PathogensPub Date : 2025-03-01DOI: 10.3390/pathogens14030239
Fernando Velásquez Orozco, David Tabernero, María Gabriela Barbaglia, Lara Treviño, Begoña Trujillo, Andrés Marco, Miguel Ángel Carrillo, Gerard Ruiz Salinas, Francesc Xavier Majo Roca, Joan Colom Farran, María Buti, Tomas Pumarola-Sunyer, Francisco Rodriguez-Frias, Ariadna Rando-Segura
{"title":"Improving HCV Screening in Addiction Care Centers with Plasma Separation Cards.","authors":"Fernando Velásquez Orozco, David Tabernero, María Gabriela Barbaglia, Lara Treviño, Begoña Trujillo, Andrés Marco, Miguel Ángel Carrillo, Gerard Ruiz Salinas, Francesc Xavier Majo Roca, Joan Colom Farran, María Buti, Tomas Pumarola-Sunyer, Francisco Rodriguez-Frias, Ariadna Rando-Segura","doi":"10.3390/pathogens14030239","DOIUrl":"10.3390/pathogens14030239","url":null,"abstract":"<p><p>Globally, 50 million people are infected with hepatitis C virus (HCV), many of whom are people who inject drugs. These individuals face healthcare barriers, necessitating innovative diagnostic tools. This study evaluated the impact of cobas plasma separation cards (PSCs) for dry plasma collection in Barcelona's outpatient drug addiction centers (CAS). From February to December 2021, nine CASs were invited to implement PSC for HCV screening; three centers participated, allowing for the assessment of its impact on HCV detection. Of the 679 clients screened, 54 (8%) provided finger-prick blood samples via PSC due to their refusal or inability to undergo venipuncture. Overall, 100 (14.7%) clients tested positive for HCV antibodies, with 24 (24%) confirmed as HCV-RNA positive. Among venipuncture clients, 9.1% had positive antibodies, with 15.8% showing active infection. In contrast, 79.6% of PSC clients had positive antibodies and 34.9% had detectable HCV RNA, contributing to 62.5% of the active infections detected. The odds ratio was 26.3, indicating that refusal or inability to undergo venipuncture correlated with a significantly higher burden of active HCV infection. The findings highlight PSC as a valuable alternative for diagnosing HCV in people with substance use disorders, addressing accessibility barriers and improving linkage to care in high-risk populations.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathogensPub Date : 2025-03-01DOI: 10.3390/pathogens14030238
Elke Müller, Stefan Monecke, Marc Armengol Porta, Marco Vinicio Narvaez Encalada, Annett Reissig, Lukas Rüttiger, Percy Schröttner, Ilona Schwede, Hans-Herman Söffing, Alexander Thürmer, Ralf Ehricht
{"title":"Rapid Detection of Panton-Valentine Leukocidin Production in Clinical Isolates of <i>Staphylococcus aureus</i> from Saxony and Brandenburg and Their Molecular Characterisation.","authors":"Elke Müller, Stefan Monecke, Marc Armengol Porta, Marco Vinicio Narvaez Encalada, Annett Reissig, Lukas Rüttiger, Percy Schröttner, Ilona Schwede, Hans-Herman Söffing, Alexander Thürmer, Ralf Ehricht","doi":"10.3390/pathogens14030238","DOIUrl":"10.3390/pathogens14030238","url":null,"abstract":"<p><p>Panton-Valentine leukocidin (PVL) is a staphylococcal toxin associated with chronic/recurrent skin and soft tissue infections (SSTIs) and necrotizing pneumonia. Its detection in clinical isolates of <i>Staphylococcus aureus</i> warrants aggressive therapy and infection control measures. However, PVL detection relies on molecular methods of limited use, especially in outpatient or resource-poor settings. In order to aid the development of a lateral flow (LF) test for PVL, clinical isolates from SSTIs were collected in 2020/21 at three laboratories in two cities in the Eastern part of Germany. After the exclusion of duplicate and serial isolates, 83 isolates were eligible. These were tested using an experimental LF test for PVL production. They were also characterized using DNA microarrays, facilitating the detection of virulence and resistance markers as well as the assignment to clonal complexes and epidemic/pandemic strains. Thirty-nine isolates (47%) were PVL-positive, and the LF results were in 81 cases (97.6%) concordant with genotyping. One false-positive and one false-negative case were observed. This translated into a diagnostic sensitivity of 0.974 and a diagnostic specificity of 0.977. The most common PVL-positive MSSA lineages were CC152 (n = 6), CC121 (n = 4), and CC5 and CC30 (each n = 2). Thirty isolates (36%) were <i>mecA</i>-positive. The MRSA rate among PVL-negatives was 20% (nine isolates), but among the PVL-positives, it was as high as 54% (n = 21). The most common PVL-MRSA strains were CC398-MRSA-VT (n = 5), CC5-MRSA-IV \"Sri Lanka Clone\" (n = 4), CC8-MRSA-[<i>mec</i> IV+Hg] \"Latin American USA300\" (n = 4), and CC22-MRSA-IV (PVL+/<i>tst</i>+) (n = 2). While the PVL rate was similar just like the German isolates from a previous study a decade before, the MRSA rate among PVL-positives was clearly higher. All PVL-MRSA strains detected, as well as the most common methicillin-susceptible lineage (CC152), are known to be common locally in other parts of the world, and might, thus, be regarded as travel-associated. Therefore, patients with suspected PVL-associated disease should be asked for their history of travel or migration, and, in case of hospitalization, they should be treated as MRSA cases until proven otherwise.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathogensPub Date : 2025-02-28DOI: 10.3390/pathogens14030236
Mislav Peras, Ernest Bilić, Ivana Mareković
{"title":"Recent Insights into the Pathogenesis, Diagnostics, and Treatment of BK Virus Infections in Children After Hematopoietic Stem Cell Transplantation.","authors":"Mislav Peras, Ernest Bilić, Ivana Mareković","doi":"10.3390/pathogens14030236","DOIUrl":"10.3390/pathogens14030236","url":null,"abstract":"<p><p>BK polyomavirus (BKPyV) is a pathogen responsible for infectious complications in hematopoietic stem cell transplant (HSCT) recipients. This review aims to give an insight into recent data about the structure and genomic organization, epidemiology, clinical manifestations, diagnosis, and current treatment options of BKPyV infections in children after HSCT. News regarding viral replication and pathogenesis include the generation of miRNA, new mechanisms of viral shedding by releasing infectious particles via extracellular vesicles, and human bladder microvascular endothelial cells probably acting as viral reservoirs enabling low-level viral replication and persistence. In studies conducted over the past five years, BKPyV hemorrhagic cystitis (BKPyV-HC) has a prevalence rate of 4 to 27% in children undergoing HSCT. Diagnostics still has unsolved dilemmas like whole blood or plasma samples as well as the standardization of molecular methods to allow for reporting in international units. In terms of treatment, new approaches have been used in the past five years, including the use of mesenchymal stem cells (MSCs), virus-specific T cells (VSTs), and recombinant human keratinocyte growth factor (rH-KGF), although the efficacy of some of these treatments has only been documented in isolated studies. This complication continues to pose a substantial clinical challenge, characterized by an absence of effective preventive and therapeutic measures.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathogensPub Date : 2025-02-28DOI: 10.3390/pathogens14030237
Pilar Ciruela, Nuria Soldevila, Nuria Torner, Luca Basile, Maria Del Mar Mosquera, M Angeles Marcos, Anna Martínez, Mireia Jané, Cristina Rius, Angela Domínguez, The Working Group For The Catalan Influenza And Severe Acute Respiratory Infection Sentinel Surveillance Network Pidirac
{"title":"Acute Influenza Virus-Associated Encephalitis and Other Neurological Complications in Severe Hospitalized Laboratory-Confirmed Influenza Cases-Catalonia 2010-2020.","authors":"Pilar Ciruela, Nuria Soldevila, Nuria Torner, Luca Basile, Maria Del Mar Mosquera, M Angeles Marcos, Anna Martínez, Mireia Jané, Cristina Rius, Angela Domínguez, The Working Group For The Catalan Influenza And Severe Acute Respiratory Infection Sentinel Surveillance Network Pidirac","doi":"10.3390/pathogens14030237","DOIUrl":"10.3390/pathogens14030237","url":null,"abstract":"<p><p>Neurological complications associated with influenza (NCIs) are rare events in adults. Influenza-associated encephalopathy is one of the most severe and frequently reported NCIs. The aim of this study is to describe the frequency and characteristics of NCIs in adults during 10 post-2009 pandemic influenza seasons. Data were obtained from the registry of influenza cases admitted to hospitals of the PIDIRAC network for the surveillance of severe hospitalized laboratory-confirmed influenza (SHLCI) cases in Catalonia from October 2010 to March 2020. The variables analyzed were NCI, age, antiviral treatment, vaccination status, and outcome at discharge. During the study period, 9 (1.5‱) of 5931 SHLCI cases presented NCI. Five (55.6%) had influenza A and four (44.4%) had influenza B. Median age was 62 (17-67) years. One case had been vaccinated, all had received antiviral treatment, and five required ICU admission. The mean length of stay was 25.6 days (SD 25.8). Encephalitis was the most frequent complication, occurring in six cases (66.7%). Of these, three cases (50%) were caused by influenza A (two AH1N1pdm09 strains and one AH3N2). The high frequency of influenza-associated encephalitis caused by both type A and B influenza viruses suggests that both should be considered as potential etiologic factors for encephalopathy and other neurological diseases in adults. This recommendation would allow for the prompt antiviral treatment and prevention of severe outcomes.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathogensPub Date : 2025-02-27DOI: 10.3390/pathogens14030234
Akshita Jain, Tongda Li, John Wainer, Jacqueline Edwards, Brendan C Rodoni, Timothy I Sawbridge
{"title":"High-Throughput Sequencing Enables Rapid Analyses of Nematode Mitochondrial Genomes from an Environmental Sample.","authors":"Akshita Jain, Tongda Li, John Wainer, Jacqueline Edwards, Brendan C Rodoni, Timothy I Sawbridge","doi":"10.3390/pathogens14030234","DOIUrl":"10.3390/pathogens14030234","url":null,"abstract":"<p><p>Mitochondrial genomes serve as essential tools in evolutionary biology, phylogenetics, and population genetics due to their maternal inheritance, lack of recombination, and conserved structure. Traditional morphological methods for identifying nematodes are often insufficient for distinguishing cryptic species complexes. This study highlights recent advancements in nematode mitochondrial genome research, particularly the impact of long-read sequencing technologies such as Oxford Nanopore. These technologies have facilitated the assembly of mitochondrial genomes from mixed soil samples, overcoming challenges associated with designing specific primers for long PCR amplification across different groups of parasitic nematodes. In this study, we successfully recovered and assembled eleven nematode mitochondrial genomes using long-read sequencing, including those of two plant-parasitic nematode species. Notably, we detected <i>Heterodera cruciferae</i> in Victoria, expanding its known geographic range within Australia. Additionally, short-read sequencing data from a previous draft genome study revealed the presence of the mitochondrial genome of <i>Heterodera filipjevi</i>. Comparative analyses of <i>Heterodera</i> mitogenomes revealed conserved protein-coding genes essential for oxidative phosphorylation, as well as gene rearrangements and variations in transfer RNA placement, which may reflect adaptations to parasitic lifestyles. The consistently high A+T content and strand asymmetry observed across species align with trends reported in related genera. This study demonstrates the utility of long-read sequencing for identifying coexisting nematode species in agricultural fields, providing a rapid, accurate, and comprehensive alternative to traditional diagnostic methods. By incorporating non-target endemic species into public databases, this approach enhances biodiversity records and informs biosecurity strategies. These findings reinforce the potential of mitochondrial genomics to strengthen Australia's as well as the global biosecurity framework against plant-parasitic nematode threats.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathogensPub Date : 2025-02-27DOI: 10.3390/pathogens14030233
Anthony F Barbet, David R Allred, Francy L Crosby
{"title":"Generation of Population-Level Diversity in <i>Anaplasma phagocytophilum msp2/p44</i> Gene Repertoires Through Recombination.","authors":"Anthony F Barbet, David R Allred, Francy L Crosby","doi":"10.3390/pathogens14030233","DOIUrl":"10.3390/pathogens14030233","url":null,"abstract":"<p><p><i>Anaplasma phagocytophilum</i>, a tick-borne Rickettsiales, causes an emerging disease among humans and animals called granulocytic anaplasmosis. The organism expresses an immunodominant surface protein, MSP2/P44, that undergoes rapid antigenic variation during single infections due to gene conversion at a single genomic expression site with sequences from one of ~100 transcriptionally silent genes known as \"functional pseudogenes\". Most studies have indicated that the predominant gene conversion mechanism is the insertion of complete central variable regions (CVRs) into the <i>msp2/p44</i> expression site via homologous recombination through 5' and 3' conserved regions. This suggests that it is possible that persistent infections by one strain may be self-limiting due to the exhaustion of the antigenic repertoire. However, if there is substantial recombination within the functional pseudogene repertoires themselves, it is likely that these repertoires have a high rate of change. This was investigated here by analyzing the repertoires of <i>msp2/p44</i> functional pseudogenes in genome-sequenced <i>A. phagocytophilum</i> from widely different geographic locations in the USA and Europe. The data strongly support the probability of recombination events having occurred within and between <i>msp2/p44</i> repertoires that is not limited to the 5' and 3' conserved regions of the CVR, greatly expanding the total potential variation. Continual variation of <i>msp2/p44</i> repertoires is predicted to aid the organism in overcoming existing immunity in the individual and causing superinfections among immune populations, and this may facilitate the adaptation of the microorganism to infect and cause disease in different species.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathogensPub Date : 2025-02-27DOI: 10.3390/pathogens14030231
Vanessa Vásquez, Ana María Santamaría, Dianik Moreno, Fergie Ruíz, Chystrie A Rigg, Luis F Chaves, José E Calzada
{"title":"Genetic Diversity of Potential Drug Resistance Markers in <i>Plasmodium vivax</i> Isolates from Panama, Mesoamerica.","authors":"Vanessa Vásquez, Ana María Santamaría, Dianik Moreno, Fergie Ruíz, Chystrie A Rigg, Luis F Chaves, José E Calzada","doi":"10.3390/pathogens14030231","DOIUrl":"10.3390/pathogens14030231","url":null,"abstract":"<p><p>This study evaluated the genetic diversity and potential drug resistance markers in <i>Plasmodium vivax</i> isolates from Panama, a country in Mesoamerica, aiming to eliminate local malaria transmission. We analyzed 70 <i>P. vivax</i> samples collected between 2004 and 2020 from endemic regions in Eastern and Western Panama, as well as imported cases. Four drug resistance genes (<i>pvcrt-o</i>, <i>pvmdr1</i>, <i>pvdhfr</i>, and <i>pvdhps</i>) were sequenced and analyzed. Our findings reveal low genetic diversity in <i>P. vivax</i> populations from Western Panama, indicating clonal expansion, while Eastern Panama exhibits higher diversity, influenced by higher transmission rates and imported cases. No mutations were detected in <i>pvcrt-o</i>, and the prevalence of <i>pvmdr1</i> mutations (Y976F and F1076L) linked to chloroquine was observed at low frequencies, primarily in imported samples. In <i>pvdhfr</i>, antifolate-resistant mutations S117N and S58R were detected in 14.3% of samples, predominantly from Eastern Panama near the Colombian border. Phylogenetic and haplotype network analyses highlighted distinct genetic clustering, supporting the influence of imported cases on local parasite diversity. These results provide a baseline for the molecular surveillance of <i>P. vivax</i> in Panama and emphasize the need for the continued monitoring of genetic diversity and drug resistance to guide regional malaria elimination efforts, particularly in areas with high cross-border migration.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathogensPub Date : 2025-02-27DOI: 10.3390/pathogens14030235
Hannah Solchenberger, Marcus Odendahl, Dirk Schriefer, Undine Proschmann, Georges Katoul Al Rahbani, Tjalf Ziemssen, Katja Akgün
{"title":"Extensive T-Cell Profiling Following SARS-CoV-2 mRNA Vaccination in Multiple Sclerosis Patients Treated with DMTs.","authors":"Hannah Solchenberger, Marcus Odendahl, Dirk Schriefer, Undine Proschmann, Georges Katoul Al Rahbani, Tjalf Ziemssen, Katja Akgün","doi":"10.3390/pathogens14030235","DOIUrl":"10.3390/pathogens14030235","url":null,"abstract":"<p><p>Disease-modifying therapies (DMTs) are known to impact cellular and humoral immune response in persons with multiple sclerosis (pwMS). In this study, we performed in-depth SARS-CoV-2-specific T-cell profiling using flow cytometry. T-cell immunity in pwMS with or without DMTs was evaluated before a first SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccination and at one-, two- and six-month follow-up. T-cell stimulation without SARS-CoV-2-specific antigens was used as a control. T-cell response was compared to B-cell response by evaluating SARS-CoV-2-specific antibodies. We observed an upregulation of specific subpopulations of SARS-CoV-2 spike-specific CD4<sup>+</sup> T cells. Thus, our results demonstrate the induction of a broad and distinct CD4<sup>+</sup> T-cell response in pwMS even on anti-CD20 treatment and sphingosine-1-phosphate receptor modulation after SARS-CoV-2 mRNA vaccination. This was particularly seen in CD4<sup>+high</sup> and CD4<sup>+</sup>CD154<sup>+</sup> T cells. Our results do not support the induction of a CD8<sup>+</sup> T-cell immune response. While humoral immune response was impaired in pwMS during ocrelizumab and fingolimod treatment, there was evidence of a compensatory upregulation of subpopulations of SARS-CoV-2-specific CD4<sup>+</sup> T cells at low levels of seroconversion in pwMS. In conclusion, our results provide important insights into the mechanisms of the adaptive immune response in pwMS following SARS-CoV-2 mRNA vaccination.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathogensPub Date : 2025-02-27DOI: 10.3390/pathogens14030232
Louis Tioka, Rafael Ceña Diez, Anders Sönnerborg, Maarten A A van de Klundert
{"title":"Latency Reversing Agents and the Road to a HIV Cure.","authors":"Louis Tioka, Rafael Ceña Diez, Anders Sönnerborg, Maarten A A van de Klundert","doi":"10.3390/pathogens14030232","DOIUrl":"10.3390/pathogens14030232","url":null,"abstract":"<p><p>HIV-1 infection cannot be cured due to the presence of HIV-1 latently infected cells. These cells do not produce the virus, but they can resume virus production at any time in the absence of antiretroviral therapy. Therefore, people living with HIV (PLWH) need to take lifelong therapy. Strategies have been coined to eradicate the viral reservoir by reactivating HIV-1 latently infected cells and subsequently killing them. Various latency reversing agents (LRAs) that can reactivate HIV-1 in vitro and ex vivo have been identified. The most potent LRAs also strongly activate T cells and therefore cannot be applied in vivo. Many LRAs that reactivate HIV in the absence of general T cell activation have been identified and have been tested in clinical trials. Although some LRAs could reduce the reservoir size in clinical trials, so far, they have failed to eradicate the reservoir. More recently, immune modulators have been applied in PLWH, and the first results seem to indicate that these may reduce the reservoir and possibly improve immunological control after therapy interruption. Potentially, combinations of LRAs and immune modulators could reduce the reservoir size, and in the future, immunological control may enable PLWH to live without developing HIV-related disease in the absence of therapy.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathogensPub Date : 2025-02-27DOI: 10.3390/pathogens14030230
Ahmed Farhan, Khouloud Ayed, Sara Zayati, Rym Akrout, Akram Dlala, Amal Abouda, Nesrine Zoghlami, Halima Mahjoubi, Iheb Labbane, Asma Gati
{"title":"Optimizing Clinical Management of COVID-19: A Predictive Model for Unvaccinated Patients Admitted to ICU.","authors":"Ahmed Farhan, Khouloud Ayed, Sara Zayati, Rym Akrout, Akram Dlala, Amal Abouda, Nesrine Zoghlami, Halima Mahjoubi, Iheb Labbane, Asma Gati","doi":"10.3390/pathogens14030230","DOIUrl":"10.3390/pathogens14030230","url":null,"abstract":"<p><p>This study investigates the impact of immunological and clinical factors on COVID-19 outcomes among unvaccinated individuals. A cohort of 42 unvaccinated patients admitted to an intensive care unit was analyzed, focusing on age, comorbidities, inflammatory cytokines (IL-6, TNF-α), and anti-SARS-CoV-2 spike protein antibody levels (IgG) to assess their influence on hospital stay duration, recovery time, complications, and mortality rates. The findings revealed that advanced age, cardiovascular disease, and elevated pro-inflammatory cytokines significantly heightened the risks of severe complications and mortality. Conversely, low IgG levels correlated with prolonged hospital stays and slower recovery. Multivariate analysis identified high IL-6 and TNF-α levels as strong predictors of adverse outcomes. This research emphasizes the need for the early monitoring of cytokines and targeted management strategies to mitigate the impact of COVID-19, especially among high-risk unvaccinated populations.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}