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Objective: Spirulina ( arthrospira platensis ) is a cyanobacterium proven to have anti-inflammatory, antiviral, and antioxidant effects. However, the effect of high-dose Spirulina supplementation on hospitalized adults with COVID-19 is currently unclear. This study aimed to evaluate the efficacy and safety of high-dose Spirulina platensis for SARS-CoV-2 infection., Study Design: We conducted a randomized, controlled, open-label trial involving 189 patients with COVID-19 who were randomly assigned in a 1:1 ratio to an experimental group that received 15.2g of Spirulina supplement plus standard treatment (44 non-intensive care unit (non-ICU) and 47 ICU), or to a control group that received standard treatment alone (46 non-ICU and 52 ICU). The study was conducted over six days. Immune mediators were monitored on days 1, 3, 5, and 7. The primary outcome of this study was mortality or hospital discharge within seven days, while the overall discharge or mortality was considered the secondary outcome., Results: Within seven days, there were no deaths in the Spirulina group, while 15 deaths (15.3%) occurred in the control group. Moreover, within seven days, there was a greater number of patients discharged in the Spirulina group (97.7%) in non-ICU compared to the control group (39.1%) (HR, 6.52; 95% CI, 3.50 to 12.17). Overall mortality was higher in the control group (8.7% non-ICU, 28.8% ICU) compared to the Spirulina group (non-ICU HR, 0.13; 95% CI, 0.02 to 0.97; ICU, HR, 0.16; 95% CI, 0.05 to 0.48). In non-ICU, patients who received Spirulina showed a significant reduction in the levels of IL-6, TNF-α, IL-10, and IP-10 as intervention time increased. Furthermore, in ICU, patients who received Spirulina showed a significant decrease in the levels of MIP-1α and IL-6. IFN-γ levels were significantly higher in the intervention group in both ICU and non-ICU subgroups as intervention time increased. No side effects related to Spirulina supplements were observed during the trial., Conclusion: High-dose Spirulina supplements coupled with the standard treatment of COVID-19 may improve recovery and remarkably reduce mortality in hospitalized patients with COVID-19., Clinical Trial Registration: https://irct.ir/trial/54375, Iranian Registry of Clinical Trials number (IRCT20210216050373N1)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Aghasadeghi, Zaheri Birgani, Jamalimoghadamsiyahkali, Hosamirudsari, Moradi, Jafari-Sabet, Sadigh, Rahimi, Tavakoli, Hamidi-Fard, Bahramali, Parmoon, Arjmand Hashjin, Mirzajani, Kouhkheil, Roshangaran, Khalaf, Khademi Nadoushan, Gholamiyan Yousef Abad, Shahryarpour, Izadi, Zendedel, Jahanfar, Dadras, SeyedAlinaghi and Hackett.)

Microbiota and immunity affect the host's susceptibility to SARS-CoV-2 infection and the severity of COVID-19. This study aimed to identify significant alterations in the microbiota composition, immune signaling pathways, their potential association, and candidate microRNA in COVID-19 patients using an in silico study model. Enrichment online databases and Python programming were utilized to analyze GSE164805, GSE180594, and GSE182279, as well as NGS data of microbiota composition (PRJNA650244 and PRJNA660302) associated with COVID-19, employing amplicon-based/marker gene sequencing methods. C1, TNF, C2, IL1, and CFH genes were found to have a significant impact on immune signaling pathways. Additionally, we observed a notable decrease in Bacteroides spp. and Faecalibacterium sp., while Escherichia coli, Streptococcus spp., and Akkermansia muciniphila showed increased abundance in COVID-19. Notably, A. muciniphila demonstrated an association with immunity through C1 and TNF, while Faecalibacterium sp. was linked to C2 and IL1. The correlation between E. coli and CFH, as well as IL1 and Streptococcus spp. with C2, was identified. hsa-let-7b-5p was identified as a potential candidate that may be involved in the interaction between the microbiota composition, immune response, and COVID-19. In conclusion, integrative in silico analysis shows that these microbiota members are potentially crucial in the immune responses against COVID-19., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To date there remains much ambiguity in the literature regarding the immunological interplay between SARS-CoV-2 and HIV and the true risk posed to coinfected individuals. There has been little conclusive data regarding the use of CD4 cell count and HIV viral load stratification as predictors of COVID-19 severity in this cohort., Methods: We performed a retrospective, observational cohort study on people living with HIV (PLWH) who contracted COVID-19 in central and eastern Europe. We enrolled 536 patients from 16 countries using an online survey. We evaluated patient demographics, HIV characteristics and COVID-19 presentation and outcomes. Statistical analysis was performed using SPSS 20.1., Results: The majority of the study cohort were male (76.4%) and 152 (28.3%) had a significant medical comorbidity. Median CD4 cell count at COVID-19 diagnosis was 605 cells/μL [interquartile range (IQR) 409-824]. The majority of patients on antiretroviral therapy (ART) were virally suppressed (92%). In univariate analysis, CD4 cell count <350 cells/μL was associated with higher rates of hospitalization (p < 0.0001) and respiratory failure (p < 0.0001). Univariate and multivariate analyses found that an undetectable HIV VL was associated with a lower rate of hospitalization (p < 0.0001), respiratory failure (p < 0.0001), ICU admission or death (p < 0.0001), and with a higher chance of full recovery (p < 0.0001)., Conclusion: We can conclude that detectable HIV viral load was an independent risk factor for severe COVID-19 illness and can be used as a prognostic indicator in this cohort., (© 2023 British HIV Association.)

The use of a combination of three-drug regimen has improved HIV-1 infected patients' life span and quality; however the emergence of drug-resistant strains remains a main problem. Reverse transcriptase inhibitors (RTIs) consist of a main part of highly active anti-retroviral therapy (HAART) regimen. The present study aimed to investigate resistant mutations to RTI drugs in both treatment naïve and under treatment HIV patients in Mashhad city, north-eastern Iran. RNA was extracted from sera of 22 treatment naïve and 22 under treatment patients. The mean age of under treated and treatment naive groups were 38.5±6.7 and 40.8±7.9 respectively. cDNA was synthesized and amplified with Nested PCR assay targeting specific sequences of RT gene. The PCR products were sent for sequencing. Bidirectional sequencing results were analysed using HIV drug resistance database supplied by Stanford University (HIV Drug Resistance Database, https://hivdb.stanford.edu). Among under treatment patients 10 out of 22 (45%) had at least one high-level resistance mutation which was higher than high level resistance mutation rate among treatment naive cases (P<0.01). Detected resistance mutations were as follows: K101E, K103N, K103E, V106M, V108I, E138A, V179T, Y181C, M184V, Y188L, Y188H, Y188F, G190A, L210W, T215F, T215Y, K219Q, and P225H. A high level of resistance mutations to RT inhibitors was observed that causes drug resistance especially against lamivudine (3TC). Such mutations should be considered as probable responsible for therapeutic failure. Serial surveillance studies of circulating drug resistance mutations are recommended., Competing Interests: The author declared no conflict of interest.

Background: Shigella spp., which are facultative anaerobic bacilli within the Enterobacteriaceae family, present a significant public health burden due to their role as prominent contributors to diarrheal diseases worldwide. A molecular analysis can facilitate the identification and assessment of outbreaks involving this bacterium. So, we aimed to investigate the antibiotic susceptibility pattern and clonal relatedness of clinical Shigella spp. isolates obtained from patients with diarrhea in Hormozgan province, South of Iran., Methods: From 2019 to 2021, a cross-sectional investigation was conducted on 448 stool samples obtained from patients who were experiencing diarrhea, in the southern region of Iran. Shigella spp. isolates were identified based on biochemical and serological tests. All Shigella species were verified using species-specific polymerase chain reaction (PCR), followed by susceptibility testing to antimicrobial agents. Subsequently, genotyping of all Shigella species was conducted using ERIC-PCR., Results: Out of a total of 448 stool samples, the presence of Shigella was detected in 62 cases, accounting for a prevalence rate of 13.84%. Among the identified isolates, the majority were attributed to S. flexneri, representing 53.23% of the cases. This was followed by S. sonnei at 24.19% and S. boydii at 22.58%. Notably, no instances of S. dysenteriae were found. The highest prevalence of Shigella isolates was observed in infants and children under the age of five. A significant proportion of the identified isolates demonstrated resistance to various antibiotics. Specifically, high resistance rates were noted for ampicillin (90.78%), piperacillin-tazobactam (87.1%), cefixime (83.87%), trimethoprim-sulfamethoxazole (83.87%), cefotaxime (82.26%), and ceftriaxone (80.65%). In addition, a substantial number (87.1%) of the isolates exhibited a multidrug-resistant (MDR) phenotype. Using the ERIC-PCR method, a total of 11 clusters and 6 distinct single types were identified among all the Shigella isolates., Conclusion: A notable occurrence of antibiotic-resistant Shigella species has been noted, with multi-drug resistant (MDR) strains presenting an increasing challenge for treating shigellosis worldwide, and this includes Iran. Techniques such as ERIC-PCR are useful for assessing the genetic variation and connections between Shigella strains, which indirectly contributes to understanding antimicrobial resistance patterns. Further research is needed to explore the specific correlation between resistance genes and ERIC genotyping patterns in Shigella strains., (© 2023. The Author(s).)

The procedures currently used for hepatitis B (HB) detection are not suitable for screening, clinical diagnosis, and point-of-care testing (POCT). Therefore, we developed and tested a QCM-based immunosensor by surface modification with AuNP-PEIs to amplify the signal and provide an oriented-immobilization surface. The AuNP-PEIs were characterized by ICP-Mass, UV/Vis, DLS, FE-SEM, and ATR-FTIR. After coating AuNP-PEIs on the gold electrode surface, anti-HBsAg antibodies were immobilized using NHS/EDC chemistry based on response surface methodology (RSM) optimization. The efficiency of the immunosensor was assessed by human sera and data were compared to gold-standard ELISA using receiver-operating-characteristic (ROC) analysis. FE-SEM, AFM, EDS, and EDS mapping confirmed AuNP-PEIs are homogeneously distributed on the surface with a high density and purity. After antibody immobilization, the immunosensor exhibited good recognition of HBsAg with a calibration curve of ∆F =  - 6.910e -7 x + 10(R 2  = 0.9905), a LOD of 1.49 ng/mL, and a LOQ of 4.52 ng/mL. The immunosensor yielded reliable and accurate results with a specificity of 100% (95% CI 47.8-100.0) and sensitivity of 100% (95% CI 96.2-100.0). In conclusion, the fabricated immunosensor has the potential as an analytic tool with high sensitivity and specificity. However, further investigations are needed to convert it to a tiny lab-on-chip for HB diagnosis in clinical samples., (© 2023. The Author(s).)

Introduction: The human gut microbiota plays a crucial role in mental health through the gut-brain axis, impacting central nervous system functions, behavior, mood, and anxiety. Consequently, it is implicated in the development of neuropsychiatric disorders. This study aimed to assess and compare the gut microbiota profiles and populations of individuals with bipolar disorder and healthy individuals in Iran., Methods: Fecal samples were collected from 60 participants, including 30 bipolar patients (BPs) and 30 healthy controls (HCs), following rigorous entry criteria. Real-time quantitative PCR was utilized to evaluate the abundance of 10 bacterial genera/species and five bacterial phyla., Results: Notably, Actinobacteria and Lactobacillus exhibited the greatest fold change in BPs compared to HCs at the phylum and genus level, respectively, among the bacteria with significant population differences. Ruminococcus emerged as the most abundant genus in both groups, while Proteobacteria and Bacteroidetes showed the highest abundance in BPs and HCs, respectively, at the phylum level. Importantly, our investigation revealed a lower Firmicutes/Bacteroidetes ratio, potentially serving as a health indicator, in HCs compared to BPs., Conclusion: This study marks the first examination of an Iranian population and provides compelling evidence of significant differences in gut microbiota composition between BPs and HCs, suggesting a potential link between brain functions and the gut microbial profile and population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rashnaei, Akhavan Sepahi, Siadat, Shahsavand-Ananloo and Bahramali.)

Background: Melanoma differentiation-associated gene 7 (Mda-7) encodes IL-24, which can induce apoptosis in cancer cells. A novel gene therapy approach to treat deadly brain tumors, recombinant mda-7 adenovirus (Ad/mda-7) efficiently kills glioma cells. In this study, we investigated the factors affecting cell survival and apoptosis and autophagy mechanisms that destroy glioma cells by Ad/IL-24., Methods: Human glioblastoma U87 cell line was exposed to a multiplicity of infections of Ad/IL-24. Antitumor activities of Ad/IL-24 were assessed by cell proliferation (MTT) and lactate dehydrogenase (LDH) release analysis. Using flow cytometry, cell cycle arrest and apoptosis were investigated. Using the ELISA method, the tumor necrosis factor (TNF-α) level was determined as an apoptosis-promoting factor and Survivin level as an anti-apoptotic factor. The expression levels of TNF-related apoptosis inducing ligand(TRAIL) and P38 MAPK genes were assessed by the Reverse transcription-quantitative polymerase chain reaction(RT‑qPCR) method. The expression levels of caspase-3 and protein light chain 3-II (LC3-II) proteins were analyzed by flow cytometry as intervening factors in the processes of apoptosis and autophagy in the cell death signaling pathway, respectively., Results: The present findings demonstrated that transduction of IL-24 inhibited cell proliferation and induced cell cycle arrest and cell apoptosis in glioblastoma. Compared with cells of the control groups, Ad/IL24-infected U87 cells exhibited significantly increased elevated caspase-3, and TNF-α levels, while the survivin expression was decreased. TRAIL was shown to be upregulated in tumor cells after Ad/IL-24 infection and studies of the apoptotic cascade regulators indicate that Ad/IL-24 could further enhance the activation of apoptosis through the TNF family of death receptors. In the current study, we demonstrate that P38 MAPK is significantly activated by IL-24 expression. In addition, the overexpression of mda-7/IL-24 in GBM cells induced autophagy, which was triggered by the upregulation of LC3-II., Conclusions: Our study demonstrates the antitumor effect of IL-24 on glioblastoma and may be a promising therapeutic approach for GBM cancer gene therapy., (© 2023. The Author(s).)

Introduction: In the last decade, substantial differences in the epidemiology of, antiretroviral therapy (ART) for, cascade of care in and support to people with HIV in vulnerable populations have been observed between countries in Western Europe, Central Europe (CE) and Eastern Europe (EE). The aim of this study was to use a survey to explore whether ART availability and therapies have evolved in CE and EE according to European guidelines., Methods: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group conducted two identical multicentre cross-sectional online surveys in 2019 and 2021 concerning the availability and use of antiretroviral drugs (boosted protease inhibitors [bPIs], integrase inhibitors [INSTIs] and nucleoside reverse transcriptase inhibitors [NRTIs]), the introduction of a rapid ART start strategy and the use of two-drug regimens (2DRs) for starting or switching ART. We also investigated barriers to the implementation of these strategies in each region., Results: In total, 18 centres participated in the study: four from CE, six from EE and eight from Southeastern Europe (SEE). Between those 2 years, older PIs were less frequently used and darunavir-based regimens were the main PIs (83%); bictegravir-based and tenofovir alafenamide-based regimens were introduced in CE and SEE but not in EE. The COVID-19 pandemic did not significantly interrupt delivery of ART in most centres. Two-thirds of centres adopted a rapid ART start strategy, mainly in pregnant women and to improve linkage of care in vulnerable populations. The main obstacle to rapid ART start was that national guidelines in several countries from all three regions did not support such as strategy or required laboratory tests first; an INSTI/NRTI combination was the most commonly prescribed regimen (75%) and was exclusively prescribed in SEE. 2DRs are increasingly used for starting or switching ART (58%), and an INSTI/NRTI was the preferred regimen (75%) in all regions and exclusively prescribed in SEE, whereas the use of bPIs declined. Metabolic disorders and adverse drug reactions were the main reasons for starting a 2DR; in the second survey, HIV RNA <500 000 c/ml and high cluster of differentiation (CD)-4 count emerged as additional important reasons., Conclusions: In just 2 years and in spite of the emergence of the COVID-19 pandemic, significant achievements concerning ART availability and strategies have occurred in CE, EE and SEE that facilitate the harmonization of those strategies with the European AIDS Clinical Society guidelines. Few exceptions exist, especially in EE. Continuous effort is needed to overcome various obstacles (administrative, financial, national guideline restrictions) in some countries., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Objective: The innate immune response in humans involves a wide variety of factors, including the tripartite motif-containing 5α (TRIM5α) and 22 (TRIM22) as a cluster of genes on chromosome 11 that have exhibited antiviral activity in several viral infections. We analyzed the correlation of the expression of TRIM5α and TRIM22 with the severity of Coronavirus Disease 2019 (COVID-19) in blood samples of 330 patients, divided into two groups of severe and mild disease, versus the healthy individuals who never had contact with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)., Methods: The transcription level of TRIM5α and TRIM22 was determined by quantitative real-time polymerase chain reaction (qPCR). The laboratory values were collected from the patients' records., Results: The expression of both genes was significantly lower in the severe group containing the hospitalized patients than in both the mild group and the control group. However, in the mild group, TRIM22 expression was significantly higher (p <0.0001) than in the control group while TRIM5α expression was not significantly different between these two groups. We found a relationship between the cycle threshold (Ct) value of patients and the expression of the aforementioned genes., Conclusion: The results of our study indicated that lower Ct values or higher RNA viral load might be associated with the downregulation of TRIM5α and TRIM22 and the severity of COVID-19. Additional studies are needed to confirm the results of this study., Competing Interests: Conflict of Interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

Biomarkers-based QCM-biosensors are suitable tools for the label-free detection of infectious diseases. In the current study, a QCM-biosensor was developed for the detection of HBsAg. Briefly, anti-HBsAg antibodies were covalently bound to the primary amines after PEI and thiolated-PEI surface modifications of gold-electrode. After RSM optimization, the statistical analysis revealed no significant difference between the immobilization yields of modified layers. Therefore, the PEI-modified QCM-biosensor was selected for further analysis. The PEI-surface was evaluated by FESEM, AFM, ATR-FTIR, and CA measurement. The surface hydrophilicity and its roughness were increased after PEI-coating. Also, FTIR confirmed the PEI-layering on the gold-surface. RSM optimization increased the antibody immobilization yield up to 80%. The QCM-biosensor showed noteworthy results with a wide dynamic range of 1-1 × 10 3  ng/mL, LOD of 3.14 ng/mL, LOQ of 9.52 ng/mL, and detection capability in human-sera, which were comparable with the ELISA. The mean accuracy of the QCM-biosensor was obtained at 91% when measured by the spike recovery test using human-sera. The biosensor was completely regenerated using 50 mM NaOH and 1% SDS. The benefits provided by the developed biosensor such as broad dynamic range, sensitivity, selectivity, stability, regenerate ability, and low cost suggest its potential application for the non-invasive and timely monitoring of HBV-biomarker., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: One of the problems with treating HIV-infected patients with ARVs is that the treatment can reduce viral load and does not increase the number of CD4 cells (immunological discordance). There are still challenges to treating HIV-positive patients., Aim: This study aimed to investigate the expression level of 18 miRNAs involved in the proliferation and differentiation of CD4 + T cells in a target (discordant immune response) and a control (immune response) group., Methods: In this case-control study, 18 miRNAs were selected and synthesized according to the in-silico analysis and published literatures. RNA extraction was performed from PBMC cells of 30 HIV-1 positive patients in the sample bank. The expression level of microRNAs was calculated by the relative q PCR method (2 -ΔΔCt method), and data were analyzed using GraphPad Prism software version 8.0.2., Results: The results of fold change calculation and statistical analysis showed that the expression levels of miR-30b (p value: 0.01, fold change: 0.23), miR-155 (p value: 0.04, fold change: 0.44), miR-181a (p value: 0.01, fold change: 0.37), and miR-190b (p value: 0.01, fold change: 0.39) had a significant decrease in the target group compared to the control group., Conclusion: In summary, various studies have shown that miRNAs, including miR-30b, miR-155, miR-181a, and miR-190b, are involved in the proliferation, differentiation, and development of CD4 + T cells. One reason for the lack of increase in CD4 + T cells may be the reduced expression of these miRNAs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

For adenoviruses (Ads) to be optimally effective in cancer theranostics, they need to be retargeted toward target cells and lose their natural tropism. Typically, this is accomplished by either engineering fiber proteins and/or employing bispecific adapters, capable of bonding Ad fibers and tumor antigen receptors. This study aimed to present a simple and versatile method for generating Ad-based bionanoparticles specific to target cells, using the SpyTag-SpyCatcher system. The SpyTag peptide was inserted into the HI loop of fiber-knob protein, which could act as a covalent anchoring site for a targeting moiety fused to a truncated SpyCatcher (SpyCatcherΔ) pair. After confirming the presence and functionality of SpyTag on the Ad type-5 (Ad5) fiber knob, an adapter molecule, comprising of SpyCatcherΔ fused to an anti-vascular endothelial growth factor receptor 2 (VEGFR2) nanobody, was recombinantly expressed in Escherichia coli and purified before conjugation to fiber-modified Ad5 (fmAd5). After evaluating fmAd5 detargeting from its primary coxsackie and adenovirus receptor (CAR), the nanobody-decorated fmAd5 could be efficiently retargeted to VEGFR2-expressing 293/KDR and human umbilical vein endothelial (HUVEC) cell lines. In conclusion, a plug-and-play platform was described in this study for detargeting and retargeting Ad5 through the SpyTag-SpyCatcher system, which could be potentially applied to generate tailored bionanoparticles for a broad range of specific targets; therefore, it can be introduced as a promising approach in cancer nanotheranostics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kadkhodazadeh, Mohajel, Behdani, Baesi, Khodaei, Azadmanesh and Arashkia.)

Background: Background: In spite of many reports on persistent low CD4 T cell counts and change in immune-related gene expression level in patients with HIV infection, there is still uncertainty about significant association between gene expression level and HIV infection in patients with and without discordant immune response (DIR). The aim of this study was to compare the expression level of CD4, CCL5, IFN-γ, STAT1, APOBEC3G, CD45, and ICAM-1 genes in HIV-1-positive patients with and without DIR., Methods: Methods: In this study, 30 HIV-1-positive patients (15 patients with and 15 patients without DIR [control group]) were included. PBMCs of the patients were collected through density radient centrifugation with Ficoll-Hypaque. RNeasy Plus Mini kit was used to extract RNA. Relative expression levels of CD4, CCL5, IFN-γ, STAT1, APOBEC3G, CD45, and ICAM-1 genes were evaluated by real-time PCR. The data were analyzed using one-way ANOVA., Results: Results: CD4 T cell counts were significantly lower in DIR patients than the control group (p < 0.01). While there was no significant difference in the relative expression levels of CD4, CCL5, IFN-γ, STAT1, CD45, and ICAM-1 between patients with DIR and control group, APOBEC3G expression level was significantly higher in the patients with DIR as compare to the control group (p < 0.01)., Conclusion: Conclusion: Our findings suggest a significantly higher APOBEC3G expression level in patients with DIR, suggesting the potential role of APOBEC3G in patients with immunological discordance besides its suppressing role in HIV-1 infection. Confirmation of this hypothesis requires further research.

Background: Tripartite motif-containing 28 (TRIM28) is an impressive regulator of the epigenetic control of the antiviral immune response. This study evaluated if the differential expression of TRIM28 correlates with the severity of coronavirus disease 2019 (COVID-19) infection., Methods: A total of 330 COVID-19 patients, including 188 mild and 142 severe infections, and 160 healthy controls were enrolled in this study. Quantitative real-time polymerase chain reaction (qPCR) was used to determine the expression levels of TRIM28 in the studied patients., Results: TRIM28 mRNA levels were significantly lower in both groups of patients versus the control group and in the severe group indicated further reduction in comparison to mild infection. The multivariate logistic regression analysis showed the mean age, lower levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol, lower 25-hydroxyvitamin D, and PCR cycle threshold (Ct) value and higher levels of erythrocyte sedimentation rate (ESR) and differential expression of TRIM28 were linked to the severity of COVID-19 infection., Conclusion: The results of this study proved that the downregulation of TRIM28 might be associated with the severity of COVID-19 infection. Further studies are required to determine the association between the COVID-19 infection severity and TRIM family proteins., (© 2022. The Author(s).)

Chronic kidney disease (CKD) is a significant cause of morbidity and mortality among patients infected with human immunodeficiency virus (HIV). The Central and East Europe (CEE) region consists of countries with highly diversified HIV epidemics, health care systems and socioeconomic status. The aim of the present study was to describe variations in CKD burden and care between countries. The Euroguidelines in the CEE Network Group includes 19 countries and was initiated to improve the standard of care for HIV infection in the region. Information on kidney care in HIV-positive patients was collected through online surveys sent to all members of the Network Group. Almost all centres use regular screening for CKD in all HIV (+) patients. Basic diagnostic tests for kidney function are available in the majority of centres. The most commonly used method for eGFR calculation is the Cockcroft-Gault equation. Nephrology consultation is available in all centres. The median frequency of CKD was 5% and the main cause was comorbidity. Haemodialysis was the only modality of treatment for kidney failure available in all ECEE countries. Only 39% of centres declared that all treatment options are available for HIV+ patients. The most commonly indicated barrier in kidney care was patients' noncompliance. In the CEE region, people living with HIV have full access to screening for kidney disease but there are important limitations in treatment. The choice of dialysis modality and access to kidney transplantation are limited. The main burden of kidney disease is unrelated to HIV infection. Patient care can be significantly improved by addressing noncompliance.

Objectives: The aim of this international multicentre study was to review potential drug-drug interactions (DDIs) for real-life coadministration of combination antiretroviral therapy (cART) and coronavirus disease 2019 (COVID-19)-specific medications., Methods: The Euroguidelines in Central and Eastern Europe Network Group initiated a retrospective, observational cohort study of HIV-positive patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data were collected through a standardized questionnaire and DDIs were identified using the University of Liverpool's interaction checker., Results: In total, 524 (94.1% of 557) patients received cART at COVID-19 onset: 117 (22.3%) were female, and the median age was 42 (interquartile range 36-50) years. Only 115 (21.9%) patients were hospitalized, of whom 34 required oxygen therapy. The most frequent nucleoside reverse transcriptase inhibitor (NRTI) backbone was tenofovir disoproxil fumarate (TDF)/tenofovir alafenamide (TAF) with lamivudine or emtricitabine (XTC) (79.3%) along with an integrase strand transfer inhibitor (INSTI) (68.5%), nonnucleoside reverse transcriptase inhibitor (NNRTI) (17.7%), protease inhibitor (PI) (13.7%) or other (2.5%). In total, 148 (28.2%) patients received COVID-19-specific treatments: corticosteroids (15.7%), favipiravir (7.1%), remdesivir (3.1%), hydroxychloroquine (2.7%), tocilizumab (0.6%) and anakinra (0.2%). In total, 62 DDI episodes were identified in 58 patients (11.8% of the total cohort and 41.9% of the COVID-19-specific treatment group). The use of boosted PIs and elvitegravir accounted for 43 DDIs (29%), whereas NNRTIs were responsible for 14 DDIs (9.5%)., Conclusions: In this analysis from the Central and Eastern European region on HIV-positive persons receiving COVID-19-specific treatment, it was found that potential DDIs were common. Although low-dose steroids are mainly used for COVID-19 treatment, comedication with boosted antiretrovirals seems to have the most frequent potential for DDIs. In addition, attention should be paid to NNRTI coadministration., (© 2021 British HIV Association.)

Introduction: The COVID-19 pandemic has been challenging time for medical care, especially in the field of infectious diseases (ID), but it has also provided an opportunity to introduce new solutions in HIV management. Here, we investigated the changes in HIV service provision across Central and Eastern European (CEE) countries before and after the COVID-19 outbreak., Methods: The Euroguidelines in Central and Eastern Europe Network Group consists of experts in the field of ID from 24 countries within the CEE region. Between 11 September and 29 September 2021, the group produced an on-line survey, consisting of 32 questions on models of care among HIV clinics before and after the SARS-CoV-2 outbreak., Results: Twenty-three HIV centers from 19 countries (79.2% of all countries invited) participated in the survey. In 69.5% of the countries, there were more than four HIV centers, in three countries there were four centers (21%), and in four countries there was only one HIV center in each country. HIV care was based in ID hospitals plus out-patient clinics (52%), was centralized in big cities (52%), and was publicly financed (96%). Integrated services were available in 21 clinics (91%) with access to specialists other than ID, including psychologists in 71.5% of the centers, psychiatrists in 43%, gynecologists in 47.5%, dermatologists in 52.5%, and social workers in 62% of all clinics. Patient-centered care was provided in 17 centers (74%), allowing consultations and tests to be planned for the same day. Telehealth tools were used in 11 centers (47%) before the COVID-19 pandemic outbreak, and in 18 (78%) after ( p = 0.36), but were represented mostly by consultations over the telephone or via e-mail. After the COVID-19 outbreak, telehealth was introduced as a new medical tool in nine centers (39%). In five centers (28%), no new services or tools were introduced., Conclusions: As a consequence of the COVID-19 pandemic, tools such as telehealth have become popularized in CEE countries, challenging the traditional approach to HIV care. These implications need to be further evaluated in order to ascertain the best adaptations, especially for HIV medicine.

HIV-positive patients may present lungs with multiple infections, which may hinder differential diagnoses and the choice of treatment in the course of COVID-19, especially in countries with limited access to high-standard healthcare. Here, we aim to investigate the association between radiological changes and poor COVID-19 outcomes among HIV-positive patients from Central and Eastern Europe. Between November 2020 and May 2021, the Euroguidelines in Central and Eastern Europe Network Group started collecting observational data on HIV and COVID-19 co-infections. In total, 16 countries from Central and Eastern European submitted data (eCRF) on 557 HIV-positive patients. The current analyses included patients who had a radiological examination performed. Logistic regression models were used to identify the factors associated with death, ICU admission, and partial recovery (poor COVID-19 outcomes). Factors that were significant in the univariate models (p < 0.1) were included in the multivariate model. Radiological data were available for 224 (40.2%) patients, 108 (48.2%) had computed tomography, and 116 (51.8%) had a chest X-ray. Of these, 211 (94.2%) were diagnosed using RT-PCR tests, 212 (94.6%) were symptomatic, 123 (55.6%) were hospitalized, 37 (16.6%) required oxygen therapy, and 28 (13.1%) either died, were admitted to ICU, or only partially recovered. From the radiologist’s description, 138 (61.6%) patients had typical radiological changes, 18 (8.0%) atypical changes, and 68 (30.4%) no changes. In the univariate models, CD4 count (OR = 0.86 [95% CI: 0.76−0.98]), having a comorbidity (2.33 [1.43−3.80]), HCV and/or HBV co-infection (3.17 [1.32−7.60]), being currently employed (0.31 [0.13−0.70]), being on antiretroviral therapy (0.22 [0.08−0.63]), and having typical (3.90 [1.12−13.65]) or atypical (10.8 [2.23−52.5]) radiological changes were all significantly associated with poor COVID-19 outcomes. In the multivariate model, being on antiretroviral therapy (OR = 0.20 [95% CI:0.05−0.80]) decreased the odds of poor COVID-19 outcomes, while having a comorbidity (2.12 [1.20−3.72]) or either typical (4.23 [1.05−17.0]) or atypical (6.39 [1.03−39.7]) radiological changes (vs. no changes) increased the odds of poor COVID-19 outcomes. Among HIV patients diagnosed with symptomatic SARS-CoV-2 infection, the presence of either typical or atypical radiological COVID-19 changes independently predicted poorer outcomes.

Introduction: People living with HIV (PLWH) are at higher risk of poorer COVID-19 outcomes. Vaccination is a safe and effective method of prevention against many infectious diseases, including COVID-19. Here we investigate the strategies for national COVID-19 vaccination programmes across central and eastern Europe and the inclusion of PLWH in vaccination programmes., Methods: The Euroguidelines in Central and Eastern Europe Network Group consists of experts in the field of infectious diseases from 24 countries in the region. Between 1 November 2020 and 19 March 2021 the group proceeded an on-line survey consisting of 20 questions., Results: Twenty-two countries (out of 24 invited) participated in the survey and 20/22 countries in the period between December 2020 and March 2021 had already started their COVID-19 vaccination programme. In total, seven different vaccines were used by participating countries. In 17/21 countries (81%), vaccinated persons were centralized within the national registry. In 8/21 countries (38%) PLWH were prioritized for vaccination (the Czech Republic, Greece, Hungary, Lithuania, Montenegro, Romania, Slovakia, Slovenia) and the Czech Republic, Greece and Serbia had put in place national guidelines for vaccination of PLWH. In 14/20 countries (70%) vaccination was only provided by designated centres. Eighteen respondents (18/21; 85.7%) reported that they planned to follow up HIV patients vaccinated against COVID-19, mainly by measuring antibody levels and checking COVID-19 incidence (11/21; 52.3%)., Conclusions: This survey-based study suggests that there are significant differences in terms of prioritizing PLWH, the types of vaccines used, vaccination coverage, and the development and implementation of a vaccination programmes within the region. Regardless of heterogenicity and existing barriers within the region, systematic vaccination in PLWH should have the highest priority, especially in those with severe immunodeficiency, risk factors, and in the elderly, aiming for prompt and high vaccination coverage., (© 2021 British HIV Association.)

Objective: In this study, we describe the synthesis, docking study and biological evaluation of 1,2-benzothiazines 1,1-dioxide derivatives., Methods: Taking the well-known drug, Piroxicam as a lead compound, we designed and synthesized two series of 1,2-benzothiazines 1,1-dioxide derivatives to assay their ability in inhibition of HIV-1 replication in cell culture., Results: Most of the new compounds were active in the cell-based anti-HIV-1 assay with EC50 < 50 μM. Among them, compound 7g was found to be the most active molecule.Docking study using 3OYA pdb code on the most active molecule 7g with EC50 values of 10 μM showed a similar binding mode to the HIV integrase inhibitors., Conclusion: Since all the compounds showed no remarkable cytotoxicity (CC50> 500 μM), the designed scaffold is promising structure for the development of new anti-HIV-1 agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

HIV, the virus that causes AIDS (acquired immunodeficiency syndrome), is one of the world's most severe health and development challenges. In this study, a novel series of 2-(diphenyl methylidene) malonic acid derivatives were designed as triple inhibitors of HIV reverse transcriptase, integrase, and protease. Docking models revealed that the target compounds have appropriate affinities to the active sites of the three HIV key enzymes. The synthesized malonic acid analogs were evaluated for their activities against the HIV virus (NL4-3) in HeLa cells cultures. Among them, compound 3 was the most potent anti-HIV agent with 55.20% inhibition at 10 μM and an EC50 of 8.4 μM. Interestingly, all the synthesized compounds do not show significant cytotoxicity at a concentration of 10 μM. As a result, these compounds may serve as worthy hits for the development of novel anti-HIV-agents., Competing Interests: Conflict of Interests: The authors announce that the work reported in this paper was not influenced by established conflicting financial interests or personal relationships., (Copyright © 2022, Author(s).)

Background: The recent pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has elevated several clinical and scientific questions. These include how host genetic factors influence the pathogenesis and disease susceptibility. Therefore, the aim of this study was to evaluate the impact of interferon lambda 3 and 4 (IFNL3/4) gene polymorphisms and clinical parameters on the resistance and susceptibility to coronavirus disease 2019 (COVID-19) infection., Methods: A total of 750 SARS-CoV-2 positive patients (375 survivors and 375 nonsurvivors) were included in this study. All single-nucleotide polymorphisms (SNPs) on IFNL3 (rs12979860, rs8099917, and rs12980275) and IFNL4 rs368234815 were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method., Results: In this study, a higher viral load (low PCR Ct value) was shown in nonsurvivor patients. In survivor patients, the frequency of the favorable genotypes of IFNL3/4 SNPs (rs12979860 CC, rs12980275 AA, rs8099917 TT, and rs368234815 TT/TT) was significantly higher than in nonsurvivor patients. Multivariate logistic regression analysis has shown that a higher low-density lipoprotein (LDL), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and PCR Ct value, and lower 25-hydroxyvitamin D, and also IFNL3 rs12979860 TT, IFNL3 rs8099917 GG, IFNL3 rs12980275 GG, and IFNL4 rs368234815 ∆G/∆G genotypes were associated with the severity of COVID-19 infection., Conclusions: The results of this study proved that the severity of COVID-19 infection was associated with clinical parameters and unfavorable genotypes of IFNL3/IFNL4 SNPs. Further studies in different parts of the world are needed to show the relationship between severity of COVID-19 infection and host genetic factors., (© 2021. The Author(s).)