Dr. Yang Zhong: an explorer on the road forever

On the morning of September 25th 2017, grievous news spread from the remote Ordos region of Inner Mongolia to Fudan University campus in Shanghai. Professor Yang Zhong, a famous botanist and the Dean of Fudan University’s graduate school, passed away in a tragic car accident while on a business trip

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

Phylogeography and genomic epidemiology of SARS-CoV-2 in Italy and Europe with newly characterized Italian genomes between February-June 2020

: The aims of this study were to characterize new SARS-CoV-2 genomes sampled all over Italy and to reconstruct the origin and the evolutionary dynamics in Italy and Europe between February and June 2020. The cluster analysis showed only small clusters including < 80 Italian isolates, while most of the Italian strains were intermixed in the whole tree. Pure Italian clusters were observed mainly after the lockdown and distancing measures were adopted. Lineage B and B.1 spread between late January and early February 2020, from China to Veneto and Lombardy, respectively. Lineage B.1.1 (20B) most probably evolved within Italy and spread from central to south Italian regions, and to European countries. The lineage B.1.1.1 (20D) developed most probably in other European countries entering Italy only in the second half of March and remained localized in Piedmont until June 2020. In conclusion, within the limitations of phylogeographical reconstruction, the estimated ancestral scenario suggests an important role of China and Italy in the widespread diffusion of the D614G variant in Europe in the early phase of the pandemic and more dispersed exchanges involving several European countries from the second half of March 2020

Accelerated SARS-CoV-2 Intrahost Evolution Leading to Distinct Genotypes During Chronic Infection

The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral genome copies. During the infection, we find an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately 2-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution results in the emergence and persistence of at least three genetically distinct genotypes, suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, we track the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, providing an opportunity for the emergence of genetically divergent variants

Population mortality during the outbreak of Severe Acute Respiratory Syndrome in Toronto

<p>Abstract</p> <p>Background</p> <p>Extraordinary infection control measures limited access to medical care in the Greater Toronto Area during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. The objective of this study was to determine if the period of these infection control measures was associated with changes in overall population mortality due to causes other than SARS.</p> <p>Methods</p> <p>Observational study of death registry data, using Poisson regression and interrupted time-series analysis to examine all-cause mortality rates (excluding deaths due to SARS) before, during, and after the SARS outbreak. The population of Ontario was grouped into the Greater Toronto Area (N = 2.9 million) and the rest of Ontario (N = 9.3 million) based upon the level of restrictions on delivery of clinical services during the SARS outbreak.</p> <p>Results</p> <p>There was no significant change in mortality in the Greater Toronto Area before, during, and after the period of the SARS outbreak in 2003 compared to the corresponding time periods in 2002 and 2001. The rate ratio for all-cause mortality during the SARS outbreak was 0.99 [95% Confidence Interval (CI) 0.93–1.06] compared to 2002 and 0.96 [95% CI 0.90–1.03] compared to 2001. An interrupted time series analysis found no significant change in mortality rates in the Greater Toronto Area associated with the period of the SARS outbreak.</p> <p>Conclusion</p> <p>Limitations on access to medical services during the 2003 SARS outbreak in Toronto had no observable impact on short-term population mortality. Effects on morbidity and long-term mortality were not assessed. Efforts to contain future infectious disease outbreaks due to influenza or other agents must consider effects on access to essential health care services.</p

Lineage Abundance Estimation for SARS-CoV-2 in Wastewater Using Transcriptome Quantification Techniques

Effectively monitoring the spread of SARS-CoV-2 mutants is essential to efforts to counter the ongoing pandemic. Predicting lineage abundance from wastewater, however, is technically challenging. We show that by sequencing SARS-CoV-2 RNA in wastewater and applying algorithms initially used for transcriptome quantification, we can estimate lineage abundance in wastewater samples. We find high variability in signal among individual samples, but the overall trends match those observed from sequencing clinical samples. Thus, while clinical sequencing remains a more sensitive technique for population surveillance, wastewater sequencing can be used to monitor trends in mutant prevalence in situations where clinical sequencing is unavailable

A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection

10.1186/1471-2334-4-34BMC Infectious Diseases4-BIDM

Pandemic influenza preparedness and health systems challenges in Asia: results from rapid analyses in 6 Asian countries

BACKGROUND: Since 2003, Asia-Pacific, particularly Southeast Asia, has received substantial attention because of the anticipation that it could be the epicentre of the next pandemic. There has been active investment but earlier review of pandemic preparedness plans in the region reveals that the translation of these strategic plans into operational plans is still lacking in some countries particularly those with low resources. The objective of this study is to understand the pandemic preparedness programmes, the health systems context, and challenges and constraints specific to the six Asian countries namely Cambodia, Indonesia, Lao PDR, Taiwan, Thailand, and Viet Nam in the prepandemic phase before the start of H1N1/2009. METHODS: The study relied on the Systemic Rapid Assessment (SYSRA) toolkit, which evaluates priority disease programmes by taking into account the programmes, the general health system, and the wider socio-cultural and political context. The components under review were: external context; stewardship and organisational arrangements; financing, resource generation and allocation; healthcare provision; and information systems. Qualitative and quantitative data were collected in the second half of 2008 based on a review of published data and interviews with key informants, exploring past and current patterns of health programme and pandemic response. RESULTS: The study shows that health systems in the six countries varied in regard to the epidemiological context, health care financing, and health service provision patterns. For pandemic preparation, all six countries have developed national governance on pandemic preparedness as well as national pandemic influenza preparedness plans and Avian and Human Influenza (AHI) response plans. However, the governance arrangements and the nature of the plans differed. In the five developing countries, the focus was on surveillance and rapid containment of poultry related transmission while preparation for later pandemic stages was limited. The interfaces and linkages between health system contexts and pandemic preparedness programmes in these countries were explored. CONCLUSION: Health system context influences how the six countries have been preparing themselves for a pandemic. At the same time, investment in pandemic preparation in the six Asian countries has contributed to improvement in health system surveillance, laboratory capacity, monitoring and evaluation and public communications. A number of suggestions for improvement were presented to strengthen the pandemic preparation and mitigation as well as to overcome some of the underlying health system constraints