Course Of Virus Infection Research Articles

Exploring the Contrasts and Similarities of Dengue and SARS-CoV-2 Infections During the COVID-19 Era.

Extensive research has been conducted on the SARS-CoV-2 virus in association with various infectious diseases to understand the pathophysiology of the infection and potential co-infections. In tropical countries, exposure to local viruses may alter the course of SARS-CoV-2 infection and coinfection. Notably, only a portion of the antibodies produced against SARS-CoV-2 proteins demonstrate neutralizing properties, and the immune response following natural infection tends to be temporary. In contrast, long-lasting IgG antibodies are common after dengue virus infections. In cases where preexisting antibodies from an initial dengue virus infection bind to a different dengue serotype during a subsequent infection, there is a potential for antibody-dependent enhancement (ADE) and the formation of immune complexes associated with disease severity. Both SARS-CoV-2 and dengue infections can result in immunodeficiency. Viral proteins of both viruses interfere with the host's IFN-I signaling. Additionally, a cytokine storm can occur after viral infection, impairing a proper response, and autoantibodies against a wide array of proteins can appear during convalescence. Most of the reported autoantibodies are typically short-lived. Vaccines against both viruses alter the immune response, affecting the course of viral infection and enhancing clearance. A comprehensive analysis of both viral infections and pathogenicity is revisited to prevent infection, severity, and mortality.

Obesity as a Risk Factor for the Severity of COVID-19 in Pediatric Patients: Possible Mechanisms-A Narrative Review.

Obesity, the current pandemic, is associated with alarming rises among children and adolescents, and the forecasts for the near future are worrying. The present paper aims to draw attention to the short-term effects of the excess adipose tissue in the presence of a viral infection, which can be life-threatening for pediatric patients, given that the course of viral infections is often severe, if not critical. The COVID-19 pandemic has been the basis of these statements, which opened the door to the study of the repercussions of obesity in the presence of a viral infection. Since 2003, with the discovery of SARS-CoV-1, interest in the study of coronaviruses has steadily increased, with a peak during the pandemic. Thus, obesity has been identified as an independent risk factor for COVID-19 infection and is correlated with a heightened risk of severe outcomes in pediatric patients. We sought to determine the main mechanisms through which obesity is responsible for the unfavorable evolution in the presence of a viral infection, with emphasis on the disease caused by SARS-CoV-2, in the hope that future studies will further elucidate this aspect, enabling prompt and effective intervention in obese patients with viral infections, whose clinical progression is likely to be favorable.

Oncoviral Infections and Small Extracellular Vesicles.

Small extracellular vesicles (sEV) are small membrane-bound nanovesicles with a size range below 200 nm that are released by all types of cells. sEV carry a diverse cargo of proteins, lipids, glycans, and nucleic acids that mimic the content of producer cells. sEV mediate intercellular communication and play a key role in a broad variety of physiological and pathological conditions. Recently, numerous reports have emerged examining the role of sEV in viral infections. A significant number of similarities in the sEV biogenesis pathways and the replication cycles of viruses suggest that sEV might influence the course of viral infections in diverse ways. Besides directly modulating virus propagation by transporting the viral cargo (complete virions, proteins, RNA, and DNA), sEV can also modify the host antiviral response and increase the susceptibility of cells to infection. The network of mutual interactions is particularly complex in the case of oncogenic viruses, deserving special consideration because of its significance in cancer progression. This review summarizes the current knowledge of interactions between sEV and oncogenic viruses, focusing on sEV abilities to modulate the carcinogenic properties of oncoviruses.

Features of TLR4 and MMP9 gene expression modified with SARS-CoV-2 antigen and benzapyrene in children

Introduction. Exposure to chemical and biological environmental factors is associated with the risk of realizing genetic predisposition to the development of asthenia and cancer-associated diseases, which determines the relevance of the search for genetic indicator markers of early abnormalities in mRNA structure in the context of modern threats and challenges to public health. The aim of the study: characteristics of the expression of TLR4 and MMP9 genes modified by the SARS-CoV-2 antigen and benz(a)pyrene in children. Materials and methods. We analyzed the polymorphism of MMP9 Gln279Arg (rs17576), TLR4 A8595G (rs1927911) genes, as well as the relative normalized expression level of MMP9 Hs00234579_m1 (20q13.12), TLR4 Hs00152939_m1 (9q33. 1) in whole blood cell culture both spontaneous and induced by 24 hour incubation with benz(a)pyrene and vaccine antigens (using SARS-CoV-2, 1.0±0.5•1011 particles as an example) in adolescents of 10–16-years. Results. Benz(a)pyrene was found to have a potentiating effect on MMP9 expression and a suppressive effect on TLR4. The combination of benz(a)pyrene exposure with SARS-CoV-2 vaccine antigens “in vitro” resulted in differently directed effects depending on the genotype (polymorphism) of the genes under study. The ability of benz(a)pyrene and SARS-CoV-2 antigens to modify “in vitro” expression of MMP9, TLR4 candidate genes was shown, which allows considering genes and products of their expression MMP9 Hs00234579_m1 and TLR4 Hs00152939_m1 as indicator genes for early diagnosis of the development of asthenia and oncoproliferative states. Limitations. Limitations of the study include the limited sample and scope of the pilot study. Conclusion. The results of experimental studies ”in vitro” showed the ability of benz(a)pyrene and SARS-CoV-2 to modify the expression of genes of matrix metalloproteinase MMP9 Gln279Arg (rs17576) and toll-like receptor TLR4 A8595G (rs1927911), which allows considering transcripts Hs00234579_m1 and Hs00152939_m1 as criteria for the formation of asthenia in the course of viral infections (SARS-CoV-2) due to activation of the enzyme that destroys the extracellular matrix for AA wild-type and AG heterozygous genotype of the MMP9 Gln279Arg gene. In the case of heterozygous AG genotype of TLR4 A8595G gene, the combination of benz(a)pyrene and SARS-CoV-2 (26 serotype) leads to the formation of immunosuppression, which phenotypically may be accompanied by the development of oncoproliferative processes. MMP9 Hs00234579_m1 and TLR4 Hs00152939_m1 transcripts are recommended as markers of early disorders associated with SARS-CoV-2+benz(a)pyrene exposure.

Structural properties of immune complexes formed by viral antigens and specific antibodies shape the inflammatory response of macrophages

Data on the course of viral infections revealed severe inflammation as a consequence of antiviral immune response. Despite extensive research, there are insufficient data on the role of innate immune cells in promoting inflammation mediated by immune complexes (IC) of viral antigens and their specific antibodies. Recently, we demonstrated that antigens of human polyomaviruses (PyVs) induce an inflammatory response in macrophages. Here, we investigated macrophage activation by IC. We used primary murine macrophages as a cell model, virus-like particles (VLPs) of PyV capsid protein as antigens, and a collection of murine monoclonal antibodies (mAbs) of IgG1, IgG2a, IgG2b subclasses. The inflammatory response was investigated by analysing inflammatory chemokines and activation of NLRP3 inflammasome. We observed a diverse pattern of chemokine secretion in macrophages treated with different IC compared to VLPs alone. To link IC properties with cell activation status, we characterised the IC by advanced optical and acoustic techniques. Ellipsometry provided precise real-time kinetics of mAb-antigen interactions, while quartz crystal microbalance measurements showed changes in conformation and viscoelastic properties during IC formation. These results revealed differences in mAb-antigen interaction and mAb binding parameters of the investigated IC. We found that IC-mediated cell activation depends more on IC characteristics, including mAb affinity, than on mAb affinity for the activating Fc receptor. IC formed by the highest affinity mAb showed a significant enhancement of inflammasome activation. This may explain the hyperinflammation related to viral infection and vaccination. Our findings demonstrate that IC promote the viral antigen-induced inflammatory response depending on antibody properties.

Prevalence and Severity of COVID-19 among Pediatric Patients with Atopy: A Cross-sectional Study in Kerman, Southeast Iran.

The tragic COVID-19 pandemic affected many children worldwide. Among the factors that may influence the course of viral infections including COVID-19, it is still uncertain whether atopy has a protective or predisposing role. The study aims to address the knowledge gap by investigating the prevalence and severity of COVID-19 among atopic children in Kerman, in 2022. A descriptive-analytical cross-sectional study on children with a history of atopy was performed in Kerman Medical University. Demographic information, type of atopy (including allergic rhinitis, Hyper-Reactive Airway Disease (HRAD) or asthma, eczema, urticaria, anaphylaxis, and food allergy), history of COVID-19 infection, and disease severity were recorded. A total of 1007 children and adolescents, (boys: 56.4%, girls: 43.6%, age:5.61±2.64 years) were included in the study. History of COVID-19 infection was positive in 53.5%, with 75.9% of the cases exhibiting mild disease severity. The frequency of atopies was HRAD or asthma (67.2%), allergic rhinitis (42.6%), and food allergy (27.4%). The frequency of COVID-19 cases was significantly higher among patients with HRAD or asthma, whereas it was significantly lower among those with food allergies, anaphylaxis, and eczema. Among atopic individuals, COVID-19 severity was significantly lower in those with allergic rhinitis, while the opposite trend was observed among food-allergic individuals. This study sheds light on the relationship between atopy and COVID-19 among pediatric patients. It seems specific types of atopies may influence the risk and severity of COVID-19 infection differently. A better understanding of these associations can inform clinical management and preventive measures for vulnerable pediatric populations.

A conformal regressor for predicting negative conversion time of Omicron patients.

In light of the situation and the characteristics of Omicron, the country has continuously optimized the rules for the prevention and control of COVID-19. The global epidemic is still spreading, and new cases of infection continue to emerge in China. To facilitate the infected person to estimate the course of virus infection, a prediction model for predicting negative conversion time is proposed in this article. The clinical features of Omicron-infected patients in Shandong Province in the first half of 2022 are retrospectively studied. These features are grouped by disease diagnosis result, clinical sign, traditional Chinese medicine symptoms, and drug use. These features are input to the eXtreme Gradient Boosting (XGBoost) model, and the output is the predicted number of negative conversion days. At the same time, XGBoost is used as the underlying algorithm of the conformal prediction (CP) framework, which can realize the probability interval estimation with a controllable error rate. The results show that the proposed model has a mean absolute error of 3.54days and has the shortest interval prediction result. This shows that the method in this paper can carry more decision-making information and help people better understand the disease and self-estimate the course of the disease to a certain extent.

The impact of polymorphic variants of interferon receptor genes on COVID-19 severity and antibiotic resistance

Single nucleotide substitutions in gene sequence associated with conformational changes in protein receptor or in expression of interferon receptors may explain variations in human susceptibility to infection and severity of COVID-19 along with other well-known risk factors. The study aimed to investigate associations between polymorphic variants of interferon receptor genes, COVID-19 severity and prevalence of antibiotic resistance genes in the gut microbiota. Materials and methods. The study was conducted using a random sample of Arkhangelsk population aged 42 to 76 years (n = 305). The research involved gathering COVID-19 data from the Federal Register, conducting blood tests for SARS-CoV-2 antibodies and polymorphic interferon receptor gene variants, and identifying antibiotic resistance genes in stool samples. Results. During the first 12–15 months of the COVID-19 pandemic, 17.4% of the study participants had symptomatic COVID-19, while 32.8% were asymptomatic. By the Autumn of 2022, symptomatic COVID-19 cases rose up to 36.4%, while asymptomatic cases increased to 61.3%. We reveal an association between the CC genotype of the IFNAR1 gene rs2257167 variant, the presence of the T allele of IFNAR2 gene rs2229207 variant, the CCTT haplotype and symptomatic COVID-19. The GCTC haplotype was associated with pneumonia and COVID-19 severity. In November 2022, macrolide resistance genes were observed in 98.4% of cases, whereas those to beta-lactams and glycopeptides — in 26.9% and 13.8% cases, respectively. Resistance to three classes of antibiotics was observed in 4.9% and was more frequently detected in individuals with the ССТТ haplotype. Genes encoding beta-lactamases were more often found in individuals with the GCTC haplotype, those who had COVID-19 with pneumonia and those who received hospital treatment. Glycopeptide resistance genes were associated with the CC genotype of the rs2257167 variant of IFNAR1 gene. Conclusion. We identified genetic determinants of susceptibility, symptomatic infection and COVID-19 severity. The associations between polymorphic variants of interferon receptor genes and COVID-19 severity can be used to identify people with a genetic predisposition to severe infection and to determine priority groups for vaccination, including the prevention of antibiotic resistance in complicated course of viral infections.

Lesions of the heart and parenchymatous organs in patients with COVID-19 and other acute respiratory infections

Based on available literature, this study aimed to critically assess the effect of SARS-CoV-2 and other respiratory viruses on the heart and parenchymatous internal organs, identify their common and distinctive features, assess the frequency of cytokine storm and “post-infection” syndrome, and identify risk factors for severe systemic reaction and damage to internal organs, particularly the heart.
 In the databases of MEDLINE/PubMed, eLibrary, Web of Science, CyberLeninka, and Openmedcom.ru, primary information (full-text and abstract databases) in English and Russian was searched using selected keywords from 2003 to 2023.
 Acute respiratory viral infection pathogens can cause not only respiratory but also cardinal, gastroenterological, neurological, and other complications.
 Acute respiratory viral infections have many similarities in their effects on parenchymal organs. The emergence of new viruses requires in-depth study, and it is important to consider both the distinctive features of the clinical picture of viral infections and the general patterns of influence on internal organs. In the medium term, patients who have COVID-19 may have complex heart damage in the form of a decrease in ventricular ejection fraction, appearance of pericardial effusion, and development of various types of focal myocardial lesions. The combined nature of damage to the heart and parenchymal organs is influenced by background diseases, nature of the course of viral infection, and features of therapy. The features of lesions of parenchymal organs and the heart after acute respiratory viral infection require further study, including their effect on the development of late complications.

Carbohydrate PL-M binds galectin-3 to inhibit SARS-CoV-2 viral entry into cells

Galectin-3 (Gal-3) binds to glycans on the spike protein S1 domain of the SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) virus, thereby facilitating viral entry into cells. Because little is known about how to antagonize Gal-3 to block viral activity, we developed a pectin-derived polysaccharide of a(1-6)-D-mannopyranose (termed “ProLectin M” or PL-M) and studied its effect on Vero cells being infected with SARS-CoV-2 virus. Using this novel glycovirology approach, we demonstrated a significant reduction in viral load with no demonstrable cytotoxicity. We also evaluated the efficacy of PL-M in a randomized, double-blinded, placebo-controlled clinical study in 34 patients with mild to moderately severe COVID-19. Overall, treatment with PL-M significantly (p = 0.001) increased RT-PCR cycle counts for N and ORF genes on days 3 (Ct values 32.09 ± 2.39 and 30.69 ± 3.38, respectively) and 7 (Ct values 34.91 ± 0.39 and 34.85 ± 0.61, respectively) compared to placebo. From day 3 post-treatment, all subjects were RT-PCR negative for both genes in the PL-M treatment group, whereas placebo subjects remained positive. On the molecular level, our NMR studies show that PL-M binds relatively strongly to Gal-3, supporting the idea of an antagonist effect on the lectin. Gal-3 also binds strongly to sugar binding sites on the SARS-CoV2 virus spike protein S1 domain as evidenced by competitive lactose binding. In this regard, PL-M competes with the spike protein for binding to Gal-3 and thereby compromises viral entry into susceptible target cells, thus helping to explain our positive clinical effect from PL-M on the course of viral infection. This report provides a brief review of what is already known about PL-M and its effects on SARS-CoV2 virus, as well as new results on an expanded clinical trial with PL-M and NMR studies on the molecular mechanism of action of PL-M, Gal-3, and the SARS-CoV2 viral spike protein S1 from the Omicron variant.

Expression of the TR53 oncosuppressor gene modified with benzo[a]pyrene and the SARS-COV-2 vaccine antigen in an in vitro experiment

Introduction. The impact of chemical and biological environmental factors is associated with the risk of a genetic predisposition to the development of cardiovascular and cancer-associated diseases, which determines the relevance of the search for genetic indicator markers of early disorders in the mRNA structure.
 Materials and methods. The analysis of TP53 rs1042522 gene polymorphism, as well as the relative normalized expression level of TP53 hs1034249_m1 transcript, in whole blood cell culture in healthy volunteers, both spontaneous and induced by 24-hour incubation with benzo[a]pyrene and SARS-CoV-2 vaccine antigen 
 (at concentrations of 0.006 mg/kg). Ml), was conducted.
 Results. Comparative analysis of spontaneous and antigen-induced levels of TP53 hs1034249_m1 mRNA expression allowed establishing individual and group values of relative expression associated with the polymorphism features of the TP53 rs1042522 gene. Benzo[a]pyrene and SARS-CoV-2 were found to have opposite effects on the expression of hs1034249_m1 TP53 genes in the case of the CG rs1042522 genotype, while the combined effect of benzo[a]pyrene and SARS-CoV-2, which reflected the inhibition of the expression of hs00900055_m1 of the TP53 gene was associated with the GG genotype.
 The limitations of the study are the use of a relatively small sample and a limited number of whole blood samples. 
 Conclusion. The ability of benzo[a]pyrene and SARS-CoV-2 at concentrations of 6 µg/L to modify the expression of the TP53 apoptosis gene in vitro has been shown, which makes it possible to consider the increase in the expression of hs00900055_m1 of the TP53 gene induced by benzo[a]pyrene as one of the mechanisms for aggravating the course of viral infections (SARS-CoV-2) in connection with loss of p53-controlling for the development of inflammation (its proliferative phase) for owners of the heterozygous variant of CG TP53 rs1042522. In the case of variant monozygotic polymorphism GG TP53 rs1042522, the combination of benzo[a]pyrene and SARS-CoV-2 leads to inhibition of the expression of hs00900055_m1 mRNA of the TP53 gene, which is phenotypically reflected by the formation of asthenia, immunosuppression and onco-proliferative complications. The hs00900055_m1 transcript of the TP53 gene is recommended as an indicator for the tasks of diagnosing early disorders associated with the combination of SARS-CoV-2+ benzo[a]pyrene. The experiment simulates the natural conditions of real combinations of influencing factors.

Modern view on the features of the development and course of the antiviral immune response

The review article summarizes recent literature data on immunopathogenetic features that influence the nature of the development and course of viral infections.
 According to the impact on a cell, cytopathic and non-cytopathic viruses are isolated. The course of viral infections is accompanied by cell death, immunopathology, immunosuppression, oncogenesis, and in later stages molecular mimicry and immune amnesia. The acute course of infections is controlled mainly by the mechanisms of innate immunity. The severity of the course of such infections is associated with the genetic variability of viruses and resistance to the antibodies' neutralizing effects. Viruses that are non-cytopathic in their natural mouse hosts can cause acute and chronic infections in humans. The activity of viral reproduction, the persistent infection may be associated with the peculiarities of the expression of gene profiles of the infected cell. The synthesis of endogenous interferons can also affect the nature of the infection development. Disturbances in signaling through Toll-like receptors may contribute to the persistence of infection. Some of the viral proteins block the presentation by the molecules of the main histocompatibility complex of I, II class of viral antigens, interfering with various stages of the presentation. This process is facilitated by a decrease in the transcription of genes of the main histocompatibility complex, blocking the secretion of immunogenic peptides by the proteasome or interfering with the subsequent assembly and transport of the peptide complex to the cell surface. A number of viral proteins stimulate the virus reproduction and inhibit apoptosis. It is believed that the B7-2 molecule is most important for triggering the immune response. Immunodominant epitopes of viral antigens, mutants of cytotoxic lymphocytes are key factors in the immunopathogenesis of persistent, latent infections. Changes in the viral genome of even a single amino acid allow them to avoid recognizing epitopes by an activated T-lymphocyte. Another mechanism for viruses to escape the immune system control is the death of activated T-cells.

Ukrainian War Refugee Children With Particularly Severe Viral Infections: A Case Series Report.

The humanitarian crisis in Ukraine in 2022 led to a massive migration of refugees to Poland. Immigrant children, living in overcrowded humanitarian hubs, were exposed to multiple stressful factors likely affecting their immune systems. This case series study aimed to describe a particularly severe course of common viral infections, in Ukrainian refugee children. We present 2 case series of Ukrainian refugee children: 5 hospitalized due to either adenovirus (AdV) and 8 with rotavirus (RV) infection, admitted within 3 months in each case series, recruited retrospectively. Most patients lived in humanitarian hubs and were neglected on admission (dehydrated, with poor hygiene and anxious). All RV infection cases had symptoms of severe gastroenteritis requiring intravenous rehydration. Metabolic acidosis was present in 6 children, and hypoglycemia in 4 participants. None of them were vaccinated against RV. All children with AdV infection had prolonged fever, dyspnea requiring oxygen therapy and hyperinflammation. In 2 AdV infection cases with no clinical improvement and increasing inflammatory markers, intravenous immunoglobulins and glucocorticosteroids were used. The combination of stressful factors and living in overcrowded hubs during the high prevalence of viral infections led to a particularly severe course of viral infections in Ukrainian refugee children.

Outpatient management of sarcoidosis in the COVID-19 pandemic

Introduction. COVID-19 infection alters the body’s immune tolerance, which can affect the course of systemic diseases caused by alterations in immune function. Patients with sarcoidosis, just like patients with systemic diseases, have impaired immune system function. They receive immunosuppressive therapy, so they are at risk of infectious diseases, including the viral ones.Aim. To investigate the course of sarcoidosis in the period 2020-2022, the incidence of COVID-19 infection in patients treated by the pulmonologist of the sarcoidosis-polyclinic office of the Krasnoyarsk Regional Clinical Hospital and to evaluate the incidence of sarcoidosis after COVID-19.Materials and methods. 301 outpatient charts of patients diagnosed with sarcoidosis were analyzed. Anamnestic data, information on vaccination against COVID-19, results of physical examination, multispiral computed tomography of thoracic organs in dynamics, data and methods of morphological verification, the volume of the received therapy for sarcoidosis were assessed.Results. There was evidence that the combination of active sarcoidosis and COVID-19 did not contribute to a severe course of viral infection and progression in the course of granulomatosis. In patients with baseline moderate or severe pulmonary function impairment due to sarcoidosis and long-term use of systemic glucocorticosteroids, no increase in the incidence of adverse COVID-19 outcomes was noted. When analyzing fatal cases, it became known that in the first case, chronic recurrent sarcoidosis and prolonged use of systemic glucocorticosteroids were the factors determining the adverse prognosis in COVID- 19 In the second case, the combination of sarcoidosis with cardiovascular disease, diabetes mellitus, and obesity were adverse outcome factors. New cases of sarcoidosis after COVID-19 have been reported, this may be explained by the interaction between SARS-CoV-2 and human immune system, imbalance of proand anti-inflammatory cytokines, disruption of interferon production. However, this statement requires further research.

Epigenetic reprogramming around IFN1 and IFNy2 promoters in rainbow trout cells inoculated with infectious pancreatic necrosis virus (IPNV).

Infectious pancreatic necrosis virus (IPNV) has proven to effectively evade the host antiviral responses. This study clarifies whether the modulation of the antiviral immune response exerted by IPNV involves epigenetic mechanisms. An in-silico characterization of the rainbow trout IFN1 and IFNγ2 promoters was performed, identifying the islands or sequences rich in CpG dinucleotides and the putative transcription factor binding sites (TBS) for both gene promoters. RTS11 cells (rainbow trout monocyte/macrophage) were infected with IPNV, and the course of viral infection was followed up to 48h post infection (hpi). Infected cells showed increased IFN1 and IFNγ2 transcriptional expression at 6 and 24 hpi, respectively. IPNV infection caused increases and decreases in global IFNγ2 promoter methylation at 6 and 24 hpi, respectively. The CpG dinucleotides at positions -392 and+38 of this promoter were the most sensitive to methylation changes. The IFN1 promoter remained fully unmethylated during the course of the infection, similar to the control. The changes in the methylation pattern observed for the IFNγ2 promoter were coincident with the changes in DNA methyltransferase (DNMT) expression levels, increasing at 6 hpi and decreasing below basal level at 24 hpi. Similarly, the H4 histones associated with the IFN1 and IFNγ2 promoters were hyperacetylated at 6 hpi, subsequently decreasing their acetylation below basal levels at 24 hpi, in both promoters. Coincidentally with the above, overexpression of histone acetyltransferase (HAT) was observed at 6 hpi and of histone deacetylase (HDAC) at 24 hpi, with return to baseline of HAT. These results suggest that IPNV would epigenetically modulate the expression of IFN1 by changing acetylation levels of the histones H4 associated with its promoter. Also, the modulation of the expression of IFNy2 would be by switching methylation/demethylation levels of its promoter, in addition to changes in acetylation levels of histones H4 associated with this promoter. This study is the first to demonstrate the effect of epigenetic reprogramming after IPNV infection in salmonid cells, demonstrating that promoter methylation/demethylation level and changes in the histone code associated with promoters may play a role in the modulation of the immune response induced by the virus.

Toll-like Receptors as Pro-Thrombotic Drivers in Viral Infections: A Narrative Review.

Toll-like receptors (TLRs) have a critical role in the pathogenesis and disease course of viral infections. The induced pro-inflammatory responses result in the disturbance of the endovascular surface layer and impair vascular homeostasis. The injury of the vessel wall further promotes pro-thrombotic and pro-coagulatory processes, eventually leading to micro-vessel plugging and tissue necrosis. Moreover, TLRs have a direct role in the sensing of viruses and platelet activation. TLR-mediated upregulation of von Willebrand factor release and neutrophil, as well as macrophage extra-cellular trap formation, further contribute to (micro-) thrombotic processes during inflammation. The following review focuses on TLR signaling pathways of TLRs expressed in humans provoking pro-thrombotic responses, which determine patient outcome during viral infections, especially in those with cardiovascular diseases.

Symptoms and complications of SARS-CoV-2virus infection in the aspect of speech therapyrehabilitation – literature review

<b>Introduction:</b> The past three years have seen the publication of numerous scientific studies from around the world, investigating the etiology, symptoms and complications of SARS CoV-2 virus infection, which causes COVID-19 disease. Until now, the long-term complications resulting from systemic dysfunction are unknown, but researchers are continually publishing the results of studies to date. Some of them already reliably show the various symptoms of the infection and their consequences. Furthermore, based on the course of the development of the infection and the associated management, scientists are predicting the complications of COVID-19.</br></br> <b>Aim:</b> The aim of this article is to present the possible complications of SARS-CoV-2 virus infection from the perspective of speech therapy rehabilitation, based on a review of the worldwide literature. The sequelae of the infection shown herein are mainly related to disorders of all laryngeal functions, i.e. respiratory, protective and phonatory functions, as well as olfactory and/or taste disorders and language and communication disorders. Moreover, the article presents the possibilities of speech therapy rehabilitation for each of the disorders.</br></br> <b>Conclusions:</b> Research indicates a number of symptoms and complications of COVID-19 infection, the vast majority of which relate to head and neck complications. The diagnosis and speech therapy of patients during the course of virus infection and during the post-infection recovery period is particularly important for the safety of patients and their comfort in life. Furthermore, it contributes to faster recovery, which seems particularly important in the case of active patients. In addition, multidisciplinary management in cooperation with doctors, physiotherapists and psychologists is necessary.

Humanized Mice for Studies of HIV-1 Persistence and Elimination.

A major roadblock to achieving a cure for human immunodeficiency virus type one (HIV-1) is the persistence of latent viral infections in the cells and tissue compartments of an infected human host. Latent HIV-1 proviral DNA persists in resting memory CD4+ T cells and mononuclear phagocytes (MPs; macrophages, microglia, and dendritic cells). Tissue viral reservoirs of both cell types reside in the gut, lymph nodes, bone marrow, spleen, liver, kidney, skin, adipose tissue, reproductive organs, and brain. However, despite the identification of virus-susceptible cells, several limitations persist in identifying broad latent reservoirs in infected persons. The major limitations include their relatively low abundance, the precise identification of latently infected cells, and the lack of biomarkers for identifying latent cells. While primary MP and CD4+ T cells and transformed cell lines are used to interrogate mechanisms of HIV-1 persistence, they often fail to accurately reflect the host cells and tissue environments that carry latent infections. Given the host specificity of HIV-1, there are few animal models that replicate the natural course of viral infection with any precision. These needs underlie the importance of humanized mouse models as both valuable and cost-effective tools for studying viral latency and subsequently identifying means of eliminating it. In this review, we discuss the advantages and limitations of humanized mice for studies of viral persistence and latency with an eye toward using these models to test antiretroviral and excision therapeutics. The goals of this research are to use the models to address how and under which circumstances HIV-1 latency can be detected and eliminated. Targeting latent reservoirs for an ultimate HIV-1 cure is the task at hand.

Psychological care reflecting the specifics of the course of viral infection in SARS-CoV-2 oncological patients with oxygenation disorder - a case series.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients treated with acute coronavirus disease 2019 (COVID-19) in intensive care units (ICU) have suffered from neuropsychiatric complications such as anxiety, depression, and confusion. Conditions related to the environment have the potential to worsen these symptoms. In combination with virus-dependent neuroinflammation, they form a "toxic" mixture. Discussion and planning strategies for providing psychological care in the ICU during the pandemic have revealed a great current challenge. We share our experience concerning psychological interventions for oncological patients with oxygen saturation depletion. Our observation of two SARS-CoV-2 patients suggests a close time-related association between the increase in inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) and intensive anxiety in the fast development of breath shortening in acute COVID-19 infection due to brain hypoxia and potential neuroinflammation. As cytokine IL-6 regulates induction of CRP gene expression, the changes in IL-6 concentrations associated with anxiety symptoms and breath shortening in the observed cluster can be detected hours earlier than changes in CRP levels, with a diagnostic implication for the clinicians. The SARS-CoV-2 patients with oncological diseases treated in our ICU asked for personal bedside contact with clinical psychologists, considered it irreplaceable and reported this psychological care as beneficial.

P148 Mixed bacterial-viral lung infections in patients with cystic fibrosis (CF) during an exacerbation

Chronic lung infection in patients with cystic fibrosis in more than 70% of cases is mixed. About 40% of CF patients during exacerbations of a chronic lung infection require hospital treatment. CF, like other congenital pathologies of the respiratory system, is a risk factor for a more unfavourable course of viral infections of the respiratory tract.