Surveillance for variants of SARS-CoV-2 to inform risk assessments.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged, some leading to large increases in infections, hospitalizations and deaths globally. The virus's impact on public health depends on many factors, including the emergence of new viral variants and their global spread. Consequently, the early detection and surveillance of variants and characterization of their clinical effects are vital for assessing their health risk. The unprecedented capacity for viral genomic sequencing and data sharing built globally during the pandemic has enabled new variants to be rapidly detected and assessed. This article describes the main variants circulating globally between January 2020 and June 2023, the genetic features driving variant evolution, and the epidemiological impact of these variants across countries and regions. Second, we report how integrating genetic variant surveillance with epidemiological data and event-based surveillance, through a network of World Health Organization partners, supported risk assessment and helped provide guidance on pandemic responses. In addition, given the evolutionary characteristics of circulating variants and the immune status of populations, we propose future directions for the sustainable genomic surveillance of SARS-CoV-2 variants, both nationally and internationally: (i) optimizing variant surveillance by including environmental monitoring; (ii) coordinating laboratory assessment of variant evolution and phenotype; (iii) linking data on circulating variants with clinical data; and (iv) expanding genomic surveillance to additional pathogens. Experience during the COVID-19 pandemic has shown that genomic surveillance of pathogens can provide essential, timely and evidence-based information for public health decision-making.

Depuis le début de la pandémie de coronavirus survenue en 2019 (COVID-19), de nombreux variants du coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2) sont apparus, certains entraînant une forte augmentation du nombre d'infections, d'hospitalisations et de décès dans le monde. L'impact du virus sur la santé publique dépend de nombreux facteurs, notamment l'émergence de nouveaux variants viraux et leur propagation à l'échelle mondiale. Par conséquent, la détection précoce et la surveillance des variants ainsi que la caractérisation de leurs effets cliniques sont essentielles pour évaluer leur risque pour la santé. La capacité sans précédent de séquençage du génome viral et de partage des données, capacité mise en place à l'échelle mondiale pendant la pandémie, a permis de détecter et d'évaluer rapidement de nouveaux variants. Le présent article décrit les principaux variants circulant dans le monde entre janvier 2020 et juin 2023, les caractéristiques génétiques à l'origine de leur évolution et leur impact épidémiologique dans les différents pays et régions. Ensuite, nous expliquerons comment l'intégration de la surveillance des variants génétiques aux données épidémiologiques et à la surveillance fondée sur les événements, par l'intermédiaire d'un réseau de partenaires de l'Organisation mondiale de la santé, a permis de faciliter l'évaluation des risques et de fournir des orientations sur les mesures à prendre en période de pandémie. En outre, compte tenu des caractéristiques évolutives des variants en circulation et de l'état immunitaire des populations, nous proposons des orientations futures pour une surveillance génomique durable des variants du SARS-CoV-2, au niveau tant national qu'international: (i) optimiser la surveillance des variants en incluant le suivi environnemental; (ii) coordonner l'évaluation en laboratoire de l'évolution des variants et du phénotype; (iii) établir un lien entre les données sur les variants en circulation et les données cliniques; et (iv) étendre la surveillance génomique à d'autres agents pathogènes. L'expérience de la pandémie de COVID-19 a mis en évidence que la surveillance génomique des agents pathogènes peut fournir en temps utile des informations essentielles fondées sur des preuves en vue de la prise de décisions en matière de santé publique.

Desde el inicio de la pandemia de la enfermedad por coronavirus de 2019 (COVID-19), han aparecido numerosas variantes del coronavirus de tipo 2 causante del síndrome respiratorio agudo severo (SRAS-CoV-2), algunas de las que han provocado un gran aumento de las infecciones, hospitalizaciones y muertes en todo el mundo. El impacto del virus en la salud pública depende de muchos factores, entre ellos la aparición de nuevas variantes víricas y su propagación mundial. En consecuencia, la detección y vigilancia tempranas de las variantes y la caracterización de sus efectos clínicos son vitales para evaluar su riesgo sanitario. La capacidad sin precedentes de secuenciación genómica viral y de intercambio de datos creada a nivel mundial durante la pandemia ha permitido detectar y evaluar rápidamente variantes nuevas. En este artículo se describen las principales variantes que circulan a nivel mundial entre enero de 2020 y junio de 2023, la característica genética que impulsa la evolución de las variantes y el impacto epidemiológico de estas variantes en los diferentes países y regiones. En segundo lugar, se informa de cómo la integración de la vigilancia de variantes genéticas con los datos epidemiológicos y la vigilancia basada en eventos, a través de una red de asociados de la Organización Mundial de la Salud, apoyó la evaluación de riesgos y ayudó a proporcionar orientación sobre las respuestas a la pandemia. Además, dadas las características evolutivas de las variantes circulantes y el estado inmunitario de las poblaciones, se proponen orientaciones futuras para la vigilancia genómica sostenible de las variantes del SRAS-CoV-2, tanto a nivel nacional como internacional: (i) optimizar la vigilancia de las variantes mediante la inclusión de la monitorización ambiental; (ii) coordinar la evaluación de laboratorio de la evolución y el fenotipo de las variantes; (iii) vincular los datos sobre las variantes circulantes con los datos clínicos; y (iv) ampliar la vigilancia genómica a patógenos adicionales. La experiencia durante la pandemia de la COVID-19 ha demostrado que la vigilancia genómica de patógenos puede proporcionar información esencial, oportuna y basada en evidencias para la toma de decisiones en materia de salud pública.

An overview of the National West Nile Virus Surveillance System in Canada: A One Health approach.

National West Nile virus (WNV) surveillance was established in partnership with the federal, provincial and territorial governments starting in 2000, with the aim to monitor the emergence and subsequent spread of WNV disease in Canada. As the disease emerged, national WNV surveillance continued to focus on early detection of WNV disease outbreaks in different parts of the country. In Canada, the WNV transmission season occurs from May to November. During the season, the system adopts a One Health approach to collect, integrate, analyze and disseminate national surveillance data on human, mosquito, bird and other animal cases. Weekly and annual reports are available to the public, provincial/territorial health authorities, and other federal partners to provide an ongoing national overview of WNV infections in Canada. While national surveillance allows a jurisdiction-by-jurisdiction comparison of data, it also helps to guide appropriate disease prevention strategies such as education and awareness campaigns at the national level. This paper aims to describe both the establishment and the current structure of national WNV surveillance in Canada.

Hepatitis B virus-related hepatocarcinogenesis: molecular oncogenic potential of clear or occult infections.

Chronic viral infection is the most important oncogenetic factor, and hepatitis B virus (HBV) plays an important role in the development of hepatocellular carcinoma (HCC). HBV-related carcinogenesis is a multi-step process, encompassing the combination of different, not mutually exclusive effects such as the induction of chronic liver inflammation and regeneration, its integration into the hepatocyte genome and the transactivating and transforming activity of several viral proteins (HBx and truncated Pre-S2/S) that may stimulate cellular oncogenes or suppress growth-regulating genes. Data related to the influence of different hepatitis B virus genotypes and the emergence of selective variants as biomarkers of HCC development still remain controversial. At last, recent studies on occult HBV infection, as defined by serologically undetectable hepatitis B surface antigen (HBsAg-), despite the presence of circulating HBV DNA, suggest that the occult viral strains, maintaining the transcriptional activity and the pro-oncogenetic assets of the clear HBV infection (HBsAg+), may harbour a potential risk for liver cancer development.

Evolution of hepatitis C virus non-structural 5A gene in the progression of liver disease to hepatocellular carcinoma.

BACKGROUND: The interaction between the hepatitis C virus (HCV) non-structural 5A (NS5A) protein of HCV and the protein kinase R (PKR), which is an effector of the cellular antiviral response and has been defined as a tumour suppressor, may affect the control of protein synthesis and cell growth. AIM: We investigated the genetic evolution of the NS5A region in the NS5A PKR-binding domain (NS5A-PKRbd) of patients with HCV 1b-related cirrhosis who subsequently developed or not hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The quasispecies composition of NS5A-PKRbd was inferred by sequencing an average of 15 clones per sample in specimens obtained from 26 patients with cirrhosis who developed or not HCC during a follow-up of 5 years. RESULTS: At baseline, 13/17 patients with final HCC and six out of nine patients with cirrhosis who subsequently did not develop HCC harboured a wild-type (wt) strain master sequence. Over time, the prevalence of wt strain was higher in patients who developed HCC with respect to those who maintained the cirrhosis status (15/17 vs 4/9, respectively; P=0.0166). CONCLUSION: The maintenance of or evolution to the wt strain of the NS5A domain in cirrhotic patients with final HCC highlights the central role of NS5A protein in the viral life cycle and in the progression of liver disease.

Prevalence of wild-type in NS5A-PKR protein kinase binding domain in HCV-related hepatocellular carcinoma.

BACKGROUND/AIMS: Experimental studies have demonstrated that the wild-type PKR-NS5A strain of hepatitis C virus (HCV) may have oncogenic potential through the binding and functional repression of PKR protein kinase. To assess whether the NS5A-PKR-binding domain may be involved in HCV-related liver carcinogenesis, its sequence was analyzed in the sera of 85 patients with hepatocellular carcinoma (HCC) and in 51 patients with chronic active hepatitis (CAH). In 13 HCC cases sequence analysis was also performed in tumor and nontumor liver tissues. METHODS: The nucleotide sequences of the PKR-binding domain were inferred by direct sequencing of the amplified HCV products and deduced amino acids were compared with the sequence of HCV-J. RESULTS: A wild-type or single mutated strain which retains PKR-binding activity was found in 88% of HCC and 69% of CAH cases (P=0.0096). All but three HCC cases showed no divergences in amino acid changes between serum and liver tissues. The wild-type strains were equally distributed between the HCC with or without cirrhosis. CONCLUSIONS: The prevalance of the wild-type NS5A-PKR strain is significantly higher in HCC than in CAH. These data suggest that inhibition of PKR activity by HCV might represent a potential mechanism of HCV-related carcinogenesis.