SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Portuguese network for SARS-CoV-2 genomics (Consortium): Agostinho José S Lira, Aida M Sousa Fernandes, Alexandra Estrada, Alexandra Nunes, Alfredo Rodrigues, Ana Caldas, Ana Constança, Ana Margarida Henriques, Ana Miguel Matos, Ana Oliveira, Ana Paula Dias, Ana Pelerito, Ana Rita Couto, Anabela Vilares, António Albuquerque, Baltazar Nunes, Bruna R Gouveia, Carina de Fátima Rodrigues, Carla Feliciano, Carla Roque, Carlos Cardoso, Carlos Sousa, Cathy Paulino, Célia Rodrigues Bettencourt, Claudia C Branco, Cláudia Nunes Dos Santos, Conceição Godinho, Constantino P Caetano, Cristina Correia, Cristina Toscano, Cristina Veríssimo, Daniela Silva, Diana Patrícia Pinto da Silva, Eliana Costa, Elizabeth Pádua, Fátima Martins, Fátima Vale, Fernanda Vilarinho, Fernando Branca, Filomena Caldeira, Filomena Lacerda, Francisca Rocha, Graça Andrade, Helena Ribeiro, Helena Rodrigues, Herberto Jesus, Hugo Sousa, Idalina Ferreira, Inês Baldaque, Inês Costa, Inês Gomes, Inna Slobidnyk, Isabel Albergaria, Isabel Dias, Isabel Fernandes, Isabel Lopes de Carvalho, Ivone Água-Doce, Jácome Bruges Armas, Joana Ramos, João Carlos Sousa, João Costa, João Dias, João Rodrigues, João Sobral, Jorge Machado, Jorge Meneses, José Alves, José Vicente Constantino, Laura Brum, Leonor Silveira, Líbia Zé-Zé, Lidia Santos, Ludivina Freitas, Luís Silva, Luisa Mota-Vieira, Lurdes Lopes, Lurdes Monteiro, Márcia Faria, Margarida Farinha, Margarida Vaz, Maria Alice Pinto, Maria Ana Pessanha, Maria Beatriz Tomaz, Maria Calle Vellés, Maria da Graça Maciel de Soveral, Maria Helena Ramos, Maria Isabel Veiga, Maria João Gargate, Maria João Peres, Maria José Borrego, Maria Matos Figueiredo, Mariana Martins, Mariana Viana, Maurício Melim, Miguel Babarro Jorreto, Miguel Fevereiro, Miguel Pinheiro, Mónica Oleastro, Nair Seixas, Nelson Ventura, Nuno Verdasca, Olga Costa, Patrícia Barros, Patricia Fonseca, Patricia Miguel, Paula Bajanca-Lavado, Paula Branquinho, Paula Palminha, Paula Soares, Paula Valente, Paulo Leandro, Paulo Pereira, Pedro Cardoso, Pedro Pechirra, Pedro Ramos, Raquel Neves, Raquel Rocha, Raquel Rodrigues, Raquel Sabino, Regina Sá, Ricardo Filipe Romão Ferreira, Ricardo Rodrigues, Rita C Veloso, Rita Cordeiro, Rita Côrte-Real, Rita de Sousa, Rita Gralha, Rita Macedo, Rita Matos, Rita Rodrigues, Sandra Paulo, Sara Sousa, Sílvia Lopo, Sónia Marta Santos Magalhães, Sónia Rodrigues, Sónia Silva, Susana Ladeiro, Susana Martins, Susana Silva, Teresa Salvado, Tiago Luís, Valquíria Alves, Vera ManageiroBackground: 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.Plain language summary: Analysing SARS-CoV-2 genetic material and how it changes over time can help us understand how the virus spreads between countries and determine the impact of control measures. In this study, we investigated SARS-CoV-2 transmission and evolution in the early stages of the COVID-19 pandemic in Portugal. In particular, we reconstructed the routes and timeliness of viral introductions into the country and assessed the relative contribution of each introduction in terms of how the epidemic evolved over time. We detected at least 277 independent 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. This study reflects an unprecedented effort in the field of the infectious diseases in Portugal, highlighting the need for systematic and geographically-representative surveillance to aid public health efforts to control the virus.This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Por tugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

Trends and predictors of transmitted drug resistance (TDR) and clusters with TDR in a local Belgian HIV-1 epidemic

We aimed to study epidemic trends and predictors for transmitted drug resistance (TDR) in our region, its clinical impact and its association with transmission clusters. We included 778 patients from the AIDS Reference Center in Leuven (Belgium) diagnosed from 1998 to 2012. Resistance testing was performed using population-based sequencing and TDR was estimated using the WHO-2009 surveillance list. Phylogenetic analysis was performed using maximum likelihood and Bayesian techniques. The cohort was predominantly Belgian (58.4%), men who have sex with men (MSM) (42.8%), and chronically infected (86.5%). The overall TDR prevalence was 9.6% (95% confidence interval (CI): 7.7-11.9), 6.5% (CI: 5.0-8.5) for nucleoside reverse transcriptase inhibitors (NRTI), 2.2% (CI: 1.4-3.5) for non-NRTI (NNRTI), and 2.2% (CI: 1.4-3.5) for protease inhibitors. A significant parabolic trend of NNRTI-TDR was found (p = 0.019). Factors significantly associated with TDR in univariate analysis were male gender, Belgian origin, MSM, recent infection, transmission clusters and subtype B, while multivariate and Bayesian network analysis singled out subtype B as the most predictive factor of TDR. Subtype B was related with transmission clusters with TDR that included 42.6% of the TDR patients. Thanks to resistance testing, 83% of the patients with TDR who started therapy had undetectable viral load whereas half of the patients would likely have received a suboptimal therapy without this test. In conclusion, TDR remained stable and a NNRTI up-and-down trend was observed. While the presence of clusters with TDR is worrying, we could not identify an independent, non-sequence based predictor for TDR or transmission clusters with TDR that could help with guidelines or public health measures

A comprehensive SARS-CoV-2 and COVID-19 review, Part 2: host extracellular to systemic effects of SARS-CoV-2 infection

COVID-19, the disease caused by SARS-CoV-2, has caused significant morbidity and mortality worldwide. The betacoronavirus continues to evolve with global health implications as we race to learn more to curb its transmission, evolution, and sequelae. The focus of this review, the second of a three-part series, is on the biological effects of the SARS-CoV-2 virus on post-acute disease in the context of tissue and organ adaptations and damage. We highlight the current knowledge and describe how virological, animal, and clinical studies have shed light on the mechanisms driving the varied clinical diagnoses and observations of COVID-19 patients. Moreover, we describe how investigations into SARS-CoV-2 effects have informed the understanding of viral pathogenesis and provide innovative pathways for future research on the mechanisms of viral diseases

Application of Phylodynamic Tools to Inform the Public Health Response to COVID-19: Qualitative Analysis of Expert Opinions

Background: In the wake of the SARS-CoV-2 pandemic, scientists have scrambled to collect and analyze SARS-CoV-2 genomic data to inform public health responses to COVID-19 in real time. Open source phylogenetic and data visualization platforms for monitoring SARS-CoV-2 genomic epidemiology have rapidly gained popularity for their ability to illuminate spatial-temporal transmission patterns worldwide. However, the utility of such tools to inform public health decision-making for COVID-19 in real time remains to be explored. Objective: The aim of this study is to convene experts in public health, infectious diseases, virology, and bioinformatics—many of whom were actively engaged in the COVID-19 response—to discuss and report on the application of phylodynamic tools to inform pandemic responses. Methods: In total, 4 focus groups (FGs) occurred between June 2020 and June 2021, covering both the pre- and postvariant strain emergence and vaccination eras of the ongoing COVID-19 crisis. Participants included national and international academic and government researchers, clinicians, public health practitioners, and other stakeholders recruited through purposive and convenience sampling by the study team. Open-ended questions were developed to prompt discussion. FGs I and II concentrated on phylodynamics for the public health practitioner, while FGs III and IV discussed the methodological nuances of phylodynamic inference. Two FGs per topic area to increase data saturation. An iterative, thematic qualitative framework was used for data analysis. Results: We invited 41 experts to the FGs, and 23 (56%) agreed to participate. Across all the FG sessions, 15 (65%) of the participants were female, 17 (74%) were White, and 5 (22%) were Black. Participants were described as molecular epidemiologists (MEs; n=9, 39%), clinician-researchers (n=3, 13%), infectious disease experts (IDs; n=4, 17%), and public health professionals at the local (PHs; n=4, 17%), state (n=2, 9%), and federal (n=1, 4%) levels. They represented multiple countries in Europe, the United States, and the Caribbean. Nine major themes arose from the discussions: (1) translational/implementation science, (2) precision public health, (3) fundamental unknowns, (4) proper scientific communication, (5) methods of epidemiological investigation, (6) sampling bias, (7) interoperability standards, (8) academic/public health partnerships, and (9) resources. Collectively, participants felt that successful uptake of phylodynamic tools to inform the public health response relies on the strength of academic and public health partnerships. They called for interoperability standards in sequence data sharing, urged careful reporting to prevent misinterpretations, imagined that public health responses could be tailored to specific variants, and cited resource issues that would need to be addressed by policy makers in future outbreaks. Conclusions: This study is the first to detail the viewpoints of public health practitioners and molecular epidemiology experts on the use of viral genomic data to inform the response to the COVID-19 pandemic. The data gathered during this study provide important information from experts to help streamline the functionality and use of phylodynamic tools for pandemic responses