Dysbiosis: An Indicator of COVID-19 Severity in Critically Ill Patients.

Here, we examined the dynamics of the gut and respiratory microbiomes in severe COVID-19 patients in need of mechanical ventilation in the intensive care unit (ICU). We recruited 85 critically ill patients (53 with COVID-19 and 32 without COVID-19) and 17 healthy controls (HCs) and monitored them for up to 4 weeks. We analyzed the bacterial and fungal taxonomic profiles and loads of 232 gut and respiratory samples and we measured the blood levels of Interleukin 6, IgG, and IgM in COVID-19 patients. Upon ICU admission, the bacterial composition and load in the gut and respiratory samples were altered in critically ill patients compared with HCs. During their ICU stay, the patients experienced increased bacterial and fungal loads, drastic decreased bacterial richness, and progressive changes in bacterial and fungal taxonomic profiles. In the gut samples, six bacterial taxa could discriminate ICU-COV(+) from ICU-COV(-) cases upon ICU admission and the bacterial taxa were associated according to age, PaO2/FiO2, and CRP levels. In the respiratory samples of the ICU-COV(+) patients, bacterial signatures including Pseudomonas and Streptococcus were found to be correlated with the length of ICU stay. Our findings demonstrated that the gut and respiratory microbiome dysbiosis and bacterial signatures associated with critical illness emerged as biomarkers of COVID-19 severity and could be a potential predictor of ICU length of stay. We propose using a high-throughput sequencing approach as an alternative to traditional isolation techniques to monitor ICU patient infection.

COVID-19 vaccine effectiveness against hospitalization due to SARS-CoV-2: A test-negative design study based on Severe Acute Respiratory Infection (SARI) sentinel surveillance in Spain.

BACKGROUND: With the emergence of SARS-CoV-2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for acute respiratory infection (ARI) surveillance in primary care and a network of sentinel hospitals for severe ARI (SARI) surveillance in hospitals. METHODS: Using a test-negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID-19 vaccine effectiveness (VE) against hospitalization, by age group, vaccine type, time since vaccination, and SARS-CoV-2 variant. RESULTS: VE was 89% (95% CI: 83-93) against COVID-19 hospitalization overall in persons aged 20 years and older. VE was higher for mRNA vaccines, and lower for those aged 80 years and older, with a decrease in protection beyond 3 months of completing vaccination, and a further decrease after 5 months. We found no differences between periods with circulation of Alpha or Delta SARS-CoV-2 variants, although variant-specific VE was slightly higher against Alpha. CONCLUSIONS: The SiVIRA sentinel hospital surveillance network in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations and provide estimates of COVID-19 VE in the population under surveillance. Our estimates add to evidence of high effectiveness of mRNA vaccines against severe COVID-19 and waning of protection with time since vaccination in those aged 80 or older. No substantial differences were observed between SARS-CoV-2 variants (Alpha vs. Delta).

[Trichinellosis outbreaks in Aragón (1998-2017)]. / Brotes epidémicos de triquinosis ocurridos en Aragón durante el periodo 1998 ­ 2017.

OBJECTIVE: In Aragon, official veterinary controls to detect the presence of Trichinella in meat products have allowed trichinosis to be a low-incidence disease in the form of outbreaks associated with family consumption of meat products that are not sanitarily controlled. The aim of the work was to describe the epidemiological characteristics of the trichinosis outbreaks that occurred in Aragon during the study period and the action measures carried out, which served as a basis for redesigning and strengthening prevention and control measures. METHODS: Descriptive study of the characteristics of time, place, person, food implicated, etiological agent and control measures implemented in the outbreaks identified by the Epidemiological Surveillance Network of Aragón from 01/01/1998 to 31/12/2017. For the descriptive analysis, the mean with its standard deviation and proportions were calculated. RESULTS: During the study period (from 01/01/1998 until 31/12/2017) there were 7 family outbreaks with 294 exposed, 103 cases (Attack Rate 35%), of which 29 were hospitalized (28.1%). The case fatality rate was 1%. The average age of the cases was 43.3 years (standard deviation 15.9). 70.8% of the cases were male. Outbreaks were concentrated between December and May. Five outbreaks originated after consumption of wild boar. The etiological agent identified in meat and/or biological samples from the cases was Trichinella spiralis in four outbreaks and Trichinella britovi in two other outbreaks, while the agent could not be identified in one outbreak. In all outbreaks, actions were carried out in accordance with the recommendations established by the National Epidemiological Surveillance Network (RENAVE). CONCLUSIONS: Trichinosis in Aragon takes the form of sporadic family outbreaks coinciding with the time of wild boar hunting and home slaughtering of pigs and is associated with the consumption of meat products not controlled sanitarily, so it is necessary to strengthen health education and intersectoral collaboration in the development and implementation of prevention and control strategies.

OBJETIVO: En Aragón, los controles oficiales veterinarios para detectar la presencia de triquina en productos cárnicos, han permitido que la triquinosis sea una enfermedad de baja incidencia, que se presenta en forma de brotes, asociados al consumo familiar de productos cárnicos no controlados sanitariamente. El objetivo del trabajo fue describir las características epidemiológicas de los brotes de triquinosis ocurridos en Aragón durante el periodo de estudio y las medidas de actuación llevadas a cabo, lo que sirvió de base para rediseñar y fortalecer las medidas de prevención y control. METODOS: Estudio descriptivo de las características tiempo, lugar, persona, alimentos implicados, agente etiológico y medidas de control implementadas en los brotes identificados por la Red de Vigilancia Epidemiológica de Aragón desde el 01/01/1998 al 31/12/2017. Para el análisis descriptivo se calcularon la media con su desviación estándar y las proporciones. RESULTADOS: Durante el periodo de estudio (desde el 01/01/1998 hasta el 31/12/2017) se declararon 7 brotes familiares con 294 expuestos, 103 casos (Tasa de Ataque 35%), de los que 29 fueron hospitalizados (28,1%). La tasa de letalidad fue del 1%. La media de edad de los casos fue de 43,3 años (desviación típica 15,9). El 70,8% de los casos fueron varones. Los brotes se concentraron entre diciembre y mayo. Cinco brotes se originaron tras el consumo de jabalí. El agente etiológico aislado en muestras cárnicas y/o muestras biológicas procedentes de los casos, fue Trichinella spiralis en cuatro brotes y Trichinella britovi en otros dos brotes. En todos los brotes las actuaciones se realizaron conforme a las recomendaciones establecidas por la Red Nacional de Vigilancia Epidemiológica (RENAVE). CONCLUSIONES: La triquinosis en Aragón se presenta en forma de brotes familiares esporádicos coincidentes con la época de caza de jabalí y matanza domiciliaria del cerdo y se asocia al consumo de productos cárnicos no controlados sanitariamente, por lo que es necesario reforzar la educación para la salud y la colaboración intersectorial en la elaboración e implantación de estrategias de prevención y control.

Short-term effect of antibiotics on human gut microbiota.

From birth onwards, the human gut microbiota rapidly increases in diversity and reaches an adult-like stage at three years of age. After this age, the composition may fluctuate in response to external factors such as antibiotics. Previous studies have shown that resilience is not complete months after cessation of the antibiotic intake. However, little is known about the short-term effects of antibiotic intake on the gut microbial community. Here we examined the load and composition of the fecal microbiota immediately after treatment in 21 patients, who received broad-spectrum antibiotics such as fluoroquinolones and ß-lactams. A fecal sample was collected from all participants before treatment and one week after for microbial load and community composition analyses by quantitative PCR and pyrosequencing of the 16S rRNA gene, respectively. Fluoroquinolones and ß-lactams significantly decreased microbial diversity by 25% and reduced the core phylogenetic microbiota from 29 to 12 taxa. However, at the phylum level, these antibiotics increased the Bacteroidetes/Firmicutes ratio (p = 0.0007, FDR = 0.002). At the species level, our findings unexpectedly revealed that both antibiotic types increased the proportion of several unknown taxa belonging to the Bacteroides genus, a Gram-negative group of bacteria (p = 0.0003, FDR<0.016). Furthermore, the average microbial load was affected by the treatment. Indeed, the ß-lactams increased it significantly by two-fold (p = 0.04). The maintenance of or possible increase detected in microbial load and the selection of Gram-negative over Gram-positive bacteria breaks the idea generally held about the effect of broad-spectrum antibiotics on gut microbiota.

Microbiome composition by pyrosequencing in mesenteric lymph nodes of rats with CCl4-induced cirrhosis.

BACKGROUND: The cross talk between the gut microbiota and the immune system, which is essential to maintain homeostasis, takes place at the intestinal lymphoid tissue such as the mesenteric lymph nodes (MLNs). Here, we investigated the presence of bacterial DNA in MLNs of control and cirrhotic rats and its relationship with inflammatory responses. METHODS: The MLN microbiome of cirrhotic rats with ascites, which was induced by carbon tetrachloride (CCl4), was compared to that of control rats using quantitative real-time PCR and pyrosequencing of the 16S rRNA gene. Cytokines in blood samples were assessed by ELISA. RESULTS: Unexpectedly, sequence analysis revealed a high microbial diversity in the MLNs of both control and cirrhotic rats with Proteobacteria as one of the most dominant phylum. CCl4-induced liver injury was not associated with a change in bacterial load, but it was linked to a decrease in microbial diversity (p < 0.05) and alterations in the microbial community in MLNs. A high proportion of Bifidobacterium animalis was also positively correlated with elevated interleukin-10 expression (p = 0.002, false discovery rate = 0.03, r = 0.94). CONCLUSIONS: For the first time, the high microbial diversity observed in MLNs of both controls and CCl4-induced cirrhotic rats provides evidence that bacterial translocation is more than a mere dichotomic phenomenon.

Blockage of the afferent sensitive pathway prevents sympathetic atrophy and hemodynamic alterations in rat portal hypertension.

BACKGROUND AND AIMS: Portal hypertension causes arterial vasodilation and sympathetic atrophy in the splanchnic area. We aimed to demonstrate a relationship between hemodynamic alterations and sympathetic atrophy by investigating a pathway from sensitive afferent signals to mesenteric sympathetic ganglia. METHODS: Experiments were conducted in sham and portal vein ligated (PVL) adult and neonatal rats treated with vehicle or capsaicin. Hemodynamic parameters, and immunohistochemistry, immunofluorescence and Western blot of different tissues were analysed. RESULTS: cFos expression in the brain supraoptic nuclei was used to confirm abrogation of the afferent signal in capsaicin-treated PVL rats (effectively afferent blocked). Neonatal and adult PVL afferent blocked rats showed simultaneous prevention of hemodynamic alterations and sympathetic atrophy (measured by tyrosine hydroxylase expression in nerve structures of splanchnic vasculature). Not effectively afferent blocked rats showed none of these effects, behaving as PVL vehicle. All capsaicin treated animals presented loss of calcitonin gene-related peptide in superior mesenteric artery and ganglia, whereas neuronal nitric oxide synthase remained unaffected. Neuronal markers semaphorin-3A, nerve growth factor, its precursor and p75 neurotrophic receptor, were significantly over-expressed in the PVL sympathetic ganglia compared with sham, but not in effectively afferent blocked rats. Semaphorin-3A staining in mesenteric ganglia co-localized with vesicular acetylcholine transporter, but not with adrenergic, nitrergic and sensory axons, suggesting that semaphorin-3A might originate in preganglionic neurons. CONCLUSION: These results indicate that the nervous system has a central role in the genesis of the circulatory abnormalities of portal hypertension, and support that mesenteric sympathetic atrophy contributes to splanchnic arterial vasodilation.

Atrophy of mesenteric sympathetic innervation may contribute to splanchnic vasodilation in rat portal hypertension.

BACKGROUND AND AIMS: Portal hypertension is associated with downregulation of mRNA and proteins involved in adrenergic transmission in the superior mesenteric artery (SMA) in portal vein-ligated (PVL) and cirrhotic rats. We aimed to investigate whether SMA adrenergic dysfunction was accompanied by sympathetic nerve structural changes and whether it was extensive to resistance mesenteric arteries. We also attempted to localize the origin of mRNA of specific adrenergic genes. METHODS AND RESULTS: In situ hybridization showed tyrosine hydroxylase (Th) mRNA expression in neuronal bodies of superior mesenteric ganglia and inside axonal fibres surrounding proximal SMA sections. Comparison of SMA by Th immunohistochemistry, both in PVL and bile duct-ligated (BDL) rats, demonstrated a significant decrease in the number of nervous structures (69% PVL; 62% BDL), total nervous area (70% PVL; 52% BDL) and Th-stained nervous area (89% PVL; 64% BDL) compared with sham rats. A strong correlation was detected between the Th-stained nervous area and the haemodynamic parameters, mainly with SMA resistance (r=0.9, P<0.001 for PVL and r=0.75, P=0.018 for BDL). Western blot analysis of Th, dopamine beta-hydroxylase and synaptosome-associated protein of 25 kDa indicated a significant inhibition in protein expression (35-58%) in mesenteric resistance arteries from both portal hypertension models compared with sham. By contrast, nervous structure analysis and protein expression in renal arteries showed no differences between sham and PVL rats. CONCLUSION: Portal hypertension is associated with sympathetic nerve atrophy/regression in the mesenteric arterial vasculature that could contribute to the splanchnic vasodilation associated with portal hypertension.

[Outbreak of scabies at a home for the elderly in the province of Huesca]. / Brote de escabiosis en una residencia para personas mayores en la provincia de Huesca.

BACKGROUND: Individuals residing in institutionalized living facilities are currently a high-risk group as regards scabies outbreaks. This study is aimed at analyzing the characteristics of one of these outbreaks, which occurred at a senior citizen living facility located in the municipality of Barbastro (Huesca) through the Huesca Provincial Epidemiological Monitoring Division. METHODS: Following the initial notification of cases, a specific scabies prevention protocol was set out. An epidemiological investigation was conducted, proceeding to an active search for cases among all of the individuals residing or working at the facility in question. The information gathered on the cases and contacts by means of a validated survey was included in a database using Epiinfo 6.0. The attack rate and the relative risk of those residing in each area of the center were estimated, taking as a reference that having the lowest attack rate. RESULTS: A total of nineteen (18 and 1 respectively) cases of scabies were detected among the 104 residents and 20 workers employed at the facility. The source of the outbreak could not be specifically determined, although at least two of the first cases had begun to show some symptoms six months prior to their detection. The average delay in diagnosis was 53 days. This outbreak had a greater effect on the males in the assisted living quarters (TA = 77%; RR = 18.5, C195% = 2.7-128.7). The only employee affected was the person in charge of this area, who had not employed the universal personal protection measures during his caregiving tasks. CONCLUSIONS: This is a scabies outbreak at a senior citizen living facility, probably due to the delay in diagnosing the first cases and the failure on the part of one caregiver to have employed the personal protection measures. A specific scabies-prevention protocol having been implemented was fundamental for the control of this outbreak.