Dispersal patterns and influence of air travel during the global expansion of SARS-CoV-2 variants of concern.

The Alpha, Beta, and Gamma SARS-CoV-2 variants of concern (VOCs) co-circulated globally during 2020 and 2021, fueling waves of infections. They were displaced by Delta during a third wave worldwide in 2021, which, in turn, was displaced by Omicron in late 2021. In this study, we use phylogenetic and phylogeographic methods to reconstruct the dispersal patterns of VOCs worldwide. We find that source-sink dynamics varied substantially by VOC and identify countries that acted as global and regional hubs of dissemination. We demonstrate the declining role of presumed origin countries of VOCs in their global dispersal, estimating that India contributed <15% of Delta exports and South Africa <1%-2% of Omicron dispersal. We estimate that >80 countries had received introductions of Omicron within 100 days of its emergence, associated with accelerated passenger air travel and higher transmissibility. Our study highlights the rapid dispersal of highly transmissible variants, with implications for genomic surveillance along the hierarchical airline network.

4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification.

BACKGROUND AND AIMS: Developing novel therapies to battle the global public health burden of heart failure remains challenging. This study investigates the underlying mechanisms and potential treatment for 4-hydroxynonenal (4-HNE) deleterious effects in heart failure. METHODS: Biochemical, functional, and histochemical measurements were applied to identify 4-HNE adducts in rat and human failing hearts. In vitro studies were performed to validate 4-HNE targets. RESULTS: 4-HNE, a reactive aldehyde by-product of mitochondrial dysfunction in heart failure, covalently inhibits Dicer, an RNase III endonuclease essential for microRNA (miRNA) biogenesis. 4-HNE inhibition of Dicer impairs miRNA processing. Mechanistically, 4-HNE binds to recombinant human Dicer through an intermolecular interaction that disrupts both activity and stability of Dicer in a concentration- and time-dependent manner. Dithiothreitol neutralization of 4-HNE or replacing 4-HNE-targeted residues in Dicer prevents 4-HNE inhibition of Dicer in vitro. Interestingly, end-stage human failing hearts from three different heart failure aetiologies display defective 4-HNE clearance, decreased Dicer activity, and miRNA biogenesis impairment. Notably, boosting 4-HNE clearance through pharmacological re-activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) using Alda-1 or its improved orally bioavailable derivative AD-9308 restores Dicer activity. ALDH2 is a major enzyme responsible for 4-HNE removal. Importantly, this response is accompanied by improved miRNA maturation and cardiac function/remodelling in a pre-clinical model of heart failure. CONCLUSIONS: 4-HNE inhibition of Dicer directly impairs miRNA biogenesis in heart failure. Strikingly, decreasing cardiac 4-HNE levels through pharmacological ALDH2 activation is sufficient to re-establish Dicer activity and miRNA biogenesis; thereby representing potential treatment for patients with heart failure.

Molecular characterization and sequecing analysis of SARS-CoV-2 genome in Minas Gerais, Brazil.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, is the causative agent of the coronavirus disease 2019 (COVID-19). Since its first notification in São Paulo state (SP) on 26th February 2020, more than 22,300,000 cases and 619,000 deaths were reported in Brazil. In early pandemic, SARS-CoV-2 spread locally, however, over time, this virus was disseminated to other regions of the country. Herein, we performed genomic sequencing and phylogenetic analysis of SARS-CoV-2 using 20 clinical samples of COVID-19 confirmed cases from 9 cities of Minas Gerais state (MG), in order to evaluate the molecular properties of circulating viral strains in this locality from March to May 2020. Our analyses demonstrated the circulation of B.1 lineage isolates in the investigated locations and nucleotide substitutions were observed into the genomic regions related to important viral structures. Additionally, sequences generated in this study clustered with isolates from SP, suggesting a dissemination route between these two states. Alternatively, monophyletic groups of sequences from MG and other states or country were observed, indicating independent events of virus introduction. These results reinforce the need of genomic surveillance for understand the ongoing spread of emerging viral pathogens.

Fatal Outcome of Chikungunya Virus Infection in Brazil.

BACKGROUND: Chikungunya virus (CHIKV) emerged in the Americas in 2013 and has caused approximately 2.1 million cases and >600 deaths. A retrospective investigation was undertaken to describe clinical, epidemiological, and viral genomic features associated with deaths caused by CHIKV in Ceará state, northeast Brazil. METHODS: Sera, cerebrospinal fluid (CSF), and tissue samples from 100 fatal cases with suspected arbovirus infection were tested for CHIKV, dengue virus (DENV), and Zika virus (ZIKV). Clinical, epidemiological, and death reports were obtained for patients with confirmed CHIKV infection. Logistic regression analysis was undertaken to identify independent factors associated with risk of death during CHIKV infection. Phylogenetic analysis was conducted using whole genomes from a subset of cases. RESULTS: Sixty-eight fatal cases had CHIKV infection confirmed by reverse-transcription quantitative polymerase chain reaction (52.9%), viral antigen (41.1%), and/or specific immunoglobulin M (63.2%). Co-detection of CHIKV with DENV was found in 22% of fatal cases, ZIKV in 2.9%, and DENV and ZIKV in 1.5%. A total of 39 CHIKV deaths presented with neurological signs and symptoms, and CHIKV-RNA was found in the CSF of 92.3% of these patients. Fatal outcomes were associated with irreversible multiple organ dysfunction syndrome. Patients with diabetes appear to die at a higher frequency during the subacute phase. Genetic analysis showed circulation of 2 CHIKV East-Central-South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome. CONCLUSIONS: The investigation of the largest cross-sectional cohort of CHIKV deaths to date reveals that CHIKV-ECSA strains can cause death in individuals from both risk and nonrisk groups, including young adults.

Local Transmission of SARS-CoV-2 Lineage B.1.1.7, Brazil, December 2020.

In December 2020, research surveillance detected the B.1.1.7 lineage of severe acute respiratory syndrome coronavirus 2 in São Paulo, Brazil. Rapid genomic sequencing and phylogenetic analysis revealed 2 distinct introductions of the lineage. One patient reported no international travel. There may be more infections with this lineage in Brazil than reported.

Rare Pathogenic Variants in Mitochondrial and Inflammation-Associated Genes May Lead to Inflammatory Cardiomyopathy in Chagas Disease.

Cardiomyopathies are an important cause of heart failure and sudden cardiac death. Little is known about the role of rare genetic variants in inflammatory cardiomyopathy. Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory cardiomyopathy prevalent in Latin America, developing in 30% of the 6 million patients chronically infected by the protozoan Trypanosoma cruzi, while 60% remain free of heart disease (asymptomatic (ASY)). The cytokine interferon-γ and mitochondrial dysfunction are known to play a major pathogenetic role. Chagas disease provides a unique model to probe for genetic variants involved in inflammatory cardiomyopathy. METHODS: We used whole exome sequencing to study nuclear families containing multiple cases of Chagas disease. We searched for rare pathogenic variants shared by all family members with CCC but absent in infected ASY siblings and in unrelated ASY. RESULTS: We identified heterozygous, pathogenic variants linked to CCC in all tested families on 22 distinct genes, from which 20 were mitochondrial or inflammation-related - most of the latter involved in proinflammatory cytokine production. Significantly, incubation with IFN-γ on a human cardiomyocyte line treated with an inhibitor of dihydroorotate dehydrogenase brequinar (enzyme showing a loss-of-function variant in one family) markedly reduced mitochondrial membrane potential (ΔψM), indicating mitochondrial dysfunction. CONCLUSION: Mitochondrial dysfunction and inflammation may be genetically determined in CCC, driven by rare genetic variants. We hypothesize that CCC-linked genetic variants increase mitochondrial susceptibility to IFN-γ-induced damage in the myocardium, leading to the cardiomyopathy phenotype in Chagas disease. This mechanism may also be operative in other inflammatory cardiomyopathies.

Genomic detection of a virus lineage replacement event of dengue virus serotype 2 in Brazil, 2019.

BACKGROUND Despite efforts to mitigate the impact of dengue virus (DENV) epidemics, the virus remains a public health problem in tropical and subtropical regions around the world. Most DENV cases in the Americas between January and July 2019 were reported in Brazil. São Paulo State in the southeast of Brazil has reported nearly half of all DENV infections in the country. OBJECTIVES To understand the origin and dynamics of the 2019 DENV outbreak. METHODS Here using portable nanopore sequencing we generated20 new DENV genome sequences from viremic patients with suspected dengue infection residing in two of the most-affected municipalities of São Paulo State, Araraquara and São José do Rio Preto. We conducted a comprehensive phylogenetic analysis with 1,630 global DENV strains to better understand the evolutionary history of the DENV lineages that currently circulate in the region. FINDINGS The new outbreak strains were classified as DENV2 genotype III (American/Asian genotype). Our analysis shows that the 2019 outbreak is the result of a novel DENV lineage that was recently introduced to Brazil from the Caribbean region. Dating phylogeographic analysis suggests that DENV2-III BR-4 was introduced to Brazil in or around early 2014, possibly from the Caribbean region. MAIN CONCLUSIONS Our study describes the early detection of a newly introduced and rapidly-expanding DENV2 virus lineage in Brazil.

Blood Gene Signatures of Chagas Cardiomyopathy With or Without Ventricular Dysfunction.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 7 million people in Latin American areas of endemicity. About 30% of infected patients will develop chronic Chagas cardiomyopathy (CCC), an inflammatory cardiomyopathy characterized by hypertrophy, fibrosis, and myocarditis. Further studies are necessary to understand the molecular mechanisms of disease progression. Transcriptome analysis has been increasingly used to identify molecular changes associated with disease outcomes. We thus assessed the whole-blood transcriptome of patients with Chagas disease. Microarray analysis was performed on blood samples from 150 subjects, of whom 30 were uninfected control patients and 120 had Chagas disease (1 group had asymptomatic disease, and 2 groups had CCC with either a preserved or reduced left ventricular ejection fraction [LVEF]). Each Chagas disease group displayed distinct gene expression and functional pathway profiles. The most different expression patterns were between CCC groups with a preserved or reduced LVEF. A more stringent analysis indicated that 27 differentially expressed genes, particularly those related to natural killer (NK)/CD8+ T-cell cytotoxicity, separated the 2 groups. NK/CD8+ T-cell cytotoxicity could play a role in determining Chagas disease progression. Understanding genes associated with disease may lead to improved insight into CCC pathogenesis and the identification of prognostic factors for CCC progression.

Myocardial Infarction-Associated Transcript, a Long Noncoding RNA, Is Overexpressed During Dilated Cardiomyopathy Due to Chronic Chagas Disease.

Long noncoding RNAs (lncRNAs) modulate gene expression at the epigenetic, transcriptional, and posttranscriptional levels. Dysregulation of the lncRNA known as myocardial infarction-associated transcript (MIAT) has been associated with myocardial infarction. Chagas disease causes a severe inflammatory dilated chronic cardiomyopathy (CCC). We investigated the role of MIAT in CCC. A whole-transcriptome analysis of heart biopsy specimens and formalin-fixed, paraffin-embedded samples revealed that MIAT was overexpressed in patients with CCC, compared with subjects with noninflammatory dilated cardiomyopathy and controls. These results were confirmed in a mouse model. Results suggest that MIAT is a specific biomarker of CCC.

Pathophysiology of chikungunya virus infection associated with fatal outcomes.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections.

Genetic differences of dengue virus 2 in patients with distinct clinical outcome.

The genetic diversity of the dengue virus is characterized by four circulating serotypes, several genotypes, and an increasing number of existing lineages that may have differences in the potential to cause epidemics and disease severity. Accurate identification of the genetic variability of the virus is essential to identify lineages responsible for an epidemic and understanding the processes of virus spread and virulence. Here, we characterize, using portable nanopore genomic sequencing, different lineages of dengue virus 2 (DENV-2) detected in 22 serum samples from patients with and without dengue warning signs attended at Hospital de Base of São José do Rio Preto (SJRP) in 2019, during a DENV-2 outbreak. Demographic, epidemiological, and clinical data were also analyzed. The phylogenetic reconstruction and the clinical data showed that two lineages belonging to the American/Asian genotype of DENV-2-BR3 and BR4 (BR4L1 and BR4L2)-were co-circulating in SJRP. Although preliminary, these results indicate no specific association between clinical form and phylogenetic clustering at the virus consensus sequence level. Studies with larger sample sizes and which explore single nucleotide variants are needed. Therefore, we showed that portable nanopore genome sequencing could generate quick and reliable sequences for genomic surveillance to monitor viral diversity and its association with disease severity as an epidemic unfolds.

Convergent trends and spatiotemporal patterns of Aedes-borne arboviruses in Mexico and Central America.

BACKGROUND: Aedes-borne arboviruses cause both seasonal epidemics and emerging outbreaks with a significant impact on global health. These viruses share mosquito vector species, often infecting the same host population within overlapping geographic regions. Thus, comparative analyses of the virus evolutionary and epidemiological dynamics across spatial and temporal scales could reveal convergent trends. METHODOLOGY/PRINCIPAL FINDINGS: Focusing on Mexico as a case study, we generated novel chikungunya and dengue (CHIKV, DENV-1 and DENV-2) virus genomes from an epidemiological surveillance-derived historical sample collection, and analysed them together with longitudinally-collected genome and epidemiological data from the Americas. Aedes-borne arboviruses endemically circulating within the country were found to be introduced multiple times from lineages predominantly sampled from the Caribbean and Central America. For CHIKV, at least thirteen introductions were inferred over a year, with six of these leading to persistent transmission chains. For both DENV-1 and DENV-2, at least seven introductions were inferred over a decade. CONCLUSIONS/SIGNIFICANCE: Our results suggest that CHIKV, DENV-1 and DENV-2 in Mexico share evolutionary and epidemiological trajectories. The southwest region of the country was determined to be the most likely location for viral introductions from abroad, with a subsequent spread into the Pacific coast towards the north of Mexico. Virus diffusion patterns observed across the country are likely driven by multiple factors, including mobility linked to human migration from Central towards North America. Considering Mexico's geographic positioning displaying a high human mobility across borders, our results prompt the need to better understand the role of anthropogenic factors in the transmission dynamics of Aedes-borne arboviruses, particularly linked to land-based human migration.

Clinical markers of post-Chikungunya chronic inflammatory joint disease: A Brazilian cohort.

BACKGROUND: Chikungunya-fever (CHIKF) remains a public health major issue. It is clinically divided into three phases: acute, post-acute and chronic. Chronic cases correspond to 25-40% individuals and, though most of them are characterized by long-lasting arthralgia alone, many of them exhibit persistent or recurrent inflammatory signs that define post-Chikungunya chronic inflammatory joint disease (pCHIKV-CIJD). We aimed to identify early clinical markers of evolution to pCHIKV-CIJD during acute and post-acute phases. METHODOLOGY/PRINCIPAL FINDINGS: We studied a prospective cohort of CHIKF-confirmed volunteers with longitudinal clinical data collection from symptoms onset up to 90 days, including a 21-day visit (D21). Of 169 patients with CHIKF, 86 (50.9%) completed the follow-up, from whom 39 met clinical criteria for pCHIKV-CIJD (45.3%). The relative risk of chronification was higher in women compared to men (RR = 1.52; 95% CI = 1.15-1.99; FDR = 0.03). None of the symptoms or signs presented at D0 behaved as an early predictor of pCHIKV-CIJD, while being symptomatic at D21 was a risk factor for chronification (RR = 1.31; 95% CI = 1.09-1.55; FDR = 0.03). Significance was also observed for joint pain (RR = 1.35; 95% CI = 1.12-1.61; FDR = 0.02), reported edema (RR = 3.61; 95% CI = 1.44-9.06; FDR = 0.03), reported hand and/or feet small joints edema (RR = 4.22; 95% CI = 1.51-11.78; FDR = 0.02), and peri-articular edema observed during physical examination (RR = 2.89; 95% CI = 1.58-5.28; FDR = 0.002). Furthermore, patients with no findings in physical examination at D21 were at lower risk of chronic evolution (RR = 0.41, 95% CI = 0.24-0.70, FDR = 0.01). Twenty-nine pCHIKV-CIJD patients had abnormal articular ultrasonography (90.6% of the examined). The most common findings were synovitis (65.5%) and joint effusion (58.6%). CONCLUSION: This cohort has provided important insights into the prognostic evaluation of CHIKF. Symptomatic sub-acute disease is a relevant predictor of evolution to chronic arthritis with synovitis, drawing attention to joint pain, edema, multiple articular involvement including small hand and feet joints as risk factors for chronification beyond three months, especially in women. Future studies are needed to accomplish the identification of accurate and early biomarkers of poor clinical prognosis, which would allow better understanding of the disease's evolution and improve patients' management, modifying CHIKF burden on global public health.

Spatiotemporal dynamics and recurrence of chikungunya virus in Brazil: an epidemiological study.

BACKGROUND: Chikungunya virus (CHIKV) is an Aedes mosquito-borne virus that has caused large epidemics linked to acute, chronic, and severe clinical outcomes. Currently, Brazil has the highest number of chikungunya cases in the Americas. We aimed to investigate the spatiotemporal dynamics and recurrence pattern of chikungunya in Brazil since its introduction in 2013. METHODS: In this epidemiological study, we used CHIKV genomic sequencing data, CHIKV vector information, and aggregate clinical data on chikungunya cases from Brazil. The genomic data comprised 241 Brazilian CHIKV genome sequences from GenBank (n=180) and the 2022 CHIKV outbreak in Ceará state (n=61). The vector data (Breteau index and House index) were obtained from the Brazilian Ministry of Health for all 184 municipalities in Ceará state and 116 municipalities in Tocantins state in 2022. Epidemiological data on laboratory-confirmed cases of chikungunya between 2013 and 2022 were obtained from the Brazilian Ministry of Health and Laboratory of Public Health of Ceará. We assessed the spatiotemporal dynamics of chikungunya in Brazil via time series, mapping, age-sex distribution, cumulative case-fatality, linear correlation, logistic regression, and phylogenetic analyses. FINDINGS: Between March 3, 2013, and June 4, 2022, 253 545 laboratory-confirmed chikungunya cases were reported in 3316 (59·5%) of 5570 municipalities, mainly distributed in seven epidemic waves from 2016 to 2022. To date, Ceará in the northeast has been the most affected state, with 77 418 cases during the two largest epidemic waves in 2016 and 2017 and the third wave in 2022. From 2016 to 2022 in Ceará, the odds of being CHIKV-positive were higher in females than in males (odds ratio 0·87, 95% CI 0·85-0·89, p<0·0001), and the cumulative case-fatality ratio was 1·3 deaths per 1000 cases. Chikungunya recurrences in the states of Ceará, Tocantins (recurrence in 2022), and Pernambuco (recurrence in 2021) were limited to municipalities with few or no previously reported cases in the previous epidemic waves. The recurrence of chikungunya in Ceará in 2022 was associated with a new East-Central-South-African lineage. Population density metrics of the main CHIKV vector in Brazil, Aedes aegypti, were not correlated spatially with locations of chikungunya recurrence in Ceará and Tocantins. INTERPRETATION: Spatial heterogeneity of CHIKV spread and population immunity might explain the recurrence pattern of chikungunya in Brazil. These results can be used to inform public health interventions to prevent future chikungunya epidemic waves in urban settings. FUNDING: Global Virus Network, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, São Paulo Research Foundation, Brazil Ministry of Education, UK Medical Research Council, Brazilian National Council for Scientific and Technological Development, and UK Royal Society. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Epidemiological and genomic investigation of chikungunya virus in Rio de Janeiro state, Brazil, between 2015 and 2018.

Since 2014, Brazil has experienced an unprecedented epidemic caused by chikungunya virus (CHIKV), with several waves of East-Central-South-African (ECSA) lineage transmission reported across the country. In 2018, Rio de Janeiro state, the third most populous state in Brazil, reported 41% of all chikungunya cases in the country. Here we use evolutionary and epidemiological analysis to estimate the timescale of CHIKV-ECSA-American lineage and its epidemiological patterns in Rio de Janeiro. We show that the CHIKV-ECSA outbreak in Rio de Janeiro derived from two distinct clades introduced from the Northeast region in mid-2015 (clade RJ1, n = 63/67 genomes from Rio de Janeiro) and mid-2017 (clade RJ2, n = 4/67). We detected evidence for positive selection in non-structural proteins linked with viral replication in the RJ1 clade (clade-defining: nsP4-A481D) and the RJ2 clade (nsP1-D531G). Finally, we estimate the CHIKV-ECSA's basic reproduction number (R0) to be between 1.2 to 1.6 and show that its instantaneous reproduction number (Rt) displays a strong seasonal pattern with peaks in transmission coinciding with periods of high Aedes aegypti transmission potential. Our results highlight the need for continued genomic and epidemiological surveillance of CHIKV in Brazil, particularly during periods of high ecological suitability, and show that selective pressures underline the emergence and evolution of the large urban CHIKV-ECSA outbreak in Rio de Janeiro.

Emergence and widespread circulation of a recombinant SARS-CoV-2 lineage in North America.

Although recombination is a feature of coronavirus evolution, previously detected recombinant lineages of SARS-CoV-2 have shown limited circulation thus far. Here, we present a detailed phylogenetic analysis of four SARS-CoV-2 lineages to investigate the possibility of virus recombination among them. Our analyses reveal well-supported phylogenetic differences between the Orf1ab region encoding viral non-structural proteins and the rest of the genome, including Spike (S) protein and remaining reading frames. By accounting for several deletions in NSP6, Orf3a, and S, we conclude that the B.1.628 major cluster, now designated as lineage XB, originated from a recombination event between viruses of B.1.631 and B.1.634 lineages. This scenario is supported by the spatiotemporal distribution of these lineages across the USA and Mexico during 2021, suggesting that the recombination event originated in this geographical region. This event raises important questions regarding the role and potential effects of recombination on SARS-CoV-2 evolution.

Cardiac MicroRNA Expression Profile After Experimental Brain Death Is Associated With Myocardial Dysfunction and Can Be Modulated by Hypertonic Saline.

BACKGROUND: Brain death (BD) is associated with systemic inflammatory compromise, which might affect the quality of the transplanted organs. This study investigated the expression profile of cardiac microRNAs (miRNAs) after BD, and their relationship with the observed decline in myocardial function and with the changes induced by hypertonic saline solution (HSS) treatment. METHODS: Wistar rats were assigned to sham-operation (SHAM) or submitted to BD with and without the administration of HSS. Cardiac function was assessed for 6 h with left ventricular (LV) pressure-volume analysis. We screened 641 rodent miRNAs to identify differentially expressed miRNAs in the heart, and computational and functional analyses were performed to compare the differentially expressed miRNAs and find their putative targets and their related enriched canonical pathways. RESULTS: An enhanced expression in canonical pathways related to inflammation and myocardial apoptosis was observed in BD induced group, with 2 miRNAs, miR-30a-3p, and miR-467f, correlating with the level of LV dysfunction observed after BD. Conversely, HSS treated after BD and SHAM groups showed similar enriched pathways related to the maintenance of heart homeostasis regulation, in agreement with the observation that both groups did not have significant changes in LV function. CONCLUSIONS: These findings highlight the potential of miRNAs as biomarkers for assessing damage in BD donor hearts and to monitor the changes induced by therapeutic measures like HSS, opening a perspective to improve graft quality and to better understand the pathophysiology of BD. The possible relation of BD-induced miRNA's on early and late cardiac allograft function must be investigated.

Global Expansion of SARS-CoV-2 Variants of Concern: Dispersal Patterns and Influence of Air Travel.

In many regions of the world, the Alpha, Beta and Gamma SARS-CoV-2 Variants of Concern (VOCs) co-circulated during 2020-21 and fueled waves of infections. During 2021, these variants were almost completely displaced by the Delta variant, causing a third wave of infections worldwide. This phenomenon of global viral lineage displacement was observed again in late 2021, when the Omicron variant disseminated globally. In this study, we use phylogenetic and phylogeographic methods to reconstruct the dispersal patterns of SARS-CoV-2 VOCs worldwide. We find that the source-sink dynamics of SARS-CoV-2 varied substantially by VOC, and identify countries that acted as global hubs of variant dissemination, while other countries became regional contributors to the export of specific variants. We demonstrate a declining role of presumed origin countries of VOCs to their global dispersal: we estimate that India contributed <15% of all global exports of Delta to other countries and South Africa <1-2% of all global Omicron exports globally. We further estimate that >80 countries had received introductions of Omicron BA.1 100 days after its inferred date of emergence, compared to just over 25 countries for the Alpha variant. This increased speed of global dissemination was associated with a rebound in air travel volume prior to Omicron emergence in addition to the higher transmissibility of Omicron relative to Alpha. Our study highlights the importance of global and regional hubs in VOC dispersal, and the speed at which highly transmissible variants disseminate through these hubs, even before their detection and characterization through genomic surveillance. Highlights: Global phylogenetic analysis reveals relationship between air travel and speed of dispersal of SARS-CoV-2 variants of concern (VOCs)Omicron VOC spread to 5x more countries within 100 days of its emergence compared to all other VOCsOnward transmission and dissemination of VOCs Delta and Omicron was primarily from secondary hubs rather than initial country of detection during a time of increased global air travelAnalysis highlights highly connected countries identified as major global and regional exporters of VOCs.

Shotgun metagenomic sequencing of the first case of monkeypox virus in Brazil, 2022.

Monkeypox virus (MPXV), a zoonotic virus endemic to the African continent, has been reported in 33 non-endemic countries since May 2022. We report an almost complete genome of the first confirmed case of MPXV in Brazil. Shotgun metagenomic sequencing was completed in 18 hours, from DNA extraction to consensus sequence generation.