Interim safety and immunogenicity results from an NDV-based COVID-19 vaccine phase I trial in Mexico.

There is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737.

Obesity and the Obesity Paradox in Patients with Severe COVID-19 Obesidad y Paradoja de la Obesidad en Pacientes con COVID-19 Severo: Resultados de Dos Cohortes Prospectivas

Objective To test the presence of the obesity paradox in two cohorts of patients hospitalized for COVID-19. Design Two multicenter prospective cohorts. Setting Three fourth level institutions. Patients Adults hospitalized in the general ward for confirmed COVID-19 in the three institutions and those admitted to one of the 9 critical care units of one of the institutions Interventions None Main variables of interest: categorized weight and its relationship with admission to the ICU in hospitalized patients and death in the ICU. Result Of 402 hospitalized patients, 30.1% were obese. Of these, 36.1% were admitted to the ICU vs. 27.1% of non-obese patients. Of the 302 ICU patients, 46.4% were obese. Of these, mortality was 45.0% vs. 52.5% for non-obese. The requirement to transfer hospitalized patients to the ICU admission get a HR of 1.47 (95%CI 0.87-2.51, p = 0.154) in the multivariate analysis. In intensive care patients, an HR of 0.99 (95%CI: 0.92 - 1.07, p = 0.806) was obtained to the association of obesity with mortality. Conclusions The present study does not demonstrate an association between obesity and risk of inpatient transfer to intensive care or death of intensive care patients due to COVID-19 therefore, the presence of an obesity paradox is not confirmed.

Hemodialysis-Associated Immune Dysregulation in SARS-CoV-2-Infected End-Stage Renal Disease Patients.

Patients on hemodialysis show dysregulated immunity, basal hyperinflammation and a marked vulnerability to COVID-19. We evaluated the immune profile in COVID-19 hemodialysis patients and the changes associated with clinical deterioration after the hemodialysis session. Recruited patients included eight hemodialysis subjects with active, PCR-confirmed SARS-CoV-2 infection, five uninfected hemodialysis patients and five healthy controls. In SARS-CoV-2-infected hemodialysis patients TNF-α, IL-6 and IL-8 were particularly increased. Lymphopenia was mostly due to reduction in CD4+ T, B and central memory CD8+ T cells. There was a predominance of classical and intermediate monocytes with reduced HLA-DR expression and enhanced production of pro-inflammatory molecules. Immune parameters were analysed pre- and post-hemodialysis in three patients with COVID-19 symptoms worsening after the hemodialysis session. There was a higher than 2.5-fold increase in GM-CSF, IFN-γ, IL-1ß, IL-2, IL-6, IL-17A and IL-21 in serum, and augmentation of monocytes-derived TNF-α, IL-1ß and IL-8 and CXCL10 (p < 0.05). In conclusion, COVID-19 in hemodialysis patients associates with alteration of lymphocyte subsets, increasing of pro-inflammatory cytokines and monocyte activation. The observed worsening during the hemodialysis session in some patients was accompanied by augmentation of particular inflammatory cytokines, which might suggest biomarkers and therapeutic targets to prevent or mitigate the hemodialysis-related deterioration during SARS-CoV-2 infection.

The impact of COVID-19 infection on labor outcomes of Mexican formal workers.

The outbreak of the COVID-19 pandemic had an immediate and severe impact on the economy. However, we do not know whether the disease may have a longer-term effect on people's employment opportunities. In this study, we focus on the effects of COVID-19 infection on labor market outcomes 12 months after diagnosis. We use a unique dataset that includes all formal private sector workers in the Mexican social security system and that links health outcomes with administrative records. We implement two alternative identification strategies to estimate the impact: matching estimators and individual fixed effects models. Our study finds that COVID-19 infection does not harm employment probabilities or wages. On the contrary, we find that workers who had tested positive for COVID had a higher likelihood of keeping their formal sector jobs and higher wages than those who did not. Moreover, our results describe mostly low-income workers.

Online customer engagement in the post-pandemic scenario: a hybrid thematic analysis of the luxury fashion industry

The COVID-19 pandemic had a strong impact on all businesses, and especially the luxury sector. As an adaptation strategy, businesses are engaging in a digital transformation, moving all or most of their activities to online platforms. However, the nature of the luxury industry, deeply rooted in exclusivity and a high degree of human contact, is at odds with the mass-oriented, accessible, and automated nature of e-commerce, thus raising concerns about this industry's ability to reap the benefits of digital transformation. The present paper elucidates how luxury fashion firms can overcome this apparent incompatibility with e-commerce and engage with their customers successfully. Through hybrid thematic analysis of qualitative data from YouTube videos of 96 luxury fashion industry experts and using a conceptual model of Customer Engagement, recommendations were developed to help luxury firms improve their current and prospective online customer engagement efforts systematically. By highlighting their top priorities-including innovative solutions, era adaptation, and resource allocation-, luxury firms could enhance and manage customer activities more effectively in the context of a digital transformation, and ultimately establish a strong post-pandemic position.

Online Grocery Shopping in Germany: Assessing the Impact of COVID-19

Online grocery shopping in Germany has shown a strong growth in the past years and is expected to further develop in the future, especially through the influence of COVID-19. The main purpose of this study was to examine six theoretical customer-oriented factors and their influence on consumer online grocery purchase intentions. Additionally, this study compares consumer perceptions before and since the COVID-19 outbreak. Since the health crisis is very recent, the research on its impact on online grocery purchasing behavior is limited. A total of 402 valid questionnaires were collected in Germany. The data were analyzed using the software SPSS IBM 28. The results indicate that perceived risk still has a negative influence on purchase intentions, thus remaining relevant in online grocery shopping. However, the consumers' perceived risk is considered lower compared to the pre-COVID-19 scenario. Moreover, perceived usefulness, perceived ease of use, perceived trust, convenience, as well as situational factors were found to have a positive relationship with purchase intention, both before the COVID-19 crisis and since then. The COVID-19 pandemic shows a strong reduction in perceived risk, while the remaining characteristics increase at moderate levels. Online grocery businesses could use the insights of this study to reduce perceived risks as well as successfully communicate the benefits of online shopping to consumers.

A fuzzy Einstein-based decision support system for public transportation management at times of pandemic

Optimal decision-making has become increasingly more difficult due to their inherent complexity exacerbated by uncertain and rapidly changing environmental conditions in which they are defined. Hence, with the aim of improving the uncertainty management and facilitating the weighting criteria, this paper introduces an improved fuzzy Einstein Combined Compromise Solution (CoCoSo) methodology. Such a CoCoSo model improves previous CoCoSo proposals by using nonlinear fuzzy weighted Einstein functions for defining weighted sequences. In addition, it proposes a novel algorithm for determining the criteria weights based on the fuzzy logarithmic function, therefore it allows decision-makers a better perception of the relationship between the criteria, as it considers the relationships between adjacent criteria;high consistency of expert comparisons;and enables the definition of weighting coefficients of a larger set of criteria, without the need to cluster (group) the criteria. Nonlinear fuzzy Einstein functions implemented in the fuzzy Einstein CoCoSo methodology enable the processing of complex and uncertain information. Such characteristics contribute to the rational definition of compromise strategies and enable objective reasoning when solving real-world decision problems. The efficiency, effectiveness, and robustness of the proposed fuzzy Einstein CoCoSo model are illustrated by a case study to create a conceptual framework to evaluate and rank the prioritization of public transportation management at the time of the COVID-19 pandemic. The results reveal its good performance in determining the transportation management systems strategy.

First computational design using lambda-superstrings and in vivo validation of SARS-CoV-2 vaccine.

Coronavirus disease 2019 (COVID-19) is the greatest threat to global health at the present time, and considerable public and private effort is being devoted to fighting this recently emerged disease. Despite the undoubted advances in the development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, uncertainty remains about their future efficacy and the duration of the immunity induced. It is therefore prudent to continue designing and testing vaccines against this pathogen. In this article we computationally designed two candidate vaccines, one monopeptide and one multipeptide, using a technique involving optimizing lambda-superstrings, which was introduced and developed by our research group. We tested the monopeptide vaccine, thus establishing a proof of concept for the validity of the technique. We synthesized a peptide of 22 amino acids in length, corresponding to one of the candidate vaccines, and prepared a dendritic cell (DC) vaccine vector loaded with the 22 amino acids SARS-CoV-2 peptide (positions 50-71) contained in the NTD domain (DC-CoVPSA) of the Spike protein. Next, we tested the immunogenicity, the type of immune response elicited, and the cytokine profile induced by the vaccine, using a non-related bacterial peptide as negative control. Our results indicated that the CoVPSA peptide of the Spike protein elicits noticeable immunogenicity in vivo using a DC vaccine vector and remarkable cellular and humoral immune responses. This DC vaccine vector loaded with the NTD peptide of the Spike protein elicited a predominant Th1-Th17 cytokine profile, indicative of an effective anti-viral response. Finally, we performed a proof of concept experiment in humans that included the following groups: asymptomatic non-active COVID-19 patients, vaccinated volunteers, and control donors that tested negative for SARS-CoV-2. The positive control was the current receptor binding domain epitope of COVID-19 RNA-vaccines. We successfully developed a vaccine candidate technique involving optimizing lambda-superstrings and provided proof of concept in human subjects. We conclude that it is a valid method to decipher the best epitopes of the Spike protein of SARS-CoV-2 to prepare peptide-based vaccines for different vector platforms, including DC vaccines.

Impact of the withdrawal of renin-angiotensin-aldosterone inhibitors on mortality in COVID-19 patients.

Background: Chronic use of Angiotensin-converting enzyme (ACE) inhibitors (ACEi) and aldosterone-receptor blockers (ARB) is not associated with worse outcomes in patients with COVID-19. However, evidence on the impact of their discontinuation during hospital admission is scarce. Our aim was to determine whether withdrawal of ACEi, ARB and mineralocorticoid receptor antagonists (MRA) is associated with all-cause mortality in a real-life large cohort of patients with SARS-CoV-2 infection. Methods: Observational cohort study from a large referral center from 1 March 2020 to 20 April 2020. Withdrawal of renin-angiotensin-aldosterone system inhibitors was defined as the absence of any received dose during hospital admission in patients receiving chronic treatment. Prescriptions during admission were confirmed by data from the central pharmacy computerized system. Results: A total of 2042 patients (mean age 68.4±17.6, 57.1% male) with confirmed COVID-19 were included. During a median follow-up of 57 (21-55) days, 583 (28.6%) died. Prior to hospital admission 468 (22.9%), 343 (16.8%) and 83 (4.1%) patients were receiving ACEi, ARB and MRA respectively. During the study period, 216 (46.2%), 193 (56.3%) and 41 (49.4%) were withdrawn from the corresponding drug. After adjusting for age, cardiovascular risk factors, baseline comorbidities and in-hospital COVID-19 dedicated treatment, withdrawal of ACE inhibitors (hazard ration [HR] 1.48 [95% confidence interval -CI- 1.16-1.89]) and MRA (HR 2.01 [95% CI 1.30-3.10]) were shown to be independent predictors of all-cause mortality. No independent relationship between ARB withdrawal and mortality was observed. Conclusion: ACEi and MRA withdrawal were associated with higher mortality. Strong consideration should be given to not discontinuing these medications during hospital admission.

Introdução: O uso crónico de inibidores da ECA (IECA) e de antagonistas dos recetores de aldosterona (ARA) não está associado a resultados piores em doentes com Covid-19. No entanto, a evidência relativa ao impacto da sua retirada durante a admissão hospitalar é escassa. O nosso objetivo foi determinar se a retirada do IECA, ARA e antagonistas dos recetores dos mineralocorticóides (ARM) está associada à mortalidade por todas as causas numa grande coorte real de doentes com infeção por SRA-CoV-2. Métodos: Estudo coorte observacional a partir de um grande centro de referência de 1 de março de 2020 a 20 de abril de 2020. A retirada dos inibidores do sistema RAAS foi definida como a ausência de qualquer dose recebida durante a admissão hospitalar em doentes que recebem tratamento prolongado. As prescrições durante a admissão foram confirmadas por dados do sistema informático da farmácia central. Resultados: Um total de 2042 doentes (idade média de 68,4 ±17,6, 57,1% do sexo masculino) com COVID-19 confirmado foram incluídos. Durante um acompanhamento médio de 57 (21-55) dias, 583 (28,6%) morreram. Conclusão: A retirada do IECA e do ARM foi associada a uma mortalidade mais elevada. Deve ser dada grande atenção para não interromper estes medicamentos durante a admissão hospitalar.

Design and Implementation of Adaptable Self-Protection Plans for Public Buildings: A Nursing Home Case in Spain

COVID-19 is reflecting the importance of self-protection plans in nursing homes, especially when it concerns persons of older age. Self-protection plans intend to prevent and control the risks of residential buildings. The goal of this research is to develop a design process for self-protection plans of public buildings, and specifically a nursing home. In this regard, it is key for the viability of the nursing home operations to be capable of adapting to any potential future event. Starting from some initial hypotheses that establish the need for adaptability, a self-protection plan model is developed for public buildings based on a new approach consisting of four elements and three steps. It was applied to an elderly residence which is currently under construction. The methodology followed has consisted of a process by stages, to design and implement a novel self-protection plan for public buildings. Subsequently, it has been applied to the specific case study, using the most common tools and applications available for later analysis of the result obtained with the starting hypotheses. The results show how the research allows an increase in the adaptability of self-protection plans for any publicly owned building, although there is an extensive and precise subsequent work of adaptation to specific cases considering the different legal frameworks which makes the work challenging. Finally, the research on adaptability and its application for elderly residences enabled the derivation of recommendations regarding self-protection plans in general and specifically in homes for the elderly.

Efficacy and Safety of Lithium Treatment in SARS-CoV-2 Infected Patients.

At the beginning of the pandemic, we observed that lithium carbonate had a positive effect on the recovery of severely ill patients with COVID-19. Lithium is able to inhibit the replication of several types of viruses, some of which are similar to the SARS-CoV-2 virus, increase the immune response and reduce inflammation by preventing or reducing the cytokine storm. Previously, we published an article with data from six patients with severe COVID-19 infection, where we proposed that lithium carbonate could be used as a potential treatment for COVID-19. Now, we set out to conduct a randomized clinical trial number EudraCT 2020-002008-37 to evaluate the efficacy and safety of lithium treatment in patients infected with severe SARS-CoV-2. We showed that lithium was able to reduce the number of days of hospital and intensive care unit admission as well as the risk of death, reduces inflammatory cytokine levels by preventing cytokine storms, and also reduced the long COVID syndromes. We propose that lithium carbonate can be used to reduce the severity of COVID-19.

Characterization of myocardial injury in a cohort of patients with SARS-CoV-2 infection.

BACKGROUND: Myocardial injury has been identified as a common complication in patients with COVID-19. However, recent research has serious limitations, such as non-guideline definition of myocardial injury, heterogenicity of troponin sampling or very short-term follow-up. Using data from a large European cohort, we aimed to overcome these pitfalls and adequately characterize myocardial damage in COVID-19. METHODS: Consecutive patients with confirmed SARS-CoV-2 infection and available high-sensitive troponin I (hs-TnI), from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. RESULTS: A total of 918 patients (mean age 63.2 ± 15.5 years, 60.1% male) with a median follow-up of 57 (49-63) days were included. Of these, 190 (20.7%) fulfilled strict criteria for myocardial injury (21.1% chronic, 76.8% acute non-ischemic, 2.1% acute ischemic). Time from onset of symptoms to maximum hs-TnI was 11 (7-18) days. Thrombotic and bleeding events, arrhythmias, heart failure, need for mechanical ventilation and death were significantly more prevalent in patients with higher hs-TnI concentrations, even without fulfilling criteria for myocardial injury. hs-TnI was identified as an independent predictor of mortality [HR 2.52 (1.57-4.04) per 5-logarithmic units increment] after adjusting for multiple relevant covariates. CONCLUSION: Elevated hs-TnI is highly prevalent among patients with SARS-CoV-2 infection. Even mild elevations well below the 99th URL were significantly associated with higher rates of cardiac and non-cardiac complications, and higher mortality. Future research should address the role of serial hs-TnI assessment to improve COVID-19 prognostic stratification and clinical outcomes.

ANTECEDENTES: El daño miocárdico parece una complicación frecuente en pacientes con COVID-19. Sin embargo, la literatura al respecto presenta serias limitaciones, como definiciones incorrectas, heterogeneidad de las determinaciones de troponina o seguimientos cortos. Utilizando datos de una cohorte amplia, el objetivo del trabajo fue caracterizar adecuadamente el daño miocárdico en pacientes con COVID-19 utilizando una metodología adecuada. MÉTODOS: Se estudió a pacientes consecutivos con infección confirmada y determinaciones disponibles de troponina I de alta sensibilidad (hs-TnI), desde el 1 de marzo hasta el 20 de abril del 2020, que hubieran completado al menos un mes de seguimiento o fallecieran durante el periodo de estudio. RESULTADOS: Se incluyó a 918 pacientes (edad 63,2 ± 15,5 años, 60,1% varones) con un seguimiento mediano de 57 (49-63) días. De estos, 190 (20,7%) cumplían criterios estrictos de lesión miocárdica (21,1% crónica, 76,8% aguda no isquémica, 2,1% aguda isquémica). El tiempo desde el inicio de los síntomas hasta la hs-TnI máxima fue de 11 (7-18) días. Los eventos trombóticos y hemorrágicos, las arritmias, la insuficiencia cardíaca, la necesidad de ventilación mecánica y la muerte fueron significativamente más frecuentes en pacientes con concentraciones elevadas de hs-TnI, incluso por debajo del nivel de lesión miocárdica. La hs-TnI resultó un predictor independiente de mortalidad (HR 2,52 [(1,57-4,04] por cada 5 unidades logarítmicas). CONCLUSIÓN: La hs-TnI elevada es altamente prevalente entre los pacientes con COVID-19. Elevaciones leves muy por debajo del límite para definir lesión miocárdica se asociaron con más complicaciones y mayor mortalidad. La determinación protocolizada de hs-TnI en estos enfermos podría mejorar su estratificación pronóstica y los resultados clínicos.

Sickness Presenteeism in the Aftermath of COVID-19: Is Presenteeism Remote-Work Behavior the New (Ab)normal?

Due to the confinement imposed by the COVID-19 pandemic situation, companies adopted remote work more than ever. The rapid rise of remote work also affected local life and many employers introduced or extended their telework activities because of the associated advantages. However, despite the evident positive benefits, some employees were pressured to work remotely while ill. This evidence brought new challenges to the presenteeism literature. This article investigates how individual, economic/societal, and organizational/sectorial/supervisory-related variables can moderate the role of a contagious disease, such as the COVID-19, in explaining presenteeism behavior. Moreover, the current research presents a multi-level conceptual model (i.e., organizational, individual, supervisory factors) to describe how a new construct of remote-work presenteeism behavior mediates the relationship between different post pandemic health conditions (e.g., allergies, back pain, depression, anxiety) and future cumulative negative consequences. The authors suggested that the widespread pervasive adoption of remote work because of COVID-19 has important implications for the presenteeism literature and opens avenues for further research.

The income gradient in COVID-19 mortality and hospitalisation: An observational study with social security administrative records in Mexico.

BACKGROUND: The COVID-19 pandemic revealed large structural inequalities that led to disparities in health outcomes related to socioeconomic status. So far, most of the evidence is based on aggregated data or simulations with individual data, which point to various possible mechanisms behind the association. To date, there have been no studies regarding an income gradient in COVID-19 mortality based on individual-level data and adjusting for comorbidities or access to healthcare. METHODS: In this paper, we use linked employee-patient data for patients tested for COVID-19 at the Mexican Institute of Social Security. We estimate the association of the probability of dying with income centiles, using a probit estimation and adjusting for COVID-19 diagnosis, sociodemographic variables, and comorbidities. FINDINGS: After controlling for all these variables, we find that persons in the lowest income decile still had a probability of dying from COVID-19 five times greater than those at the top decile. INTERPRETATION: Our results imply that the association between income and COVID outcomes is not explained by the prevalence of comorbidities or by a lack of access to healthcare among the low-income population. FUNDING: This study was not supported by any external funding source.

Safety and Immunogenicity of a Newcastle Disease Virus Vector-Based SARS-CoV-2 Vaccine Candidate, AVX/COVID-12-HEXAPRO (Patria), in Pigs.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were developed in record time and show excellent efficacy and effectiveness against coronavirus disease 2019 (COVID-19). However, currently approved vaccines cannot meet the global demand. In addition, none of the currently used vaccines is administered intranasally to potentially induce mucosal immunity. Here, we tested the safety and immunogenicity of a second-generation SARS-CoV-2 vaccine that includes a stabilized spike antigen and can be administered intranasally. The vaccine is based on a live Newcastle disease virus vector expressing a SARS-CoV-2 spike protein stabilized in a prefusion conformation with six beneficial proline substitutions (AVX/COVID-12-HEXAPRO; Patria). Immunogenicity testing in the pig model showed that both intranasal and intramuscular application of the vaccine as well as a combination of the two induced strong serum neutralizing antibody responses. Furthermore, substantial reactivity to B.1.1.7, B.1.351, and P.1 spike variants was detected. Finally, no adverse reactions were found in the experimental animals at any dose level or delivery route. These results indicate that the experimental vaccine AVX/COVID-12-HEXAPRO (Patria) is safe and highly immunogenic in the pig model. IMPORTANCE Several highly efficacious vaccines for SARS-CoV-2 have been developed and are used in the population. However, the current production capacity cannot meet the global demand. Therefore, additional vaccines-especially ones that can be produced locally and at low cost-are urgently needed. This work describes preclinical testing of a SARS-CoV-2 vaccine candidate which meets these criteria.

A single dose of SARS-CoV-2 FINLAY-FR-1A vaccine enhances neutralization response in COVID-19 convalescents, with a very good safety profile: An open-label phase 1 clinical trial.

BACKGROUND: As a first step towards a vaccine protecting COVID-19 convalescents from reinfection, we evaluated FINLAY-FR-1A vaccine in a clinical trial. METHODS: Thirty COVID-19 convalescents aged 22-57 years were studied: convalescents of mild COVID-19, asymptomatic convalescents, both with PCR-positive at the moment of diagnosis; and individuals with subclinical infection detected by viral-specific IgG. They received a single intramuscular injection of the FINLAY-FR-1A vaccine (50 µg of the recombinant dimeric receptor binding domain). The primary outcomes were safety and reactogenicity, assessed over 28 days after vaccination. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following vaccination was evaluated by ELISA and live-virus neutralization test. The effector T cellular response was also assessed. Cuban Public Registry of Clinical Trials, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. FINDINGS: No serious adverse events were reported. Minor adverse events were found, the most common, local pain: 3 (10%) and redness: 2 (6·7%). The vaccine elicited a >21 fold increase in IgG anti-RBD antibodies 28 days after vaccination. The median of inhibitory antibody titres (94·0%) was three times greater than that of the COVID-19 convalescent panel. Virus neutralization titres higher than 1:160 were found in 24 (80%) participants. There was also an increase in RBD-specific T cells producing IFN-γ and TNF-α. INTERPRETATION: A single dose of the FINLAY-FR-1A vaccine against SARS-CoV-2 was an efficient booster of pre-existing natural immunity, with excellent safety profile. FUNDING: Partial funding for this study was received from the Project-2020-20, Fondo de Ciencia e Innovación (FONCI), Ministry of Science, Technology and the Environment, Cuba.   RESUMEN. ANTECEDENTES: Como un primer paso hacia una vacuna que proteja a los convalecientes de COVID-19 de la reinfección, evaluamos la vacuna FINLAY-FR-1A en un ensayo clínico. MÉTODOS: Se estudiaron treinta convalecientes de COVID-19 de 22 a 57 años: convalecientes de COVID-19 leve y convalecientes asintomáticos, ambos con prueba PCR positiva al momento del diagnóstico; e individuos con infección subclínica detectada por IgG específica viral. Los participantes recibieron una dosis única por vía intramuscular de la vacuna FINLAY-FR-1A (50 µg del dominio de unión al receptor recombinante dimérico del SARS CoV-2). Las variables de medida primarias fueron la seguridad y la reactogenicidad, evaluadas durante 28 días después de la vacunación. La variable secundaria, la inmunogenicidad. La respuesta humoral, al inicio del estudio y después de la vacunación, se evaluó por ELISA y mediante la prueba de neutralización del virus vivo. También se evaluó la respuesta de células T efectoras. Registro Público Cubano de Ensayos Clínicos, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. RESULTADOS: No se reportaron eventos adversos graves. Se encontraron eventos adversos leves, los más comunes, dolor local: 3 (10%) y enrojecimiento: 2 (6·7%). La vacuna estimuló un incremento >21 veces de los anticuerpos IgG anti-RBD 28 días después de la vacunación. La mediana de los títulos de anticuerpos inhibidores (94·0%) fue aproximadamente tres veces mayor que la del panel de convalecientes de COVID-19. Se encontraron títulos de neutralización viral superiores a 1:160 en 24 (80%) de los participantes. También hubo un aumento en las células T específicas de RBD que producen IFN-γ y TNF-α. INTERPRETACIÓN: Una sola dosis de la vacuna FINLAY-FR-1A contra el SARS-CoV-2 reforzó eficazmente la inmunidad natural preexistente, con un excelente perfil de seguridad. FINANCIAMIENTO: Se recibió un financiamiento parcial del Proyecto-2020-20, Fondo de Ciencia e Innovación (FONCI), Ministerio de Ciencia, Tecnología y Medio Ambiente, Cuba.

Prediction of thromboembolic events and mortality by the CHADS2 and the CHA2DS2-VASc in COVID-19.

AIMS: Age, sex, and cardiovascular disease have been linked to thromboembolic complications and poorer outcomes in COVID-19. We hypothesize that CHADS2 and CHA2DS2-VASc scores may predict thromboembolic events and mortality in COVID-19. METHODS AND RESULTS: COVID-19 hospitalized patients with confirmed SARS-CoV-2 infection from 1 March to 20 April 2020 who completed at least 1-month follow-up or died were studied. CHADS2 and CHA2DS2-VASc scores were calculated. Given the worse prognosis of male patients in COVID-19, a modified CHA2DS2-VASc score (CHA2DS2-VASc-M) in which 1 point was given to male instead of female was also calculated. The associations of these scores with laboratory results, thromboembolic events, and death were analysed. A total of 3042 patients (mean age 62.3 ± 20.3 years, 54.9% male) were studied and 115 (3.8%) and 626 (20.6%) presented a definite thromboembolic event or died, respectively, during the study period [median follow 59 (50-66) days]. Higher score values were associated with more marked abnormalities of inflammatory and cardiac biomarkers. Mortality was significantly higher with increasing scores for CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M (P < 0.001 for trend). The CHA2DS2-VASc-M showed the best predictive value for mortality [area under the receiver operating characteristic curve (AUC) 0.820, P < 0.001 for comparisons]. All scores had poor predictive value for thromboembolic events (AUC 0.497, 0.490, and 0.541, respectively). CONCLUSION: The CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M scores are significantly associated with all-cause mortality but not with thromboembolism in COVID-19 patients. They are simple scoring systems in everyday use that may facilitate initial 'quick' prognostic stratification in COVID-19.

Gas Exchange Impairment During COVID-19 Recovery.

BACKGROUND: Persistent impairment of pulmonary function and exercise capacity has been known to last for months or even years in the survivors who recovered from other coronavirus pneumonia. Some reports showed that subjects with coronavirus disease 2019 pneumonia after being discharged could have several sequelae, but there are few studies on gas exchange and exercise capacity complications in these subjects. AIMS: To describe residual gas exchange abnormalities during recovery from coronavirus disease 2019 pneumonia. METHODS: In an observational study, ∼90 d after onset of disease, we scheduled almost 200 subjects for an out-patient visit with pulmonary function testing and computed tomography of the lungs. Lung mechanics by using body plethysmography, gas exchange with diffusing lung capacity for carbon monoxide determined by the single-breath technique (DLCOsb) and diffusing lung capacity for nitric oxide determined by the single-breath technique (DLNOsb), and exercise ability by using the 6-min walk test (6MWT) were measured in the subjects. The results were compared between those who required invasive mechanical ventilation and those who did not. RESULTS: A total of 171 subjects were included, the majority (96%) had signs of residual pneumonia (such as an excess of high attenuation areas) on computed tomography of the lungs. The DLCOSB results were below the lower limit of the normal range in 29.2% of the subjects; during the 6MWT, 67% experienced oxygen desaturation ([Formula: see text]) > 4%; and, in 81 (47%), the dropped below 88%. Subjects who required invasive mechanical ventilation (49.7%) were more likely to have lower lung volumes, more gas exchange abnormality, less exercise capacity and more radiologic abnormality. CONCLUSIONS: Subjects who recovered from severe COVID-19 pneumonia continued to have abnormal lung function and abnormal radiologic findings.