SARS-COV-2. Origin, vaccines, variants and the future of the pandemic

Desde fines de 2019 estamos viviendo un evento pandémico único en la historia de la humanidad. El antecedente más cercano, por su duración ysus consecuencias fue la pandemia de la gripe de 1918. A pesar de las múltiples consecuencias de este evento para salud pública, hoy nos encontramos mucho mejor preparados para combatir esta virosis y tratar a los pacientes con COVID-19. Conocimos rápidamente la identidad y las principales características del agente etiológico y apoco másde un año de declarada la emergencia sanitaria se han desarrollado vacunas que vienen mostrando ser efectivas y seguras. El objetivo de este trabajoes repasar las principales características del virus SARS-COV-2ylas diferencias y similitudes con otros coronavirus relacionados. Revisaremos los tipos yel desempeño de las vacunas actualmente en uso, y los desafíos que enfrentamos ante el surgimiento de ciertas variantes virales.Since the end of 2019 we are living a unique pandemic event in the human history. The closest precedent, for its lasting and consequences was the 1918 influenza pandemic. Despite the multiple consequences for public health, we are now much better prepared to fight this agent and to provide a better treatment to COVID-19 patients. The scientific community discovered soon the identity and the key biologic characteristics of the COVID-19 etiologic agent, and just over a year and a half from the pandemic declaration, safe and effective vaccines were developed. In the present work, we aim to look over the main characteristics of SARS-CoV-2, as well as the differences and similarities with related coronaviruses. We will review the different vaccine platforms and the performances of the vaccines in use and discuss the future challenges of the emergence of viral variants

Ecological and conservation significance of herpesvirus infection in Neotropical bats

Bats are the second most diverse order of mammals and key species for ecosystem functioning, providing a wide range of ecosystem services, from pest control to seed dispersal. Chiropterans are known for hosting a large diversity of viruses, in some cases with little or no effect to their health. Here, we report on the results of a screening for DNA (Herpesviridae) and RNA viruses (Rhabdovirus and Pneumovirus), finding a high prevalence and wide diversity of both Beta- and Gamma-Herpesvirus in insectivorous and hematopha-gous bats of the southern cone of South America. Our findings suggest that bats in the southern neotropics harbor a high diversity of herpesviruses and, at least in some cases, the viral community in the bat species is more strongly associated with ecological traits of the hosts, rather than their taxonomy. The presence of a separate clade into the Gammaherpesvirinae subfamily in the common vampire bat suggests the independent circulation of herpesviruses in hematophagous and insectivorous bats and highlights the properness of these viruses to track vampire bats’ population structure for rabies studies. Hence, we suggest that as other pathogens viruses may be used to track the population dynamics of their hosts, including movement and demographics.ANII: FCE_1_2019_1_15557

Biogeografía de los roedores Akodontini como reservorio de hantavirus en Sudamérica.

Las zoonosis emergentes conforman unas de las amenazas más relevantes para la salud pública global. En Sudamérica, la hantavirosis es una zoonosis autóctona causada por la transmisión a humanos a través de pequeños roedores de la tribu Akodontini, pertenecientes a distintas especies. La infección se produce principalmente por la inhalación de partículas virales presentes en la orina, heces y saliva de roedores infectados, o por el contacto directo. La enfermedad se caracteriza por causar fiebre hemorrágica o síndrome pulmonar por hantavirus (SPH), presentando una alta mortalidad. No existe tratamiento, por lo que es esencial adoptar medidas de prevención, como evitar el contacto con roedores infectados. La función la favorabilidad como modelo de distribución de las especies (SDM), permite determinar la relación entre las especies y el ambiente, con independencia de la prevalencia en sus distribuciones. A partir de la distribución de los roedores de la tribu Akodontini en Sudamérica (13 especies) y un conjunto de 35 predictores ambientales (espaciales, climáticas, hidrológicas, topográficas y antrópicas), se aplicó una regresión logística multifactorial y el algoritmo de la favorabilidad para determinar los factores explicativos de estas distribuciones, y predecir los territorios más favorables. Todos los factores ambientales resultaron representados en algún modelo. El componente espacial como factor histórico, y la influencia humana, fueron los factores más explicativos. Con excepción del noroeste de Sudamérica, el resto del subcontinente obtuvo valores altos de favorabilidad para alguna de las especies de roedores, por lo tanto, favorables para el reservorio de hantavirus. Los modelos se ajustaron adecuadamente a las presencias conocidas, e indicaron territorios favorables no ocupados, aportando un insumo cartográfico útil para adoptar medidas preventivas con la finalidad de reducir las posibilidades de contacto entre el humano y estos roedores.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Juquitiba-like Hantavirus from 2 Nonrelated Rodent Species, Uruguay

Serologic and genetic analyses indicate that a Juquitiba-like hantavirus circulates in Maldonado, Uruguay. This virus is carried by 2 rodent species, Oligoryzomys nigripes and Oxymycterus nasutus. The same hantavirus in 2 nonrelated species can be explained by a spillover infection or a host-switching event

Alphavirus Identification in Neotropical Bats

Alphaviruses (Togaviridae) are arthropod-borne viruses responsible for several emerging diseases, maintained in nature through transmission between hematophagous arthropod vectors and susceptible vertebrate hosts. Although bats harbor many species of viruses, their role as reservoir hosts in emergent zoonoses has been verified only in a few cases. With bats being the second most diverse order of mammals, their implication in arbovirus infections needs to be elucidated. Reports on arbovirus infections in bats are scarce, especially in South American indigenous species. In this work, we report the genomic detection and identification of two different alphaviruses in oral swabs from bats captured in Northern Uruguay. Phylogenetic analysis identified Río Negro virus (RNV) in two different species: Tadarida brasiliensis (n = 6) and Myotis spp. (n = 1) and eastern equine encephalitis virus (EEEV) in Myotis spp. (n = 2). Previous studies of our group identified RNV and EEEV in mosquitoes and horse serology, suggesting that they may be circulating in enzootic cycles in our country. Our findings reveal that bats can be infected by these arboviruses and that chiropterans could participate in the viral natural cycle as virus amplifiers or dead-end hosts. Further studies are warranted to elucidate the role of these mammals in the biological cycle of these alphaviruses in Uruguay.ANII:FCE_1_2019_1_15557

Genomic characterization and seroprevalence studies on alphaviruses in Uruguay

Alphaviruses (Togaviridae) are arboviruses frequently associated with emerging infectious diseases. In this study, we aimed to investigate the presence of alphaviruses in Uruguay by detecting the viral genome in mosquitoes and neutralizing antibodies in equines. A total of 3,575 mosquitoes were analyzed for alphavirus genome detection. Serologic studies were performed on 425 horse sera by plaque reduction neutralization test (PRNT80) against Venezuelan equine encephalitis virus (VEEV) subtype IAB, Pixuna virus (PIXV), Rio Negro virus (RNV), western equine encephalitis virus (WEEV), and Madariaga virus (MADV). Mosquitoes belonging to six genera were captured and 82.9% were identified as Culex pipiens. Two Cx. pipiens pools collected in Fray Bentos and Las Toscas localities were alphavirus positive, and phylogenetic analyses showed that the sequences grouped into two different clusters: the lineage I of eastern equine encephalitis virus and RNV (VEEV complex), respectively. Plaque reduction neutralization test assays showed antibodies against strains of the VEEV complex, MADV, and WEEV. Rio Negro virus was the most geographically widespread virus, showing higher seroprevalences (up to 20%). Seroprevalences against VEEV IAB ranged between 4.6% and 13%; antibodies against PIXV, WEEV, and MADV were less frequent (3–4%). In conclusion, RNV exhibited the highest seroprevalence in horses, a wide geographical distribution, and viral genome was detected in Cx. pipiens mosquitoes. Madariaga virus had a low seroprevalence in equines, but an epizootic lineage typical of North America was detected in Cx. pipiens mosquitoes. Taken together, our results show that alphaviruses are present in Uruguay with variable occurrence and geographical distribution being a potential threat for human and equine health

A deletion in SARS-CoV- 2 ORF7 identified in COVID-19 outbreak in Uruguay

The analysis of genetic diversity in SARS-CoV-2 is the focus of several studies, providing insights into how the virus emerged and evolves. Most common changes in SARS-CoV-2 are single or point nucleotide substitutions; meanwhile, insertions and deletions (indels) have been identified as a less frequent source of viral genetic variability. Here, we report the emergence of a 12-nucleotide deletion in ORF7a, resulting in a 4-amino acid in-frame deletion. The Δ12 variant was identified in viruses from patients of a single outbreak and represents the first report of this deletion in South American isolates. Phylogenetic analysis revealed that Δ12 strains belong to the lineage B.1.1 and clustered separated from the remaining Uruguayan strains. The ∆12 variant was detected in 14 patients of this outbreak by NGS sequencing and/or two rapid and economic methodologies: Sanger amplicon sequencing and capillary electrophoresis. The presence of strong molecular markers as the deletion described here are useful for tracking outbreaks and reveal a significant aspect of the SARS-CoV-2 evolution on the robustness of the virus to keep its functionality regardless loss of genetic material

Genome sequences of SARS-CoV-2 P.1 (Variant of Concern) and P.2 (Variant of Interest) identified in Uruguay

Two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants associated with increased transmission and immune evasion, P.1 and P.2, emerged in Brazil and spread throughout South America. Here, we report genomes corresponding to these variants that were recently detected in Uruguay. These P.1 and P.2 genomes share all substitutions that are characteristic of these variants

Transmission cluster of COVID-19 cases from Uruguay: emergence and spreading of a novel SARS-CoV-2 ORF6 deletion

BACKGROUND Evolutionary changes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include indels in nonstructural, structural, and accessory open reading frames (ORFs) or genes. OBJECTIVES We track indels in accessory ORFs to infer evolutionary gene patterns and epidemiological links between outbreaks. METHODS Genomes from Coronavirus disease 2019 (COVID-19) case-patients were Illumina sequenced using ARTIC_V3. The assembled genomes were analysed to detect substitutions and indels. FINDINGS We reported the emergence and spread of a unique 4-nucleotide deletion in the accessory ORF6, an interesting gene with immune modulation activity. The deletion in ORF6 removes one repeat unit of a two 4-nucleotide repeat, which shows that directly repeated sequences in the SARS-CoV-2 genome are associated with indels, even outside the context of extended repeat regions. The 4-nucleotide deletion produces a frameshifting change that results in a protein with two inserted amino acids, increasing the coding information of this accessory ORF. Epidemiological and genomic data indicate that the deletion variant has a single common ancestor and was initially detected in a health care outbreak and later in other COVID-19 cases, establishing a transmission cluster in the Uruguayan population. MAIN CONCLUSIONS Our findings provide evidence for the origin and spread of deletion variants and emphasise indels’ importance in epidemiological studies, including differentiating consecutive outbreaks occurring in the same health facility

Consecutive deletions in a unique Uruguayan SARS-CoV-2 lineage evidence the genetic variability potential of accessory genes

Deletions frequently occur in the six accessory genes of SARS-CoV-2, but most genomes with deletions are sporadic and have limited spreading capability. Here, we analyze deletions in the ORF7a of the N.7 lineage, a unique Uruguayan clade from the Brazilian B.1.1.33 lineage. Thirteen samples collected during the early SARS-CoV-2 wave in Uruguay had deletions in the ORF7a. Complete genomes were obtained by Illumina next-generation sequencing, and deletions were confirmed by Sanger sequencing and capillary electrophoresis. The N.7 lineage includes several individuals with a 12-nucleotide deletion that removes four amino acids of the ORF7a. Notably, four individuals underwent an additional 68-nucleotide novel deletion that locates 44 nucleotides downstream in the terminal region of the same ORF7a. The simultaneous occurrence of the 12 and 68-nucleotide deletions fuses the ORF7a and ORF7b, two contiguous accessory genes that encode transmem- brane proteins with immune-modulation activity. The fused ORF retains the signal peptide and the complete Ig-like fold of the 7a protein and the transmembrane domain of the 7b protein, suggesting that the fused protein plays similar functions to original proteins in a single format. Our findings evidence the remarkable dynamics of SARS-CoV-2 and the possibility that single and consecutive deletions occur in accessory genes and promote changes in the genomic organization that help the virus explore genetic variations and select for new, higher fit changes