om as , F e r na n d o G on zález Candelas, SeqCOVID-SPAIN consortium, Tanja Stadler & Richard A. NeherThis is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

Venezuela’s tumbling economy and authoritarian rule have precipitated an unprecedented humanitarian crisis. Hyperinflation rates now exceed 45,000%, and Venezuela’s health system is in free fall. The country is experiencing a massive exodus of biomedical scientists and qualified healthcare professionals. Reemergence of arthropod-borne and vaccine-preventable diseases has sparked serious epidemics that also affect neighboring countries. In this article, we discuss the ongoing epidemics of measles and diphtheria in Venezuela and their disproportionate impact on indigenous populations. We also discuss the potential for reemergence of poliomyelitis and conclude that action to halt the spread of vaccine-preventable diseases within Venezuela is a matter of urgency for the country and the region. We further provide specific recommendations for addressing this crisis.

Background and Purpose-There is growing evidence suggesting that C-reactive protein (CRP) is an effecter molecule able to induce and promote atherothrombosis. The presence of CRP in atherosclerotic plaques may reflect local production or infiltration from circulating CRP increased in general inflammatory responses. Our aim was to analyze the presence of CRP in human advanced carotid artery plaques with differential anatomo-pathological characteristics and to assess local expression of CRP and other proinflammatory genes in these lesions. Methods-Human carotid artery specimens from 38 patients undergoing scheduled endarterectomy were classified into 3 groups: ulcerated (noncomplicated) (UNC, nϭ19), fibrous (F, nϭ12) and ulcerated (complicated/hemorrhagic) plaques (UC, nϭ7). The presence of CRP was evaluated by immunohistochemistry, and plasma samples were screened for circulating high-sensitivity C-reactive protein. TaqMan Low-density Arrays were used for study of genes related to inflammation (CRP, interleukin-6, macrophage colony-stimulating factor-1, monocyte chemotactic protein-1, cyclooxygenase-2). Results-CRP mRNA levels were predominantly detected in UNC-high risk plaques but not in UC (Pϭ0.001). UNC also exhibit the highest expression levels of other genes involved in the inflammatory responses: cyclooxygenase-2 (PϽ0.005 versus F and versus UC), IL-6 (PϽ0.005 versus F and versus UC) and monocyte chemoattractant protein-1 (PϽ0.01 versus F and versus UC). Plaque CRP mRNA levels correlated with immunohistochemical findings but were independent of plasma high-sensitivity CRP. In UNC plaques endothelial cells and inflammatory cells were strongly positive for CRP around areas of newly formed microvessels. Conclusions-In human high-risk carotid artery plaques (UNC) CRP expression reflects an active proinflammatory stage. Local synthesis of CRP could be involved in plaque neovascularization and increased risk of hemorrhagic transformation. (Stroke.

It is not clear if 18FDG-PET can be useful for detection of inflammation in low to moderate carotid stenosis. We studied 15 patients scheduled for endarterectomy with contralateral carotids with less than 50% stenosis. 18-FDG-PET was performed prior to CEA and 3 months following surgery. FDG-uptake values were calculated based on maximum standardized uptake value (SUV) and corresponding uptake ratios. We confirmed by CD68 macrophage staining that FDG accumulation corresponds to active inflammation (R=0.8 p less than 0.005). We found significant correlation between the FDG-uptake in the carotids scheduled for CEA and contralateral carotids with low to moderate stenosis (R=0.9 p less than 0.001). The FDG uptake ratio in the contralateral arteries remained stable on the follow-up imaging (1.15+/-0.2 vs. 1.14+/-0.1, R=0.7 p=0.006). We did not find correlation between FDG uptake and symptomatic or asymptomatic patients, degree of carotid stenosis and vascular risk factors. This is a prospective, preliminary in vivo study demonstrating that low to moderate carotid atherosclerosis can be detected using 18-FDG-PET imaging and highlights the truly systemic nature of atherosclerosis.

Hypoxia, angiogenesis and inflammation leads to plaque progression and remodelling and may significantly contribute towards plaque rupture and subsequent cerebrovascular events. Our aim was to study, markers of hypoxia and inflammation previously identified by microarray analysis, in atherosclerotic carotid arteries with low to moderate stenosis. We hoped to describe different cellular populations expressing the studied markers. The location of selected inflammatory molecules obtained as vascular transplants from organ donors were analysed by immunohistochemistry with monoclonal and polyclonal antibodies. Paraffin-embedded sections were cut and probed with antibodies recognizing active B and T-lymphocytes (CD30), hypoxia-inducible factor-1alpha, endoglin (CD105), Interleukin-6 and C-reactive protein. We observed a notable overexpression of HIF-1alpha in inflammatory and hypoxic areas of carotid arteries in all types of lesions from type II-V taken from the patients with carotid stenosis less than 50%. This suggests that HIF-1alpha may have a putative role in atherosclerosis progression and angiogenesis. Dynamic changes in the non-occluding plaques may explain some of the clinical events in patients with low to moderate carotid stenosis.

Although vaccines have been developed to prevent COVID-19, vaccine hesitancy is a significant barrier for vaccination programs. Most research on COVID-19 vaccine hesitancy has blamed misinformation and misstated concerns about effectiveness, safety, and side effects of these vaccines. The preponderance of these studies has been performed in the Global North. Although Latin American has been substantially and negatively impacted by COVID-19, few studies have examined COVID-19 vaccine hesitancy there. We explored reasons volunteered for COVID-19 vaccine hesitancy from a sample of 1,173 Colombians, Ecuadorians, and Venezuelans. Overall, COVID-19 vaccine hesitancy in these three countries is higher than desirable, but most people who are COVID-19 vaccine hesitant offered one reason or fewer. The reasons offered are diverse, including myths and exaggerations, but also individual-level contraindications for vaccination and structural barriers. Because of the diversity of reasons, single-issue mass campaigns are unlikely to bring about large shifts in COVID-19 vaccine hesitancy in Colombia, Ecuador, and Venezuela. Our data suggest that interpersonal communication, particularly in Ecuador, and addressing structural concerns, particularly in Venezuela, are likely to have the greatest impact on vaccine uptake.

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Background COVID-19 threatens health systems worldwide, but Venezuela’s system is particularly vulnerable. To prevent the spread of COVID-19, individuals must adopt preventive behaviors. However, to encourage behavior change, we must first understand current knowledge, attitudes, and practices (KAPs) that inform response to this health threat. Methods We explored KAPs among Venezuelans using a cross-sectional, internet-based questionnaire. The questionnaire explored individuals’ knowledge about COVID-19; their attitudes toward the world’s and the Venezuelan authorities’ abilities to control it; and their self-reported practices. We also collected demographic data. Binomial logistic regression analyses were used to predict the adoption of preventive behaviors based on demographic variables, individual knowledge level, and individual attitudes. Results 3122 individuals completed the questionnaire. Participants had a high level of knowledge about COVID-19. They expressed high levels of optimism that the world would eventually control COVID-19, but they were very pessimistic about the public authorities in Venezuela. Most participants adopted preventive practices. Binomial regression suggests younger people, less educated people, and manual laborers hold lower levels of knowledge, and these groups, as well as men, were less likely to adopt preventive practices. Knowledge, by itself, had no association with optimism and little association with self-reported practices. Conclusions As other KAP studies in Latin America found, knowledge is not sufficient to prompt behavior change. Venezuelans’ pessimism about their own country’s ability should be explored in greater depth. Health promotion in Venezuela may wish to target the most at risk groups: men, younger people, less educated people, and manual laborers.