Routes of importation and spatial dynamics of SARS-CoV-2 variants during localised interventions in Chile (preprint)

South America suffered large SARS-CoV-2 epidemics between 2020 and 2022 caused by multiple variants of interest and concern, some causing substantial morbidity and mortality. However, their transmission dynamics are poorly characterised. The epidemic situation in Chile enables us to investigate differences in the distribution and spread of variants Alpha, Gamma, Lambda, Mu and Delta. Chile implemented non-pharmaceutical interventions and an integrated genomic and epidemiological surveillance system that included airport and community surveillance to track SARS-CoV-2 variants. Here we combine viral genomic data and anonymised human mobility data from mobile phones to characterise the routes of importation of different variants into Chile, the relative contributions of airport-based importations to viral diversity versus land border crossings and test the impact of the mobility network on the diffusion of viral lineages within the country. We find that Alpha, Lambda and Mu were identified in Chile via airport surveillance six, four and five weeks ahead of their detection via community surveillance, respectively. Further, some variants that originated in South America were imported into Chile via land rather than international air travel, most notably Gamma. Different variants exhibited similar trends of viral dissemination throughout the country following their importation, and we show that the mobility network predicts the time of arrival of imported lineages to different Chilean comunas. Higher stringency of local NPIs was also associated with fewer domestic viral importations. Our results show how genomic surveillance combined with high resolution mobility data can help predict the multi-scale geographic expansion of emerging infectious diseases. Significance statementGlobal preparedness for pandemic threats requires an understanding of the global variations of spatiotemporal transmission dynamics. Regional differences are important because the local context sets the conditions for the unfolding of local epidemics, which in turn affect transmission dynamics at a broader scale. Knowledge gaps from the SARS-CoV-2 pandemic remain for regions like South America, where distinct sets of viral variants emerged and spread from late 2020 onwards, and where changes in human behaviour resulted in epidemics which differed from those observed in other regions. Our interdisciplinary analysis of the SARS-CoV-2 epidemic in Chile provides insights into the spatiotemporal trends of viral diffusion in the region which shed light on the drivers that can influence future epidemic waves and pandemics.

Prevalence and Associations between Anxiety, Depression, and Stress among Peruvian University Students during the covid-19 Pandemic / Prevalencia y asociaciones de ansiedad, depresión y estrés en estudiantes universitarios peruanos durante la pandemia de covid-19 / Prevalência e associações de ansiedade, depressão e estresse em estudantes universitários peruanos durante a pandemia de covid-19

The pandemic has brought about social changes, which may have affected mental health.The purpose of this study was to determine the prevalence of and associations between anxiety, depression, and stress among Peruvian university students during the covid-19 pandemic. Materials and Methods: This was an analytical, multi-centered, cross-sectional study conducted with 2,572 university students from 16 Peruvian cities. Depression, anxiety, and stress diagnoses were obtained with the dass-21 scale (stress alpha: 0.85; anx-iety alpha: 0.84; and depression alpha: 0.87). The values were crossed with significant social and educational variables. Results: Anxiety was the most common condition (extremely severe in 4 %, severe in 3 %, and mod-erate in 10 %). Whereas stress and depression were not associated with the course of studies (p > 0.330 and p > 0.440, respectively), anxiety was lower among students pursuing health-related degrees (p = 0.011). Women showed higher levels of stress (p = 0.040) and anxiety (p = 0.017). Older participants had relatively lower stress (p = 0.002), depression (p = 0.006), and anxiety (p = 0.044) levels. Third-year students had higher depression levels than first-year students (p = 0.011). Conclusions: Significant prevalence levels and associations were identified for the three conditions, which should be monitored to determine their current status, given the possible future occurrence of panic attacks or post-traumatic stress, among other complications.

la pandemia vivida obligó a cambios sociales que pudieron influir en la salud mental. El objetivo fue determinar la prevalencia y asociaciones de ansiedad, depresión y estrés en estudiantes universitarios peruanos durante la pandemia por covid-19. Materiales y métodos: estudio transversal analítico y multicéntrico, en 2572 estudiantes universitarios de 16 ciudades de Perú. Los diagnósticos de depresión, ansiedad y estrés se obtuvieron con la escala dass-21 (alfa estrés: 0.85; alfa ansiedad: 0.84 y alfa depresión: 0.87). A estos se los cruzó con importantes variables socioeducativas. Resultados: la ansiedad fue la patología más frecuente (4 % de forma extrema severa, 3 % de forma severa y 10 % de forma mode-rada); el estrés y la depresión no tienen asociación con la carrera profesional (p > 0.330 y p > 0.440, res-pectivamente); en cambio, la ansiedad fue menor en los estudiantes de carreras de salud (p = 0.011). Las mujeres tuvieron más estrés (p = 0.040) y ansiedad (p = 0.017). A mayor edad, hubo menos estrés (p = 0.002), depresión (p = 0.006) y ansiedad (p = 0.044). Los de tercer año tuvieron más depresión en comparación con los de primer año (p = 0.011). Conclusiones: existen importantes prevalencias y asociaciones de las tres patologías evaluadas, lo que debe ser monitorizado según como están actualmente. Esto por las posibles futuras manifestaciones de crisis de pánico, estrés postraumático, entre otras.

a pandemia que estamos vivenciando forçou mudanças sociais, que podem influenciar na saúde mental. O objetivo do estudo é determinar a prevalência e associações de ansiedade, depressão e estresse em estudantes universitários peruanos durante a pandemia de covid-19. Materiais e métodos:estudo transversal analítico e multicêntrico, com 2572 estudantes universitários provenientes de 16 cidades do Peru. Os diagnósticos de depressão, ansiedade e estresse foram obtidos com a escala dass-21 (Alpha para estresse: 0,85; Alpha para ansiedade: 0,84 e Alpha para depressão: 0,87), estes foram cruza-dos com importantes variáveis socioeducativas. Resultados: a ansiedade foi a patologia mais frequente (4 % em sua forma extremamente grave, 3 % forma grave e 10 % forma moderada); estresse e depressão não foram associados à carreira profissional (p > 0,330 e p > 0,440, respectivamente); por outro lado, a ansiedade foi menor nos estudantes da carreira da saúde (p = 0,011). As mulheres apresentaram mais estresse (p = 0,040) e ansiedade (p = 0,017); quanto maior a idade houve menos estresse (p = 0,002), depressão (p = 0,006) e ansiedade (p = 0,044). Estudantes do 3º ano apresentaram mais depressão em comparação aos do 1º ano (p = 0,011). Conclusões: existem prevalências e associações importantes entre as três patologias avaliadas, que devem ser monitoradas de acordo com a forma como se encontram atualmente. Isso se deve às possíveis manifestações futuras de ataques de pânico, estresse pós-traumá-tico, entre outras complicações.

THE EUROPEAN GREEN DEAL AND THE ENERGY TRANSITION: CHALLENGES AND OPPORTUNITIES FOR INDUSTRIAL COMPANIES

Este artículo repasa los retos y oportunidades a los que se enfrentan las empresas industriales en Europa como consecuencia de la aplicación del Pacto Verde Europeo, la estrategia de crecimiento y competitividad para la Unión Europea anunciada por la Comisión Europea en diciembre de 2019. El objetivo de lograr una reducción del 55% de las emisiones de gases de efecto invernadero (GEI) en 2030 con respecto a 1990 y cero emisiones netas en 2050 obligará a las empresas industriales a tomar medidas urgentes para descarbonizar sus actividades. Esto implicará profundos cambios en su forma de operar y la necesidad de invertir en nuevas tecnologías y procesos y sustituir los combustibles fósiles convencionales por energía limpia. Para apoyar esta transformación, deben ponerse en marcha políticas de innovación adecuadas y debe desarrollarse un ecosistema de finanzas sostenibles eficiente. El artículo explora cómo pueden transformar sus negocios las empresas industriales y, al mismo tiempo, cumplir con los grandes objetivos del Pacto Verde Europeo y mantener e incluso mejorar su competitividad.Alternate :This article reviews the challenges and opportunities facing industrial companies in Europe as a result of the implementation of the European Green Deal, the growth and competitiveness strategy for the European Union announced by the European Commission in December 2019. The objective of achieving a reduction of 55% in greenhouse gas (GHG) emissions in 2030 relative to 1990 and zero net emissions in 2050 will force industrial companies to take urgent steps to decarbonize their activities. This will imply profound changes in their business operations and the need to invest in new technologies and processes and substitute clean energy for conventional fossil fuels. In order to support this transformation, sound innovation policies must be put in place and an efficient sustainable finance ecosystem must be developed. The article explores how industrial companies can transform their operations while simultaneously complying with the grand objectives of the European Green Deal and preserving and even enhancing their competitiveness.

Prevalence and Associations between Anxiety, Depression, and Stress among Peruvian University Students during the covid-19 Pandemic / Prevalencia y asociaciones de ansiedad, depresión y estrés en estudiantes universitarios peruanos durante la pandemia de covid-19 / Prevalência e associações de ansiedade, depressão e estresse em estudantes universitários peruanos durante a pandemia de covid-19

The pandemic has brought about social changes, which may have affected mental health.The purpose of this study was to determine the prevalence of and associations between anxiety, depression, and stress among Peruvian university students during the covid-19 pandemic. Materials and Methods: This was an analytical, multi-centered, cross-sectional study conducted with 2,572 university students from 16 Peruvian cities. Depression, anxiety, and stress diagnoses were obtained with the dass-21 scale (stress alpha: 0.85; anx-iety alpha: 0.84; and depression alpha: 0.87). The values were crossed with significant social and educational variables. Results: Anxiety was the most common condition (extremely severe in 4 %, severe in 3 %, and mod-erate in 10 %). Whereas stress and depression were not associated with the course of studies (p > 0.330 and p > 0.440, respectively), anxiety was lower among students pursuing health-related degrees (p = 0.011). Women showed higher levels of stress (p = 0.040) and anxiety (p = 0.017). Older participants had relatively lower stress (p = 0.002), depression (p = 0.006), and anxiety (p = 0.044) levels. Third-year students had higher depression levels than first-year students (p = 0.011). Conclusions: Significant prevalence levels and associations were identified for the three conditions, which should be monitored to determine their current status, given the possible future occurrence of panic attacks or post-traumatic stress, among other complications.

la pandemia vivida obligó a cambios sociales que pudieron influir en la salud mental. El objetivo fue determinar la prevalencia y asociaciones de ansiedad, depresión y estrés en estudiantes universitarios peruanos durante la pandemia por covid-19. Materiales y métodos: estudio transversal analítico y multicéntrico, en 2572 estudiantes universitarios de 16 ciudades de Perú. Los diagnósticos de depresión, ansiedad y estrés se obtuvieron con la escala dass-21 (alfa estrés: 0.85; alfa ansiedad: 0.84 y alfa depresión: 0.87). A estos se los cruzó con importantes variables socioeducativas. Resultados: la ansiedad fue la patología más frecuente (4 % de forma extrema severa, 3 % de forma severa y 10 % de forma mode-rada); el estrés y la depresión no tienen asociación con la carrera profesional (p > 0.330 y p > 0.440, res-pectivamente); en cambio, la ansiedad fue menor en los estudiantes de carreras de salud (p = 0.011). Las mujeres tuvieron más estrés (p = 0.040) y ansiedad (p = 0.017). A mayor edad, hubo menos estrés (p = 0.002), depresión (p = 0.006) y ansiedad (p = 0.044). Los de tercer año tuvieron más depresión en comparación con los de primer año (p = 0.011). Conclusiones: existen importantes prevalencias y asociaciones de las tres patologías evaluadas, lo que debe ser monitorizado según como están actualmente. Esto por las posibles futuras manifestaciones de crisis de pánico, estrés postraumático, entre otras.

a pandemia que estamos vivenciando forçou mudanças sociais, que podem influenciar na saúde mental. O objetivo do estudo é determinar a prevalência e associações de ansiedade, depressão e estresse em estudantes universitários peruanos durante a pandemia de covid-19. Materiais e métodos:estudo transversal analítico e multicêntrico, com 2572 estudantes universitários provenientes de 16 cidades do Peru. Os diagnósticos de depressão, ansiedade e estresse foram obtidos com a escala dass-21 (Alpha para estresse: 0,85; Alpha para ansiedade: 0,84 e Alpha para depressão: 0,87), estes foram cruza-dos com importantes variáveis socioeducativas. Resultados: a ansiedade foi a patologia mais frequente (4 % em sua forma extremamente grave, 3 % forma grave e 10 % forma moderada); estresse e depressão não foram associados à carreira profissional (p > 0,330 e p > 0,440, respectivamente); por outro lado, a ansiedade foi menor nos estudantes da carreira da saúde (p = 0,011). As mulheres apresentaram mais estresse (p = 0,040) e ansiedade (p = 0,017); quanto maior a idade houve menos estresse (p = 0,002), depressão (p = 0,006) e ansiedade (p = 0,044). Estudantes do 3º ano apresentaram mais depressão em comparação aos do 1º ano (p = 0,011). Conclusões: existem prevalências e associações importantes entre as três patologias avaliadas, que devem ser monitoradas de acordo com a forma como se encontram atualmente. Isso se deve às possíveis manifestações futuras de ataques de pânico, estresse pós-traumá-tico, entre outras complicações.

Effectiveness and duration of a second COVID-19 vaccine booster (preprint)

Using a prospective national cohort of 3.75 million individuals aged 20 or older, we evaluated the effectiveness against COVID-19 related ICU admissions and death of mRNA-based second vaccine boosters for four different three-dose background regimes: BNT162b2 primary series plus a homologous booster, and CoronaVac primary series plus an mRNA booster, a homologous booster, and a ChAdOx-1 booster. We estimated the vaccine effectiveness weekly from February 14 to August 15, 2022, by estimating hazard ratios of immunization over non-vaccination, accounting for relevant confounders. The overall adjusted effectiveness of a second mRNA booster shot was 88.2% (95%CI, 86.2-89.9) and 90.5% (95%CI 89.4-91.4) against ICU admissions and death, respectively. Vaccine effectiveness showed a mild decrease for all regimens and outcomes, probably associated with the introduction of BA.4 and BA.5 Omicron sub-lineages and immunity waning. The duration of effectiveness suggests that no additional boosters are needed six months following a second booster shot.

Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults (preprint)

The SARS-CoV-2 Omicron variant has challenged the control of the COVID-19 pandemic even in highly vaccinated countries. While a second booster of mRNA vaccines improved the immunity against SARS-CoV-2, the humoral and cellular responses induced by a second booster of an inactivated SARS-CoV-2 vaccine have not been studied. In the context of a phase 3 clinical study, we report that a second booster of CoronaVac increased the neutralizing response against the ancestral virus yet showed poor neutralization against the Omicron variant. Additionally, isolated PBMCs displayed equivalent activation of specific CD4+ T lymphocytes and IFN-{gamma} production when stimulated with a mega-pool of peptides derived from the spike protein of the ancestral virus or the Omicron variant. In conclusion, a second booster dose of CoronaVac does not improve the neutralizing response against the Omicron variant compared with the first booster dose, yet it helps maintain a robust spike-specific CD4+ T cell response.

Differential immune response induced by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial (preprint)

BackgroundThe development of vaccines to control the COVID-19 pandemic progression is a worldwide priority. CoronaVac(R) is an inactivated SARS-CoV-2 vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. MethodsThis study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged [≥]18 years. Volunteers received two doses of CoronaVac(R) separated by two (0-14 schedule) or four weeks (0-28 schedule). 2,302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. ResultsBoth schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern between schedules. Stimulation of PBMCs with MPs induced the secretion of IFN-{gamma} and the expression of activation induced markers for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-{gamma} secretion. ConclusionsImmunization with CoronaVac(R) in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule. FundingMinistry of Health, Government of Chile, Confederation of Production and Commerce & Millennium Institute on Immunology and Immunotherapy, Chile. Clinical trial numberNCT04651790. summaryTwo immunization schedules were evaluated for the inactivated SARS-CoV-2 vaccine, Coronavac(R), with two doses of the vaccine separated by two or four weeks. We compared humoral and cellular immune responses, showing they are mostly similar, with differences in neutralization capacities.

NUEVOS MODELOS DE NEGOCIO EN MOVILIDAD URBANA COMPARTIDA

Este artículo revisa los modelos de negocio en movilidad urbana compartida que se están implantando en todo el mundo. Se presentan los fundamentos conceptuales de los sistemas de movilidad sostenible y se describen los principales modelos de negocio basados en el concepto de «movilidad como servicio». Además, se identifican los retos que deberán superarse para desarrollar modelos más sostenibles de movilidad urbana y se delinean líneas de actuación para impulsar modelos de negocio innovadores en movilidad. En la parte final del artículo se discute, brevemente, el efecto de la pandemia del coronavirus sobre la movilidad urbana.Alternate :This article reviews the new business models in shared mobility that are being implemented in cities around the world. It presents the conceptual foundations of sustainable mobility systems and describes the main business models based on the concept of «mobility as a service». It also identifies the challenges that must be overcome in order to develop more sustainable urban mobility systems and outlines lines of action to promote innovative mobility business models. The final part of the article briefly discusses the effect of the coronavirus pandemic on urban mobility.

Effectiveness of CoronaVac in children 3 to 5 years during the omicron SARS-CoV-2 outbreak (preprint)

The outbreak of the B.1.1.529 lineage of SARS-CoV-2 (omicron) has caused an unprecedented number of Covid-19 cases, including pediatric hospital admissions. Policymakers urgently need evidence of vaccine effectiveness in children to balance the costs and benefits of vaccination campaigns, but the evidence is sparse or non-existing. Leveraging a population-based cohort of 490,694 children aged 3–5 years, we estimated the effectiveness of administering a two-dose schedule, 28 days apart, of CoronaVac using inverse probability-weighted survival regression models to estimate hazard ratios of complete immunization over non-vaccination, accounting for time-varying vaccination exposure and relevant confounders. The study was conducted between December 6, 2021, and February 26, 2022, during the omicron outbreak in Chile. The estimated vaccine effectiveness was 38.2% (95%CI, 36.5–39.9) against Covid-19, 64.6% (95%CI, 49.6–75.2) against hospitalization, and 69.0% (95%CI, 18.6–88.2) to prevent intensive care unit admission. The effectiveness was modest; however, protection against severe disease remained high.

An inactivated SARS-CoV-2 vaccine is safe and induces humoral and cellular immunity against virus variants in healthy children and adolescents in Chile (preprint)

BackgroundMultiple vaccines against SARS-CoV-2 have been evaluated in clinical trials, but very few include the pediatric population. The inactivated vaccine CoronaVac(R) has shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. This study is an interim safety and immunogenicity report of a phase 3 clinical trial for CoronaVac(R) in healthy children and adolescents in Chile. MethodsParticipants aged 3 to 17 years old received two doses of CoronaVac(R) in a four-week interval. Local and systemic adverse reactions were registered in 699 participants that received the first dose and 381 that received the second dose until December 31st, 2021. Whole blood samples were collected from 148 participants for humoral and cellular immunity analyses. ResultsThe primary adverse reaction reported after the first and second dose was pain at the injection site. The adverse reactions observed were primarily mild and local, and no severe adverse events were reported. Four weeks after the second dose, a significant increase in the levels of total and neutralizing antibodies was observed. Increased activation of specific CD4+ T cells was also observed four weeks after the second dose. Although antibodies induced by vaccination neutralize variants Delta and Omicron, titers were lower than the D614G variant. Importantly, comparable T cell responses were detected against these variants of concern. ConclusionsCoronaVac(R) is safe and immunogenic in subjects aged 3-17 years old and is thus likely to confer protection against infection caused by SARS-CoV-2 variants in this target population.

Mutational signatures and transmissibility of SARS-CoV-2 Gamma and Lambda variants (preprint)

The emergence of SARS-CoV-2 variants of concern endangers the long-term control of COVID-19, especially in countries with limited genomic surveillance. In this work, we explored genomic drivers of contagion in Chile. We sequenced 3443 SARS-CoV-2 genomes collected between January and July 2021, where the Gamma (P.1), Lambda (C.37), Alpha (B.1.1.7), B.1.1.348, and B.1.1 lineages were predominant. Using a Bayesian model tailored for limited genomic surveillance, we found that Lambda and Gamma variants' reproduction numbers were about 5% and 16% larger than Alpha's, respectively. We observed an overabundance of mutations in the Spike gene, strongly correlated with the variant's transmissibility. Furthermore, the variants' mutational signatures featured a breakpoint concurrent with the beginning of vaccination (mostly CoronaVac, an inactivated virus vaccine), indicating an additional putative selective pressure. Thus, our work provides a reliable method for quantifying novel variants' transmissibility under subsampling (as newly-reported Delta, B.1.617.2) and highlights the importance of continuous genomic surveillance.

CIGB-300 Synthetic Peptide, an Antagonist of CK2 Kinase Activity, as a Treatment for Covid-19. A Computational Biology Approach (preprint)

Background: Similarities in the hijacking mechanisms used by SARS-CoV-2 and several type of cancer, suggest the repurposing of cancer drugs to treat Covid-19. CK2 kinase antagonists have been proposed for the treatment of cancer. A recent study in cells infected with SARS-CoV-2 virus found a significant CK2 kinase activity, and the use of a CK2 inhibitor showed antiviral responses. CIGB-300, originally designed as an anticancer peptide, is an antagonist of CK2 kinase activity that binds to CK2 phospho-acceptor sites. Recent preliminary results show an antiviral activity of CIGB-300 versus a surrogate model of coronavirus. Here we present a computational biology study that provides evidences at the molecular level of how CIGB-300 might interfere with SARS-CoV-2 life cycle inside infected human cells. Methods: Sequence analysis and phosphorylation studies data were combined to predict infection-induced molecular mechanism that can be interfered by CIGB-300. Next we integrated multi-omics data on SARS-CoV-2 infection and data on the antagonistic effect on CK2 kinase activity of CIGB-300 to predict the potential benefits of its treatment in COVID-19 patients. A combination of network and functional enrichment analysis was used.Results: First, from SARS-CoV studies, we infer the potential incidence of CIGB-300 in SARS-CoV-2 interference on immune response. Next, from the analysis of multiple Omics data, we propose the action of CIGB-300 since early stage of viral infections perturbing the virus hijacking of RNA splicing machinery. It was also predicted the interference of CIGB-300 in virus-host interactions responsible for the high infectivity and the particular immune response to SARS-CoV-2 infection. Further, we provide evidences of CIGB-300 attenuation of phenotypes related to muscle, bleeding, coagulation and respiratory disorders.Conclusions: We have evidenced the potential benefits of using CIGB-300 to treat COVID-19 patients and strongly suggest its use since early stages of viral infection.

CIGB-300 synthetic peptide, an antagonist of CK2 kinase activity, as a treatment for Covid-19. A computational biology approach (preprint)

Drug repositioning became the first choice for treating Covid-19 patients due to the urgent need to deal with the pandemic. Similarities in the hijacking mechanisms used by SARS-CoV-2 and several type of cancer, suggest the repurposing of cancer drugs to treat Covid-19. CK2 kinase antagonists have been proposed for the treatment of cancer. A recent study in cells infected with SARS-CoV-2 virus found a significant CK2 kinase activity, and the use of a CK2 inhibitor showed antiviral responses. CIGB-300, originally designed as an anticancer peptide, is an antagonist of CK2 kinase activity that binds to CK2 phospho-acceptor sites. Recent preliminary results show an antiviral activity of CIGB-300 versus a surrogate model of coronavirus. Here we present a computational biology study that provides evidences at the molecular level of how CIGB-300 might interfere with SARS-CoV-2 life cycle inside infected human cells. First, from SARS-CoV studies, we infer the potential incidence of CIGB-300 in SARS-CoV-2 interference on immune response. Next, from the analysis of multiple Omics data, we propose the action of CIGB-300 since early stage of viral infections perturbing the virus hijacking of RNA splicing machinery. It was also predicted the interference of CIGB-300 in virus-host interactions responsible for the high infectivity and the particular immune response to SARS-CoV-2 infection. Further, we provide evidences of CIGB-300 attenuation of phenotypes related to muscle, bleeding, coagulation and respiratory disorders.

Interim Report: Safety And Immunogenicity Of An Inactivated Vaccine Against Sars-Cov-2 In Healthy Chilean Adults In A Phase 3 Clinical Trial (preprint)

Background: The ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile. Methods: This is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov (NCT04651790). Findings: The recruitment of participants occurred between November 27th, 2020, until January 9th, 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were over 60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the over 60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the over 60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The over 60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants over 60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-gamma; upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity. Interpretation: Immunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-gamma upon recognition of SARS-CoV-2 antigens. Funding: Ministry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.

Swine viral detection by adapted Next-Generation Sequencing (NGS) for RNA and DNA species reveals first detection of porcine circovirus type 3 (PCV3) in Chile (preprint)

The outbreak and propagation of COVID-19 have posed a significant challenge to our society, highlighting the relevance of epidemiological monitoring of animal pathogens closely related to humans due to potential zoonosis. To find previously undetected viruses inside Chilean swine farms, we collected non-invasive samples from animals suspected to undergo any viral disease. After screening by Next Generation Sequencing (NGS) adapted to identify viral species with RNA and DNA genomes simultaneously, different viral species were successfully detected. Among viruses with an RNA genome, Porcine Rotavirus A (RVA), Porcine Astrovirus type 5 (PAstV-5) and Porcine Feces-Associated IASV-like virus (PfaIV) were identified; whereas among viruses with DNA genome, Porcine Parvovirus 1 (PPV1), Porcine Circovirus type 1 (PCV1) and Porcine Circovirus type 3 (PCV3) were found. PCV3, a recently described pathogenic virus, was detected for the first time in Chile in different samples from mummified tissue of stillbirths. The whole genome sequence of PCV3 was completed using conventional PCR and Sanger sequencing and compared with previously reported genomes. To the best of our knowledge, this is the first time that an adapted NGS system is used for the screening of DNA and RNA viral species simultaneously inside the Chilean swine industry. This adapted NGS system might be useful for the detection of swine viral emerging diseases worldwide.