Evolutionary and phenotypic characterization of two spike mutations in European lineage 20E of SARS-CoV-2.

We have detected two mutations in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at amino acid positions 1163 and 1167 that appeared independently in multiple transmission clusters and different genetic backgrounds. Furthermore, both mutations appeared together in a cluster of 1,627 sequences belonging to clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information on the S protein in the pre- and postfusion conformations predicts that both mutations confer rigidity, which could potentially decrease viral fitness. Accordingly, we observed reduced infectivity of this spike genotype relative to the ancestral 20E sequence in vitro, and the levels of viral RNA in nasopharyngeal swabs were not significantly higher. Furthermore, the mutations did not impact thermal stability or antibody neutrali- zation by sera from vaccinated individuals but moderately reduce neutralization by convalescent-phase sera from the early stages of the pandemic. Despite multi- ple successful appearances of the two spike mutations during the first year of SARS-CoV-2 evolution, the genotype with both mutations was displaced upon the expansion of the 20I (Alpha) variant. The midterm fate of the genotype investi- gated was consistent with the lack of advantage observed in the clinical and ex- perimental data

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Pericranial nerve blockade as a preventive treatment for migraine: Experience in 60 patients

Introduction: Anaesthetic blockade of pericranial nerves is frequently used to treat headache disorders. There is no evidence on indication of this treatment for migraine. We aim to evaluate its effectiveness as a preventive treatment for migraine using specific indication criteria. Methods: Between January 2009 and May 2013 we offered pericranial nerve blockade to migraine patients with a history of preventive drug intolerance or failure. We selected patients with tenderness to palpation of at least one greater occipital nerve (GON) or supraorbital nerve (SON). Responses at 3 months were categorised as complete response (no pain), partial response (reduction of at least 50% in severity or frequency of headache episodes), or no response. Results: Anaesthetic blockade was performed in 60 patients (52 females, 8 males; mean age 40.6 ± 12.4 years, range 19-76). The most common procedure was blockade of GON and SON on both sides. Complete response lasting at least 2 weeks was recorded in 23 patients (38.3%), with partial response in 24 patients (40%), and no response in 13 (21.7%). In the group presenting complete response, age and length of history of migraine were significantly lower. No severe side effects were detected. Response time ranged from 2 weeks to 3 months. Conclusions: Pericranial nerves blockade using tenderness to palpation as an inclusion criterion is safe and potentially effective as prophylactic treatment for migraine. The best responses in our series were observed in younger patients with shorter histories of migraine. Resumen: Introducción: El bloqueo anestésico de nervios pericraneales es utilizado con frecuencia en el tratamiento de diferentes cefaleas. No hay evidencia acerca de su indicación en pacientes migrañosos. Pretendemos evaluar su eficacia como tratamiento preventivo de migraña con criterios determinados. Métodos: Entre enero del 2009 y mayo del 2013 se ofreció este tratamiento a migrañosos con fracaso o intolerancia de fármacos preventivos. Seleccionamos a aquellos con sensibilidad a la palpación en al menos un nervio supraorbitario u occipital mayor. A los 3 meses, consideramos la respuesta completa (sin dolor), parcial (reducción al menos de un 50% en severidad y/o frecuencia de episodios) o ausente. Resultados: Se practicó un bloqueo anestésico en 60 pacientes (52 mujeres, 8 varones, edad media ± desviación estándar: 40,6 ± 12,4 años, rango 19-76). El procedimiento más habitual fue el bloqueo de ambos nervios occipitales y supraorbitarios. Hubo respuesta completa de al menos 2 semanas en 23 (38,3%), parcial en 24 (40%) y ausente en 13 (21,7%). En el grupo con respuesta completa, la edad y el tiempo de evolución de la migraña eran significativamente inferiores. Sin efectos adversos significativos. Tiempo de respuesta entre 2 semanas y 3 meses. Conclusiones: El bloqueo anestésico de nervios pericraneales utilizando la sensibilidad a la palpación como criterio de selección es un procedimiento seguro y potencialmente eficaz como tratamiento preventivo de migraña. Las mayores respuestas en nuestra serie se observan en pacientes jóvenes con menos tiempo de evolución de la migraña. Keywords: Anaesthetic blockade, Migraine, Chronic migraine, Great occipital nerve, Supraorbital nerve, Preventive therapy, Palabras clave: Bloqueo anestésico, Migraña, Migraña crónica, Nervio occipital mayor, Nervio supraorbitario, Tratamiento preventiv

Bloqueo anestésico de nervios pericraneales como tratamiento preventivo de migraña: experiencia en una serie de 60 pacientes

Resumen: Introducción: El bloqueo anestésico de nervios pericraneales es utilizado con frecuencia en el tratamiento de diferentes cefaleas. No hay evidencia acerca de su indicación en pacientes migrañosos. Pretendemos evaluar su eficacia como tratamiento preventivo de migraña con criterios determinados. Métodos: Entre enero del 2009 y mayo del 2013 se ofreció este tratamiento a migrañosos con fracaso o intolerancia de fármacos preventivos. Seleccionamos a aquellos con sensibilidad a la palpación en al menos un nervio supraorbitario u occipital mayor. A los 3 meses, consideramos la respuesta completa (sin dolor), parcial (reducción al menos de un 50% en severidad y/o frecuencia de episodios) o ausente. Resultados: Se practicó un bloqueo anestésico en 60 pacientes (52 mujeres, 8 varones, edad media ± desviación estándar: 40,6 ± 12,4 años, rango 19-76). El procedimiento más habitual fue el bloqueo de ambos nervios occipitales y supraorbitarios. Hubo respuesta completa de al menos 2 semanas en 23 (38,3%), parcial en 24 (40%) y ausente en 13 (21,7%). En el grupo con respuesta completa, la edad y el tiempo de evolución de la migraña eran significativamente inferiores. Sin efectos adversos significativos. Tiempo de respuesta entre 2 semanas y 3 meses. Conclusiones: El bloqueo anestésico de nervios pericraneales utilizando la sensibilidad a la palpación como criterio de selección es un procedimiento seguro y potencialmente eficaz como tratamiento preventivo de migraña. Las mayores respuestas en nuestra serie se observan en pacientes jóvenes con menos tiempo de evolución de la migraña. Abstract: Introduction: Anaesthetic blockade of pericranial nerves is frequently used to treat headache disorders. There is no evidence on indication of this treatment for migraine. We aim to evaluate its effectiveness as a preventive treatment for migraine using specific indication criteria. Methods: Between January 2009 and May 2013 we offered pericranial nerve blockade to migraine patients with a history of preventive drug intolerance or failure. We selected patients with tenderness to palpation of at least one greater occipital nerve (GON) or supraorbital nerve (SON). Responses at 3 months were categorised as complete response (no pain), partial response (reduction of at least 50% in severity or frequency of headache episodes), or no response. Results: Anaesthetic blockade was performed in 60 patients (52 females, 8 males; mean age 40.6 ± 12.4 years, range 19-76). The most common procedure was blockade of GON and SON on both sides. Complete response lasting at least 2 weeks was recorded in 23 patients (38.3%), with partial response in 24 patients (40%), and no response in 13 (21.7%). In the group presenting complete response, age and length of history of migraine were significantly lower. No severe side effects were detected. Response time ranged from 2 weeks to 3 months. Conclusions: Pericranial nerves blockade using tenderness to palpation as an inclusion criterion is safe and potentially effective as prophylactic treatment for migraine. The best responses in our series were observed in younger patients with shorter histories of migraine. Palabras clave: Bloqueo anestésico, Migraña, Migraña crónica, Nervio occipital mayor, Nervio supraorbitario, Tratamiento preventivo, Keywords: Anaesthetic blockade, Migraine, Chronic migraine, Great occipital nerve, Supraorbital nerve, Preventive therap

The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant

The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants