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

Community Strains of Methicillin-Resistant Staphylococcus aureus as Potential Cause of Healthcare-associated Infections, Uruguay, 2002–2004

Community-associated MRSA appears to be replacing healthcare-associated MRSA strain types in at least 1 facility and is a cause of healthcare-onset infections

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

Infecções respiratórias agudas em crianças de famílias pobres de Montevideo

Para obter informação básica sobre a incidência, duração, características clínicas e etiologia das infecções respiratórias agudas (IRA), foram observadas 276 crianças de famílias pobres que moram em Montevidéo durante 32 meses. A população alvo foi dividida em dois grupos para análise dos resultados: Crianças com menos de 12 meses e acima dessa idade. Durante o período de seguimento foram registrados 1056 episódios de IRA. A incidência de IRA foi 5.2 por criança/ano. Foi 87% mais alta nos lactentes do que nos grupos de mais idade, com duração maior dos episódios. A maioria das infecções foi pouco grave. Observaram-se poucos casos com taquipnéia e retrações, mas 12 crianças foram hospitalizadas e dois lactentes morreram. Etiologia viral foi identificada em 15.3% dos episódios. RSV foi o agente predominante, produzindo epidemias anuais. Registrou-se durante os episódios de IRA a colonização moderada até alta no trato respiratório superior de S. pneumoniae (32.3%) e Hemophilus sp. (18.9%). Este estudo de comunidade forneceu informações originais sobre IRA no Uruguai. Permitiu avaliar o impacto destas infecções nas crianças.To obtain base line data on incidence, duration, clinical characteristics and etiology of acute respiratory infections (ARI), 276 children from deprived families living in Montevideo were followed during 32 months. The target population was divided into two groups for the analysis of the results: children aged less than 12 months and those older than this age. During the follow-up period 1.056 ARI episodes were recorded. ARI incidence was 5.2 per child/year. It was 87% higher in infants than in the older group, as was the duration of the episodes. Most of the diseases were mild. Tachypnea and retractions were seldom observed, but 12 children were refered to the hospital, and 2 infants died. Viral etiology was identified in 15.3% of the episodes. RSV was the predominant agent producing annual outbreaks. Moderate to heavy colonization of the upper respiratory tract by Streptococcus pneumoniae (32.3%) and Hemophilus sp. (18.9%) was recorded during ARI episodes. This community-based study furnish original data on ARI in Uruguay. It enabled to asses the impact of these infections on childhood

Etiologia e severidade de pneumonia adquirida comunitariamente em crianças uruguaias: um estudo de 4 anos

The 4-year study (1987-1990) covered the major clinical-epidemiological characteristics of pneumonia in children as diagnosed at the emergency service of the Children's Hospital, as well as etiologies, and factors involved in the most severe cases. Etiology was determined in 47.7% of the 541 pneumonia cases, involving 283 pathogens of which 38.6% were viruses and 12.6% bacteria. Viral and mixed etiologies were more frequent in children under 12 months of age. Bacteria predominated in ages between 6 and 23 months. Among the viruses, respiratory syncytial virus predominated (66%). The bacterial pneumonias accounted for 12.2% of the recognized etiologies. The most important bacterial agents were S. pneumoniae (64%) and H. influenzae (19%). H. influenzae and mixed infections had a relevant participation during the 1988 season, pointing to annual variations in the relative participation of pathogens and its possible implication in severity of diseases. Correlation of severity and increased percentage of etiological diagnosis was assessed: patients with respiratory rates over 70 rpm, or pleural effusion and/or extensive pulmonary parenchyma compromise yielded higher positive laboratory results. Various individual and family risk factors were recognized when comparing pneumonia children with healthy controls.O estudo de quatro anos de duração (1987-1990) abarcou as principais características clínico-epidemiológicas de pneumonia em crianças, tal como foi diagnosticado no serviço de emergência do Hospital Infantil, e também as etiologias e fatores implicados nos casos mais severos. Determinou-se a etiologia em 47.7% dos 541 casos de pneumonia, que incluíam 283 patógenos, dos quais 38.6% eram virus e 12.6% bactérias. Observou-se etiologia viral e mista mais freqüentemente nas crianças de menos de 12 meses. A etiologia bacteriana prevaleceu nas idades entre 6 e 23 meses. Com relação aos virus, a predominância foi de RSV com prevalência de 66% do total de virus. Os mais importantes agentes bacterianos foram S. pneumoniae (64%) e H. influenzae (19%). O H. influenzae e as infecções mistas incidiram significativamente durante 1988 assinalando variações anuais na severidade das doenças. Observou-se correlação entre a gravidade dos casos e a alta porcentagem de diagnóstico etiológico: pacientes com ritmos respiratórios mais altos que 70rpm, derrame pleural ou com comprometimento extenso de parênquima pulmonar, apresentaram maior índice de positividade laboratorial. Reconheceu-se vários fatores de risco individuais e familiares ao comparar crianças com pneumonia com controles sadios