Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 is critical to preventing future zoonotic outbreaks before they become the next pandemic. The Huanan ...Seafood Wholesale Market in Wuhan, China, was identified as a likely source of cases in early reports, but later this conclusion became controversial. We show here that the earliest known COVID-19 cases from December 2019, including those without reported direct links, were geographically centered on this market. We report that live SARS-CoV-2-susceptible mammals were sold at the market in late 2019 and that within the market, SARS-CoV-2-positive environmental samples were spatially associated with vendors selling live mammals. Although there is insufficient evidence to define upstream events, and exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred through the live wildlife trade in China and show that the Huanan market was the epicenter of the COVID-19 pandemic.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). Little is known about the interplay between preexisting immunity to endemic seasonal ...coronaviruses and the development of a SARS-CoV-2-specific IgG response. We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal and epidemic coronaviruses at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed antibody reactivity to nucleocapsid and spike antigens and correlated this IgG response to SARS-CoV-2 neutralization. Patients with COVID-19 mounted a mostly type-specific SARS-CoV-2 response. Additionally, IgG clones directed against a seasonal coronavirus were boosted in patients with severe COVID-19. These boosted clones showed limited cross-reactivity and did not neutralize SARS-CoV-2. These findings indicate a boost of poorly protective CoV-specific antibodies in patients with COVID-19 that correlated with disease severity, revealing "original antigenic sin."
With rapidly changing ecology, urbanization, climate change, increased travel and fragile public health systems, epidemics will become more frequent, more complex and harder to prevent and contain. ...Here we argue that our concept of epidemics must evolve from crisis response during discrete outbreaks to an integrated cycle of preparation, response and recovery. This is an opportunity to combine knowledge and skills from all over the world-especially at-risk and affected communities. Many disciplines need to be integrated, including not only epidemiology but also social sciences, research and development, diplomacy, logistics and crisis management. This requires a new approach to training tomorrow's leaders in epidemic prevention and response.
Arboviruses represent a significant burden to public health and local economies due to their ability to cause unpredictable and widespread epidemics. To maximize early detection of arbovirus ...emergence in non-endemic areas, surveillance efforts should target areas where circulation is most likely. However, identifying such hotspots of potential emergence is a major challenge. The ecological conditions leading to arbovirus outbreaks are shaped by complex interactions between the virus, its vertebrate hosts, arthropod vector, and abiotic environment that are often poorly understood. Here, we systematically review the ecological risk factors associated with the circulation of six arboviruses that are of considerable concern to northwestern Europe. These include three mosquito-borne viruses (Japanese encephalitis virus, West Nile virus, Rift Valley fever virus) and three tick-borne viruses (Crimean-Congo hemorrhagic fever virus, tick-borne encephalitis virus, and louping-ill virus). We consider both intrinsic (e.g. vector and reservoir host competence) and extrinsic (e.g. temperature, precipitation, host densities, land use) risk factors, identify current knowledge gaps, and discuss future directions. Our systematic review provides baseline information for the identification of regions and habitats that have suitable ecological conditions for endemic circulation, and therefore may be used to target early warning surveillance programs aimed at detecting multi-virus and/or arbovirus emergence.
Abstract The hemagglutination inhibition (HI) assay has been used for the antigenic characterization of influenza viruses for decades. However, the majority of recent seasonal influenza A viruses of ...the H3N2 subtype has lost the capacity to agglutinate erythrocytes of various species. The hemagglutination (HA) activity of other A(H3N2) strains is generally sensitive to the action of the neuraminidase inhibitor oseltamivir, which indicates that the neuraminidase and not the hemagglutinin is responsible for the HA activity. These findings complicate the antigenic characterization and selection of A(H3N2) vaccine strains, calling for alternative antigenic characterization assays. Here we describe the development and use of the ViroSpot microneutralization (MN) assay as a reliable and robust alternative for the HI assay. Serum neutralization of influenza A(H3N2) reference virus strains and epidemic isolates was determined by automated readout of immunostained cell monolayers, in a format designed to minimize the influence of infectious virus doses on serum neutralization titers. Neutralization of infection was largely independent from rates of viral replication and cell-to-cell transmission, facilitating the comparison of different virus isolates. Other advantages of the ViroSpot MN assay include its relative insensitivity to variation in test dose of infectious virus, automated capture and analyses of residual infection patterns, and compatibility with standardized large scale analyses. Using this assay, a number of epidemic influenza A(H3N2) strains that failed to agglutinate erythrocytes, were readily characterized antigenically.
The COVID-19 pandemic necessitates better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high-throughput multiplex assay to detect ...antibodies to SARS-CoV-2 to assess immunity to the virus in the general population.
Spike protein subunits S1 and receptor binding domain, and nucleoprotein were coupled to microspheres. Sera collected before emergence of SARS-CoV-2 (n = 224) and of non-SARS-CoV-2 influenza-like illness (n = 184), and laboratory-confirmed cases of SARS-CoV-2 infection (n = 115) with various severities of COVID-19 were tested for SARS-CoV-2-specific IgG concentrations.
Our assay discriminated SARS-CoV-2-induced antibodies and those induced by other viruses. The assay specificity was 95.1%-99.0% with sensitivity 83.6%-95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to nonhospitalized cases.
The bead-based serological assay for quantitation of SARS-CoV-2-specific antibodies proved to be robust and can be conducted in many laboratories. We demonstrated that testing of antibodies against multiple antigens increases sensitivity and specificity compared to single-antigen-specific IgG determination.
Following a proposal made by the French and German Ministers for Foreign Affairs at the November 2020 Paris Peace Forum, 4 global partners, the Food and Agriculture Organization (FAO), the World ...Organization for Animal Health (OIE), the United Nations Environment Programme (UNEP), and the World Health Organization (WHO), in May 2021 established the interdisciplinary One Health High-Level Expert Panel (OHHLEP) (https://www.who.int/groups/one-health-high-level-expert-panel) to enhance their cross-sectoral collaboration. There is no shortage of “One Health” definitions in the published literature and among institutions and organizations. ...an immediate priority for OHHLEP was to develop consensus around a working definition as a solid basis to support a common understanding among the panel members and the partner organizations. Key underlying principles including 1. equity between sectors and disciplines; 2. sociopolitical and multicultural parity (the doctrine that all people are equal and deserve equal rights and opportunities) and inclusion and engagement of communities and marginalized voices; 3. socioecological equilibrium that seeks a harmonious balance between human–animal–environment interaction and acknowledging the importance of biodiversity, access to sufficient natural space and resources, and the intrinsic value of all living things within the ecosystem; 4. stewardship and the responsibility of humans to change behavior and adopt sustainable solutions that recognize the importance of animal welfare and the integrity of the whole ecosystem, thus securing the well-being of current and future generations; and 5. transdisciplinarity and multisectoral collaboration, which includes all relevant disciplines, both modern and traditional forms of knowledge and a broad representative array of perspectives. PLoS Pathog 18(6): e1010537. https://doi.org/10.1371/journal.ppat.1010537 About the Authors: One Health High-Level Expert Panel (OHHLEP) Wiku B. Adisasmito Affiliation: Universitas Indonesia, Depok, West Java, Indonesia Salama Almuhairi Affiliation: National Emergency Crisis and Disasters Management Authority, Abu Dhabi, United Arab Emirates Casey Barton Behravesh Affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America Pépé Bilivogui Affiliation: World Health Organization, Guinea Country Office, Conakry, Guinea Salome A. Bukachi Affiliation: Institute of Anthropology, Gender and African Studies, University of Nairobi, Nairobi, Kenya Natalia Casas Affiliation: National Ministry of Health, Autonomous City of Buenos Aires, Argentina Natalia Cediel Becerra Affiliation: School of Agricultural Sciences, Universidad de La Salle, Bogotá, Colombia Dominique F. Charron Affiliation: International Development Research Centre, Ottawa, Canada Abhishek Chaudhary Affiliation: Indian Institute of Technology (IIT), Kanpur, India Janice R. Ciacci Zanella Affiliation: Brazilian Agricultural Research Corporation (Embrapa), Embrapa Swine and Poultry, Concórdia, Santa Catarina, Brazil Andrew A. Cunningham Affiliation: Institute of Zoology, Zoological Society of London, London, United Kingdom Osman Dar Affiliations Global Operations Division, United Kingdom Health Security Agency, London, United Kingdom, Global Health Programme, Chatham House, Royal Institute of International Affairs, London, United Kingdom Nitish Debnath Affiliation: Fleming Fund Country Grant to Bangladesh, DAI Global, Dhaka, Bangladesh Baptiste Dungu Affiliations Afrivet B M, Pretoria, South Africa, Faculty of Veterinary Science, University of Kinshasa, Kinshasa, Democratic Republic Congo Elmoubasher Farag Affiliation: Ministry of Public Health, Health Protection & Communicable Diseases Division, Doha, Qatar George F. Gao Affiliation: Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China David T. S. Hayman Affiliation: Molecular Epidemiology and Public Health Laboratory, Massey University, Palmerston North, New Zealand Margaret Khaitsa Affiliation: Mississippi State University, Starkville, Mississippi,
Metagenomics poses opportunities for clinical and public health virology applications by offering a way to assess complete taxonomic composition of a clinical sample in an unbiased way. However, the ...techniques required are complicated and analysis standards have yet to develop. This, together with the wealth of different tools and workflows that have been proposed, poses a barrier for new users. We evaluated 49 published computational classification workflows for virus metagenomics in a literature review. To this end, we described the methods of existing workflows by breaking them up into five general steps and assessed their ease-of-use and validation experiments. Performance scores of previous benchmarks were summarized and correlations between methods and performance were investigated. We indicate the potential suitability of the different workflows for (1) time-constrained diagnostics, (2) surveillance and outbreak source tracing, (3) detection of remote homologies (discovery), and (4) biodiversity studies. We provide two decision trees for virologists to help select a workflow for medical or biodiversity studies, as well as directions for future developments in clinical viral metagenomics.
•3D-based primary intestinal organoids support the infection of both experimental and patient-derived rotavirus strains.•Rotavirus infection provokes the induction of interferon-stimulated genes in ...organoids.•Interferon-alpha and ribavirin inhibit rotavirus replication in organoids.•Organoids infected with patient rotavirus can be potentially utilized for personalized evaluation of antivirals.
Despite the introduction of oral vaccines, rotavirus still kills over 450,000 children under five years of age annually. The absence of specific treatment prompts research aiming at further understanding of pathogenesis and the development of effective antiviral therapy, which in turn requires advanced experimental models. Given the intrinsic limitations of the classical rotavirus models using immortalized cell lines infected with laboratory-adapted strains in two dimensional cultures, our study aimed to model infection and antiviral therapy of both experimental and patient-derived rotavirus strains using three dimensional cultures of primary intestinal organoids. Intestinal epithelial organoids were successfully cultured from mouse or human gut tissues. These organoids recapitulate essential features of the in vivo tissue architecture, and are susceptible to rotavirus. Human organoids are more permissive to rotavirus infection, displaying an over 10,000-fold increase in genomic RNA following 24h of viral replication. Furthermore, infected organoids are capable of producing infectious rotavirus particles. Treatment of interferon-alpha or ribavirin inhibited viral replication in organoids of both species. Importantly, human organoids efficiently support the infection of patient-derived rotavirus strains and can be potentially harnessed for personalized evaluation of the efficacy of antiviral medications. Therefore, organoids provide a robust model system for studying rotavirus–host interactions and assessing antiviral medications.
In the first wave of the COVID-19 pandemic (April 2020), SARS-CoV-2 was detected in farmed minks and genomic sequencing was performed on mink farms and farm personnel. Here, we describe the outbreak ...and use sequence data with Bayesian phylodynamic methods to explore SARS-CoV-2 transmission in minks and humans on farms. High number of farm infections (68/126) in minks and farm workers (>50% of farms) were detected, with limited community spread. Three of five initial introductions of SARS-CoV-2 led to subsequent spread between mink farms until November 2020. Viruses belonging to the largest cluster acquired an amino acid substitution in the receptor binding domain of the Spike protein (position 486), evolved faster and spread longer and more widely. Movement of people and distance between farms were statistically significant predictors of virus dispersal between farms. Our study provides novel insights into SARS-CoV-2 transmission between mink farms and highlights the importance of combining genetic information with epidemiological information when investigating outbreaks at the animal-human interface.
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