How has research on the effectiveness and safety of COVID-19 vaccination been evaluated: a scope review with emphasis on CoronaVac.

Introduction: The control of the COVID-19 epidemic has been focused on the development of vaccines against SARS-CoV-2. All developed vaccines have reported safety and efficacy results in preventing infection and its consequences, although the quality of evidence varies depending on the vaccine considered. Different methodological designs have been used for their evaluation, which can influence our understanding of the effects of these interventions. CoronaVac is an inactivated vaccine, and it has been assessed in various studies, including clinical trials and observational studies. Given these differences, our objective was to explore the published information to answer the question: how has the efficacy/effectiveness and safety of CoronaVac been evaluated in different studies? This is to identify potential gaps and challenges to be addressed in understanding its effect. Methods: A scoping review was carried out following the methodology proposed by the Joanna Briggs Institute, which included studies carried out in humans as of 2020, corresponding to systematic reviews, clinical trials, analytical or descriptive observational studies, in which the effectiveness and/or safety of vaccines for COVID19 were evaluated or described. There were no age restrictions for the study participants. Results: The efficacy/effectiveness and safety of this vaccine was assessed through 113 studies. Nineteen corresponded to experimental studies, 7 of Phase II, 5 of Phase IV, and 4 were clinical trials with random assignment. Although some clinical trials with random assignment have been carried out, these have limitations in terms of feasibility, follow-up times, and with this, the possibility of evaluating safety outcomes that occur with low frequencies. Not all studies have used homogeneous methods of analysis. Both the prevention of infection, and the prevention of outcomes such as hospitalization or death, have been valued through similar outcomes, but some through multivariate analysis of dependencies, and others through analysis that try to infer causally through different control methods of confounding. Conclusion: Published information on the evaluation of the efficacy/effectiveness and safety of the CoronaVac is abundant. However, there are differences in terms of vaccine application schedules, population definition, outcomes evaluated, follow-up times, and safety assessment, as well as non-standardization in the reporting of results, which may hinder the generalizability of the findings. It is important to generate meetings and consensus strategies for the methods and reporting of this type of studies, which will allow to reduce the heterogeneity in their presentation and a better understanding of the effect of these vaccines.

Incidence of major cardiovascular events at 1, 2, and 5 years and mortality in incident patients on peritoneal dialysis regarding their nutritional status by bioimpedanciometry: A multicenter study in Colombia.

BACKGROUND: The nutritional status of incident patients on peritoneal dialysis (PD) has been associated with survival outcomes. Bioimpedanciometry (BCM) enables to establish a nutritional diagnosis, the volume status, and correlates these findings with survival. METHODS: This study used a retrospective multicenter historical cohort. RESULTS: In this study, which included 420 incident patients on peritoneal dialysis with a 5-year follow-up, a cumulative incidence of major adverse cardiovascular events (MACE) of 28.8% was found, being higher in the diabetic population at 36.8%. In regard to the nutritional status in this population, it was found that approximately 44% had altered nutritional status; 34% were found to be in sarcopenia; 6.7% sarcopenic obesity; and 2.8% in obesity (p < 0.001). In the survival analysis, a lower probability of survival was found in patients with overhydration (OH) greater than 3 L (p < 0.001) and in patients with altered nutritional status due to sarcopenia, sarcopenic obesity, and obesity (p 0.016). According to survival in the subgroup of the diabetic population, a lower probability of survival was found in this group of patients (p: 0.011). The overall mortality of the study population was 18%, being higher in the first 2 years, with the most important causes of mortality being cardiovascular. Of the deceased population, 51% were diabetic patients (p: 0.012). CONCLUSION: In incident patients on peritoneal dialysis, sarcopenic obesity, sarcopenia, overhydration status determined by BCM, and having a diagnosis of diabetes are related to a lower probability of survival; MACE outcomes are more frequent in the diabetic population.

AG5 is a potent non-steroidal anti-inflammatory and immune regulator that preserves innate immunity.

An archetypal anti-inflammatory compound against cytokine storm would inhibit it without suppressing the innate immune response. AG5, an anti-inflammatory compound, has been developed as synthetic derivative of andrographolide, which is highly absorbable and presents low toxicity. We found that the mechanism of action of AG5 is through the inhibition of caspase-1. Interestingly, we show with in vitro generated human monocyte derived dendritic cells that AG5 preserves innate immune response. AG5 minimizes inflammatory response in a mouse model of lipopolysaccharide (LPS)-induced lung injury and exhibits in vivo anti-inflammatory efficacy in the SARS-CoV-2-infected mouse model. AG5 opens up a new class of anti-inflammatories, since contrary to NSAIDs, AG5 is able to inhibit the cytokine storm, like dexamethasone, but, unlike corticosteroids, preserves adequately the innate immunity. This is critical at the early stages of any naïve infection, but particularly in SARS-CoV-2 infections. Furthermore, AG5 showed interesting antiviral activity against SARS-CoV-2 in humanized mice.

PRESCRIBING PATTERNS AND THE USE OF ANTHELMINTIC DRUGS IN COLOMBIAN PATIENTS: A CROSS-SECTIONAL STUDY.

Intestinal parasites continue to be a public health problem in low- and middle-income countries. Broad use of anthelmintics during deworming programs is still necessary in many regions. However, description of the usage of these medications in general medical practice has been limited. The objective of this study was to determine the use of anthelmintic drugs and their indications in a group of Colombian patients. This was a descriptive study from a drug-dispensing database, identifying patients with prescriptions for anthelmintic drugs. A total of 381 cases were randomly selected, and their medical records were reviewed, analyzing sociodemographic, clinical, and pharmacological variables (indication of use). The lack of diagnosis registration or clinical manifestations of parasites was determined as a prescription without indication. In total, 50.9% (n = 194) of patients were female, and 67.4% of all patients were under 18 yr of age. The diagnosis of helminthiases was clearly stated in 114 (29.9%) patients, and only 4.2% (n = 16) of these had microbiological confirmation. The most commonly used anthelmintic drug was albendazole (70.4% of all prescriptions). The use of anthelmintics was not indicated in 266 cases (69.8%). Nutritional supplements or vitamin prescriptions were associated with using anthelmintics without indication (odds ratio: 2.25; 95% confidence interval: 1.26-4.03). A high proportion of patients lacked symptoms or diagnoses in their clinical records that supported the use of anthelmintic drugs.

Predicting open education competency level: A machine learning approach.

This article aims to study open education competency data through machine learning models to determine whether models can be built on decision rules using the features from the students' perceptions and classify them by the level of competency. Data was collected from a convenience sample of 326 students from 26 countries using the eOpen instrument. Based on a quantitative research approach, we analyzed the eOpen data using two machine learning models considering these findings: 1) derivation of decision rules from students' perceptions of knowledge, skills, and attitudes or values related to open education to predict their competence level using Decision Trees and Random Forests models, 2) analysis of the prediction errors in the machine learning models to find bias, and 3) description of decision trees from the machine learning models to understand the choices that both models made to predict the competency levels. The results confirmed our hypothesis that the students' perceptions of their knowledge, skills, and attitudes or values related to open education and its sub-competencies produced satisfactory data for building machine learning models to predict the participants' competency levels.

The impact of national culture in the development of complexity reasoning skills: An international comparison.

There is a clear inequality in gender distribution for the STEM areas (Science, Technology, Engineering, and Mathematics). Furthermore, there is a noticeable lack of diversity and a socio-economic gap that requires actionable solutions. To explore potential factors that affect the participation of women in STEM, this paper reviews two possible groups of determinants: national culture and complexity thinking. A survey with 684 respondents from higher education institutions in Chile, Ecuador, Mexico, and Spain was undertaken. The instrument measured four components of complexity thinking namely critical, scientific, innovative, and systemic). Using analysis of variance between two groups and between multiple groups, differences were observed between the countries' samples and between genders. Once the significance was confirmed, boxplots for each dimension were elaborated to facilitate the visualization of the distributions. The scores were compared with the national culture values to seek possible behavioral patterns in the data. The results reveal two groups between the observed countries. Also, there are clear indications of a relationship between the national culture dimensions and the complex thinking components.

Combination of MCL-1 and BCL-2 inhibitors is a promising approach for a host-directed therapy for tuberculosis.

Tuberculosis (TB) accounts for 1.6 million deaths annually and over 25% of deaths due to antimicrobial resistance. Mycobacterium tuberculosis (M.tb) drives MCL-1 expression (family member of anti-apoptotic BCL-2 proteins) to limit apoptosis and grow intracellularly in human macrophages. The feasibility of re-purposing specific MCL-1 and BCL-2 inhibitors to limit M.tb growth, using inhibitors that are in clinical trials and FDA-approved for cancer treatment has not be tested previously. We show that specifically inhibiting MCL-1 and BCL-2 induces apoptosis of M.tb-infected macrophages, and markedly reduces M.tb growth in human and murine macrophages, and in a pre-clinical model of human granulomas. MCL-1 and BCL-2 inhibitors limit growth of drug resistant and susceptible M.tb in macrophages and act in additive fashion with the antibiotics isoniazid and rifampicin. This exciting work uncovers targeting the intrinsic apoptosis pathway as a promising approach for TB host-directed therapy. Since safety and activity studies are underway in cancer clinics for MCL-1 and BCL-2 inhibitors, we expect that re-purposing them for TB treatment should translate more readily and rapidly to the clinic. Thus, the work supports further development of this host-directed therapy approach to augment current TB treatment.

Genetic bases of resistance to the rice hoja blanca disease deciphered by a quantitative trait locus approach.

Rice hoja blanca (RHB) is one of the most serious diseases in rice-growing areas in tropical Americas. Its causal agent is RHB virus (RHBV), transmitted by the planthopper Tagosodes orizicolus Müir. Genetic resistance is the most effective and environment-friendly way of controlling the disease. So far, only 1 major quantitative trait locus (QTL) of Oryza sativa ssp. japonica origin, qHBV4.1, that alters the incidence of the virus symptoms in 2 Colombian cultivars has been reported. This resistance has already started to be broken, stressing the urgent need for diversifying the resistance sources. In the present study, we performed a search for new QTLs of O. sativa indica origin associated with RHB resistance. We used 4 F2:3-segregating populations derived from indica-resistant varieties crossed with a highly susceptible japonica pivot parent. Besides the standard method for measuring disease incidence, we developed a new method based on computer-assisted image processing to determine the affected leaf area (ALA) as a measure of symptom severity. Based on the disease severity and incidence scores in the F3 families under greenhouse conditions and SNP genotyping of the F2 individuals, we identified 4 new indica QTLs for RHB resistance on rice chromosomes 4, 6, and 11, namely, qHBV4.2WAS208, qHBV6.1PTB25, qHBV11.1, and qHBV11.2, respectively. We also confirmed the wide-range action of qHBV4.1. Among the 5 QTLs, qHBV4.1 and qHBV11.1 had the largest effects on incidence and severity, respectively. These results provide a more complete understanding of the genetic bases of RHBV resistance in the cultivated rice gene pool and can be used to develop marker-aided breeding strategies to improve RHB resistance. The power of joint- and meta-analyses allowed precise mapping and candidate gene identification, providing the basis for positional cloning of the 2 major QTLs qHBV4.1 and qHBV11.1.

Robust design of a logistics system using FePIA procedure and analysis of trade-offs between CO2 emissions and net present value.

The problems of flexible planning of the design of logistics systems for the collection of food products such as raw milk can result in a decrease in the performance of critical indicators for their performance. This paper proposes a new efficient methodology for robustly designing a first-mile logistics system for storing and refrigerating milk as a perishable product considering decisions related to open facilities and the flow of products, including sustainability indices. The proposed approach is modeled as a bi-objective problem by considering the minimization of greenhouse gas emissions (CO2) produced by milk transportation canteens and the maximization of the system configuration's net present value (NPV). We have analyzed and determined the most robust configuration for the first time and explained the robustness-NPV and robustness-CO2 relationships. The proposed mathematical model is solved by the Epsilon constraints method, and the robustness is calculated considering an extension of the FePIA methodology for multiobjective problems. A novel contribution is a balance in the possible future values generated by the company related to its cash flows and the generation of CO2 emissions when using a motorized transport frequently used in the shipment of raw milk considering a new important aspect such as the volume of product transported and the slope of the path between the production farm and the storage cooling tanks.

SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling.

SARS-CoV-2, the cause of the COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood. In this study, transcriptomics analysis revealed that both WNT5A and IL11 were significantly up-regulated in A549 cells expressing individual accessory proteins ORF6, ORF8, ORF9b or ORF9c from SARS-CoV-2 (Wuhan-Hu-1 isolate). IL11 is a member of the IL6 family of cytokines. IL11 signaling-related genes were also differentially expressed. Bioinformatics analysis disclosed that both WNT5A and IL11 were involved in pulmonary fibrosis idiopathic disease and functional assays confirmed their association with profibrotic cell responses. Subsequently, data comparison with lung cell lines infected with SARS-CoV-2 or lung biopsies from patients with COVID-19, evidenced altered profibrotic gene expression that matched those obtained in this study. Our results show ORF6, ORF8, ORF9b and ORF9c involvement in inflammatory and profibrotic responses. Thus, these accessory proteins could be targeted by new therapies against COVID-19 disease.

Influence of non-osteoporotic treatments in patients on active anti-osteoporotic therapy: evidence from the OSTEOMED registry.

PURPOSE: To evaluate the effect of different non-osteoporotic drugs on the increase or decrease in the risk of incident fragility fractures (vertebral, humerus or hip) in a cohort of patients diagnosed with osteoporosis on active anti-osteoporotic therapy. METHODS: For this retrospective longitudinal study, baseline and follow-up data on prescribed non-osteoporotic treatments and the occurrence of vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression models. The drugs evaluated with a possible beneficial effect were thiazides and statins, while the drugs evaluated with a possible harmful effect were antiandrogens, aromatase inhibitors, proton pump inhibitors, selective serotonin reuptake inhibitors, benzodiazepines, GnRH agonists, thyroid hormones, and oral and inhaled corticosteroids. RESULTS: Logistic regression analyses indicated that no treatment significantly improved fracture risk, with the only treatments that significantly worsened fracture risk being letrozole (OR = 0.18, p-value = 0.03) and oral corticosteroids at doses ≤ 5 mg/day (OR = 0.16, p-value = 0.03) and > 5 mg/day (OR = 0.27, p-value = 0.04). CONCLUSION: The potential beneficial or detrimental effects of the different drugs evaluated on fracture risk are masked by treatment with anabolic or antiresorptive drugs that have a more potent action on bone metabolism, with two exceptions: letrozole and oral corticosteroids. These findings may have important clinical implications, as patients receiving these treatments are not fully protected by bisphosphonates, which may imply the need for more potent anti-osteoporotic drugs such as denosumab or teriparatide.

Alpha-methyl acetyl-coA racemase deficiency. Magnetic resonance imaging findings of three patients with encephalopathy, epilepsy, and stroke-like episodes.

Alpha-methyl acyl-CoA racemase deficiency (AMACRD) is a rare peroxisomal disorder that results in the accumulation of pristanic acid and 16 cases have been reported in the literature. Here, we present three additional patients, two confirmed by genomic study and one suspected. Three siblings who were born to healthy unrelated parents developed recurrent episodes of encephalopathy, seizures, and behavioral disturbances. In all 3, brain MRI showed lesions in the thalami, cerebral peduncles, and mesencephalic tegmentum, as well as brain volume loss. In addition, one patient had a chronic hemispheric infarct and an acute contralateral infarct, and another had a subacute infarct involving multiple vascular territories without abnormalities on MR angiography.

Gender prediction based on University students' complex thinking competency: An analysis from machine learning approaches.

This article aims to study machine learning models to determine their performance in classifying students by gender based on their perception of complex thinking competency. Data were collected from a convenience sample of 605 students from a private university in Mexico with the eComplexity instrument. In this study, we consider the following data analyses: 1) predict students' gender based on their perception of complex thinking competency and sub-competencies from a 25 items questionnaire, 2) analyze models' performance during training and testing stages, and 3) study the models' prediction bias through a confusion matrix analysis. Our results confirm the hypothesis that the four machine learning models (Random Forest, Support Vector Machines, Multi-layer Perception, and One-Dimensional Convolutional Neural Network) can find sufficient differences in the eComplexity data to classify correctly up to 96.94% and 82.14% of the students' gender in the training and testing stage, respectively. The confusion matrix analysis revealed partiality in gender prediction among all machine learning models, even though we have applied an oversampling method to reduce the imbalance dataset. It showed that the most frequent error was to predict Male students as Female class. This paper provides empirical support for analyzing perception data through machine learning models in survey research. This work proposed a novel educational practice based on developing complex thinking competency and machine learning models to facilitate educational itineraries adapted to the training needs of each group to reduce social gaps existing due to gender.

"How about me giving blood for the COVID vaccine and not being able to get vaccinated?" A cognitive interview study on understanding of and agreement with broad consent for future use of data and samples in Colombia and Nicaragua.

Broad consent for future use, wherein researchers ask participants for permission to share participant-level data and samples collected within the study for purposes loosely related to the study objectives, is central to enabling ethical data and sample reuse. Ensuring that participants understand broad consent-related language is key to maintaining trust in the study and public health research. We conducted 52 cognitive interviews to explore cohort research participants' and their parents' understanding of the broad consent-related language in the University of California at Berkeley template informed consent (IC) form for biomedical research. Participants and their parents were recruited from long-standing infectious disease cohort studies in Nicaragua and Colombia and interviewed during the COVID-19 pandemic. We conducted semi-structured interviews to assess participants' agreement with the key concepts in the IC after clarifying them through the cognitive interview. Participants did not understand abstract concepts, including collecting and reusing genetic data. Participants wanted to learn about incidental findings, future users and uses. Trust in the research team and the belief that sharing could lead to new vaccines or treatments were critical to participant support for data and sample sharing. Participants highlighted the importance of data and sample sharing for COVID-19 response and equitable access to vaccines and treatments developed through sharing. Our findings on participants' understanding of broad consent and preferences for data and sample sharing can help inform researchers and ethics review committees working to enable ethical and equitable data and sample sharing.

Metabolic changes underlying drug resistance in the multiple myeloma tumor microenvironment.

Multiple myeloma (MM) is characterized by the clonal expansion of malignant plasma cells in the bone marrow (BM). MM remains an incurable disease, with the majority of patients experiencing multiple relapses from different drugs. The MM tumor microenvironment (TME) and in particular bone-marrow stromal cells (BMSCs) play a crucial role in the development of drug resistance. Metabolic reprogramming is emerging as a hallmark of cancer that can potentially be exploited for cancer treatment. Recent studies show that metabolism is further adjusted in MM cells during the development of drug resistance. However, little is known about the role of BMSCs in inducing metabolic changes that are associated with drug resistance. In this Perspective, we summarize current knowledge concerning the metabolic reprogramming of MM, with a focus on those changes associated with drug resistance to the proteasome inhibitor Bortezomib (BTZ). In addition, we present proof-of-concept fluxomics (glucose isotope-tracing) and Seahorse data to show that co-culture of MM cells with BMSCs skews the metabolic phenotype of MM cells towards a drug-resistant phenotype, with increased oxidative phosphorylation (OXPHOS), serine synthesis pathway (SSP), TCA cycle and glutathione (GSH) synthesis. Given the crucial role of BMSCs in conveying drug resistance, insights into the metabolic interaction between MM and BMSCs may ultimately aid in the identification of novel metabolic targets that can be exploited for therapy.

Implementation of an integrated care strategy for child contacts of tuberculosis patients: a quasi-experimental study protocol.

BACKGROUND: Childhood tuberculosis continues to be a major public health problem. Although the visibility of the epidemic in this population group has increased, further research is needed. OBJECTIVE: To design, implement and evaluate an integrated care strategy for children under five years old who are household contacts of bacteriologically confirmed pulmonary tuberculosis patients in Medellín and the Metropolitan Area. METHODS: A quasi-experimental study in which approximately 300 children who are household contacts of bacteriologically confirmed pulmonary tuberculosis patients from Medellín and the Metropolitan Area will be evaluated and recruited over one year. A subgroup of these children, estimated at 85, who require treatment for latent tuberculosis, will receive an integrated care strategy that includes: some modifications of the current standardized scheme in Colombia, with rifampicin treatment daily for four months, follow-up under the project scheme with nursing personnel, general practitioners, specialists, professionals from other disciplines such as social work, psychology, and nutritionist. Additionally, transportation and food assistance will be provided to encourage treatment compliance. This strategy will be compared with isoniazid treatment received by a cohort of children between 2015 and 2018 following the standardized scheme in the country. The study was approved by the CIB Research Ethics Committee and UPB. CLINICALTRIALS: gov identifier NCT04331262. DISCUSSION: This study is expected to contribute to the development of integrated care strategies for the treatment of latent tuberculosis in children. The results will have a direct impact on the management of childhood tuberculosis contributing to achieving the goals proposed by the World Health Organization's End TB Strategy. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04331262 . Implementation of an Integrated Care Strategy for Children Contacts of Patients with Tuberculosis. Registered 2 April 2020.

Infección con SARS-CoV2, antes y después de la vacunación, en funcionarios de un hospital de mediana y alta complejidad / Sars-CoV2 infection, before and after vaccination, in health care workers of a medium and high complexity hospital

Introducción: La pandemia de COVID-19 evidenció la importancia de los trabajadores esen-ciales de la salud. Objetivo: Estimar la ocurrencia de la infección por el virus Sars_CoV2 en funcionarios de un hospital, antes y después de implementación del programa de vacunación institucional y la fracción preventiva atribuible a la vacunación. Material y métodos: Estudio de cohorte histórica, teniendo como punto de inicio la fecha del primer funcionario diagnosticado con la Covid19 en el Hospital. Alrededor de mil traba-jadores fueron examinados, durante el periodo de estudio comprendido entre junio de 2020 y octubre 2021. Se utilizó el estadístico de Kaplan-Meier, para comparar la velocidad de infección y la fracción preventiva atribuible al programa de vacunación. Resultados. Hubo diferencias estadísticamente significativas en la reducción de casos según tipo de trabajo, los trabajadores asistenciales experimentaron una reducción del 58,1%, de 124 a 52 y la diferencia en la mediana de la velocidad de infección, antes y después, Log Rank = 127,4 gl = 1 p = 0,000; los administrativos 51,7% de 29 a 14, mediana log Rank = 34,4 gl = 1 p = 0,000, y los operativos 45,5% de 11 a 6, mediana Log Rank = 13,5 gl = 1 p = 0,000. La fracción atribuible preventiva entre los asistenciales fue 47,5% (37,4­54,9); 85,2% (77,7­88,9) en administrativos y una reducción no significativa de 43,6% (-20,7, 63,2) en operativos. Conclusiones: Los trabajadores asistenciales tienen un riesgo alto de contraer la infección por Sars_CoV2. Fue una acertada decisión vacunar a todos los trabajadores del hospital, el impacto es demostrable.

Introduction: The COVID-19 pandemic highlighted the importance of essential health care workers.Objective: To estimate the occurrence of Sars_CoV2 virus infection in hospital staff before and after implementation of the institutional vaccination program and the preventive fraction attributable to vaccination. Material and methods: Historical cohort study, having as starting point the date of the first employee diagnosed with Covid19 in the Hospital. About one thousand workers were exa-mined, during the study period from June 2020 to October 2021. The Kaplan-Meier statistic was used to compare the infection, rate and the preventive fraction attributable to the vac-cination program. Results: There were statistically significant differences in the reduction of cases according to type of work, with the assistential workers experiencing a reduction of 58.1%, from 124 to 52 and the difference in median infection rate, before and after, Log Rank = 127.4 gl = 1 p = 0.000; the administrative 51.7% from 29 to 14, median Log Rank = 34.4 gl = 1 p = 0.000, and the operatives 45.5% from 11 to 6, median Log Rank = 13.5 gl = 1 p = 0.000. The preventive attributable fraction among assistants was 47.5% (37.4-54.9); 85.2% (77.7-88.9) in adminis-trative and a non-significant reduction of 43.6% (-20.7, 63.2) in operatives.Conclusions: Healthcare workers are at high risk of contracting Sars_CoV2 infection. It was a wise decision to vaccinate all hospital workers, the impact is demonstrable.

Non-replicative antibiotic resistance-free DNA vaccine encoding S and N proteins induces full protection in mice against SARS-CoV-2.

SARS-CoV-2 vaccines currently in use have contributed to controlling the COVID-19 pandemic. Notwithstanding, the high mutation rate, fundamentally in the spike glycoprotein (S), is causing the emergence of new variants. Solely utilizing this antigen is a drawback that may reduce the efficacy of these vaccines. Herein we present a DNA vaccine candidate that contains the genes encoding the S and the nucleocapsid (N) proteins implemented into the non-replicative mammalian expression plasmid vector, pPAL. This plasmid lacks antibiotic resistance genes and contains an alternative selectable marker for production. The S gene sequence was modified to avoid furin cleavage (Sfs). Potent humoral and cellular immune responses were observed in C57BL/6J mice vaccinated with pPAL-Sfs + pPAL-N following a prime/boost regimen by the intramuscular route applying in vivo electroporation. The immunogen fully protected K18-hACE2 mice against a lethal dose (105 PFU) of SARS-CoV-2. Viral replication was completely controlled in the lungs, brain, and heart of vaccinated mice. Therefore, pPAL-Sfs + pPAL-N is a promising DNA vaccine candidate for protection from COVID-19.

Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b.

SARS-CoV-2, the causative agent of the present COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome, and some have been implicated in facilitating infection and pathogenesis through their interaction with cellular components. Among these proteins, accessory protein ORF7a and ORF7b functions are poorly understood. In this study, A549 cells were transduced to express ORF7a and ORF7b, respectively, to explore more in depth the role of each accessory protein in the pathological manifestation leading to COVID-19. Bioinformatic analysis and integration of transcriptome results identified defined canonical pathways and functional groupings revealing that after expression of ORF7a or ORF7b, the lung cells are potentially altered to create conditions more favorable for SARS-CoV-2, by inhibiting the IFN-I response, increasing proinflammatory cytokines release, and altering cell metabolic activity and adhesion. Based on these results, it is plausible to suggest that ORF7a or ORF7b could be used as biomarkers of progression in this pandemic.