Identification of IL-6 Signalling Components as Predictors of Severity and Outcome in COVID-19.

IL-6 is one of the major mediators of the hyper-inflammatory responses with complex biological functions as it can signal via different modes of action. IL-6 by classical signalling has anti-inflammatory and antibacterial activities, while trans-signalling mediates pro-inflammatory effects. The net biological effect of IL-6 is established by multiple factors beyond its absolute concentration. Here, we assess the relationship between IL-6 signalling variables [IL-6, soluble IL-6R (sIL-6R) and soluble gp130 (sgp130)] and outcomes in a cohort of 366 COVID-19 patients. The potential trans-signalling was evaluated by a ratio between the pro-inflammatory binary IL-6:sIL-6R complex and the inactive ternary IL-6:sIL-6R:sgp130 complex (binary/ternary complex) and the fold molar excess of sgp130 over sIL-6R (FME). Our data provide new evidence that high levels of IL-6, sIL-6R, sgp130, binary/ternary complex ratio, and low FME are independent predictors of COVID-19 severity in survivor patients (without death), and the combination of IL-6 + sIL-6R + sgp130 exhibited the most robust classification capacity. Conversely, in a subgroup of patients with a very poor prognosis, we found that high levels of IL-6 and low levels of sIL-6R, sgp130, and binary/ternary complex ratio were predictors of death. In this context, the highest predictive capacity corresponded to the combined analysis of IL-6 + FME + lymphopenia + creatinine. Herein, we present IL-6 signalling variables as a helpful tool for the early identification and stratification of patients with clear implications for treatment and clinical decision-making.

Severe immunosuppression is related to poorer immunogenicity to SARS-CoV-2 vaccines among people living with HIV.

OBJECTIVES: The aim of this study was to assess the immunogenicity of SARS-CoV-2 available vaccines among people living with HIV (PLWH) after a complete vaccination scheme, and determine predictors of seroconversion. METHODS: This multicentre prospective cohort study included 420 PLWH who had received a standard immunization, either with mRNA or adenoviral-vectored COVID-19 vaccines. Antibody response was evaluated within 1 to 2 months after the last dose of the vaccine with a quantitative determination of antitrimeric spike protein-specific IgG antibodies and IgG neutralizing antibodies. RESULTS: Overall, 384 of 420 PLWH (91%) showed antibody response to vaccination. Seroconversion was observed in 308 of 326 individuals with cluster of differentiation 4 (CD4) counts ≥350 cells/mm3 (95%), 55 of 61 PLWH with 200 to 349 cells/mm3 (90%), and 21 of 33 PLWH with CD4 counts <200 cells/mm3 (64%; p < 0.001). The median log10 IgG neutralization levels were 2.4 IU/mL (Q1-Q3, 1.0-3.1) among PLWH with CD4 counts <200 cells/mm3, 3.1 IU/mL (Q1-Q3, 2.8-3.4) for the 200 to 349 cells/mm3 group, and 3.1 IU/mL (Q1-Q3, 2.7-3.4) for PLWH with CD4 counts ≥350 cells/mm3 (p = 0.016). In the multivariate analysis, CD4 counts ≥350 cells/mm3 (OR: 7.10; 95% CI, 1.91-26.46; p = 0.004) and receiving mRNA-vectored COVID-19 vaccines (OR: 8.19; 95% CI, 3.24-20.70; p ≤ 0.001) were independently associated with a higher probability of response to vaccination. DISCUSSION: HIV-related immunosuppression impairs the antibody response to SARS-CoV-2 vaccines. Specific vaccination schemes should be urgently tailored in this setting, particularly in patients with CD4 cell counts <200 cells/µL. Adenoviral-vectored vaccines should be avoided in PLWH whenever possible.

Incidence of and factors associated with SARS-CoV-2 infection among people living with HIV in Southern Spain after one year of pandemic.

Whether people living with HIV (PLWH) are at greater risk of acquiring SARS-CoV-2 infection is currently unknown. Prospective serologic studies may allow seroincidence analyses, where all infections are accurately identified. Because of this, we evaluated the incidence of associated factors with and the clinical outcome of SARS-CoV-2 infection in PLWH in Southern Spain. This prospective cohort study included PLWH from a Tertiary University Hospital in Southern Spain. Patients were enrolled in the study if (1) they had attended as outpatients our Unit from 1 August 2019 to 8 February 2020 and (2) had two subsequent evaluations from 9 February 2020 to 4 March 2021. SARS-CoV-2 infections were diagnosed by PCR, antigen detection or serology. Seven hundred and nine PLWH were included in the study. Of them, 55 [7.8%, 95% confidence interval (95% CI) 5.9%-9.9%] patients developed SARS-CoV-2 infection. Between 18 May and 29 November 2020, the rate of seroconversion was 5.3% (95% CI: 3.1%-9.0%) for the general population in the area of Seville and 2.3% (95% CI: 1.3%-2.6%) for PLWH in this study (p = .001). After multivariable analysis, adjusted by age, sex, and risk factors for HIV infection, active tobacco use and CDC stage, active tobacco smoking was the only factor independently associated with lower risk of SARS-Cov-2 infection [Incidence rate ratio: 0.29 (95% CI 0.16-0.55) p < .001]. In conclusion, the incidence of SARS-CoV-2 infection among PLWH in Southern Spain during the ongoing pandemic was lower than that reported for the general population in the same area.

Physico-chemical and microbiological changes in commercial tilapia (Oreochromis niloticus) during cold storage / Cambios fisico-químicos y microbiológicos en tilapia comercial (Oreochromis niloticus) durante almacenamiento refrigerado

Background: The microbiological and chemical processes are the main responsible for deterioration of fresh fish. Therefore, it is essential to avoid these processes by applying good manufacturing practices during fish handling, distribution and storage. Objective: The aim of this paper was to evaluate the physico-chemical and microbial changes in commercial tilapia (Oreochromis niloticus) during cold storage in order to establish the shelf life since its arrival at the supermarket. Methods: 27 aquacultured tilapia specimens were analyzed at 0, 2, 4, and 7 days of storage at 4ºC. Measurements of texture, color, water holding capacity, total volatile basic nitrogen (TVB-N), thiobarbituric acid index, ATP-related compounds, as well as microbial analyses were carried out. Results: The TVB-N content was high at the beginning of the study, remaining stable during the storage. Lipid oxidation of samples was minimum, so this process did not contribute to the fish spoilage. It was observed the breakdown of inosine-5'- monophosphate (IMP) into Ino (inosine), and Ino into Hx (hypoxantine). The texture parameters and colour underwent changes as a consequence of the fish spoilage. Low microbial counts were observed at day 0, but Enterobacteriaceae and mesophilic counts gradually increased throughout storage. Conclusions: The K1 -value showed the progressive spoilage of the fish during the cold storage. The decrease of hardness and firmness confirmed the loss of quality throughout the time of study. The low microbial counts at the beginning of the study demonstrated the good quality of the tilapia; however, the increase of the mesophilic counts at the end of the studied period showed that tilapia was not fit for human consumption at day 7.

Antecedentes: Los procesos microbiológicos y químicos son los principales responsables del deterioro del pescado fresco. Por tanto, es esencial evitar estos procesos aplicando buenas prácticas de fabricación durante la manipulación, distribución y almacenamiento del pescado. Objetivo: El objetivo de este trabajo fue evaluar los cambios físico-químicos y microbiológicos en tilapia comercial (Oreochromis niloticus) durante el almacenamiento refrigerado con el fin de establecer la vida útil desde su llegada al supermercado. Métodos: 27 especímenes de tilapia fueron analizados a día 0, 2, 4 y 7 de almacenamiento a 4 ºC. Se llevaron a cabo medidas de textura, color, capacidad de retención de agua, nitrógeno básico volátil total (N-BVT), índice del ácido tiobarbitúrico, compuestos relacionados con el ATP, así como análisis microbianos. Resultados: El contenido en N-BVT fue alto al principio del estudio, siendo estable durante el almacenamiento. La oxidación lipídica de las muestras fue mínima, por lo que este proceso no contribuyó al deterioro del pescado. Se observó la degradación de inosina-5'- monofosfato (IMP) a Ino (inosina), y de Ino a Hx (hipoxantina). Los parámetros de textura y color sufrieron cambios como consecuencia del deterioro del pescado. Se observaron bajos recuentos microbianos a día 0, pero los recuentos de Enterobacteriaceae y de mesófilos aumentaron gradualmente durante el almacenamiento. Conclusiones: El valor K1 mostró el deterioro progresivo del pescado durante el almacenamiento en refrigeración. La disminución de dureza y firmeza confirmó la pérdida de calidad a lo largo del tiempo de estudio. Los bajos recuentos microbianos al principio del estudio demostraron la buena calidad de la tilapia; sin embargo, el aumento de los recuentos de mesófilos al final del periodo estudiado mostraron que la tilapia no era adecuada para el consumo humado a día 7.