Tracking the international spread of SARS-CoV-2 lineages B.1.1.7 and B.1.351/501Y-V2

Publisher Copyright: © 2021 O'Toole Á et al.Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.Peer reviewe

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Vaccine Breakthrough Hypoxemic COVID-19 Pneumonia in Patients with Auto-Abs Neutralizing Type I IFNs

Life-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Implementation of a metagenomics workflow for the surveillance of respiratory viruses

Les infections respiratoires virales sont responsables d’une morbidité et mortalité importantes. Des traitements et des vaccins sont disponibles pour lutter contre certaines infections, mais la diversité génétique importante des virus impliqués peut être associée à des échecs thérapeutiques ou à une baisse de l’efficacité vaccinale. Les méthodes de détection actuelles des virus respiratoires sont représentées principalement par des méthodes de PCR ciblant des virus connus qui ne sont donc pas adaptées à la détection des virus rares ou émergents. En outre, la surveillance génomique des virus respiratoires a longtemps été basée sur des méthodes de séquençage ciblant une région génomique particulière d’un virus donné, conduisant à une perte d’information génétique importante, ce qui peut impacter notamment la classification phylogénétique des virus respiratoires. La métagénomique correspond à la détection simultanée de génomes viraux, bactériens, fongiques ou parasitaires contenus dans un prélèvement par séquençage haut-débit (NGS pour Next Generation Sequencing). Ces méthodes permettent un séquençage sans a priori, applicable pour la caractérisation du génome complet de tous les virus respiratoires incluant les virus rares, émergents ou divergents. Les objectifs de ce travail ont été d’évaluer une méthode de métagénomique sur un panel de virus respiratoires connus, d’appliquer cette méthode pour la caractérisation génétique de la famille des Anelloviridae dans un contexte d’infection respiratoire avec ou sans étiologie et, d’appliquer cette méthode pour la caractérisation de virus émergents (Enterovirus-D68, SARS-CoV-2). Le protocole de métagénomique évalué comprend un système de contrôle qualité qui a permis de valider 34/37 des prélèvements sélectionnés pour l’évaluation. Pour les prélèvements validés, le génotype de l’ensemble des virus respiratoires a pu être déterminé avec une couverture du génome viral médiane d’environ 70 %. Les pourcentages de couverture les plus élevés étaient retrouvés pour les plus fortes charges virales et pour les virus ARN. Après cette phase d’évaluation, nous avons mis en évidence une forte prévalence du genre betatorquevirus, principalement l’espèce TTMV-10, dans les prélèvements respiratoires d’enfants présentant une infection respiratoire, notamment en cas d’absence d’étiologie. Dans une troisième partie du travail, la méthode de métagénomique évaluée a permis de déterminer les premières séquences complètes européennes de l'entérovirus D68 clade D1 qui représentait la majorité des virus séquencés en 2018 alors qu’il n’avait été détecté que ponctuellement auparavant. Enfin nous avons utilisé cette méthode pour réaliser le séquençage du génome complet du SARS-CoV-2 lors du premier cluster français de COVID-19 en février 2020. La métagénomique a ensuite été mise en place en routine dans notre laboratoire pour la surveillance du SARS-CoV-2 jusqu'à octobre 2020. Dans le but d’augmenter le débit de séquençage et les capacités de surveillance du SARS-CoV-2, nous avons ensuite mis en place un protocole de séquençage ciblé qui présentait une meilleure sensibilité que la métagénomique. En conclusion, nous avons, au cours de ce travail, évalué et utilisé un protocole de métagénomique pour la surveillance des infections respiratoires virales. Cette méthode peut être utilisée en première ligne pour la détection et la surveillance d’un virus émergent ou rare, lorsque des méthodes ciblées ne sont pas disponibles ou peu efficaces. En deuxième ligne, la métagénomique a sa place pour l’investigation des infections non documentées après échec des méthodes diagnostiques conventionnelles. Ce protocole, universel, peut être immédiatement opérationnel pour caractériser de futurs virus émergents sans mise au point technique complémentaire significative et sur différents types de prélèvements.Respiratory viral infections are responsible for significant morbidity and mortality. Treatments and vaccines are available to control certain infections, but the high genetic diversity of the viruses involved may be associated with therapeutic failures or reduced vaccine efficacy. Current detection methods for respiratory viruses are mainly represented by PCR methods targeting known viruses. These methods are therefore not adapted to the detection of rare or emerging viruses. On the other hand, genomic surveillance of respiratory viruses has long been based on sequencing methods targeting a particular genomic region of a given virus, leading to a significant loss of genetic information, which can impact the phylogenetic classification of respiratory viruses. Metagenomics is the simultaneous detection of viral, bacterial, fungal or parasitic genomes contained in a sample by high-throughput sequencing. Metagenomics methods allow the whole genome characterization of all respiratory viruses including rare, emerging or divergent viruses. The objectives of this work were to evaluate a metagenomics method on a representative panel of known respiratory viruses, to apply this method for the genetic characterization of the Anelloviridae family in a context of respiratory infection with or without etiology and to apply this method for the characterization of emerging viruses (Enterovirus-D68, SARS-CoV-2). The metagenomics protocol evaluated herein includes a quality control system that allowed the validation of 34/37 of the samples selected for evaluation. For the validated samples, the genotype of all respiratory viruses could be determined with a median viral genome coverage of approximately 70%. The highest coverage percentages were found for the highest viral loads and for RNA viruses. After this evaluation phase, we found a high prevalence of the betatorquevirus genus, mainly TTMV-10 species, in respiratory specimens from children with respiratory infection, especially in the absence of etiology. In a third part of the work, the metagenomics method evaluated allowed us to determine the first complete European sequences of the enterovirus D68 clade D1 during the 2018 outbreak. Finally, we used this method to perform the whole genome sequencing of SARS-CoV-2 during the first french COVID-19 cluster in February 2020. Metagenomics was then routinely implemented in our laboratory for SARS-CoV-2 surveillance until October 2020. In order to scale up SARS-CoV-2 genomic surveillance, we then implemented a targeted sequencing protocol that had better sensitivity than metagenomics. In conclusion, we evaluated and implemented a metagenomics protocol for surveillance of viral respiratory infections. This method can be used for the first-line detection and surveillance of an emerging or rare virus, when targeted methods are not available or not very efficient. Metagenomics can also be helpful for the investigation of unexplained infections after failure of conventional diagnostic methods. This universal protocol can be immediately operational to characterize future emerging viruses without significant additional technical development and on different types of samples

Sotrovimab drives SARS-CoV-2 omicron variant evolution in immunocompromised patients

International audienc

Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic

International audienc