcomes of COVID-19 in patients with rheumatic diseases. Finally, immune-mediated reactions and processes secondary to SARS-CoV-2 vaccination was displayed. Due to the immense importance of all of the topics addressed and while several hundreds of works were presented which cannot be summed up in one paper, we aimed hereby to highlight some of the outstanding abstracts and presentations during AUTO12.


Assuntos
Doenças Autoimunes , COVID-19 , Doenças Autoimunes/epidemiologia , Autoimunidade , Vacinas contra COVID-19 , Humanos , Pandemias , SARS-CoV-2 , Paladar
5.
Am J Reprod Immunol ; 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407240

RESUMO

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.

6.
Harefuah ; 160(8): 527-532, 2021 Aug.
Artigo em Hebraico | MEDLINE | ID: mdl-34396729

RESUMO

INTRODUCTION: Besides its role in iron homeostasis and storage, ferritin is also regarded as an acute-phase reactant. Extreme Hyperferritinemia is seen in severe inflammatory conditions, severe infections, iron storage diseases and malignancies. A direct linkage between high ferritin levels and poor prognosis has been observed. OBJECTIVES: To characterize patients with extreme high ferritin levels in the serum for possible etiologies and assessment of the correlation between ferritin levels, prognosis and mortality. METHODS: We conducted a retrospective cohort study between the years 2002-2016 using the large database of Clalit Health Services. Patients older than 18 years with ferritin levels above 10,000 ng/ml that were taken during hospitalization and ambulatory visits were included in the study. After examining the medical files of each patient, we evaluated the demographic characteristics, etiologies, clinical presentation and relevant laboratory parameters. We calculated the proportion of this data and compared it to the general population by using chi square test. RESULTS: The incidence of extreme hyperferritinemia was statistically significant in patients with autoimmune and rheumatologic diseases in particular adult onset Still's disease compared to the general population. Among hospitalized patients, bacterial and viral infections were the leading cause in 62% of cases. In ambulatory patients, hyperferritinemia was mainly secondary to chronic blood transfusions in patients with hemoglobinopathies and poor compliance to iron chelators. Among 21 biopsies from involved organs including lymph nodes, bone marrow and liver, hemophagocytosis was only observed in 5 cases (6.8%). CONCLUSIONS: Extreme hyperferritinemia with values higher than 10,000 ng/ml can be attributed to many inflammatory autoimmune conditions.


Assuntos
Hiperferritinemia , Doença de Still de Início Tardio , Adulto , Ferritinas , Humanos , Prognóstico , Estudos Retrospectivos
8.
Nutr Rev ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34338776

RESUMO

CONTEXT: A gluten-free diet (GFD) is the recommended treatment for gluten-dependent disease. In addition, gluten withdrawal is popular and occasionally is suggested as a treatment for other autoimmune diseases (ADs). OBJECTIVE: The current systematic review summarizes those entities and discusses the logic behind using a GFD in classical non-gluten-dependentADs. DATA SOURCES: A search for medical articles in PubMed/MEDLINE, Web of Sciences, LILACS, and Scielo published between 1960 and 2020 was conducted, using the key words for various ADs and GFDs. DATA EXXTRACTION: Eight-three articles were included in the systematic review (using PRISMA guidelines). DATA ANALYSIS: Reduction in symptoms of ADs after observance of a GFD was observed in 911 out of 1408 patients (64.7%) and in 66 out of the 83 selected studies (79.5%). The age of the patients ranged from 9 months to 69 years. The duration of the GFD varied from 1 month to 9 years. A GFD can suppress several harmful intraluminal intestinal events. Potential mechanisms and pathways for the action of GFD in the gut - remote organs' axis have been suggested. CONCLUSION: A GFD might represent a novel nutritional therapeutic strategy for classical non-gluten-dependent autoimmune conditions.

9.
Isr Med Assoc J ; 23(6): 373-375, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34155851

RESUMO

BACKGROUND: Surgical interventions in patients with systemic sclerosis (SSc), in particular plastic procedures, might cause undesired consequences. Notably, liposuction seems to possess greater risk as adipose tissue has been shown to play an important role in treating wounds and ulcers in patients with SSc. While anticentromere antibodies were found to be correlated with vasculopathy in SSc, patients with SSc and anticentromere antibodies might be more vulnerable to surgical wound complications following liposuction. A 46-year-old female patient, who had been diagnosed with SSc at the age of 31 years, had antinuclear as well as anticentromere antibodies. She underwent abdominoplasty with liposuction and developed severe skin necrosis of the abdomen following the procedure and at the site of liposuction. The correlation with anticentromere and the role of liposuction in skin necrosis in SSc are presented.


Assuntos
Abdominoplastia , Tecido Adiposo/imunologia , Obesidade Abdominal/cirurgia , Escleroderma Sistêmico , Pele/patologia , Deiscência da Ferida Operatória , Abdominoplastia/efeitos adversos , Abdominoplastia/métodos , Anticorpos Antinucleares/sangue , Cicatriz/diagnóstico , Cicatriz/etiologia , Contraindicações de Procedimentos , Feminino , Humanos , Lipectomia/efeitos adversos , Lipectomia/métodos , Pessoa de Meia-Idade , Necrose/etiologia , Necrose/imunologia , Necrose/cirurgia , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico , Reoperação/efeitos adversos , Reoperação/métodos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/cirurgia , Cirurgia Plástica/efeitos adversos , Cirurgia Plástica/métodos , Deiscência da Ferida Operatória/diagnóstico , Deiscência da Ferida Operatória/etiologia , Deiscência da Ferida Operatória/cirurgia , Resultado do Tratamento
11.
Artigo em Inglês | MEDLINE | ID: mdl-34069883

RESUMO

Fever of unknown origin (FUO) poses a diagnostic challenge, and 18-fluorodexoyglucose positron emission tomography with computed tomography (18FDG-PET/CT) may identify the source. We aimed to evaluate the diagnostic yield of 18FDG-PET/CT in the work-up of FUO. The records of patients admitted to Sheba Medical Center between January 2013 and January 2018 who underwent 18FDG-PET/CT for the evaluation of FUO were reviewed. Following examination of available medical test results, 18FDG-PET/CT findings were assessed to determine whether lesions identified proved diagnostic. Of 225 patients who underwent 18FDG-PET/CT for FUO work-up, 128 (57%) met inclusion criteria. Eighty (62.5%) were males; mean age was 59 ± 20.3 (range: 18-93). A final diagnosis was made in 95 (74%) patients. Of the 128 18FDG-PET/CT tests conducted for the workup of FUO, 61 (48%) were true positive, 26 (20%) false positive, 26 (20%) true negative, and 15 (12%) false negative. In a multivariate analysis, weight loss and anemia were independently associated with having a contributary results of 18FDG-PET/CT. The test yielded a sensitivity of 70%, specificity of 37%, positive predictive value of 70%, and negative predictive value of 37%. 18FDG-PET/CT is a valuable tool in the diagnostic workup of FUO. It proved effective in diagnosing almost half the patients, especially in those with anemia and weight loss.


Assuntos
Febre de Causa Desconhecida , Fluordesoxiglucose F18 , Adulto , Idoso , Febre de Causa Desconhecida/diagnóstico por imagem , Febre de Causa Desconhecida/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos
12.
Artigo em Inglês | MEDLINE | ID: mdl-33992069

RESUMO

The population worldwide is largely exposed to bisphenol A (BPA), a commonly used plasticizer, that has a similar molecular structure to endogenous estrogens. Therefore, it is able to influence physiological processes in human body, taking part in the pathophysiology of various endocrinopathies, as well as, cardiovascular, neurological and oncological diseases. BPA has been found to affect the immune system, leading to the development of autoimmunity and allergies, too. In the last few decades, the prevalence of autoimmune diseases has significantly increased, that could be explained by a rising exposure of the population to environmental factors, such as BPA. BPA has been found to play a role in the pathogenesis of systemic autoimmune diseases and also organ-specific autoimmunity (thyroid autoimmunity, diabetes mellitus type 1, myocarditis, inflammatory bowel disease, multiple sclerosis, encephalomyelitis etc), but the results of some studies remain still controversial, so further research is needed.

13.
J Autoimmun ; 121: 102663, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34020254

RESUMO

As the novel SARS-CoV-2 continues to infect numerous individuals worldwide, one of the leading approaches in dealing with the global health crisis is vaccination against the COVID-19. Due to recent reports, vaccination with ChAdOx1 nCov-19 (developed by Oxford and AstraZeneca) may result in a vaccine-induced catastrophic thrombotic thrombocytopenia disorder. Thus, as of March 16 of 2021, vaccination programs in 18 countries had been suspended until further examination, including Sweden, Germany and France. This disorder presents as extensive thrombosis in atypical sites, primarily in the cerebral venous, alongside thrombocytopenia and the production of autoantibody against platelet-factor 4 (PF4). PF4 autoantibody has the ability to binds the human FcRγIIA receptor of platelets and contribute to their aggregation. This rare adverse effect extremely resembles the clinical presentation of the classical immune-mediated HIT disorder, which occurs following exposure to heparin. Surprisingly, none of these patients had been pre-exposed to heparin before disease onset, leading to the hypothesis that a viral antigen from the vaccine had triggered the response. Importantly, COVID-19 had been associated with numerous autoimmune manifestations, including the production of pathogenic autoantibodies, new onset of autoimmune diseases and disorders. As the ChAdOx1 nCov-19 vaccination leads to the synthesis of specific SARS-CoV-2-proteins, they may trigger a production of PF4 autoantibody though molecular mimicry phenomena, while vaccination compounds lead to a rigorous bystander activation of immune cells. If existing, removing such homological sequences from the vaccine may eliminate this phenomenon. In contrast, it needs to be emphasized that the ChAdOx1 nCoV-19 vaccine was found to be safe and efficacious against symptomatic COVID-19 in randomized controlled trials, which included 23,848 participants from the UK, Brazil and South Africa.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/imunologia , Púrpura Trombocitopênica Idiopática/imunologia , SARS-CoV-2/imunologia , Antígenos Virais/imunologia , Autoanticorpos/imunologia , COVID-19/patologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/uso terapêutico , Humanos , Fator Plaquetário 4/imunologia , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Púrpura Trombocitopênica Idiopática/patologia
14.
Medicine (Baltimore) ; 100(18): e25591, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950936

RESUMO

INTRODUCTION: Intravenous immunoglobulin (IVIg) is currently used with considerable success for the treatment of many autoimmune diseases, including systemic lupus erythematosus (SLE). Among its various indications, IVIg has also been found to be beneficial in myocarditis, whether or not it is associated with an autoimmune disease. Nevertheless, data regarding IVIg treatment for myocarditis/cardiomyopathy in patients with SLE are sparse. The objective of this case series was to describe our experience with IVIg as a treatment for lupus myocarditis and to review the literature for IVIg for this indication. PATIENT CONCERNS: We report 5 female patients with SLE, who presented with signs of acute heart failure including pulmonary congestion and arrhythmias. DIAGNOSIS: Echocardiography demonstrated new reduced left ventricular ejection fraction of 20% to 30%. Two patients underwent coronary artery angiography, which demonstrated normal coronary arteries, supporting the diagnosis of myocarditis or nonischemic cardiomyopathy. INTERVENTIONS: High-dose IVIg treatment was initiated in all 5 patients. OUTCOMES: Following the treatment, clinical and echocardiographic improvement in cardiac function occurred within a few days to 1 month. This dramatic improvement persisted for several years. CONCLUSION: Based on our case series, we believe that IVIg has an important role in the management of lupus acute cardiomyopathy. This safe, well-tolerated optional treatment should be considered, especially in severe cases.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Imunoglobulinas Intravenosas/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Miocardite/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Doença Aguda/terapia , Adulto , Angiografia Coronária , Relação Dose-Resposta a Droga , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/imunologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Pessoa de Meia-Idade , Miocardite/diagnóstico , Miocardite/imunologia , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/imunologia
15.
Parasitol Int ; 83: 102350, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33894388
16.
J Autoimmun ; 120: 102631, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33799099

RESUMO

IMPORTANCE AND OBJECTIVES: There is unmet medical need to understand the pathogenic mechanism of the panoply of clinical manifestations associated with silicone breast implants (SBIs) such as severe fatigue, widespread pain, palpitations, dry mouth and eyes, depression, hearing loss etc. We aimed to determine whether autoantibodies against the autonomic nervous system receptors can explain the enigmatic and subjective clinical manifestation reported by women with SBIs. RESULTS: Circulating level of autoantibodies against G protein-coupled receptors (GPCRs) of the autonomic nervous system (adrenergic, muscarinic, endothelin and angiotensin receptors) have been evaluated in symptomatic women with SBIs using an ELISA method. These women with SBIs addressed our clinic due to various subjective and autonomic-related manifestations such as chronic severe fatigue, cognitive impairment, widespread pain, memory loss, sleep disorders, palpitations, depression, hearing abnormalities etc. We report for the first time, a significant reduction in the sera level of anti-ß1 adrenergic receptor (p < 0.001), anti-angiotensin II type 1 receptor (p < 0.001) and anti-endothelin receptor type A (p = 0.001) autoantibodies in women with SBIs (n = 93) as compared with aged matched healthy women (n = 36). Importantly, anti-ß1 adrenergic receptor autoantibody was found to significantly correlate with autonomic-related manifestations such as: sleep disorders and depression in women with SBIs. CONCLUSIONS: Chronic immune stimulation by silicone material may lead to an autoimmune dysautonomia in a subgroup of potentially genetically susceptible women with SBIs. The appearance of autoantibodies against GPCRs of the autonomic nervous system serve as an explanation for the subjective autonomic-related manifestations reported in women with SBIs.

17.
Lupus ; 30(7): 1094-1099, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33794705

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease characterized by antibody production against a myriad of autoantigens. Familial Mediterranean fever (FMF) is a genetic autoinflammatory disorder, triggered by FMF-associated point genes mutations. It has been hypothesized that the two conditions rarely coexist. AIM: The aim of this study was to examine the proportions of FMF among SLE patients compared with the general population without SLE. We hypothesized that the proportion of FMF among SLE patients might be higher than the general population. METHODS: To conduct this cross-sectional study, data of adult patients with a physician diagnosis of SLE were retrieved from Clalit Health Services database, the largest Health Maintenance Organization in Israel, serving 4,400,000 members. Chi-square and T-test was used for univariate analysis. RESULTS: The study population included 4,886 SLE patients and 24,430 age and sex matched controls. Within the SLE group we detected a significantly higher proportion of FMF patients compared with non-SLE controls (0.68% and 0.21% respectively; p < 0.001). CONCLUSIONS: Our study indicated that FMF is more prevalent in an Israeli population of SLE patients.

18.
Psychiatr Danub ; 33(1): 3-17, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33857035

RESUMO

BACKGROUND: The review analyzes the possible role of autoimmune processes in the pathogenesis of schizophrenia and the evolution of concepts on this issue from its origin to the present. RESULTS: Risks of autoimmune processes causing schizophrenia are associated with several factors: an impaired functioning of dopaminergic and glutamatergic systems in the brain, kynurenine pathway disorder with overproduction of quinolinic, anthranilic, and kynurenic acids (possibly altering both neurons and T-regulators), increased intestinal permeability, as well as food antigens' effects, stress and infections with various pathogens at different stages of ontogenesis. An increase in the levels of proinflammatory cytokines and chemokines as well as a decrease in the levels of anti-inflammatory ones also may contribute to schizophrenia risks. Schizophrenia often occurs in those patients having various autoimmune diseases and their first-degree relatives. CONCLUSION: Cases of schizophrenia resulted from autoimmune pathogenesis (including autoimmune encephalitis caused by autoantibodies against various neuronal antigens) are characterized by quite severe cognitive and psychotic symptoms and a less favorable prognosis. This severe course may result from the chronic immune damage of the neuronal receptors such as NMDA, GABA, and others and depend on hyperprolactinemia, induced by antipsychotics, but aggravating autoimmune processes.


Assuntos
Antipsicóticos , Transtornos Psicóticos , Esquizofrenia , Humanos , Ácido Cinurênico , Cinurenina
19.
Vaccines (Basel) ; 9(3)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802310

RESUMO

According to an analysis of published data, only 20% of patients with the new coronavirus infection develop severe life-threatening complications. Currently, there are no known biomarkers, the determination of which before the onset of the disease would allow assessing the likelihood of its severe course. The purpose of this literature review was to analyze possible genetic factors characterizing the immune response to the new coronavirus infection that could be associated with the expression of angiotension-converting enzyme 2 (ACE-2) and related proteins as predictors of severe Corona virus disease 2019 (COVID-19). We analyzed original articles published in Medline, PubMed and Scopus databases from December 2019 to November 2020. For searching articles, we used the following keywords: New coronavirus infection, Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), COVID-19, severe course, complications, thrombosis, cytokine storm, ACE-2, biomarkers. In total, 3714 publications were selected using the keywords, of which 8 were in congruence with all the criteria. The literature analysis of the association of immunogenic characteristics and the expression of ACE-2 and related proteins with the development of severe COVID-19 revealed following genetic factors: HLA-B*46:01 genotype, CXCR6 gene hypoexpression, CCR9 gene expression, TLR7, rs150892504 mutations in the ERAP2 gene, overexpression of wild-type ACE-2, TMPRSS2 and its different polymorphisms. Genes, associated with the severe course, are more common among men. According to the analysis data, it can be assumed that there are population differences. However, the diagnostic significance of the markers described must be confirmed with additional clinical studies.

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