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Article: Co-Expression of Immunohistochemical Markers MRP2, CXCR4, and PD-L1 in Gallbladder Tumors Is Associated with Prolonged Patient Survival.

Tittarelli, Andrés / Barría, Omar / Sanders, Evy / Bergqvist, Anna / Brange, Daniel Uribe / Vidal, Mabel / Gleisner, María Alejandra / Vergara, Jorge Ramón / Niechi, Ignacio / Flores, Iván / Pereda, Cristián / Carrasco, Cristian / Quezada-Monrás, Claudia / Salazar-Onfray, Flavio

Cancers

2023 Volume 15, Issue 13

Abstract: Gallbladder cancer (GBC) is a rare pathology in Western countries. However, it constitutes a relevant health problem in Asia and Latin America, with a high mortality in middle-aged Chilean women. The limited therapeutic options for GBC require the ... ...

Abstract	Gallbladder cancer (GBC) is a rare pathology in Western countries. However, it constitutes a relevant health problem in Asia and Latin America, with a high mortality in middle-aged Chilean women. The limited therapeutic options for GBC require the identification of targetable proteins with prognostic value for improving clinical management support. We evaluated the expression of targetable proteins, including three epithelial tumor markers, four proteins associated with multidrug and apoptosis resistance, and eleven immunological markers in 241 primary gallbladder adenocarcinomas. We investigated correlations between tumor marker expression, the primary tumor staging, and GBC patients' survival using automated immunohistochemistry, a semi-automatic method for image analysis, univariate and multivariate statistical analyses, and machine learning algorithms. Our data show a significant association between the expression of MRP2 (
Language	English
Publishing date	2023-06-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15133440
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Article: A retrospective study suggests 55 days of persistence of SARS-CoV-2 during the first wave of the pandemic in Santiago de Chile.

Acuña-Castillo, Claudio / Vidal, Mabel / Vallejos-Vidal, Eva / Luraschi, Roberto / Barrera-Avalos, Carlos / Inostroza-Molina, Ailen / Molina-Cabrera, Sonia / Valdes, Daniel / Schafer, Carolina / Maisey, Kevin / Imarai, Mónica / Vera, Rodrigo / Vargas, Sergio / Rojo, Leonel E / Leiva-Salcedo, Elías / Escobar, Alejandro / Reyes-Cerpa, Sebastián / Gaete, Alexis / Palma-Vejares, Ricardo /

Travisany, Dante / Torres, Claudio / Reyes-López, Felipe E / Sandino, Ana María

Heliyon

2024 Volume 10, Issue 7, Page(s) e24419

Abstract: Background: As the COVID-19 pandemic persists, infections continue to surge globally. Presently, the most effective strategies to curb the disease and prevent outbreaks involve fostering immunity, promptly identifying positive cases, and ensuring their ... ...

Abstract	Background: As the COVID-19 pandemic persists, infections continue to surge globally. Presently, the most effective strategies to curb the disease and prevent outbreaks involve fostering immunity, promptly identifying positive cases, and ensuring their timely isolation. Notably, there are instances where the SARS-CoV-2 virus remains infectious even after patients have completed their quarantine. Objective: Understanding viral persistence post-quarantine is crucial as it could account for localized infection outbreaks. Therefore, studying and documenting such instances is vital for shaping future public health policies. Design: This study delves into a unique case of SARS-CoV-2 persistence in a 60-year-old female healthcare worker with a medical history of hypertension and hypothyroidism. The research spans 55 days, marking the duration between her initial and subsequent diagnosis during Chile's first COVID-19 wave, with the analysis conducted using RT-qPCR. Results: Genomic sequencing-based phylogenetic analysis revealed that the SARS-CoV-2 detected in both Nasopharyngeal swab samples (NPSs) was consistent with the 20B clade of the Nextstrain classification, even after a 55-day interval. Conclusion: This research underscores the need for heightened vigilance concerning cases of viral persistence. Such instances, albeit rare, might be pivotal in understanding sporadic infection outbreaks that occur post-quarantine.
Language	English
Publishing date	2024-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2024.e24419
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Article ; Online: An ecological study on reinfection rates using a large dataset of RT-qPCR tests for SARS-CoV-2 in Santiago of Chile.

Acuña-Castillo, Claudio / Barrera-Avalos, Carlos / Bachelet, Vivienne C / Milla, Luis A / Inostroza-Molina, Ailén / Vidal, Mabel / Luraschi, Roberto / Vallejos-Vidal, Eva / Mella-Torres, Andrea / Valdés, Daniel / Reyes-López, Felipe E / Imarai, Mónica / Rojas, Patricio / Sandino, Ana María

Frontiers in public health

2023 Volume 11, Page(s) 1191377

Abstract: Introduction: As the SARS-CoV-2 continues to evolve, new variants pose a significant threat by potentially overriding the immunity conferred by vaccination and natural infection. This scenario can lead to an upswing in reinfections, amplified baseline ... ...

Abstract	Introduction: As the SARS-CoV-2 continues to evolve, new variants pose a significant threat by potentially overriding the immunity conferred by vaccination and natural infection. This scenario can lead to an upswing in reinfections, amplified baseline epidemic activity, and localized outbreaks. In various global regions, estimates of breakthrough cases associated with the currently circulating viral variants, such as Omicron, have been reported. Nonetheless, specific data on the reinfection rate in Chile still needs to be included. Methods: Our study has focused on estimating COVID-19 reinfections per wave based on a sample of 578,670 RT-qPCR tests conducted at the University of Santiago of Chile (USACH) from April 2020 to July 2022, encompassing 345,997 individuals. Results: The analysis reveals that the highest rate of reinfections transpired during the fourth and fifth COVID-19 waves, primarily driven by the Omicron variant. These findings hold despite 80% of the Chilean population receiving complete vaccination under the primary scheme and 60% receiving at least one booster dose. On average, the interval between initial infection and reinfection was found to be 372 days. Interestingly, reinfection incidence was higher in women aged between 30 and 55. Additionally, the viral load during the second infection episode was lower, likely attributed to Chile's high vaccination rate. Discussion: This study demonstrates that the Omicron variant is behind Chile's highest number of reinfection cases, underscoring its potential for immune evasion. This vital epidemiological information contributes to developing and implementing effective public health policies.
MeSH term(s)	Humans ; Female ; Adult ; Middle Aged ; SARS-CoV-2/genetics ; COVID-19/diagnosis ; COVID-19/epidemiology ; Chile/epidemiology ; Reinfection/epidemiology
Language	English
Publishing date	2023-07-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2023.1191377
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Article ; Online: Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of Cancer.

Vidal, Mabel / Fraga, Marco / Llerena, Faryd / Vera, Agustín / Hernández, Mauricio / Koch, Elard / Reyes-López, Felipe / Vallejos-Vidal, Eva / Cabrera-Vives, Guillermo / Nova-Lamperti, Estefanía

International journal of molecular sciences

2022 Volume 23, Issue 19

Abstract: CD8+ and CD4+ T-cells play a key role in cellular immune responses against cancer by cytotoxic responses and effector lineages differentiation, respectively. These subsets have been found in different types of cancer; however, it is unclear whether tumor- ...

Abstract	CD8+ and CD4+ T-cells play a key role in cellular immune responses against cancer by cytotoxic responses and effector lineages differentiation, respectively. These subsets have been found in different types of cancer; however, it is unclear whether tumor-infiltrating T-cell subsets exhibit similar transcriptome profiling across different types of cancer in comparison with healthy tissue-resident T-cells. Thus, we analyzed the single cell transcriptome of five tumor-infiltrating CD4-T, CD8-T and Treg cells obtained from different types of cancer to identify specific pathways for each subset in malignant environments. An in silico analysis was performed from single-cell RNA-sequencing data available in public repositories (Gene Expression Omnibus) including breast cancer, melanoma, colorectal cancer, lung cancer and head and neck cancer. After dimensionality reduction, clustering and selection of the different subpopulations from malignant and nonmalignant datasets, common genes across different types of cancer were identified and compared to nonmalignant genes for each T-cell subset to identify specific pathways. Exclusive pathways in CD4+ cells, CD8+ cells and Tregs, and common pathways for the tumor-infiltrating T-cell subsets were identified. Finally, the identified pathways were compared with RNAseq and proteomic data obtained from T-cell subsets cultured under malignant environments and we observed that cytokine signaling, especially Th2-type cytokine, was the top overrepresented pathway in Tregs from malignant samples.
MeSH term(s)	CD8-Positive T-Lymphocytes ; Cytokines/metabolism ; Humans ; Lymphocytes, Tumor-Infiltrating ; Melanoma/metabolism ; Proteomics ; RNA/metabolism ; Transcriptome ; Tumor Microenvironment/genetics
Chemical Substances	Cytokines ; RNA (63231-63-0)
Language	English
Publishing date	2022-09-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231911065
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Article ; Online: Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model.

Ormazabal, Valeska / Nova-Lampeti, Estefanía / Rojas, Daniela / Zúñiga, Felipe A / Escudero, Carlos / Lagos, Paola / Moreno, Alexa / Pavez, Yanara / Reyes, Camila / Yáñez, Milly / Vidal, Mabel / Cabrera-Vives, Guillermo / Oporto, Katherine / Aguayo, Claudio

International journal of molecular sciences

2022 Volume 23, Issue 2

Abstract: Tissue regeneration is often impaired in patients with metabolic disorders such as diabetes mellitus and obesity, exhibiting reduced wound repair and limited regeneration capacity. We and others have demonstrated that wound healing under normal metabolic ...

Abstract	Tissue regeneration is often impaired in patients with metabolic disorders such as diabetes mellitus and obesity, exhibiting reduced wound repair and limited regeneration capacity. We and others have demonstrated that wound healing under normal metabolic conditions is potentiated by the secretome of human endothelial cell-differentiated mesenchymal stem cells (hMSC-EC). However, it is unknown whether this effect is sustained under hyperglycemic conditions. In this study, the wound healing effect of secretomes from undifferentiated human mesenchymal stem cells (hMSC) and hMSC-EC in a type-2 diabetes mouse model was analyzed. hMSC were isolated from human Wharton's jelly and differentiated into hMSC-EC. hMSC and hMSC-EC secretomes were analyzed and their wound healing capacity in C57Bl/6J mice fed with control (CD) or high fat diet (HFD) was evaluated. Our results showed that hMSC-EC secretome enhanced endothelial cell proliferation and wound healing in vivo when compared with hMSC secretome. Five soluble proteins (angiopoietin-1, angiopoietin-2, Factor de crecimiento fibroblástico, Matrix metallopeptidase 9, and Vascular Endothelial Growth Factor) were enriched in hMSC-EC secretome in comparison to hMSC secretome. Thus, the five recombinant proteins were mixed, and their pro-healing property was evaluated in vitro and in vivo. Functional analysis demonstrated that a cocktail of these proteins enhanced the wound healing process similar to hMSC-EC secretome in HFD mice. Overall, our results show that hMSC-EC secretome or a combination of specific proteins enriched in the hMSC-EC secretome enhanced wound healing process under hyperglycemic conditions.
MeSH term(s)	Angiopoietin-1/metabolism ; Angiopoietin-1/pharmacology ; Angiopoietin-2/metabolism ; Angiopoietin-2/pharmacology ; Animals ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Culture Media, Conditioned/chemistry ; Culture Media, Conditioned/pharmacology ; Diabetes Mellitus, Type 2/chemically induced ; Diabetes Mellitus, Type 2/metabolism ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Humans ; Matrix Metalloproteinase 9/metabolism ; Matrix Metalloproteinase 9/pharmacology ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Mice ; Recombinant Proteins/pharmacology ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor A/pharmacology ; Wharton Jelly/cytology ; Wharton Jelly/metabolism ; Wound Healing/drug effects
Chemical Substances	Angiopoietin-1 ; Angiopoietin-2 ; Culture Media, Conditioned ; Recombinant Proteins ; Vascular Endothelial Growth Factor A ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
Language	English
Publishing date	2022-01-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23020941
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Article ; Online: Description of Symptoms Caused by the Infection of the SARS-CoV-2 B.1.621 (Mu) Variant in Patients With Complete CoronaVac Vaccination Scheme: First Case Report From Santiago of Chile.

Barrera-Avalos, Carlos / Luraschi, Roberto / Acuña-Castillo, Claudio / Vidal, Mabel / Mella-Torres, Andrea / Inostroza-Molina, Ailen / Vera, Rodrigo / Vargas, Sergio / Hernández, Iván / Perez, Christian / Vallejos-Vidal, Eva / Valdés, Daniel / Imarai, Mónica / Reyes-López, Felipe E / Sandino, Ana María

Frontiers in public health

2022 Volume 10, Page(s) 797569

Abstract: Vaccine administration is one of the most efficient ways to control the current coronavirus disease 2019 (COVID-19) pandemic. However, the appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can avoid the immunity ... ...

Abstract	Vaccine administration is one of the most efficient ways to control the current coronavirus disease 2019 (COVID-19) pandemic. However, the appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can avoid the immunity generated by vaccines. Thus, in patients with a complete vaccine schedule, the infection by SARS-CoV-2 may cause severe, mild, and asymptomatic manifestations of the disease. In this case report, we describe for the first time the clinical symptoms of four patients (three symptomatic; one asymptomatic) from Santiago of Chile, with a complete vaccination schedule with two doses of CoronaVac (Sinovac Life Science) infected with the variant of interest (VOI) B.1.621 (Mu). They were compared with four unvaccinated patients, who had a higher prevalence of symptoms after infection compared to vaccinated patients. In the CoronaVac-vaccinated group, an 80-year-old patient who registered various comorbidities required Invasive mechanical ventilation for 28 days with current home medical recovery discharge. By contrast, in the unvaccinated group, a 71-year-old presented more symptoms with more than 45 days of Invasive mechanical ventilation, which continues to date, presenting greater lung damage than the vaccinated hospitalized patient. This first report evidence differences in the clinical symptomatology of patients vaccinated and non-vaccinated infected with the VOI B.1.621 (Mu) and suggest the protective effects of CoronaVac against this variant.
MeSH term(s)	Aged ; Aged, 80 and over ; COVID-19 ; COVID-19 Vaccines ; Chile ; Humans ; SARS-CoV-2 ; Vaccination ; Vaccines
Chemical Substances	COVID-19 Vaccines ; Vaccines
Language	English
Publishing date	2022-03-21
Publishing country	Switzerland
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2022.797569
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Article ; Online: First Identification of Reinfection by a Genetically Different Variant of SARS-CoV-2 in a Homeless Person from the Metropolitan Area of Santiago, Chile.

Journal of environmental and public health

2022 Volume 2022, Page(s) 3859071

Abstract: The identification and tracking of SARS-CoV-2 infected patients in the general population are essential components of the global strategy to limit the COVID-19 viral spread, specifically for maintaining traceability and suppressing the resurgence of ... ...

Abstract	The identification and tracking of SARS-CoV-2 infected patients in the general population are essential components of the global strategy to limit the COVID-19 viral spread, specifically for maintaining traceability and suppressing the resurgence of local outbreaks. Public health programs that include continuous RT-qPCR testing for COVID-19 in the general population, viral sequencing, and genomic surveillance for highly contagious forms of the virus have allowed for the identification of SARS-CoV-2 infections and reinfections. This work identified SARS-CoV-2 reinfection in a homeless person, which occurred 58 days after the first COVID-19 diagnosis. Genomic sequencing identified a different Nextstrain classification clade (20A and 20B) and PANGO lineage, with a divergence of 4 single nucleotide variants (SNVs) in S and ORF1ab genes, suggesting reinfection by different viral variants. This study is the first from the great metropolitan area of Santiago, Chile, one of the top ten countries in the world to live during the COVID-19 pandemic. We support the importance of performing intensive genomic surveillance programs in the whole population and high-risk groups, such as homeless people, nearly 20 thousand people in Chile, and have limited access to health care services and poor viral traceability.
MeSH term(s)	COVID-19/epidemiology ; COVID-19 Testing ; Chile/epidemiology ; Homeless Persons ; Humans ; Pandemics ; Reinfection ; SARS-CoV-2/genetics
Language	English
Publishing date	2022-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2526611-1
ISSN	1687-9813 ; 1687-9813
ISSN (online)	1687-9813
ISSN	1687-9813
DOI	10.1155/2022/3859071
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Article ; Online: Large-scale transcriptional profiling of lignified tissues in Tectona grandis.

Galeano, Esteban / Vasconcelos, Tarcísio Sales / Vidal, Mabel / Mejia-Guerra, Maria Katherine / Carrer, Helaine

BMC plant biology

2015 Volume 15, Page(s) 221

Abstract: Background: Currently, Tectona grandis is one of the most valuable trees in the world and no transcript dataset related to secondary xylem is available. Considering how important the secondary xylem and sapwood transition from young to mature trees is, ... ...

Abstract	Background: Currently, Tectona grandis is one of the most valuable trees in the world and no transcript dataset related to secondary xylem is available. Considering how important the secondary xylem and sapwood transition from young to mature trees is, little is known about the expression differences between those successional processes and which transcription factors could regulate lignin biosynthesis in this tropical tree. Although MYB transcription factors are one of the largest superfamilies in plants related to secondary metabolism, it has not yet been characterized in teak. These results will open new perspectives for studies of diversity, ecology, breeding and genomic programs aiming to understand deeply the biology of this species. Results: We present a widely expressed gene catalog for T. grandis using Illumina technology and the de novo assembly. A total of 462,260 transcripts were obtained, with 1,502 and 931 genes differentially expressed for stem and branch secondary xylem, respectively, during age transition. Analysis of stem and branch secondary xylem indicates substantial similarity in gene ontologies including carbohydrate enzymes, response to stress, protein binding, and allowed us to find transcription factors and heat-shock proteins differentially expressed. TgMYB1 displays a MYB domain and a predicted coiled-coil (CC) domain, while TgMYB2, TgMYB3 and TgMYB4 showed R2R3-MYB domain and grouped with MYBs from several gymnosperms and flowering plants. TgMYB1, TgMYB4 and TgCES presented higher expression in mature secondary xylem, in contrast with TgMYB2, TgHsp1, TgHsp2, TgHsp3, and TgBi whose expression is higher in young lignified tissues. TgMYB3 is expressed at lower level in secondary xylem. Conclusions: Expression patterns of MYB transcription factors and heat-shock proteins in lignified tissues are dissimilar when tree development was evaluated, obtaining more expression of TgMYB1 and TgMYB4 in lignified tissues of 60-year-old trees, and more expression in TgHsp1, TgHsp2, TgHsp3 and TgBi in stem secondary xylem of 12-year-old trees. We are opening a door for further functional characterization by reverse genetics and marker-assisted selection with those genes. Investigation of some of the key regulators of lignin biosynthesis in teak, however, could be a valuable step towards understanding how rigidity of teak wood and extractives content are different from most other woods. The obtained transcriptome data represents new sequences of T. grandis deposited in public databases, representing an unprecedented opportunity to discover several related-genes associated with secondary xylem such as transcription factors and stress-related genes in a tropical tree.
MeSH term(s)	Gene Expression Regulation, Plant ; Heat-Shock Proteins/genetics ; Heat-Shock Proteins/metabolism ; Lamiaceae/genetics ; Lamiaceae/metabolism ; Molecular Sequence Data ; Organ Specificity ; Phylogeny ; RNA, Plant/genetics ; RNA, Plant/metabolism ; Sequence Analysis, RNA ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcriptome
Chemical Substances	Heat-Shock Proteins ; RNA, Plant ; Transcription Factors
Language	English
Publishing date	2015-09-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2059868-3
ISSN	1471-2229 ; 1471-2229
ISSN (online)	1471-2229
ISSN	1471-2229
DOI	10.1186/s12870-015-0599-x
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Article ; Online: Core Promoter Plasticity Between Maize Tissues and Genotypes Contrasts with Predominance of Sharp Transcription Initiation Sites.

Mejía-Guerra, María Katherine / Li, Wei / Galeano, Narmer F / Vidal, Mabel / Gray, John / Doseff, Andrea I / Grotewold, Erich

The Plant cell

2015 Volume 27, Issue 12, Page(s) 3309–3320

Abstract: Core promoters are crucial for gene regulation, providing blueprints for the assembly of transcriptional machinery at transcription start sites (TSSs). Empirically, TSSs define the coordinates of core promoters and other regulatory sequences. Thus, ... ...

Abstract	Core promoters are crucial for gene regulation, providing blueprints for the assembly of transcriptional machinery at transcription start sites (TSSs). Empirically, TSSs define the coordinates of core promoters and other regulatory sequences. Thus, experimental TSS identification provides an essential step in the characterization of promoters and their features. Here, we describe the application of CAGE (cap analysis of gene expression) to identify genome-wide TSSs used in root and shoot tissues of two maize (Zea mays) inbred lines (B73 and Mo17). Our studies indicate that most TSS clusters are sharp in maize, similar to mice, but distinct from Arabidopsis thaliana, Drosophila melanogaster, or zebra fish, in which a majority of genes have broad-shaped TSS clusters. We established that ∼38% of maize promoters are characterized by a broader TATA-motif consensus, and this motif is significantly enriched in genes with sharp TSSs. A noteworthy plasticity in TSS usage between tissues and inbreds was uncovered, with ∼1500 genes showing significantly different dominant TSSs, sometimes affecting protein sequence by providing alternate translation initiation codons. We experimentally characterized instances in which this differential TSS utilization results in protein isoforms with additional domains or targeted to distinct subcellular compartments. These results provide important insights into TSS selection and gene expression in an agronomically important crop.
MeSH term(s)	Gene Expression Regulation, Plant ; Gene Library ; Genome, Plant/genetics ; Genotype ; Nucleotide Motifs ; Plant Roots/cytology ; Plant Roots/genetics ; Plant Shoots/cytology ; Plant Shoots/genetics ; Promoter Regions, Genetic/genetics ; Sequence Analysis, RNA ; Transcription Initiation Site ; Zea mays/cytology ; Zea mays/genetics
Language	English
Publishing date	2015-12-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	623171-8
ISSN	1532-298X ; 1040-4651
ISSN (online)	1532-298X
ISSN	1040-4651
DOI	10.1105/tpc.15.00630
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Article: Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome.

Sanhueza, Sergio / Vidal, Mabel A / Hernandez, Mauricio A / Henriquez-Beltran, Mario E / Cabrera, Camilo / Quiroga, Romina / Antilef, Bárbara E / Aguilar, Kevin P / Castillo, Daniela A / Llerena, Faryd J / Fraga Figueroa, Marco / Nazal, Mauricio / Castro, Eritson / Lagos, Paola / Moreno, Alexa / Lastra, Jaime J / Gajardo, Jorge / Garcés, Pamela / Riffo, Benilde /

Buchert, Jorge / Sanhueza, Rocío / Ormazába, Valeska / Saldivia, Pablo / Vargas, Cristian / Nourdin, Guillermo / Koch, Elard / Zuñiga, Felipe A / Lamperti, Liliana / Bustos, Paula / Guzmán-Gutiérrez, Enrique / Tapia, Claudio A / Ferrada, Luciano / Cerda, Gustavo / Woehlbier, Ute / Riquelme, Erick / Yuseff, Maria-Isabel / Muñoz Ramirez, Braulio A / Lombardi, Giovanna / De Gonzalo-Calvo, David / Salomon, Carlos / Verdugo, Ricardo A / Quiñones, Luis A / Colombo, Alicia / Barría, Maria I / Labarca, Gonzalo / Nova-Lamperti, Estefania

Frontiers in medicine

2023 Volume 10, Page(s) 1271863

Abstract: Introduction: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the ...

Abstract	Introduction: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling. Methods: Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection. Results: Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups. Discussion: Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.
Language	English
Publishing date	2023-10-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1271863
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