Browsing by Author "Isidro, J."
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- Congenital SARS-CoV-2 Infection in a Neonate With Severe Acute Respiratory SyndromePublication . Correia, C.R.; Marçal, M.; Vieira, F.; Santos, E.; Novais, C.; Maria, A.T.; Malveiro, D.; Prior, A.R.; Aguiar, M.; Salazar, A.; Pinto, C.G.; Rodrigues, L.C.; Pessanha, M.A.; Borges, V.; Isidro, J.; Gomes, J.P.; Duarte, S.; Vieira, L.; Costa, I.; Alves, M.J.; Calhau, C.; Guiomar, R.; Tuna, M.L.Coronavirus disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is mainly transmitted through droplets, but other ways of transmission have been hypothesized. We report a case of vertical transmission of SARS-CoV-2 in a preterm born to an infected mother, confirmed by the presence of the virus in the neonatal blood, nasopharyngeal and oropharyngeal swabs collected in the first half an hour of life. The neonate presented with acute respiratory distress, similar to the findings in severely affected adults. This case highlights the importance of pregnancy, labor and neonatal period surveillance of affected mothers and their newborns.
- Investigação de um cluster de infeções por Clostridium difficile em contexto oncológicoPublication . Santos, A.; Isidro, J.; Lameiras, C.; Campilho, F.; Branca, R.; Campos, A.; Oleastro, M.A infeção por Clostridium difficile (ICD) é das infeções mais frequentemente associadas aos cuidados de saúde. A exposição prévia a antibióticos constitui o principal fator de risco para o desenvolvimento da ICD, sendo outros fatores a idade avançada e a existência de comorbilidades, como a imunossupressão. Apesar de o contacto entre indivíduos/transmissão cruzada constituir uma importante via de transmissão da ICD, tem sido demonstrado que uma parte significativa dos casos de ICD não está ligada a outros casos ocorridos no mesmo serviço hospitalar. Neste trabalho reportamos três casos de ICD ocorridos no Serviço de Transplantação de Medula Óssea do IPO do Porto, dois episódios ocorreram em dias consecutivos (28 e 29 de Outubro), o terceiro a 16 de Novembro, em 2015.
- Molecular and epidemiologic study of Clostridium difficile reveals unusual heterogeneity in clinical strains circulating in different regions in PortugalPublication . Santos, A.; Isidro, J.; Silva, C.; Boaventura, L.; Diogo, J.; Faustino, A.; Toscano, C.; Oleastro, M.Clostridium difficile infection (CDI) represents a great healthcare burden in developed countries. The emergence of the epidemic PCR ribotype (RT) 027 and its acquired fluoroquinolones resistance have accentuated the need for an active surveillance of CDI. Here we report the first countrywide study of CDI in Portugal with the characterization of 498 C. difficile clinical isolates from 20 hospitals in four regions in Portugal regarding RT, virulence factors and antimicrobial susceptibility. We identified 96 RTs with marked variations between and within regions, as only six RTs appeared in all four regions. RT027 was the most frequent RT overall (18.5%) and among healthcare facility-associated isolates (19.6%), while RT014 was the most common among community-associated isolates (12%). The north showed a high RT diversity among isolates and a low moxifloxacin (MXF) resistance rate (11.9%), being the only region in which RT027 was not predominant. In contrast, the isolates from the centre presented the highest RT027 frequency, and 53.4% were resistant to MXF. Overall, MXF resistance (33.2%) was associated (p <0.001) with the presence of binary toxin genes and mutations in tcdC regardless of the RT. Both traits appeared in almost 30% of the strains. RT027 showed a reduced susceptibility to metronidazole (p <0.01), and RT126 had higher minimum inhibitory concentrations to vancomycin (p = 0.03) compared to other RTs. The present study highlights an unusual heterogeneity of RTs in Portugal, with a high frequency of hypervirulent RTs and the emergence of virulence factors in non-027 RTs, emphasizing the need for a surveillance system for CDI in Portugal.
- Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolutionPublication . Amicone, M.; Borges, V.; Alves, M.J.; Isidro, J.; Zé-Zé, L.; Duarte, S.; Gomes, J. P.; Gordo, I.Background and objectives: To understand how organisms evolve, it is fundamental to study how mutations emerge and establish. Here, we estimated the rate of mutation accumulation of SARS-CoV- 2 in vitro and investigated the repeatability of its evolution when facing a new cell type but no immune or drug pressures. Methodology: We performed experimental evolution with two strains of SARS-CoV-2, one carrying the originally described spike protein (CoV-2-D) and another carrying the D614G mutation that has spread worldwide (CoV-2-G). After 15 passages in Vero cells and whole genome sequencing, we characterized the spectrum and rate of the emerging mutations and looked for evidences of selection across the genomes of both strains. Results: From the frequencies of the mutations accumulated, and excluding the genes with signals of selection, we estimate a spontaneous mutation rate of 1.3 10 6 6 0.2 10 6 per-base per-infection cycle (mean across both lineages of SARS-CoV-262SEM). We further show that mutation accumulation is larger in the CoV-2-D lineage and heterogeneous along the genome, consistent with the action of positive selection on the spike protein, which accumulated five times more mutations than the corresponding genomic average. We also observe the emergence of mutators in the CoV-2-G background, likely linked to mutations in the RNA-dependent RNA polymerase and/or in the error-correcting exonuclease protein. Conclusions and implications: These results provide valuable information on how spontaneous mutations emerge in SARS-CoV-2 and on how selection can shape its genome toward adaptation to new environments. Lay Summary: Each time a virus replicates inside a cell, errors (mutations) occur. Here, via laboratory propagation in cells originally isolated from the kidney epithelium of African green monkeys, we estimated the rate at which the SARS-CoV-2 virus mutates—an important parameter for understanding how it can evolve within and across humans. We also confirm the potential of its Spike protein to adapt to a new environment and report the emergence of mutators—viral populations where mutations occur at a significantly faster rate.
- SARS-CoV-2 introductions and early dynamics of the epidemic in PortugalPublication . Borges, V.; Isidro, J.; Trovão, N.S.; Duarte, S.; Cortes-Martins, H.; Martiniano, H.; Gordo, I.; Leite, R.; Vieira, L.; Portuguese network for SARS-CoV-2 genomics (Consortium); Guiomar, R.; Gomes, J.P.Background: Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods: By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARS-CoV-2 introductions and early dissemination in Portugal. Results: We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions: Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.