scholarly journals Immunogenetic Predictors of Severe COVID-19

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 211
Author(s):  
Anna Malkova ◽  
Dmitriy Kudlay ◽  
Igor Kudryavtsev ◽  
Anna Starshinova ◽  
Piotr Yablonskiy ◽  
...  

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.

2020 ◽  
pp. 227-230
Author(s):  
V.Z. Netiazhenko

Background. Analysis of the mortality structure of patients with coronavirus disease (COVID-19) had found that 69.2 % of non-survivors had hypertension. Comorbid diabetes mellitus (31.8 %) and coronary heart disease (28.2 %) were also common. During pandemic, it is necessary to maintain optimal cardiovascular therapy by continuing to administer its main drugs (acetylsalicylic acid, statins, β-blockers, angiotensin-converting enzyme inhibitors – ACEI). Objective. To describe infusion therapy (IT) for cerebrovascular and cardiovascular diseases in settings of the COVID-19 pandemic. Materials and methods. Analysis of the literature on this topic. Results and discussion. Although the spike proteins of the new coronavirus have the tropism to ACE-2, discontinuation of ACEI is unwarranted and may worsen the course of cardiovascular disease (CVD). Particular attention should be paid to the diagnosis of acute coronary syndrome (ACS) in COVID-19. In myocardial infarction, myocarditis or cardiomyopathy on the background of COVID-19, there is a moderate increase in troponin, brain natriuretic peptide and N-terminal pro-B-type natriuretic peptide. An increase in D-dimers is a prognostic marker of the unfavorable prognosis. The algorithm for the ACS diagnosis includes the detection of typical clinical symptoms, ECG analysis, detection of disorders of local contractility of the left ventricle. Determination of troponin in patients without clinical manifestations of ACS with nonspecific manifestations of COVID-19 is not recommended. As for reperfusion therapy strategies, it is indicated in patients with symptoms of ischemia lasting >12 hours and a persistent increase in ST in two adjacent leads. In the absence of prior testing for coronavirus infection, all patients should be managed according to the tactics for COVID-positive patients. In non-STEMI, patients should be stratified according to their risk level (very high, high, moderate, low). In case of high risk, the early (<24 hours) invasive strategy is reasonable, in case of intermediate risk it is reasonable to consider noninvasive treatment. It should be remembered that the use of certain drugs for the treatment of COVID-19 (azithromycin, chloroquine, hydroxychloroquine, lopinavir, ritonavir) is associated with a risk of cardiotoxicity and life-threatening arrhythmias. Cardiotoxicity monitoring (determination of the corrected QT interval) should be performed before the start of therapy and then once in 5 days, primarily in risk groups (men >55 years, women >65 years and people with the CVD history). Lopinavir and ritonavir may also decrease the levels of active metabolites of clopidogrel and increase – of ticagrelor, so prasugrel is the antiplatelet drug of choice for COVID-19. Amiodarone also interacts with a large number of antiviral drugs. In turn, statins have multiple immunomodulatory effects including increase of the innate antiviral immune response. It is recommended to continue taking those statins that were prescribed earlier. If co-administration with lopinavir and ritonavir is required, the minimum dose of rosuvastatin or atorvastatin should be started. These antivirals are able to interact with calcium channel blockers and increase their concentration, so the dose of amlodipine and diltiazem can be reduced by 50 %. Endothelial dysfunction (ED) caused by a viral infection leads to the excessive thrombin formation and inhibition of fibrinolysis, increasing the risk of thrombotic complications. Nitric oxide (NO) plays an important role in counteracting ED. NO also inhibits the replication of the acute severe respiratory syndrome coronavirus and improves the survival of infected cells. L-arginine (Tivortin, “Yuria-Pharm”) is the only substrate for NO synthase that catalyzes the formation of NO in endothelial cells. According to the results of the own study, Tivortin helped to reduce the content of fibrinogen and soluble fibrin-monomer complexes, as well as to increase the thromboplastin time. Endothelium-dependent vasodilation also improved after administration of Tivortin. Tivorel (“Yuria-Pharm”) contains L-arginine and L-carnitine, which allows this drug to increase the survival of cardiomyocytes and endothelial cells, to restore homeostasis in the affected areas of the myocardium, and to counteract the progression of atherogenesis and thrombosis. In case of COVID-19, it is also advisable to prescribe edaravone (Ksavron, “Yuria-Pharm”), which neutralizes the cytokine storm, inhibits lipid peroxidation, protects against endothelial damage and, penetrating the blood-brain barrier, counteracts cerebral edema. In case of the need in IT, it is advisable to choose Reosorbilact (“Yuria-Pharm”), which has anti-shock, rheological, detoxifying, alkalizing and osmodiuretic effects. In hypovolemic shock and intracranial hemorrhage, the use of isotonic low-molecular-weight gelatin preparations (Volutenz, “Yuria-Pharm”) has been shown. Conclusions. 1. In the absence of prior testing for coronavirus infection, all patients should be managed following the tactics for COVID-positive patients. 2. The use of azithromycin, chloroquine, hydroxychloroquine, lopinavir, ritonavir is associated with a risk of cardiotoxicity and life-threatening arrhythmias. 3. ED, caused by a viral infection, increases the risk of thrombotic complications. 4. It is reasonable to include the required solutions (Tivortin, Tivorel, Ksavron, Reosorbilact, Volutenz) into the combined IT of COVID-19 patients.


2020 ◽  
Vol 8 (1) ◽  
pp. 9-15
Author(s):  
Petrov Nikolay ◽  
◽  
Marinova R. ◽  
Odiseeva Ev.

Abstract: Intracranial aneurysm is one of the most common neurovascular complications. During the recent years the accepted treatment of enraptured cranial aneurysm is noninvasive endovascular coiling. This technique is modern but it is not without complications which can be serious and life-threatening. A clinical case of a patient admitted to the ICU of Military Medical Academy - Sofia with sub arachnoid hemorrhage is described. After a positive clinical course, the check-up magnetic resonance showed intracranial aneurism of the right carotid artery. The patient underwent angiographic endovascular treatment. Vasospasm of the middle and right brain artery and thrombosis were detected during the procedure. Attempt of thromboaspiration was made without success. This article reviews published data on broad-spectrum researches concerning complications of endovascular coiling of intracranial aneurysms and the ways to prevent and reduce them.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Franca Rosa Guerini ◽  
Matteo Cesari ◽  
Beatrice Arosio

AbstractThe risk of serious complications and the fatality rate due to COVID-19 pandemic have proven particularly higher in older persons, putting a further strain in healthcare system as we dramatically observed.COVID-19 is not exclusively gerophile (géro “old” and philia “love”) as young people can be infected, even if older people experience more severe symptoms and mortality due to their greater frailty. Indeed, frailty could complicate the course of COVID-19, much more than the number of years lived. As demonstration, there are centenarians showing remarkable capacity to recover after coronavirus infection.We hypothesize that centenarian’s portfolio could help in identifying protective biological mechanisms underlying the coronavirus infection.The human leukocyte antigen (HLA) is one of the major genetic regions associated with human longevity, due to its central role in the development of adaptive immune response and modulation of the individual’s response to life threatening diseases. The HLA locus seems to be crucial in influencing susceptibility and severity of COVID-19.In this hypothesis, we assume that the biological process in which HLA are involved may explain some aspects of coronavirus infection in centenarians, although we cannot rule out other biological mechanisms that these extraordinary persons are able to adopt to cope with the infection.


Healthcare ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 117
Author(s):  
Massimiliano Esposito ◽  
Angelo Montana ◽  
Aldo Liberto ◽  
Veronica Filetti ◽  
Nunzio Di Nunno ◽  
...  

Anaphylaxis is a life-threatening or fatal clinical emergency characterized by rapid onset, and death may be sudden. The margin of certainty about the diagnosis of anaphylactic death is not well established. The application of immunohistochemical techniques combined with the evaluation of blood tryptase concentrations opened up a new field of investigation into anaphylactic death. The present study investigated eleven autopsy cases of anaphylactic death, carried out between 2005 and 2017, by the Departments of Forensic Pathology of the Universities of Foggia and Catania (Italy). An analysis of the medical records was carried out in all autopsies. Seven autopsies were carried out on males and four on females. Of the eleven cases, one showed a history of asthma, one of food ingestion, two of oral administration of medications, six did not refer any allergy history, and one subject was unknown. All cases (100%) showed pulmonary congestion and edema; 7/11 (64%) of the cases had pharyngeal/laryngeal edema and mucus plugging in the airway; only one case (9%) had a skin reaction that was found during external examination. Serum tryptase concentration was measured in ten cases, and the mean value was 133.5 µg/L ± 177.9. The immunohistochemical examination using an anti-tryptase antibody on samples from the lungs, pharynx/larynx, and skin site of medication injection showed that all cases (100%) were strongly immunopositive for anti-tryptase antibody staining on lung samples; three cases (30%) were strongly immunopositive for anti-tryptase antibody staining on pharyngeal/laryngeal samples; and eight cases (80%) were strongly immunopositive for anti-tryptase antibody staining on skin samples. We conclude that a typical clinical history, blood tryptase level >40 µg/L, and strongly positive anti-tryptase antibody staining in the immunohistochemical investigation may represent reliable parameters in the determination of anaphylactic death with the accuracy needed for forensic purposes.


1949 ◽  
Vol 22 (1) ◽  
pp. 259-262
Author(s):  
J. F. Morley

Abstract These experiments indicate that softeners can influence abrasion resistance, as measured by laboratory machines, in some manner other than by altering the stress-strain properties of the rubber. One possible explanation is that the softener acts as a lubricant to the abrasive surface. Since this surface, in laboratory abrasion-testing machines, is relatively small, and comes repeatedly into contact with the rubber under test, it seems possible that it may become coated with a thin layer of softener that reduces its abrasive power. It would be interesting in this connection to try an abrasive machine in which a long continuous strip of abrasive material was used, no part of it being used more than once, so as to eliminate or minimize this lubricating effect. The fact that the effect of the softener is more pronounced on the du Pont than on the Akron-Croydon machine lends support to the lubrication hypothesis, because on the former machine the rate of wear per unit area of abrasive is much greater. Thus in the present tests the volume of rubber abraded per hr. per sq. cm. of abrasive surface ranges from 0.03 to 0.11 cc. on the du Pont machine and from 0.0035 to 0.0045 cc. on the Akron-Croydon machine. On the other hand, if the softener acts as a lubricant, it would be expected to reduce considerably the friction between the abrasive and the rubber and hence the energy used in dragging the rubber over the abrasive surface. The energy figures given in the right-hand columns of Tables 1 and 3, however, show that there is relatively little variation between the different rubbers. As a test of the lubrication hypothesis, it would be of interest to vary the conditions of test so that approximately the same amount of rubber per unit area of abrasive is abraded in a given time on both machines; this should show whether the phenomena observed under the present test conditions are due solely to the difference in rate of wear or to an inherent difference in the type of wear on the two machines. This could most conveniently be done by considerably reducing the load on the du Pont machine. In the original work on this machine the load was standardized at 8 pounds, but no figures are quoted to show how abrasion loss varies with the load. As an addition to the present investigation, it is proposed to examine the effect of this variation with special reference to rubbers containing various amounts and types of softener. Published data on the influence of softeners on the road wear of tire rubbers do not indicate anything like such large effects as are shown by the du Pont machine. This throws some doubt on the value of this machine for testing tire tread rubbers, a conclusion which is confirmed by information obtained from other workers.


2021 ◽  
Vol 10 (5) ◽  
pp. 1114
Author(s):  
Kerstin Jurk ◽  
Yavar Shiravand

Patients who suffer from inherited or acquired thrombocytopenia can be also affected by platelet function defects, which potentially increase the risk of severe and life-threatening bleeding complications. A plethora of tests and assays for platelet phenotyping and function analysis are available, which are, in part, feasible in clinical practice due to adequate point-of-care qualities. However, most of them are time-consuming, require experienced and skilled personnel for platelet handling and processing, and are therefore well-established only in specialized laboratories. This review summarizes major indications, methods/assays for platelet phenotyping, and in vitro function testing in blood samples with reduced platelet count in relation to their clinical practicability. In addition, the diagnostic significance, difficulties, and challenges of selected tests to evaluate the hemostatic capacity and specific defects of platelets with reduced number are addressed.


2021 ◽  
Author(s):  
Larisa A. Chipiga ◽  
Anna E. Petrova ◽  
Artem A. Mosunov ◽  
Laura T. Naurzbaeva ◽  
Stanislaus M. Kushnarenko ◽  
...  

In connection with the constantly increasing use of monoclonal antibodies labeled with 89Zr, in clinical practice, it is urgent to study their pharmacokinetics with the determination, based on the data obtained, of absorbed doses in tumor foci, as well as intact organs and tissues, and effective doses of patients. To date, there are a limited number of studies that provide patient doses for diagnostic examinations using 89Zr-labeled monoclonal antibodies. In this regard, the purpose of this work was to assess the biodistribution of various monoclonal antibodies (ramucirumab, trastuzumab, atezolizumab) labeled with 89Zr, based on published data, with subsequent calculation of absorbed doses in radiosensitive organs and tissues and effective doses of patients. Based on the analysis of experimental data on the biodistribution of monoclonal antibodies labeled with 89Zr for the diagnosis of oncological diseases from the available literature sources and our own assessments, it has been concluded that the results of the determination of absorbed in organs and tissues and effective doses are inconsistent. The absorbed doses in organs, according to different literature sources, vary up to an order of magnitude within one organ and reach 440 mGy per examination, the effective dose varies from 3 to 112 mSv per examination. This may be due to differences in study design, radiometry and dose assessment methods. Comparison with doses obtained on the basis of a general model of biodistribution of monoclonal antibodies demonstrates the possibility of using this model for a rough estimate of internal doses of patients. However, for a more accurate assessment, it is necessary to standardize approaches to the determination of internal radiation doses using the most effective methodological solutions and software products.


1992 ◽  
Vol 13 (10) ◽  
pp. 371-378
Author(s):  
Thomas C. Putnam

Many lesions involving the skin or subcutaneous tissues alarm parents and, often fearing cancer, they bring their child to a physician. Most lesions are benign and rarely life-threatening. The physician faces the problem of determining which characteristics suggest only observation of a lesion and which make biopsy necessary. Because many lesions have a predilection for certain areas of the body, this is a useful form of categorization (Table 1). On first inspection of a superficial lesion, several questions must be asked, including the known duration, change in size, presence of pain or other signs of inflammation, and any noted multiplicity. The examination includes an accurate measurement of the size and, most importantly, a determination of the level of the lesion. This will help establish the diagnosis and help to determine whether the possibility of malignancy exists. Essentially all lesions originating in the skin of children are benign. Some are obvious, such as a wart, while others may not be so clear-cut, especially if the epidermis is not altered in appearance. Upon palpation of a cutaneous mass, the skin does not move over the surface and puckers when the adjacent skin and tissues are compressed and elevated. If the skin moves freely over the mass, the nature of the lesion is not so readily apparent.


2022 ◽  
Vol 12 (2) ◽  
pp. 306-315
Author(s):  
Jie Song ◽  
Cheng Chen ◽  
Hui Zhang

Osteoarthritis (OA) is a chronic and inflammatory disease, leading to pain or even disability in severe cases. LncRNA PCGEM1 (PCGEM1) is reported to be dysregulated, serving as critical regulators in various human diseases, including OA. However, the biological role of PCGEM1 and its underlying mechanisms during OA remained unclear. In the present study, CHON-001 cells were exposed to interleukin (IL)-1β to construct the OA cell model. Expression of PCGEM1 and miR-152-3p in cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Corresponding commercial kits were used to measure the expressions of lactate dehydrogenase (LDH), inter-leukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α. Protein levels of apoptosis-related proteins, cleaved-Caspase3 and Caspase3, were detected by Western blotting. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) tetrazolium (MTT) and flow cytometry assays were utilized for the determination of cell proliferation and apoptosis. The association between PCGEN1 and miR-152-3p was confirmed by a dual-luciferase reporter assay. From the results, PCGEM1 expression was significantly increased while miR-152-3p was inhibited in CHON-001 cells after IL-1β treatment. In addition, silencing of PCGEM1 could promote proliferation, inhibit the apoptosis, suppress LDH level and alleviate inflammation response caused by IL-1β in CHON-001 cells by sponging miR-152-3p. In a word, PCGEM1 down-regulation suppressed OA progression by the regulation of miR-152-3p expression, functioning as a potential therapeutic target for OA clinical treatment.


1995 ◽  
Author(s):  
Richard Lee ◽  
Moshe Bar-Joseph ◽  
K.S. Derrick ◽  
Aliza Vardi ◽  
Roland Brlansky ◽  
...  

Citrus tristeza virus (CTV) is the most important virus disease of citrus in the world. CTV causes death of trees on sour orange rootstock and/or stem pitting of scions regardless of rootstock which results in trees of low vigor, reduced yield with reduction in size and quality of fruit. The purpose of this project was to produce monoclonal antibodies (MABs) to CTV coat protein (CP), develop single domain antibodies (dAbs) or Fab fragments which neutralize the infection by binding to the virus, and to produce transformed plants which express the dAbs. The objectives of this research have been met and putative transgenic tobacco and citrus plants have been developed. These putative transgenic plants are presently undergoing evaluation to determine the level of dAbs expression and to determine their resistance to CTV. Additionally, the CTV genome has been sequenced and the CP gene of several biologically characterized CTV strains molecular characterized. This has indicated a correlation between CP sequence homology and biological activity, and the finding of DI RNAs associated with some CTV strains. Several MABs have been produced which enable broad spectrum identification of CTV strains while other MABs enable differentiation between mild and severe strains. The use of selected MAbs and determination of the CP gene sequence has enabled predictions of biological activities of unknown CTV isolates. The epitopes of two MABs, one reacting selectively with severe CTV strains and the other reacting with all strains, have been characterized at the molecular level.


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