Reinforcing the Evidence of Mitochondrial Dysfunction in Long COVID Patients Using a Multiplatform Mass Spectrometry-Based Metabolomics Approach.

Despite the recent and increasing knowledge surrounding COVID-19 infection, the underlying mechanisms of the persistence of symptoms for a long time after the acute infection are still not completely understood. Here, a multiplatform mass spectrometry-based approach was used for metabolomic and lipidomic profiling of human plasma samples from Long COVID patients (n = 40) to reveal mitochondrial dysfunction when compared with individuals fully recovered from acute mild COVID-19 (n = 40). Untargeted metabolomic analysis using CE-ESI(+/-)-TOF-MS and GC-Q-MS was performed. Additionally, a lipidomic analysis using LC-ESI(+/-)-QTOF-MS based on an in-house library revealed 447 lipid species identified with a high confidence annotation level. The integration of complementary analytical platforms has allowed a comprehensive metabolic and lipidomic characterization of plasma alterations in Long COVID disease that found 46 relevant metabolites which allowed to discriminate between Long COVID and fully recovered patients. We report specific metabolites altered in Long COVID, mainly related to a decrease in the amino acid metabolism and ceramide plasma levels and an increase in the tricarboxylic acid (TCA) cycle, reinforcing the evidence of an impaired mitochondrial function. The most relevant alterations shown in this study will help to better understand the insights of Long COVID syndrome by providing a deeper knowledge of the metabolomic basis of the pathology.

Thioredoxin A regulates protein synthesis to maintain carbon and nitrogen partitioning in cyanobacteria.

Thioredoxins play an essential role in regulating enzyme activity in response to environmental changes, especially in photosynthetic organisms. They are crucial for metabolic regulation in cyanobacteria, but the key redox-regulated central processes remain to be determined. Physiological, metabolic, and transcriptomic characterization of a conditional mutant of the essential Synechocystis sp. PCC 6803 thioredoxin trxA gene (STXA2) revealed that decreased TrxA levels alter cell morphology and induce a dormant-like state. Furthermore, TrxA depletion in the STXA2 strain inhibited protein synthesis and led to changes in amino acid pools and nitrogen/carbon reserve polymers, accompanied by oxidation of the EF-Tu elongation factor. Transcriptomic analysis of TrxA depletion in STXA2 revealed a robust transcriptional response. Down-regulated genes formed a large cluster directly related to photosynthesis, ATP synthesis, and CO2 fixation. In contrast, up-regulated genes were grouped into different clusters related to respiratory electron transport, carotenoid biosynthesis, amino acid metabolism, and protein degradation, among others. These findings highlight the complex regulatory mechanisms that govern cyanobacterial metabolism, where TrxA acts as a critical regulator that orchestrates the transition from anabolic to maintenance metabolism and regulates carbon and nitrogen balance.

Variables epidemiológicas y clínicas en pacientes pediátricos hospitalizados por infección del tracto urinario

Fundamento la infección del tracto urinario es una de las enfermedades más frecuentes en edades pediátricas y se presenta con sintomatología no específica, en especial en los niños más pequeños, en los cuales el signo más importante es la fiebre. Objetivo caracterizar una serie de casos pediátricos hospitalizados a causa de infección del tracto urinario. Métodos se realizó un estudio descriptivo, de tipo serie de casos, en el Hospital Pediátrico de Camagüey, durante el periodo de enero a marzo de 2023. La muestra quedó conformada por 112 pacientes, una vez aplicados los criterios de selección. Fueron estudiadas las variables: grupo etario y sexo, área de salud, signos y síntomas clínicos, factores de riesgo y gérmenes aislados. El procesamiento de los datos se realizó mediante el paquete estadístico para las ciencias sociales y los resultados se expresaron en valores absolutos y porcentajes. Resultados predominó el grupo etario de menores de un año (31,2 %) y el sexo femenino (68,7 %). El Área de Salud Finlay fue la que más casos aportó (22,3 %), mientras que la fiebre resultó el síntoma preponderante (93,8 %), así como el abandono de la lactancia materna se comportó como el principal factor de riesgo (25,9 %). En el 32,1 % de los casos se aisló el germen Escherichia coli. Conclusiones la infección del tracto urinario es más frecuente en lactantes femeninas, y se constata la fiebre como síntoma principal, además de recogerse como factor de riesgo sustancial el abandono de la lactancia materna.

Foundation urinary tract infection is one of the most common diseases in children and presents with non-specific symptoms, especially in younger children, in which the most important sign is fever. Objective to characterize a series of pediatric cases hospitalized due to urinary tract infection. Methods a descriptive study, of a case series type, was carried out at the Pediatric Hospital of Camagüey, from January to March 2023. The sample was made up of 112 patients, once the selection criteria were applied. The studied variables were: age group and sex, health area, clinical signs and symptoms, risk factors and isolated germs. Data processing was carried out using the statistical package for the social sciences and the results were expressed in absolute values and percentages. Results the age group of children under one year (31.2%) and the female sex (68.7%) predominated. The Finlay Health Area was the one that contributed the most cases (22.3%), while fever was the predominant symptom (93.8%), as well as abandoning breastfeeding as the main risk factor (25.9%). In 32.1% of the cases the Escherichia coli germ was isolated. Conclusions urinary tract infection is more frequent in female infants, and fever is confirmed as the main symptom, in addition to the abandonment of breastfeeding being collected as a substantial risk factor.

Discrete magma injections drive the 2021 La Palma eruption.

Understanding the drivers of the onset, evolution, and end of eruptions and their impact on eruption style is critical in eruption forecasting and emergency management. The composition of erupted liquids is a key piece of the volcano puzzle, but untangling subtle melt variations remains an analytical challenge. Here, we apply rapid, high-resolution matrix geochemical analysis on samples of known eruption date spanning the entire 2021 La Palma eruption. Sr isotope signatures reveal distinct pulses of basanite melt driving the onset, restart, and evolution of the eruption. Elemental variations in matrix and microcrysts track progressive invasion, and draining, of a subcrustal crystal mush. Associated variations in lava flow rate, vent development, seismicity, and SO2 emission demonstrate that volcanic matrix resolves eruption patterns that could be expected in future basaltic eruptions globally.

Selective miRNA inhibition in CD8+ cytotoxic T lymphocytes enhances HIV-1 specific cytotoxic responses.

miRNAs dictate relevant virus-host interactions, offering new avenues for interventions to achieve an HIV remission. We aimed to enhance HIV-specific cytotoxic responses-a hallmark of natural HIV control- by miRNA modulation in T cells. We recruited 12 participants six elite controllers and six patients with chronic HIV infection on long-term antiretroviral therapy ("progressors"). Elite controllers exhibited stronger HIV-specific cytotoxic responses than the progressors, and their CD8+T cells showed a miRNA (hsa-miR-10a-5p) significantly downregulated. When we transfected ex vivo CD8+ T cells from progressors with a synthetic miR-10a-5p inhibitor, miR-10a-5p levels decreased in 4 out of 6 progressors, correlating with an increase in HIV-specific cytotoxic responses. The effects of miR-10a-5p inhibition on HIV-specific CTL responses were modest, short-lived, and occurred before day seven after modulation. IL-4 and TNF-α levels strongly correlated with HIV-specific cytotoxic capacity. Thus, inhibition of miR-10a-5p enhanced HIV-specific CD8+ T cell capacity in progressors. Our pilot study proves the concept that miRNA modulation is a feasible strategy to combat HIV persistence by enhancing specific cytotoxic immune responses, which will inform new approaches for achieving an antiretroviral therapy-free HIV remission.

Association between HLA-C alleles and COVID-19 severity in a pilot study with a Spanish Mediterranean Caucasian cohort.

The clinical presentations of COVID-19 may range from an asymptomatic or mild infection to a critical or fatal disease. Several host factors such as elderly age, male gender, and previous comorbidities seem to be involved in the most severe outcomes, but also an impaired immune response that causes a hyperinflammatory state but is unable to clear the infection. In order to get further understanding about this impaired immune response, we aimed to determine the association of specific HLA alleles with different clinical presentations of COVID-19. Therefore, we analyzed HLA Class I and II, as well as KIR gene sequences, in 72 individuals with Spanish Mediterranean Caucasian ethnicity who presented mild, severe, or critical COVID-19, according to their clinical characteristics and management. This cohort was recruited in Madrid (Spain) during the first and second pandemic waves between April and October 2020. There were no significant differences in HLA-A or HLA-B alleles among groups. However, despite the small sample size, we found that HLA-C alleles from group C1 HLA-C*08:02, -C*12:03, or -C*16:01 were more frequently associated in individuals with mild COVID-19 (43.8%) than in individuals with severe (8.3%; p = 0.0030; pc = 0.033) and critical (16.1%; p = 0.0014; pc = 0.0154) disease. C1 alleles are supposed to be highly efficient to present peptides to T cells, and HLA-C*12:03 may present a high number of verified epitopes from abundant SARS-CoV-2 proteins M, N, and S, thereby being allegedly able to trigger an efficient antiviral response. On the contrary, C2 alleles are usually poorly expressed on the cell surface due to low association with ß2-microglobulin (ß2M) and peptides, which may impede the adequate formation of stable HLA-C/ß2M/peptide heterotrimers. Consequently, this pilot study described significant differences in the presence of specific HLA-C1 alleles in individuals with different clinical presentations of COVID-19, thereby suggesting that HLA haplotyping could be valuable to get further understanding in the underlying mechanisms of the impaired immune response during critical COVID-19.

Vitamin D-Related Risk Factors for Maternal Morbidity during Pregnancy: A Systematic Review.

Vitamin D has well-defined classical functions related to metabolism and bone health but also has non-classical effects that may influence pregnancy. Maternal morbidity remains a significant health care concern worldwide, despite efforts to improve maternal health. Nutritional deficiencies of vitamin D during pregnancy are related to adverse pregnancy outcomes, but the evidence base is difficult to navigate. The primary purpose of this review is to map the evidence on the effects of deficiencies of vitamin D on pregnancy outcome and the dosage used in such studies. A systematic search was performed for studies on vitamin D status during pregnancy and maternal outcomes. A total of 50 studies came from PubMed, 15 studies came from Cochrane, and 150 studies came from Embase, for a total of 215 articles. After screening, 34 were identified as candidate studies for inclusion. Finally, 28 articles met the inclusion criteria, which originated from 15 countries. The studies included 14 original research studies and 13 review studies conducted between 2012 and 2021. This review was finally limited to the 14 original studies. This systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, and the quality and strength of the evidence was evaluated using the Navigation Guide Systematic Review Methodology (SING). We found evidence that supports the idea that supplementary vitamin D for pregnant women is important for reducing the risk of gestational diabetes, hypertension, preeclampsia, early labor, and other complications. The data retrieved from this review are consistent with the hypothesis that adequate vitamin D levels might contribute to a healthy pregnancy.

Dynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearance.

Background: Although human immunodeficiency virus type 1 (HIV-1) reservoir size is very stable under antiretroviral therapy (ART), individuals exposed to the Hepatitis C virus (HCV) (chronically coinfected and spontaneous clarifiers) show an increase in HIV reservoir size and in spliced viral RNA, which could indicate that the viral protein regulator Tat is being more actively synthesized and, thus, could lead to a higher yield of new HIV. However, it is still unknown whether the effect of HCV elimination with direct-acting antivirals (DAAs) could modify the HIV reservoir and splicing. Methods: This longitudinal study (48 weeks' follow-up after sustained virological response) involves 22 HIV+-monoinfected individuals, 17 HIV+/HCV- spontaneous clarifiers, and 24 HIV+/HCV+ chronically infected subjects who eliminated HCV with DAAs (all of them aviremic, viral load < 50). Viral-spliced RNA transcripts and proviral DNA copies were quantified by qPCR. Paired samples were analyzed using a mixed generalized linear model. Results: A decrease in HIV proviral DNA was observed in HIV+/HCV- subjects, but no significant differences were found for the other study groups. An increased production of multiple spliced transcripts was found in HIV+ and HIV+/HCV+ individuals. Conclusions: We conclude that elimination of HCV by DAAs was unable to revert the consequences derived from chronic HCV infection for the reservoir size and viral splicing, which could indicate an increased risk of rapid HIV-reservoir reactivation. Moreover, spontaneous clarifiers showed a significant decrease in the HIV reservoir, likely due to an enhanced immune response in these individuals.

Transcriptomic Evidence of the Immune Response Activation in Individuals With Limb Girdle Muscular Dystrophy Dominant 2 (LGMDD2) Contributes to Resistance to HIV-1 Infection.

LGMDD2 is a rare form of muscular dystrophy characterized by one of the three heterozygous deletions described within the TNPO3 gene that result in the addition of a 15-amino acid tail in the C-terminus.TNPO3 is involved in the nuclear import of splicing factors and acts as a host cofactor for HIV-1 infection by mechanisms not yet deciphered. Further characterization of the crosstalk between HIV-1 infection and LGMDD2 disease may contribute to a better understanding of both the cellular alterations occurring in LGMDD2 patients and the role of TNPO3 in the HIV-1 cycle. To this regard, transcriptome profiling of PBMCs from LGMDD2 patients carrying the deletion c.2771delA in the TNPO3 gene was compared to healthy controls. A total of 545 differentially expressed genes were detected between LGMDD2 patients and healthy controls, with a high representation of G protein-coupled receptor binding chemokines and metallopeptidases among the most upregulated genes in LGMDD2 patients. Plasma levels of IFN-ß and IFN-γ were 4.7- and 2.7-fold higher in LGMDD2 patients, respectively. An increase of 2.3-fold in the expression of the interferon-stimulated gene MxA was observed in activated PBMCs from LGMDD2 patients after ex vivo HIV-1 pseudovirus infection. Thus, the analysis suggests a pro-inflammatory state in LGMDD2 patients also described for other muscular dystrophies, that is characterized by the alteration of IL-17 signaling pathway and the consequent increase of metallopeptidases activity and TNF response. In summary, the increase in interferons and inflammatory mediators suggests an antiviral environment and resistance to HIV-1 infection but that could also impair muscular function in LGMDD2 patients, worsening disease evolution. Biomarkers of disease progression and therapeutic strategies based on these genes and mechanisms should be further investigated for this type of muscular dystrophy.

Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D.

Main cause of severe illness and death in COVID-19 patients appears to be an excessive but ineffectual inflammatory immune response that may cause severe acute respiratory distress syndrome (ARDS). Vitamin D may favour an anti-inflammatory environment and improve cytotoxic response against some infectious diseases. A multicenter, single-blind, prospective, randomized clinical trial was approved in patients with COVID-19 pneumonia and levels of 25-hydroxyvitamin D (25(OH)D) of 14.8 ng/ml (SD: 6.18) to test antiviral efficacy, tolerance and safety of 10,000 IU/day of cholecalciferol (vitamin D3) for 14 days, in comparison with 2000 IU/day. After supplementation, mean serum 25(OH)D levels increased to 19 ng/ml on average in 2000 IU/day versus 29 ng/ml in 10,000 IU/day group (p < 0.0001). Although levels of inflammatory cytokines were not modified by treatment with 10,000 IU/day, there was an increase of anti-inflammatory cytokine IL-10 and higher levels of CD4+ T cells, with predominance of T central memory subpopulation. Cytotoxic response against pseudotyped SARS-CoV-2 infected cells was increased more than 4-fold in patients who received 10,000 IU/day. Moreover, levels of IFNγ were significantly higher in this group. Beneficial effect of supplementation with 10,000 IU/day was also observed in participants who developed ARDS and stayed at the hospital for 8.0 days, whereas those who received 2000 IU/day stayed for 29.2 days (p = 0.0381). Administration of high doses of vitamin D3 as adjuvant of the standard care treatment during hospitalization for COVID-19 may improve the inflammatory environment and cytotoxic response against pseudotyped SARS-CoV-2 infected cells, shortening the hospital stay and, possibly, improving the prognosis.

Exploring the Diversity of the Thioredoxin Systems in Cyanobacteria.

Cyanobacteria evolved the ability to perform oxygenic photosynthesis using light energy to reduce CO2 from electrons extracted from water and form nutrients. These organisms also developed light-dependent redox regulation through the Trx system, formed by thioredoxins (Trxs) and thioredoxin reductases (TRs). Trxs are thiol-disulfide oxidoreductases that serve as reducing substrates for target enzymes involved in numerous processes such as photosynthetic CO2 fixation and stress responses. We focus on the evolutionary diversity of Trx systems in cyanobacteria and discuss their phylogenetic relationships. The study shows that most cyanobacteria contain at least one copy of each identified Trx, and TrxA is the only one present in all genomes analyzed. Ferredoxin thioredoxin reductase (FTR) is present in all groups except Gloeobacter and Prochlorococcus, where there is a ferredoxin flavin-thioredoxin reductase (FFTR). Our data suggest that both TRs may have coexisted in ancestral cyanobacteria together with other evolutionarily related proteins such as NTRC or DDOR, probably used against oxidative stress. Phylogenetic studies indicate that they have different evolutionary histories. As cyanobacteria diversified to occupy new habitats, some of these proteins were gradually lost in some groups. Finally, we also review the physiological relevance of redox regulation in cyanobacteria through the study of target enzymes.

Persistent Overactive Cytotoxic Immune Response in a Spanish Cohort of Individuals With Long-COVID: Identification of Diagnostic Biomarkers.

Long-COVID is a new emerging syndrome worldwide that is characterized by the persistence of unresolved signs and symptoms of COVID-19 more than 4 weeks after the infection and even after more than 12 weeks. The underlying mechanisms for Long-COVID are still undefined, but a sustained inflammatory response caused by the persistence of SARS-CoV-2 in organ and tissue sanctuaries or resemblance with an autoimmune disease are within the most considered hypotheses. In this study, we analyzed the usefulness of several demographic, clinical, and immunological parameters as diagnostic biomarkers of Long-COVID in one cohort of Spanish individuals who presented signs and symptoms of this syndrome after 49 weeks post-infection, in comparison with individuals who recovered completely in the first 12 weeks after the infection. We determined that individuals with Long-COVID showed significantly increased levels of functional memory cells with high antiviral cytotoxic activity such as CD8+ TEMRA cells, CD8±TCRγδ+ cells, and NK cells with CD56+CD57+NKG2C+ phenotype. The persistence of these long-lasting cytotoxic populations was supported by enhanced levels of CD4+ Tregs and the expression of the exhaustion marker PD-1 on the surface of CD3+ T lymphocytes. With the use of these immune parameters and significant clinical features such as lethargy, pleuritic chest pain, and dermatological injuries, as well as demographic factors such as female gender and O+ blood type, a Random Forest algorithm predicted the assignment of the participants in the Long-COVID group with 100% accuracy. The definition of the most accurate diagnostic biomarkers could be helpful to detect the development of Long-COVID and to improve the clinical management of these patients.

Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens.

Background: Because inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) to 2-drug regimens (2DR) on inflammation. Methods: Nested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3DR who achieved viral suppression in the first 48 weeks and either remained on 3DR or switched to 2DR (3TC+bPI; 3TC+DTG; DTG+RPV). We assessed the trajectories on inflammatory markers during ART using multivariate piecewise mixed models. Results: We analyzed 619 plasma samples from 148 patients (3DR, N=90; 2DR, N=58), the median follow-up was 4.6 (IQR 3.2-6.2) years. There were no significant differences in baseline characteristics between groups. After adjusting for potential confounders, patients with 3DR experienced a slow decline of IL6, hs-CRP, sCD14, sCD163, and D-dimer over time. In contrast, compared to 3DR, switching to 2DR was associated with increases in IL-6 (p=0.001), hs-CRP (p=0.003), and D-dimer (p=0.001) after year 3 from virologic suppression. 2DR was associated with a higher risk of hs-CRP quartile increase (aOR 3.3, 95%CI 1.1-10) and D-dimer quartile increase (aOR 3.7, 95%CI 1.1-13). The adjusted biomarker trajectories did not reveal a distinct pattern according to the type of 2DR used (bPI vs DTG). Conclusions: In this study in virally suppressed individuals, maintaining 3DR was associated with a more favorable long-term inflammatory profile than switching to 2DR. The potential clinical implications of these findings on the development of non-AIDS events deserve further investigation.

Dark side of cyanobacteria: searching for strategies to control blooms.

Cyanobacteria are ecologically one of the most prolific groups of photosynthetic prokaryotes in marine and freshwater habitats. They are primary producer microorganisms and are involved in the production of important secondary metabolites, including toxic compounds such as cyanotoxins. Environmental conditions promote massive growth of these microbes, causing blooms that can have critical ecological and public health implications. In this highlight, we discuss some of the approaches being addressed to prevent these blooms, such as control of nutrient loading, treatments to minimize growth or monitoring interactions with other species.

Aspectos clínico-epidemiológicos de niños ingresados por sospecha de COVID-19 en Camagüey / Aspectos clínico-epidemiológicos de crianças internadas por suspeita de COVID-19 em Camagüey / Clinical-epidemiological aspects of children admitted for suspected COVID-19 in Camagüey

Introducción: en Cuba se mantiene la vigilancia y búsqueda activa de casos y sus contactos en el nivel comunitario y, luego, su seguimiento en los servicios de salud organizados en el territorio nacional. Estas acciones en edades pediátricas constituyen una preocupación de las autoridades sanitarias. Objetivo: describir el comportamiento de las principales variables clínico-epidemiológicas de los niños atendidos en el hospital de campaña Villa Azucarera, de Camagüey, en el periodo comprendido del 4 de marzo al 17 de abril de 2021. Método: se realizó un estudio descriptivo de corte transversal en los 287 pacientes ingresados en dicho hospital con criterio diagnóstico de sospecha de COVID-19 provenientes de las áreas de salud de la provincia. Fueron analizadas las variables: edad, sexo, criterio epidemiológico, resultado RT-PCR, criterios clínicos y diagnóstico al egreso en los casos que resultaron negativos a la prueba confirmatoria. Resultados: del total de pacientes, 29 (10,1 porciento) resultaron positivos al SARS-CoV-2. Predominaron los pacientes contactos de casos confirmados (43,2 porciento). La rinorrea fue el síntoma más frecuente (13; 44,8 porciento). El catarro común (53,9 porciento) y el síndrome febril inespecífico (15,1 porciento) fueron los diagnósticos más frecuentes en los pacientes negativos. Conclusiones: la edad y el sexo no muestran diferencias significativas entre sospechosos y confirmados, las manifestaciones clínicas son similares en ambos grupos con predominio de fiebre y síntomas respiratorios altos, aunque otras manifestaciones digestivas y neurológicas son descritas. El contacto con casos confirmados es el principal factor epidemiológico relacionado con el diagnóstico de la enfermedad(AU).

Introduction: in Cuba, the surveillance and active search for COVID-19 confirming cases and their contacts are actions still performing at the community, and later keep their follow-up at the health care services organized in the national territory. These actions at pediatric ages are a health authorities concern. Objective: to describe the behavior of the main clinical-epidemiological variables of children treated at the Villa Azucarera field hospital in Camagüey, from March 4 to April 17, 2021. Methods: a descriptive cross-sectional study was carried out in 287 patients admitted to the hospital with diagnostic criteria of suspected COVID-19 from different health areas in the province. The following variables were analyzed: age, sex, epidemiological criteria, RT-PCR result, clinical criteria and diagnosis at discharge in cases that were negative to the confirmatory test. Results: twenty nine patients of the total (10.1 percent) were tested positive for SARS-CoV-2. The contacts of confirmed cases (43.21 percent) were predominant. Rhinorrhea was the most frequent symptom (13; 44.81 percent). Common cold (53.91 percent) and non-specific febrile syndrome (15.11 percent) were the most frequent diagnoses in negative patients. Conclusions: age and sex do not show significant differences between suspected and confirmed cases. Clinical manifestations are similar in both groups with predominance of fever and high respiratory symptoms, although other digestive and neurological manifestations are described. Close contact with confirmed cases is the main epidemiological factor related to the diagnosis of the disease(AU).

Introdução: em Cuba, mantém-se em nível comunitário a vigilância e busca ativa dos casos e seus contatos e, posteriormente, seu acompanhamento nos serviços de saúde organizados em território nacional. Essas ações em idade pediátrica constituem uma preocupação das autoridades de saúde. Objetivo: descrever o comportamento das principais variáveis clínico-epidemiológicas das crianças atendidas no hospital de campanha Villa Azucarera, em Camagüey, no período de 4 de março a 17 de abril de 2021. Método: foi realizado um estudo descritivo transversal - estudo seccional dos 287 pacientes internados no referido hospital com critérios diagnósticos de suspeita de COVID-19 nas áreas de saúde da província. Foram analisadas as variáveis: idade, sexo, critérios epidemiológicos, resultado do RT-PCR, critérios clínicos e diagnóstico de alta nos casos negativos no teste confirmatório. Resultados: do total de pacientes, 29 (10,1 porcento) foram positivos para SARS-CoV-2. Predominaram os contatos de casos confirmados (43,2 porcento). A rinorreia foi o sintoma mais frequente (13; 44,8 porcento). O resfriado comum (53,9 porcento) e a síndrome febril inespecífica (15,1 porcento) foram os diagnósticos mais frequentes nos pacientes negativos. Conclusões: a idade e o sexo não apresentam diferenças significativas entre os suspeitos e os confirmados, as manifestações clínicas são semelhantes nos dois grupos com predomínio de febre e sintomas respiratórios superiores, embora sejam descritas outras manifestações digestivas e neurológicas. O contato com os casos confirmados é o principal fator epidemiológico relacionado ao diagnóstico da doença(AU).

Impaired Antibody-Dependent Cellular Cytotoxicity in a Spanish Cohort of Patients With COVID-19 Admitted to the ICU.

SARS-CoV-2 infection causes COVID-19, ranging from mild to critical disease in symptomatic subjects. It is essential to better understand the immunologic responses occurring in patients with the most severe outcomes. In this study, parameters related to the humoral immune response elicited against SARS-CoV-2 were analysed in 61 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centres in Madrid, Spain, during the first pandemic peak between April and June 2020. Subjects were allocated as mild patients without hospitalization, severe patients hospitalized or critical patients requiring ICU assistance. Critical patients showed significantly enhanced levels of B cells with memory and plasmablast phenotypes, as well as higher levels of antibodies against SARS-CoV-2 with neutralization ability, which were particularly increased in male gender. Despite all this, antibody-dependent cell-mediated cytotoxicity was defective in these individuals. Besides, patients with critical COVID-19 also showed increased IgG levels against herpesvirus such as CMV, EBV, HSV-1 and VZV, as well as detectable CMV and EBV viremia in plasma. Altogether, these results suggest an enhanced but ineffectual immune response in patients with critical COVID-19 that allowed latent herpesvirus reactivation. These findings should be considered during the clinical management of these patients due to the potential contribution to the most severe disease during SARS-CoV-2 infection.

Depletion of m-type thioredoxin impairs photosynthesis, carbon fixation, and oxidative stress in cyanobacteria.

Thioredoxins (Trxs) are disulfide oxidoreductases that regulate many biological processes. The m-type thioredoxin (TrxA) is the only Trx present in all oxygenic photosynthetic organisms. Extensive biochemical and proteomic analyses have identified many TrxA target proteins in different photosynthetic organisms. However, the precise function of this essential protein in vivo is still poorly known. In this study, we generated a conditional Synechocystis sp. PCC 6803 mutant strain (STXA2) using an on-off promoter that is able to survive with only 2% of the TrxA level of the wild-type (WT) strain. STXA2 characterization revealed that TrxA depletion results in growth arrest and pronounced impairment of photosynthesis and the Calvin-Benson-Bassham (CBB) cycle. Analysis of the in vivo redox state of the bifunctional enzyme fructose-1,6-bisphosphatase/sedoheptulose-1,7-bisphosphatase showed higher levels of oxidation that affected enzyme activity in STXA2. This result implies that TrxA-mediated redox regulation of the CBB cycle is conserved in both cyanobacteria and chloroplasts, although the targets have different evolutionary origins. The STXA2 strain also accumulated more reactive oxygen species and was more sensitive to oxidative stress than the WT. Analysis of the in vivo redox state of 2-Cys peroxiredoxin revealed full oxidation, corresponding with TrxA depletion. Overall, these results indicate that depletion of TrxA in STXA2 greatly alters the cellular redox state, interfering with essential processes such as photosynthetic machinery operativity, carbon assimilation, and oxidative stress response. The TrxA regulatory role appears to be conserved along the evolution of oxygenic photosynthetic organisms.