SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replication.

Serine incorporator protein 5 (SERINC5) is a key innate immunity factor that operates in the cell to restrict the infectivity of certain viruses. Different viruses have developed strategies to antagonize SERINC5 function but, how SERINC5 is controlled during viral infection is poorly understood. Here, we report that SERINC5 levels are reduced in COVID-19 patients during the infection by SARS-CoV-2 and, since no viral protein capable of repressing the expression of SERINC5 has been identified, we hypothesized that SARS-CoV-2 non-coding small viral RNAs (svRNAs) could be responsible for this repression. Two newly identified svRNAs with predicted binding sites in the 3'-untranslated region (3'-UTR) of the SERINC5 gene were characterized and we found that the expression of both svRNAs during the infection was not dependent on the miRNA pathway proteins Dicer and Argonaute-2. By using svRNAs mimic oligonucleotides, we demonstrated that both viral svRNAs can bind the 3'UTR of SERINC5 mRNA, reducing SERINC5 expression in vitro. Moreover, we found that an anti-svRNA treatment to Vero E6 cells before SARS-CoV-2 infection recovered the levels of SERINC5 and reduced the levels of N and S viral proteins. Finally, we showed that SERINC5 positively controls the levels of Mitochondrial Antiviral Signalling (MAVS) protein in Vero E6. These results highlight the therapeutic potential of targeting svRNAs based on their action on key proteins of the innate immune response during SARS-CoV-2 viral infection.

The medium-term consequences of a COVID-19 lockdown on lifestyle among Spanish older people with hypertension, pulmonary disease, cardiovascular disease, musculoskeletal disease, depression, and cancer.

OBJECTIVES: This study investigated the associations of chronic diseases with changes in lifestyle and health behaviours in older people following the coronavirus disease 2019 (COVID-19) lockdown in Spain and compared the differences in changes over time. METHODS: 1,092 participants (80.3±5.6 years; 66.5% female) from 2 Spanish cohorts were included. Telephone-based questionnaires were conducted to evaluate lifestyle and health risk behaviours at the end of lockdown and 7 months post-lockdown. Participants were classified as having physician-diagnosed chronic diseases based on self-reported data. Cox proportional models adjusted for major confounders were used. RESULTS: Compared to those without the corresponding chronic diseases, older people with hypertension were less likely to report increased alcohol consumption (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55 to 0.99). Pulmonary diseases were associated with lower risks of increased sedentary time (HR, 0.58; 95% CI, 0.39 to 0.86) and worsened sleep quality (HR, 0.56; 95% CI, 0.36 to 0.87), while cardiovascular diseases were associated with a lower risk of decreased sedentary time (HR, 0.58; 95% CI, 0.38 to 0.88). Depression was linked to a higher likelihood of improved diet quality (HR, 1.53; 95% CI, 1.00 to 2.36). Cancer pacients were less likely to have worsened sleep quality (HR, 0.44; 95% CI, 0.22 to 0.89) but more likely to have reduced their frequency of social contact (HR, 2.05; 95% CI, 1.05 to 3.99). CONCLUSIONS: Older people with chronic diseases showed beneficial changes in lifestyle and health risk behaviours after the COVID-19 lockdown. In particular, older people with hypertension, pulmonary disease, and cancer tended to make beneficial lifestyle and health behaviour changes. However, older people with cardiovascular disease and depression engaged in more health risk behaviours.

[The sustainability of the health system and the pharmaceutical market: A permanent interaction between the cost of medications, the patent system, and disease care]. / La sostenibilidad del sistema de salud y el mercado farmacéutico: Una interacción permanente entre el costo de los medicamentos, el sistema de patentes y la atención a las enfermedades.

Taking into account the latent threat of future pandemics, the objective of this study is to analyze - particularly with respect to medications - the sustainability of the health system, healthcare coverage, budgetary efficiency, and connections with the pharmaceutical patent system. In this context, the pharmaceutical patent system acts as a determining factor, given that promoting its existence stimulates the production of research, but in turn its existence stands in the way of rapid advancements, primarily due to the development of protective legislation concerning patents, which has largely accommodated the industry. Given that the pharmaceutical industry has managed to extend the duration of patents and avoid the incorporation of generics, our analysis focuses on the influence of pharmaceutical patents; this influence has led to reflection on the possibility of combining efforts by forging alliances between numerous companies and the public sector in order to face the challenges posed by new diseases caused by viruses that give rise to epidemics and pandemics.

Ante la amenaza latente de futuras pandemias, este estudio tiene como objetivo analizar ­desde el eje de los medicamentos­ la sostenibilidad del sistema sanitario, la cobertura, la eficiencia del gasto y su vinculación al sistema de patentes farmacéuticas. En este marco, el sistema de patentes farmacéuticas adquiere un papel determinante, dado que fomentar su existencia estimula la producción de investigación pero, a su vez, su existencia no suscita un rápido avance, debido al desarrollo legislativo protector que han tenido las patentes y que ha dado lugar a un acomodamiento de la industria. Como la industria farmacéutica ha conseguido extender la duración de patentes y evitar la incorporación de genéricos, se analiza la influencia de las patentes farmacéuticas que ha dado lugar a reflexionar acerca de la posibilidad de consorciar esfuerzos realizando alianzas entre varias empresas y el sector público para afrontar los retos que plantean nuevas enfermedades producidas por virus que dan lugar a epidemias y pandemias.

Changes in Health Behaviors, Mental and Physical Health among Older Adults under Severe Lockdown Restrictions during the COVID-19 Pandemic in Spain.

We used data from 3041 participants in four cohorts of community-dwelling individuals aged ≥65 years in Spain collected through a pre-pandemic face-to-face interview and a telephone interview conducted between weeks 7 to 15 after the beginning of the COVID-19 lockdown. On average, the confinement was not associated with a deterioration in lifestyle risk factors (smoking, alcohol intake, diet, or weight), except for a decreased physical activity and increased sedentary time, which reversed with the end of confinement. However, chronic pain worsened, and moderate declines in mental health, that did not seem to reverse after restrictions were lifted, were observed. Males, older adults with greater social isolation or greater feelings of loneliness, those with poorer housing conditions, as well as those with a higher prevalence of chronic morbidities were at increased risk of developing unhealthier lifestyles or mental health declines with confinement. On the other hand, previously having a greater adherence to the Mediterranean diet and doing more physical activity protected older adults from developing unhealthier lifestyles with confinement. If another lockdown were imposed during this or future pandemics, public health programs should specially address the needs of older individuals with male sex, greater social isolation, sub-optimal housing conditions, and chronic morbidities because of their greater vulnerability to the enacted movement restrictions.