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Background & Aim: The new UCOE models we have recently developed, tested on many cell groups (including mouse ES and human iPS cells) and human mAb recombinant production studies as well, shows a powerful resistance to DNA methylation- mediated silencing and provides a higher and stable transfection profile. By the urgent need of vaccine development for COVID-19 during the pandemic, in this study we aimed to produce a potential recombinant vaccine by using the new generation UCOEs models of our own design. Methods, Results & Conclusion(s): Existing new-generation UCOE models and standard plasmid vectors to be used as control group were provided. Then, the sequences related to the PCR method were amplified for sufficient stock generation and cloning experiments. Verification in the plasmid vector was carried out in gel electrophoresis. Transfection of 293T cells was performed with clone plasmids carrying antigen genes and plasmids carrying genetic information of lentivirus units for the production of lentiviral vectors. Afterwards, 293T cells produced lentiviral vectors carrying antigen genes. Harvesting of these vectors was carried out during 48th and 72nd hours. Afterwards, CHO cells were transduced with appropriate quantity of lentiviral vectors. Isolation and purification of targeted proteins from the relevant medium were performed by HPLC and Q-TOF methods. A part of the spike and nucleocapsid gene sequences of COVID-19 were firstly cloned into our UCOE models. These UCOEs plasmids were then transferred into 293T cells along with plasmids carrying the genes that will form the lentivirus vectors (LVs). After harvesting and calculation of LV vector titers, the cloned vectors were then transfected into the CHO cells which the targeted recombinant production of the antigen proteins will be carried out. Antigenic structures were then isolated from the culture medium of CHO cells in following days for confirmation. Using HPLC and qTOF mass spectrometer methods, these structures in the medium were confirmed to be the units of spike and nucleocapsid proteins of the COVID-19 virus. In order to produce large amount of the recombinant antigens, the culture was then carried out with bioreactors in liters. At the final stage, these recombinantly produced antigen proteins were tested on rats to measure their immunogenic responses, and the study recently been completed successfully as a potential recombinant vaccine against COVID-19.Copyright © 2023 International Society for Cell & Gene Therapy
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This journal issue includes s of papers presented at the conference. Topics discusses are: stillbirth during a pandemic;analysis of the female genital tract (FGT) metabolome;effectiveness of REGEN-COV antibody combination to reduce risk of hospitalization;patterns of nucleic acid amplification testing;delta variant neutralizing antibody response following maternal COVID19 vaccination;integrated prenatal and hepatitis c virus care increases linkage;extended interval gentamicin dosing in obstetrics;maternal and infant cytomegalovirus detection among women living with HIV.
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This special issue contains 13 articles that discuss public health articles such as public perception, knowledge and factors influencing COVID-19 vaccine acceptability, determinants of enrolment in health insurance scheme among HIV patients, hypertension and associated factors among patients attending HIV clinic, determinants of visit-to-visit systolic blood pressure variability among Ghanaians with hypertension and diabetes mellitus, short-term outcomes among patients with subclinical hypothyroidism, association of erectile dysfunction with coronary artery disease, psychological correlates of COVID safety protocol adherence, ophthalmic services utilisation and associated factors, safe duration of silicon catheter replacement in urological patients, and leadership in health and medical education.
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These proceedings comprise 85 articles spanning diverse fields such as bacteriology, molecular biology, biotechnology, dermatology, infectious and parasitic diseases, epidemiology, physiotherapy, immunology, mycology, parasitology, pathology, collective health, and virology. The articles delve into a wide range of research topics, from repurposing drugs for Mycobacterium abscessus complex infections to utilising artificial intelligence for SARS-CoV-2 diagnosis. In bacteriology, investigations explore the correlation between smoking and Helicobacter pylori infection in gastric adenocarcinoma patients, as well as the resistance profiles of Staphylococcus aureus and Pseudomonas aeruginosa in tracheostomised children. Molecular biology studies focus on gene polymorphisms related to diseases like paracoccidioidomycosis. Biotechnology research emphasises bioactive molecules in species like Croton urucurana and the development of computational models for cytotoxicity prediction. Dermatology articles address stability characterisation in vegetable oil-based nanoemulsions. The section on infectious and parasitic diseases encompasses studies on COVID-19 vaccine response in pregnant women and the impact of infection prevention measures in rehabilitation hospitals. Epidemiology investigations analyse trends in premature mortality, tuberculosis in diabetic patients, and public adherence to non-pharmacological COVID-19 measures. Physiotherapy research covers topics such as telerehabilitation through a developed game and the prevalence of congenital anomalies. Immunology studies explore immune responses in HIV and Leishmaniasis, whilst mycology investigates the biotechnological potential of fungi from the cerrado biome. Parasitology research evaluates treatment efficacy against vectors parasites such as Aedes aegypti and Toxoplasma gondii. Pathology articles discuss intentional intoxication in cattle and the influence of curcumin on acute kidney injury therapy. Collective health studies focus on intervention plan development in healthcare settings and pesticide use in horticulture. Lastly, virology research investigates parvovirus occurrence in hospitalised children during the COVID-19 pandemic, hidden hepatitis B virus infection in inmates, and the prevalence of HPV and HTLV-1/2 infections in specific populations.
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This journal issue includes 15 articles that discuss continent-wide evolutionary trends of emerging SARS-CoV-2 variants;use of convalescent plasma therapy in hospitalised adult patients with non-critical COVID-19;evidence for preserved insulin responsiveness in the aging rat brain;SARS-CoV-2 infection in HIV-infected patients;different patterns of excess all-cause mortality by age and sex in Hungary during the 2nd and 3rd waves of the COVID-19 pandemic;mutational landscape of the newly emerging Omicron (B.1.1.529) variant and comparison of mutations with VOCs and VOIs.
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Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel and highly pathogenic coronavirus and is the causative agent of COVID-19, an ongoing pandemic that has posed a serious threat to public health and global economy. Thus, there is a pressing need for therapeutic interventions that target essential viral proteins and regulate virus spread and replication. To invade the host cell, the receptor-binding domain (RBD) of SARS-CoV-2 Spike protein binds to the host cell's ACE2 receptor, followed by cleavage events that allow the Spike protein to fuse with the host cell membrane. Thus, the essential role of Spike protein in ACE2 receptor binding and viral fusion makes it a prime target for therapeutic interventions. Method(s): We performed molecular docking and molecular dynamics (MD) simulation-based virtual screening against SARS-CoV-2 RBD/ACE2 interface using a commercial library of 93,835 drug-like compounds. Compounds with promising docking poses and scores were selected for further MD simulation refinement, from which ten lead compounds were identified. Antiviral potencies of ten lead compounds were evaluated against lentiviral vectors pseudotyped with SARS-CoV-2 Spike to down select to a single lead compound, SAI4. ELISA-based assays were employed to determine the binding affinities of SAI4 to recombinant SARS-CoV-2 RBD. Antiviral potential of SAI4 was validated against genuine SARS-CoV-2 in a BSL3 setting. Result(s): We identified SAI4 as a candidate small molecule, which inhibited SARS-CoV-2 pseudovirus entry with IC50 value of ~18 muM. We determined that SAI4 binds RDB with a Kd of ~20 muM. Using cells engineered to express ACE2 and cells that express physiological levels of ACE2, we found that SAI4 inhibited SARS-CoV-2 pseudovirus entry at both engineered and physiological ACE2 levels. We validated the antiviral potential of SAI4 against genuine SARS-CoV-2 and HCoV-NL63. Lastly, we demonstrated antiviral potential of SAI4 against four SARS-CoV-2 variants of concern (alpha, beta, gamma, and delta). Conclusion(s): Using virtual screening, we identified SAI4 as the promising hit compound which displayed inhibitory activities against SARS-CoV-2 entry and its four variants of concern. Thus, our study will pave the way for further development of small molecules for therapeutic targeting of SARS-CoV-2 entry to combat the COVID-19 pandemic.
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In 2021, 6.5 million cases of tuberculosis (TB) were reported globally;however, the WHO estimates that 10.6 million people (134/ 100,000) developed the condition. As many as 1.6 million people (20/100,000) died of TB. The increase in TB mortality to the 2017 level may be explained by worse access to the diagnosis and treatment of TB due to the COVID-19 pandemic. In Europe, TB primarily affects vulnerable populations such as migrants, homeless people, prisoners or HIV-positive persons. The WHO estimates the incidence of TB in Ukraine to be 71/ 100,000. Approximately a third of cases are multidrug-resistant and one in five patients is HIV-positive. The Czech Republic is among countries With the lowest TB rates globally. In 2021, 357 cases (34/100,000) were reported to the national TB registry. Data for 2022 are not available as yet but the total number of TB cases is expected to rise in the Czech Republic, resulting from more reported cases of TB in Ukrainians due to the war in Ukraine. Fortunately, TB rates in Ukrainian refugees are considerably lower than those estimated When the war started.
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Many studies have dealt with the medicinal properties of Jatropha curcas;however, there are limited studies on the scope of its antiviral potential. This is a fact associated with the current challenges posed by HIV-AIDS and COVID-19, which has reinforced the need to expand the knowledge about its antiviral resource. Based on the search for natural products with anti-HIV-1 and anti-SARS-CoV-2 activities, this work analyzed the extract of J. curcas seed, the structure of the plant whose antiviral references were not found in the literature, and the compounds that can potentiate it as a candidate for herbal medicine. GC-MS analysis was used to screen for the active substances of the J. curcas seeds, and the literature was searched to find those with anti-HIV-1 and anti-SARS-CoV-2 indication. The results showed they have 27 compounds, of which glycerol 1-palmitate, stigmasterol and gamma-sitosterol were shown to have antiviral action in the literature. Regarding glycerol 1-palmitate, no detailed description of its antiviral action was found. Stigmasterol and gamma-sitosterol act as anti-HIV-1 and anti-SARS-CoV-2, respectively, inhibiting the reverse transcriptase of HIV-1, the proteases 3CLpro, PLpro and the spike proteins of SARS-CoV-2. However, despite the fact that the extract of J. curcas seeds consist of antiviral compounds that fight against the etiological agents of HIV-AIDS and COVID-19, it is concluded that there is a need to deepen this evidence, by in vitro and in vivo assays.
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SARS-like coronaviruses, including SARS-CoV and SARS-CoV-2, encode spike proteins that bind human ACE2 protein on the cell surface to enter target cells and cause infection. The efficiency of virus entry depends on ACE2 sequence and expression levels in target cells. A small fraction of humans encodes variants of ACE2, thus altering the biochemical properties at the protein interaction interface. All humans possess cells with vastly differing amounts of ACE2 on the cell surface, ranging from cell types with high expression in the gut and lungs to lower expression in the liver and pancreas. Mastering our understanding of spike-ACE2 interaction and infection requires experiments precisely perturbing both variables. Thus, we developed a synthetic cell engineering approach compatible with high throughput assays for pseudo-typed virus infection. Our assay system is capable of assessing both variables individually and in combination. We adapted an engineered HEK293T DNA recombinase landing pad cell line capable of expressing transgenic ACE2 sequences at highly precise levels. Infection with lentiviruses pseudotyped with the spikes of SARS-like coronaviruses revealed that high ACE2 abundance could mask the effects of impaired binding thereby making it challenging to know the role of affinity altering mutations during infection. We limited the ACE2 abundance on the cell surface by expressing transgenic ACE2 behind a suboptimal Kozak sequence, thereby altering its protein translation rate. This allowed us to understand how ACE2 sequence could impact its interaction with coronavirus spike proteins as two human ACE2 variants at the binding interface, K31D and D355N, exhibited reduced infection. Our experiments suggested that we need to better understand how ACE2 expression determines the susceptibility of cells for SARS-like coronavirus binding and infection. We thus created an ACE2 Kozak library consisting of ~4,096 Kozak variants, each conferring a different ACE2 protein translation rate thus resulting in a range of ACE2 steady-state abundances. Combining fluorescence-activated cell sorting and high-throughput DNA sequencing (FACS-seq) revealed the library to span two orders of magnitude of ACE2 abundance. Challenging this library of cells with spike pseudotyped lentiviruses revealed how ACE2 abundance correlated with infection rate. The library-based experiments yielded a dynamic range wider than traditional single sample infection assay, likely more representative of infection dynamics in vivo. Now that we have characterized the impacts of ACE2 abundance on infectivity in engineered cells, our next goal is to expand the comparison to physiologically relevant cells with endogenously expressed proteins. Modulating protein abundance levels will be key to creating maximally informative functional assays for any protein in cell-based assays, and we have laid the groundwork for being able to simultaneously test the impacts of protein abundance and sequence in combination for proteins involved in diverse cellular processes. This research was supported by a National Institute of Health (NIH) grant GM142886 (KAM).Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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Background: The continued emergence of severe acute respiratory syndrome coronaviruses (SARS-CoVs) and recent explosion of the SARS-CoV-2 pandemic highlights the need for broad and potent antibody recognition and understanding the contexts in which they may develop. Antibodies with cross reactivity across SARS lineages may be of particular value in preparing for future outbreaks of new sarbecoviruses. Method(s): We isolated monoclonal antibodies (mAbs) from an individual 60-days post-vaccination, 30-days post Delta-infection. Reconstructed antibodies were screened for binding to a panel of prefusion-stabilized Spike trimers from SARS-CoV-2 and other beta-coronaviruses using enzyme-linked immunosorbent assay (ELISA). Neutralization potency and breadth was assessed using a spike-pseudotyped lentivirus neutralization assay. Additionally, epitope and escape mutant profiling was conducted by deep mutational scanning (DMS) to identify mutations that affect antibody binding. Lastly, binding breadth was further evaluated using a yeast display library of RBDs from SARS-CoV-2 variants and related sarbecoviruses. Result(s): We identified several SARS-CoV-2-specific mAbs that neutralized SARS-CoV-2 variants of concern (VOCs) and SARS-CoV-1. Notably, two of these mAbs (C68.61 and C68.185) neutralized SARS-CoV-1 with an IC50 = 307 and 139 ng/mL (respectively) that is similar to or better than the potency of S309 (IC50 = 206 ng/mL) and CR3022 (IC50 = 981 ng/mL), which are mAbs isolated from individuals with SARS-CoV-1 infections. C68.61 also neutralized all Omicron VOCs tested and retained neutralization activity against currently circulating variants BQ1.1 (IC50=790 ng/ml) and XBB (IC50=590 ng/ml). Key C68.61 mAbescape mutations identified by DMS in the Omicron BA.2 background yeast display library included sites K462, E465, R466, and I468, which are conserved sites across all VOCs and SARS-CoV-1. The isolated mAbs displayed crossreactive binding to RBDs from diverse SARS-CoV-1-related CoVs and African and European sarbecovirus isolates as well as SARS-CoV-2 VOCs. Conclusion(s): Here we describe mAbs from a SARS-CoV-2-infected individual that bound and neutralized both SARS-CoV-2 and SARS-CoV-1, including one that showed breadth across recent VOCs. Given their breadth, these SARS-CoV-2 cross-reactive mAbs may be robust to viral escape and thus could contribute to therapeutic efforts. In addition, these mAbs displayed broad cross-reactive activity across sarbecoviruses and may be beneficial against future spillover events.
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Background and Objectives: * The spike (S) protein of SARS-CoV-2 virus binds to the host cell receptor which facilitates the virus entry. This interaction is primed by host cell proteases like furin and TMPRSS2 acting at S1/S2 and S2' cleavage sites, respectively. * Both the cleavage sites have Serine and Proline residues conversed in all the coronaviruses. It has been speculated that mutations at these conserved residues may provide a gain-offunction, easing the SARS-CoV-2 entry into the host cell and cellto- cell spread, thus modulating the virulence and pathogenicity. * Unravelling the effects of these conserved residues in the S protein cleavage site in virus entry and transmission might facilitate development of novel therapeutics. Material(s) and Method(s): * This study employed a lentivirus based pseudovirus (PSV) system, where P and S residues at S1/S2 site of Spike gene, present in an expression vector, were mutated to Alanine (Fig A). * We then assessed the expression of the SARS-CoV-2-S variants in HEK293T cells and tested the infectivity and fusogenicity of mutant PSV and spike, respectively in the presence or absence of S1/S2 and S2' protease inhibitors. Results and Conclusion(s): * Conserved Serine residue mutation (S2SA) at S2' cleavage site resulted in complete loss of spike cleavage by furin and cathepsins (Fig B). * TMPRSS2 protease treatment was not able to rescue loss of spike cleavage and fusogenicity (Fig C & D). * S2SA mutant showed no significant response against E-64d and TMPRSS2 inhibitor. * Serine at S2' site in spike protein provides an ideal site to be further evaluated for the therapeutic purpose against SARS-CoV- 2.
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The article is devoted to the global problems of modern medicine - HIV infection and the COVID-19 pandemic. The review of the literature highlights current ideas about the pathogenesis and course of COVID-19 in patients with HIV infection, and also touches upon the problems of concomitant pathology and mental health of patients with HIV in the setting of the COVID-19 pandemic. It has been shown that HIV-positive patients are a risk group for the severe course of COVID-19, in particular, individuals with severe immunodeficiency (CD4+ T lymphocytes 200 cells/l) due to the development of synergetic lung damage by SARS-CoV-2 and secondary infectious agents such as cytomegalovirus and Pneumocystis carinii. It has been proven that one of the targets of the SARS-CoV-2 virus is CD4+ T cells, which in COVID-19 leads to a more rapid progression of immunodeficiency in patients with HIV infection and, thus, significantly increases the risk of secondary diseases and death. Particular attention should be paid to middle-aged and elderly people living with HIV, who, compared with HIV-negative patients, are more likely to have concomitant pathology - arterial hypertension, cardiomyopathy and diabetes mellitus, which are the risk factors for severe COVID-19. The results of studies on the effect of antiretroviral drugs on the course of COVID-19 showed that HIV-infected patients receiving tenofovir + emtricitabine have a lower risk of severe COVID-19 and associated hospitalization than patients receiving other HIV treatment regimens. Clinical and preclinical data support the potential use of tenofovir in the treatment of novel coronavirus infection.
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Background: While remarkable and rapid progress was made in fighting the SARS-CoV-2 pandemic with vaccines and therapeutic antibodies, these approaches were quickly compromised by viral evolution. Therapeutic monoclonal antibodies (mAbs) that were once authorized for clinical use, which all target the receptor binding domain (RBD), are no longer effective against current variants of concern (VOCs) due to mutations in this region of Spike. Thus, to achieve durable protection against SARS-CoV-2, novel mAbs need to show breadth and potency across VOCs and target epitopes that are more constrained. Method(s): mAbs from an individual who had a breakthrough Delta VOC infection after vaccination were isolated from Spike-specific memory B cells. mAbs were assessed for binding affinity and neutralization potency using Spike-pseudotyped lentivirus (PSV) and live SARS-CoV-2 virus neutralization assays. Epitopes were mapped using deep mutational sequencing (DMS) and structural-based methods. Result(s): Three novel mAbs (C68.3, C68.13, C68.59) demonstrated binding breadth to Spikes from various VOCs including Omicron VOCs despite that C68 had not yet been exposed to Omicron. These mAbs potently neutralized the Wuhan-Hu-1 vaccine and Delta strains (IC50 = 9-61ng/mL), and early Omicron strains BA.1, BA.2, BA.5 (IC50 = 12-149 ng/mL). C68.3 and C68.59 retained potency against recent VOCs BQ.1.1 and XBB (IC50 = 121-122 ng/mL and 56-82 ng/mL, respectively) in the PSV assay. Similar neutralization activity was observed in the live virus assay. The potency of these mAbs was greater against Omicron VOCs than all but one of the mAbs previously authorized for treatment and they showed greater breadth. The mAbs target distinct epitopes on the Spike glycoprotein, two in the RBD (C68.3, C68.13) and one in an invariant region downstream of RBD in subdomain 1 (SD1) (C68.59). Structural analysis of C68.59 Fab binding to Spike trimer revealed significant allosteric changes to regions of Spike outside of the epitope in the S2 unit. Finally, DMS escape pathways showed these mAbs target regions highly conserved across VOCs that are also functionally constrained, suggesting escape could incur a fitness cost. Conclusion(s): Overall, these mAbs are novel in their breadth across VOCs and include a potent mAb targeting a rare epitope outside of the RBD in SD1. These mAbs focus on diverse, functionally constrained regions in Spike making them candidates for development as combination therapeutics with good durability against future VOCs.
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The emergence of the human immunodeficiency virus (HIV) in the 1980s brought ethical conflicts that meant a bioethics challenge. Among others, issues of confidentiality, stigmatization, justice, duty of care and investigation arose. Bioethical reflection had been focused on conflicts involving respect for individual autonomy, nevertheless HIV highlighted the needs of the community. Almost four decades later, the COVID-19 pandemic has brought the ethical conflicts typical of public health back to the bioethical scene. Quarantines, various restrictions on mobility, the obligation of masks, poorly protected health care, rationing of scarce resources, rushed research, the vaccines allocation, stigmatization and discrimination, the immune passport, or the moralization of infectious disease have highlighted the need for an ethical framework that helps to reflect and justify public health decisions. In this article we review and analyze the ethical conflicts that arose with HIV and how they have reappeared and been reinterpreted with the COVID-19 pandemic.
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BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects humans' lower respiratory tracts and causes coronavirus disease-2019 (COVID-19). Neutralizing antibodies is one of the adaptive immune system responses that can reduce SARS-CoV-2 infection. This study aimed to develop a SARS-CoV-2 neutralization assay system using pseudo-lentivirus. METHODS: The plasmid used for pseudo-lentivirus production was characterized using restriction analysis. The gene encoding for SARS-CoV-2 spike protein was confirmed using sequencing. The transfection pseudolentivirus optimal condition was determined by choosing the transfection reagents and adding centrifugation step. Optimal pseudo-lentivirus infection was analysed using fluorescent assay and luciferase assay. The optimal condition of pseudo-lentivirus infection was determined by the target cell type and the number of pseudo-lentiviruses used for neutralization test. SARS-CoV-2 pseudo-lentivirus was used to detect neutralizing antibodies from serum samples. RESULTS: The plasmid used for pseudo-lentivirus production was characterized and confirmed to have no mutations. Lipofectamine 2000 reagent generated pseudolentivirus with a higher ability to infect target cells, as indicated by a percentage green fluorescent protein (GFP) of 12.68%. Pseudo-lentivirus centrifuged obtained more stable results in luciferase expression. Optimal pseudo-lentivirus infection conditions were obtained using puromycinselected HEK 293T-ACE2 cells as target cells. The number of pseudo-lentiviruses used in the neutralization assay system was multiplicity of infection (MOI) 0.075. Serum A samples with a 1:10 dilution had the highest neutralizing antibody activity. CONCLUSION: This study shows that SARS-CoV-2 neutralization assay system using pseudo-lentivirus successfully detected neutralizing antibodies in human serum, which were indicated by a decrease in the percentage of pseudo-lentivirus infections. © 2023 The Prodia Education and Research Institute
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Background: Coronavirus disease 2019 or known as COVID-19 is a disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2). Comorbidities that are risk factors for COVID-19 death include hypertension, diabetes, heart disease, COPD, HIV (Human Immunodeficiency Virus), kidney failure, and cancer. This study aims to estimate the magnitude of the risk of death in COVID-19 patients with comorbid HIV, with a meta-analysis of the primary studies conducted by the previous authors. Subjects and Method: This study is a systematic review and meta-analysis with the following PICO, population: COVID-19 patients. Intervention: HIV comorbidity. Comparison: without co-morbid HIV. Outcome: Mortality. The articles used in this study were obtained from four databases, namely PubMed, Google Scholar, Springerlink, and Science direct, using the search keys "HIV/AIDS" AND "Mortality" OR "death" AND "COVID-19 OR SARS-CoV-2. The included article is a full-text English language with a cohort study design from 2020 to 2021 and reports the adjusted Odds Ratio (aOR) in a multivariate analysis. Article selection is done by using PRISMA flow diagram. Articles were analyzed using the Review Manager 5.3 application. Results: A total of 9 cohort studies involving 3,397,186 COVID-19 patients from America, Europe, and Africa were selected for a systematic review and meta-analysis. The data collected showed that COVID-19 patients with HIV comorbidities had a mortality risk of 3.30 times compared to COVID-19 patients without HIV comorbidities (aOR = 3.30;95% CI = 2.87 to 3.81;p<0.001). Conclusion: HIV increases mortality risk in COVID-19 patients.
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Objective: To understand the awareness level towards coronavirus disease 2019(COVID-19) prevention and the willingness to receive COVID-19 vaccine among people living with HIV/AIDS, and to discuss the related factors. Methods: A questionnaire survey was conducted among people living with HIV/AIDS who visited the HIV clinic in the PLA General Hospital from June to December 2021.A general descriptive analysis, univariate and binary logistic regression analysis were performed to analyze data. Results: A total of 169 questionnaires were analyzed. Among them, 93.5%(158/169) would like to know more about COVID-19 related knowledge, 88.2%(149/169) were reminded to inject vaccine, 98.8%(167/169) would be far away from medium and high risk areas, 97.0%(164/169) would persuade others to follow the disease preventive requirements, 14.2%(24/169) thought that the propaganda was exaggerated, 30.8%(52/169) were worried about the safety of the vaccine, 80.5%(136/169) thought that they would feel relieved after the vaccination, and 98.2%(166/169) agreed that vaccination was the most effective way to fight against COVID-19. However, only 60.4%(102/169) were willing to receive COVID-19 vaccine. The major factors affecting vaccination intention were age and feeling safe after vaccination. Conclusions: People living with HIV/AIDS are more cautious about COVID-19 vaccination, therefore the coverage rate is relatively low.It is necessary for health providers to understand the specific situation of people living with HIV, and to enhance the heath education on the safety of COVID-19 vaccine especially among people with HIV/AIDS in order to improve the willingness to receive COVID-19 vaccine.
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In 2017, the French National Health Authority (HAS) reassessed its human immunodeficiency virus (HIV) screening strategy and in 2018, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set the goal of screening 95% of people living with HIV by 2030. The HAS recommends an approach based on target population and gives the general practitioner (GP) a key role in its implementation. It is therefore important to facilitate HIV testing by GPs and to reduce missed opportunities. To this end, a pilot study was conducted on a panel of 2,000 GPs over a 10-month period in 2020 in order to evaluate the impact of a pop-up displayed within prescription assistance software reminding about the frequency of targeted screening recommended by the HAS. The pop-up was displayed for patients with a history of sexually transmitted infection and/or hepatitis C and/or tuberculosis in the previous 12 months and without a known HIV serology or diagnosis. The impact was measured by comparing the prospective follow-up of consultations made during the "pilot" in 2020 with the retrospective follow-up of consultations made during the "pre-pilot" period in 2019. The results showed a significant increase in HIV serology prescriptions during the pilot study, despite the COVID-19 pandemic. Difficulties in objectively identifying target patient profiles and in organizing regular follow-ups to HIV testing were also revealed. This pop-up tool represents an additional means of facilitating the prescription of HIV testing by GPs.
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The severity of COVID-19 disease varies substantially between individuals, with some infections being asymptomatic while others are fatal. Several risk factors have been identified that affect the progression of SARS-CoV-2 to severe COVID-19. They include age, smoking and presence of underlying comorbidities such as respiratory illness, HIV, anemia and obesity. Given that respiratory illness is one such comorbidity and is affected by hand hygiene, it is plausible that improving access to hand washing could lower the risk of severe COVID-19 among a population. In this paper, we estimate the potential impact of improved access to hand washing on the risk of respiratory illness and its knock-on impact on the risk of developing severe COVID-19 disease across Zimbabwe. We use a geospatial model that allows us to estimate differential clinical risk at the district level. Results show that the current risk of severe disease is heterogeneous across the country, due to differences in individual characteristics and household conditions. This study demonstrates how household level improved access to handwashing could lead to reductions in the risk of severe COVID-19 of up to 16% from the estimated current levels across all districts. Taken alongside the likely impact on transmission of SARS-CoV-2 itself, as well as countless other pathogens, this result adds further support for the expansion of access to hand washing across the country. It also highlights the spatial differences in risk of severe COVID-19, and thus the opportunity for better planning to focus limited resources in high risk areas in order to potentially reduce the number of severe cases.
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Patients with severe COVID-19-associated pneumonia are at risk to develop pulmonary fibrosis. To study the underlying mechanisms, we aim to develop advanced cell culture models that reliably reflect COVID-19-related profibrotic microenvironment. To identify key cellular players, we performed pilot immunohistochemistry analysis on lung tissue from COVID-19 patients with fibrosis collected during autopsy. Results revealed diffuse alveolar damage with macrophage infiltration, and myofibroblast accumulation with enriched collagen deposition surrounding the damaged alveoli. To mimic SARS-CoV-2 infection in alveoli, we infected human primary type II alveolar epithelial cells (AEC2) and found enhanced signaling of profibrotic cytokine transforming growth factor beta (TGFbeta) in some donors. To recreate the early fibrotic niche, an alveolar-macrophage-fibroblast (AMF) tri-culture model was established. After infecting AEC2 with SARS-CoV-2 in this AMF model, gene expression analysis provided evidence for fibroblast-to-myofibroblast transition. Furthermore, we found that overexpression of SARS-CoV-2 papain-like protease (PLpro) can promote TGFbeta signaling in HEK293T and A549 cells. After infecting AEC2 with SARS-CoV-2 PLpro lentivirus in the AMF model, we found signs of epithelial-to-mesenchymal transition and fibroblast-to myofibroblast transition. In future studies, we will use a detailed analysis of COVID-19-associated lung fibrosis with other types of lung fibrosis, to further refine COVID-19-related fibrosis models, including lung-on-chip models.