Macrophage migration inhibitory factor receptor CD74 expression is associated with expansion and differentiation of effector T cells in COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused millions of COVID-19 cases and deaths worldwide. Severity of pulmonary pathologies and poor prognosis were reported to be associated with the activation non-virus-specific bystander T cells. In addition, high concentrations of the macrophage migration inhibitory factor (MIF) were found in serum of COVID-19 patients. We hypothesized that these two pathogenic factors might be related and analyzed the expression of receptors for MIF on T cells in COVID-19. T cells from PBMCs of hospitalized patients with mild and severe COVID-19 were characterized. A significantly higher proportion of CD4+ and CD8+ T cells from COVID-19 patients expressed CD74 on the cell surface compared to healthy controls. To induce intracellular signaling upon MIF binding, CD74 forms complexes with CD44, CXCR2, or CXCR4. The vast majority of CD74+ T cells expressed CD44, whereas expression of CXCR2 and CXCR4 was low in controls but increased upon SARS-CoV-2 infection. Hence, T cells in COVID-19 patients express receptors that render them responsive to MIF. A detailed analysis of CD74+ T cell populations revealed that most of them had a central memory phenotype early in infection, while cells with an effector and effector memory phenotype arose later during infection. Furthermore, CD74+ T cells produced more cytotoxic molecules and proliferation markers. Our data provide new insights into the MIF receptor and co-receptor repertoire of bystander T cells in COVID-19 and uncovers a novel and potentially druggable aspect of the immunological footprint of SARS-CoV-2.

Polymorphism of tmprss2 (rs12329760) and severity of COVID-19 in the Ukrainian population: Response.

.

Identifying the needs of older people living with HIV (≥ 50 years old) from multiple centres over the world: a descriptive analysis.

BACKGROUND: Older People Living with HIV (OPWH) combine both aging and HIV-infection features, resulting in ageism, stigma, social isolation, and low quality of life. This context brings up new challenges for healthcare professionals, who now must aid patients with a significant comorbidity burden and polypharmacy treatments. OPWH opinion on their health management is hardly ever considered as a variable to study, though it would help to understand their needs on dissimilar settings. METHODS: We performed a cross-sectional, comparative study including patients living with HIV aged ≥50 years old from multiple centers worldwide and gave them a survey addressing their perception on overall health issues, psychological problems, social activities, geriatric conditions, and opinions on healthcare. Data was analyzed through Chisquared tests sorting by geographical regions, age groups, or both. RESULTS: We organized 680 participants data by location (Center and South America [CSA], Western Europe [WE], Africa, Eastern Europe and Israel [EEI]) and by age groups (50- 55, 56-65, 66-75, >75). In EEI, HIV serostatus socializing and reaching undetectable viral load were the main problems. CSA participants are the least satisfied regarding their healthcare, and a great part of them are not retired. Africans show the best health perception, have financial problems, and fancy their HIV doctors. WE is the most developed region studied and their participants report the best scores. Moreover, older age groups tend to live alone, have a lower perception of psychological problems, and reduced social life. CONCLUSIONS: Patients' opinions outline region- and age-specific unmet needs. In EEI, socializing HIV and reaching undetectable viral load were the main concerns. CSA low satisfaction outcomes might reflect high expectations or profound inequities in the region. African participants results mirror a system where general health is hard to achieve, but HIV clinics are much more appealing to them. WE is the most satisfied region about their healthcare. In this context, age-specific information, education and counseling programs (i.e. Patient Reported Outcomes, Patient Centered Care, multidisciplinary teams) are needed to promote physical and mental health among older adults living with HIV/AIDS. This is crucial for improving health-related quality of life and patient's satisfaction.

Polymorphism of tmprss2 (rs12329760) but not ace2 (rs4240157), tmprss11a (rs353163) and cd147 (rs8259) is associated with the severity of COVID-19 in the Ukrainian population.

BACKGROUND AND AIM: Angiotensin-converting enzyme 2 (ACE2), transmembrane serine 2 and serine 11A proteases (TMPRSS2, TMPRSS11A), and a cell surface cluster of differentiation 147 (CD147) might be a gene candidate that exerts the susceptibility to and mortality from coronavirus disease 19 (COVID-19). The aim of this study was to investigate the associations between ace2, tmprss2, tmprss11a, and cd147 polymorphic variants and the severity of COVID-19 in the Ukrainian population. METHODS: The study population consisted of the Ukrainian population with COVID-19: patients without oxygen therapy (n=62), with non-invasive (n=92) and invasive (n=35) oxygen therapy, as well as control subjects (n=92). Allelic polymorphisms of ace2 rs4240157, tmprss2 rs12329760, and tmprss11a rs353163 were determined by real-time PCR, and cd147 rs8259 polymorphism was detected by PCR with subsequent restrictase analysis. We compared investigated polymorphisms distribution with other populations by meta-analysis. RESULTS: Our study is the first to obtain data about the distribution of investigated gene polymorphisms in the Ukrainian population: tmprss2 rs12329760 - CC 60.9%, CT 35.9%, TT 3.2%; tmprss11a rs353163 - CC 46.7%, CT 40.2%, TT 13.1%; ace2 rs4240157 - CC 7.6%, C 18.5%, CT 22.8%, TT 19.6%, T 31.5%; cd147 rs8259 - TT 60.9%, AT 32.6%, AA 6.5%. This distribution was similar to the Northern, Western and Southern European populations. There was a statistically significant difference in the frequency of tmprss2 polymorphic genotypes CC 57.1%, CT 28.6%, and TT 14.3% (P<0.05) in COVID-19 patients with invasive oxygen therapy in comparison with non-invasive oxygen therapy. This tmprss2 mutation occurs in the scavenger receptor cysteine-rich (SRCR) domain and might be important for protein-protein interaction in a calcium-dependent manner. CONCLUSIONS: Our study indicated the presence of an association between the tmprss2 rs12329760 polymorphism and the severity of COVID-19 in the Ukrainian population.

HEPATITIS A. THE FEATURES OF DISEASE COURSE IN ADULTS.

OBJECTIVE: The aim: To analyze the incidence of Hepatitis A in Ukraine and Poltava region and to study the clinical and epidemiological features of the course of Hepatitis A in adult patients. PATIENTS AND METHODS: Materials and methods: The course of HA in 96 hospitalized patients was analyzed. The diagnosis of HA was established on the basis of clinical and epide¬miological data and confirmed by the results of laboratory studies (serological and molecular biological). RESULTS: Results: In 2019, in the Poltava region, there was an increase in the incidence of Hepatitis A with a predominance among sick people of working age, among the urban population. This part of people aged from 60 to 75 years old constitutes 9.4%. This study showed that the waterway was the dominant way of HA transmission. The course of the disease in most hospitalized patients was typical and cyclic, with a predominance of a mixed variant of the pre-jaundice period and jaundice. One third of patients survey that they had fever, which persisted with jaundice. CONCLUSION: Conclusions: The findings of this study indicates that the patients older than 40 years were more likely to have concomitant chronic pathology than younger patients, and Hepatitis A was more severe with the development of prolonged cholestasis, wave-like course and recurrence. In most patients under the age of 40, the course of Hepatitis A was mild, but splenomegaly and severe cytolytic syndrome were more common.

ACUTE KIDNEY DAMAGE AS A COMPLICATION OF MALARIA CAUSED BY PL. MALARIA AND PL. FALCIPARUM: CLINICAL CASES.

We have described two clinical cases of severe malaria caused by different pathogens: Pl. falciparum and Pl. malaria, common to which there was a severe course, complicated by acute renal failure and hemolytic anemia. In a detailed analysis of both clinical cases, Patient 1 had acute kidney damage arose after the increase of anemia and thrombocytopenia, in combination with hemoglobinuria. This shows that the leading mechanism of kidney injure in this case is acute tubular necrosis, due to the toxic effects of free hemoglobin and sequestration in the capillaries of the glomerulus. A Patient 2 had a significant increase of anemia after appears of acute kidney damage; there was no hemoglobinuria, however, significant leukocytosis was observed. It seems, that the leading mechanism in this case is immune-mediated kidney injure or due to hypoperfusion of kidney tubules with the development of acute interstitial nephritis or immune complex glomerular injure with the development of glomerulonephritis, or a combination of them. A detailed analysis of the described two clinical cases of severe malaria caused by Pl. falciparum and Pl. malaria, respectively, and complicated by acute renal failure and hemolytic anemia, suggests that the pathogenetic mechanisms and severity of kidney damage depend on the type of malaria.

GLYCOGEN STORAGE DISEASE TYPE II: A NARRATIVE LITERATURE REVIEW AND A CASE REPORT OF LATE-ONSET POMPE DISEASE IN A YOUNG WHITE CHILD.

At all ages, skeletal muscle weakness characterizes Pompe disease, causes mobility problems and affects the respiratory system. We aimed to provide a narrative review of terminology, etiology, epidemiology, clinical manifestations, complications, and prognosis of Pompe disease, supported with a clinical case presentation. The clinical manifestation and complications of Pompe disease are illustrated with the clinical case presentation of a late-onset form in a white child. A comprehensive electronic literature search was performed on Ovid, Google Scholar, Scopus, PubMed, Embase, Cochrane Database, and World Health Organization databases to identify the articles that discussed Pompe disease.

EFFICACY OF SPECIFIC PREVENTION OF INFLUENZA IN INDIVIDUALS WITH POLYMORPHISMS ARG753GLN OF TLR-2, LEU412PHE OF TLR-3, ASP299GLY OF TLR-4 GENES.

OBJECTIVE: The aim: Is to study the efficacy of influenza vaccination for individuals with polymorphism Arg753Gln of TLR-2 gene, Leu412Phe of TLR-3 gene, and Asp299Gly of TLR-4 gene. PATIENTS AND METHODS: Materials and methods: 66 people with mutant genotypes and normal distribution of alleles of TLR-2, TLR-3, TLR-4 genes, aged 18-63, were inoculated with anti-influenza vaccine. The genotyping of Arg753Gln polymorphic site of TLR-2, Asp299Gly of TLR-4, and Leu412Phe of TLR-3 gene was carried out by polymerase chain reaction with oligonucleotide primers usage. The immunological efficacy of vaccination was evaluated by seroconversion, seroprotection, and dynamics of mean geometric titers of antibodies. RESULTS: Results: It has been established that individuals with mutant genotypes Arg/Gln of TLR-2, Leu/Phe, Phe/Phe of TLR-3, Asp/Gly of TLR-4 genes have a vaccinal response to administering anti-influenza vaccine at the level of subjects with normal distribution of TLR alleles, as evidenced by the growth in dynamics of mean geometric titers of antibodies to vaccine strains, the level of seroprotection and seroconversion. Clinical and epidemiological efficacy of vaccination in this category of people is characterized by: reduction of ARI cases in the postvaccinal period by 2,0-3,0 times; prevention of pneumonia in all vaccinated subjects; decrease in the frequency of bronchitis by 2,5-3,8 times. CONCLUSION: Conclusions: Effectiveness of influenza vaccination in individuals with Arg573Gln polymorphism of TLR-2, Leu412Phe of TLR-3, Asp299Gly of TLR-4 genes by immune and clinical epidemiological parameters is determined at the level of vaccinated subjects with normal distribution of TLR-2, TLR-3, TLR-4 alleles. Specific influenza immunization of people with polymorphic modified genotypes of TLR-2, TLR-3, TLR-4 genes can prevent the development of pneumonia and reduce the incidence of bronchitis.

Some clinical and epidemiological features of influenza-associated pneumonia depending on the etiological agent.

OBJECTIVE: The aim: To analyze the epidemiological data and clinical course of pneumonia as a complication of influenza in the Poltava region, depending on the etiological agent. PATIENTS AND METHODS: Materials and methods: We have analysed the data of the official reporting documentation provided by the State Institution "Poltava Regional Laboratory Center of the Ministry of Health of Ukraine" and the chart of patients with a laboratory confirmed diagnosis of influenza who were in inpatient treatment at the Poltava Regional Clinical Infectious Hospital (PRCIH) in 2016-2018 years. In more detail, we examined 95 patients with pneumonia, which complicated the course of the flu. There were 43 (45.26%) female patients, - 52 (54.74%) male patients, aged 18 to 80 years. RESULTS: Results: Studies have shown that despite a decrease in the incidence of influenza in recent years, the incidence of pneumonia, which complicated the course of the flu, remained consistently high (19.7% - 20.8%) with bacteriological isolation of S.pneumoniae (22.11%), S.aureus (13.68%), Haemophilus influenza (4.21%) and E.coli (3.16%). Severe course of pneumonia with bloody sputum, evident shortness of breath, bilateral lung damage, and need for oxygen support were significantly more frequently reported in patients with isolated S.pneumoniae and S.aureus. However, the severe course of the disease with the formation of abscesses in the lungs was observed only in the group S.aureus despite the relatively young age of such patients and significantly fewer risk factors for severe influenza and comorbidities. CONCLUSION: Conclusions: The study showed a consistently high incidence of pneumonia, which complicated the flu and caused by S.pneumoniae, S.aureus, Haemophilus influenza and E.coli. Pneumonia caused by S.pneumoniae and S.aureus, were characterizedthe most severe course; however, a severe course with the formation of abscesses in the lung tissue was observed only in the group of S.aureus.

Genetic polymorphism ARG753GLN of TLR-2, LEU412PHE of TLR-3, ASP299GLY of TLR-4 in patients with influenza and influenza-associated pneumonia.

OBJECTIVE: The aim of the research is to study the prevalence and to determine the prognostic significance of polymorphism ARG753GLN of the TLR-2 gene, Leu412Phe of TLR-3, Asp299Gly of TLR-4 in influenza. PATIENTS AND METHODS: Materials and methods: 112 patients with influenza were examined (63 patients with uncomplicated course and 49 with influenza-associated pneumonia). The genotyping of the polymorphic site of ARG753GLN of the TLR-2 gene, Asp299Gly of the TLR-4 gene, and Leu412Phe of the TLR-3 gene was carried out by polymerase chain reaction using oligonucleotide primers. RESULTS: Results: It has found that the prevalence of the mutant allele 299Gly of TLR-4 in patients with uncomplicated influenza is 6.4 %, with influenza- associated pneumonia - 7.1 %, which exceeds the population control indicators by 3.8-4.3 times (1.7 %, p<0.05). Mutant allele 412Phe of TLR-3 is significantly more common in patients with influenzaassociated pneumonia (42.9%), as compared with uncomplicated influenza (24.6%, p<0.01) and healthy people (30.0%, p<0.05). The increased risk of influenza development is associated with the Asp/Gly genotype of TLR-4 (OR=4.22) and combination of mutant genotypes Leu/Phe and Phe/Phe of TLR-3 with Asp/Gly of TLR-4 and Arg/Gln of TLR-2 (OR=15.0); influenza-associated pneumonia - with genotype Phe/Phe of TLR-3 (OR=4.5). CONCLUSION: Conclusions: It has been found out that among patients with influenza and influenza-associated pneumonia, the mutant allele 299Gly of TLR-4 and combinations of polymorphisms Arg753Gln of TLR-2, Leu412Phe of TLR-3, Asp299Gly of TLR-4 are detected reliably more often. The frequency of the mutant allele 412Phe of TLR-3 is higher among patients with influenza-associated pneumonia. Markers of increased risk of influenza are 299Gly allele and genotype Asp/Gly of TLR-4 and the combination of mutant genotypes Leu/Phe and Phe/Phe of TLR-3 with Asp/Gly of TLR-4 and Arg/Gln of TLR-2; for influenza-associated pneumonia - allele 412Phe and genotype Phe/Phe of TLR-3.

TLR4 and TLR7 genetic polymorphism in patients with HIV/HCV-coinfection: prevalence and gender-related features.

OBJECTIVE: Introduction: HIV-infection and chronic hepatitis C is of great concern of current infectology. The paper is aimed at the study of the prevalence of the of TLR4 gene Gly and TLR7 gene Leu polymorphic alleles among patients with HIV/HCV-coinfection in general and with regard to gender, as well as to determine their role in the development of the infection. PATIENTS AND METHODS: Materials and methods: To achieve the objective of the research a cohort and case-control study has been carried out. The total of 535 people has been examined, including: HIV/HCV-coinfected - 104, HIV-monoinfected - 90, patients with chronic hepatitis C - 166 and almost healthy people (population control group) - 175 subjects. RESULTS: Results and conclusion:The study found thatthe prevalence of the TLR4 gene Gly polymorphic allele among patients with HIV/HCV-coinfection, HIV-monoinfection and chronic hepatitis C accounted for 23.1 %, 14.4 % and 14.5 %, respectively, which is significantly higher than the similar index in controls - 3.3 %. The presence of the TLR4 gene Gly polymorphic allele in the genome increases the risk of HIV/HCV-coinfection development, in case of infection, by 9 (OR=8.70, р=0.000), HIV-monoinfection and chronic hepatitis C by 5 times (OR=4.89, р=0,016 and OR=4.9, р=0.011, respectively). TLR7 gene Leu polymorphic allele is recorded with the frequency of 19.9-26.0 % in patients with HIV/HCV-coinfection, HIV-monoinfection and chronic hepatitis C as compared to controls (25.9 %). In female patients with HIV/HCV-coinfection, HIV-monoinfection, chronic hepatitis C and healthy individuals the TLR7 gene Leu polymorphic allele is recorded by 2.1-3.6 times more frequently than in male patients.