Clinical evaluation of the Procleix SARS-CoV-2 assay, a sensitive, high-throughput test that runs on an automated system

COVID-19; Prueba de ácido nucleico; Amplificación mediada por transcripciónCOVID-19; Prova d'àcid nucleic; Amplificació mediada per la transcripcióCOVID-19; Nucleic acid test; Transcription-mediated amplificationTesting is crucial in controlling COVID-19. The Procleix® SARS-CoV-2 assay, a transcription-mediated amplification nucleic acid test that runs on an automated system, was evaluated using inactivated virus and clinical samples. The sensitivity of the assay was assessed using heat-inactivated SARS-CoV-2 and compared to 3 other tests. Clinical validation utilized 2 sets of samples: (1) Nasal, nasopharyngeal and oropharyngeal samples (n = 963) from asymptomatic individuals, and (2) nasopharyngeal samples from symptomatic patients: 100 positive and 100 negative by RT-PCR. The Procleix assay had greater sensitivity (3-fold to 100-fold) than the comparators and had high specificity (100%) in asymptomatic subjects. In symptomatic patients, the Procleix assay detected 100% of PCR-positives and found 24 positives in the initial PCR-negatives. Eighteen of these were confirmed positive and 6 were inconclusive. These studies showed that the Procleix SARS-CoV-2 assay was a sensitive and specific tool for detecting COVID-19.This work was sponsored by Grifols Diagnostic Solutions, Inc

Influenza pandemics

La grip és una malaltia amb una alta morbimortalitat associada, causada pels virus de la grip. Aquests virus es caracteritzen per tenir una gran capacitat evolutiva, tant per mutacions puntuals com per intercanvi dels segments genètics. Són els virus de la grip A amb una nova composició genòmica, per un o més esdeveniments de reordenament, que presenten unes característiques antigèniques davant les quals la població humana és susceptible, i amb capacitat per a la seva transmissió entre persones de forma eficient, els que podem considerar com a virus amb potencial pandèmic. Des de 1918, hi ha hagut fins a quatre pandèmies, causades per virus de la grip diferents i amb una capacitat de disseminació i de gravetat variables, a vegades molt condicionades per factors del medi, a més de les característiques del virus. Tenint en compte que els virus pandèmics, en tots els casos, han tingut un origen zoonòtic, és imperatiu treballar per a una vigilància global en els animals, les persones i el medi natural per a la seva detecció precoç.Influenza is associated with high morbidity and mortality and is caused by influenza viruses. These viruses are characterized by a high rate of evolution, either through point mutations or the exchange of genetic segments. Influenza A viruses with a new genetic composition due to one or more reassortment events, with antigenic characteristics to which the human population is susceptible and with the capacity for efficient human-to-human transmission, can be considered viruses with pandemic potential. Since 1918, there have been four pandemics caused by different influenza viruses, with varying degrees of transmissibility and severity, sometimes strongly influenced by environmental factors in addition to viral characteristics. Given that all pandemic viruses have been of zoonotic origin, it is imperative to work towards global surveillance in animals, humans and the natural environment for their early detection

Multi-body-site colonization screening cultures for predicting multi-drug resistant Gram-negative and Gram-positive bacteremia in hematological patients

Background To investigate the multi-drug resistant bacteria (MDRB) colonization rate in hematological patients hospitalized for any cause using a multi-body-site surveillance approach, and determine the extent to which this screening strategy helped anticipate MDRB bloodstream infections (BSI). Methods Single-center retrospective observational study including 361 admissions documented in 250 adult patients. Surveillance cultures of nasal, pharyngeal, axillary and rectal specimens (the latter two combined) were performed at admission and subsequently on a weekly basis. Blood culture samples were incubated in an automated continuous monitoring blood culturing instrument (BACTEC FX). Results In total, 3463 surveillance cultures were performed (pharyngeal, n = 1201; axillary-rectal, n = 1200; nasal, n = 1062). MDRB colonization was documented in 122 out of 361 (33.7%) admissions corresponding to 86 patients (34.4%). A total of 149 MDRB were isolated from one or more body sites, of which most were Gram-negative bacteria, most frequently non-fermenting (n = 83) followed by Enterobacterales (n = 51). BSI were documented in 102 admissions (28%) involving 87 patients. Overall, the rate of BSI caused by MDRB was significantly higher (p = 0.04) in the presence of colonizing MDRB (16 out of 47 admissions in 14 patients) than in its absence (9 out of 55 admissions in 9 patients). Colonization by any MDRB was independently associated with increased risk of MDRB-BSI (HR, 3.70; 95% CI, 1.38-9.90; p = 0.009). Conclusion MDRB colonization is a frequent event in hematological patients hospitalized for any reason and is associated with an increased risk of MDRB BSI. The data lend support to the use of MDRB colonization surveillance cultures for predicting the occurrence of MDRB BSI in this cohort

Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients

Altres ajuts: This study was partially supported by the Direcció General de Recerca i Innovació en Salut (DGRIS) Catalan Health Ministry Generalitat de Catalunya through Vall d'Hebron Institut de Recerca (VHIR) and Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant number IDI-20200297.The SARS-CoV-2 spike (S) protein, the viral mediator for binding and entry into the host cell, has sparked great interest as a target for vaccine development and treatments with neutralizing antibodies. Initial data suggest that the virus has low mutation rates, but its large genome could facilitate recombination, insertions, and deletions, as has been described in other coronaviruses. Here, we deep-sequenced the complete SARS-CoV-2 S gene from 18 patients (10 with mild and 8 with severe COVID-19), and found that the virus accumulates deletions upstream and very close to the S1/S2 cleavage site (PRRAR/S), generating a frameshift with appearance of a stop codon. These deletions were found in a small percentage of the viral quasispecies (2.2%) in samples from all the mild and only half the severe COVID-19 patients. Our results suggest that the virus may generate free S1 protein released to the circulation. We suggest that natural selection has favoured a "Don't burn down the house" strategy, in which free S1 protein may compete with viral particles for the ACE2 receptor, thus reducing the severity of the infection and tissue damage without losing transmission capability

Host-dependent editing of SARS-CoV-2 in COVID-19 patients

SARS-CoV-2; Mutacions; QuasiespècieSARS-CoV-2; Mutaciones; CuasiespecieSARS-CoV-2; Mutations; QuasispeciesA common trait among RNA viruses is their high capability to acquire genetic variability due to viral and host mechanisms. Next-generation sequencing (NGS) analysis enables the deep study of the viral quasispecies in samples from infected individuals. In this study, the viral quasispecies complexity and single nucleotide polymorphisms of the SARS-CoV-2 spike gene of coronavirus disease 2019 (COVID-19) patients with mild or severe disease were investigated using next-generation sequencing (Illumina platform). SARS-CoV-2 spike variability was higher in patients with long-lasting infection. Most substitutions found were present at frequencies lower than 1%, and had an A → G or T → C pattern, consistent with variants caused by adenosine deaminase acting on RNA-1 (ADAR1). ADAR1 affected a small fraction of replicating genomes, but produced multiple, mainly non-synonymous mutations. ADAR1 editing during replication rather than the RNA-dependent RNA polymerase (nsp12) was the predominant mechanism generating SARS-CoV-2 genetic variability. However, the mutations produced are not fixed in the infected human population, suggesting that ADAR1 may have an antiviral role, whereas nsp12-induced mutations occurring in patients with high viremia and persistent infection are the main source of new SARS-CoV-2 variants.This study was supported by the Direcció General de Recerca i Innovació en Salut (DGRIS) of the Catalan Health Ministry, Generalitat de Catalunya, through the Vall d’Hebron Institut de Recerca (VHIR); the European Regional Development Fund (ERDF) “A way to achieve Europe” by the Spanish Network for Research in Infectious Diseases [grant number REIPI RD16/0016/0003]; Instituto de Salud Carlos III [grant number FIS PI19/00301]; and Centro para el Desarrollo Tecnologico Industrial (CDTI) from the Ministry of Economic Affairs and Digital Transformation [grant number IDI-20200297]

Allogeneic Hematopoietic Stem Cell Transplantation in Transformed Follicular Lymphoma (tFL): Results of a Retrospective Multicenter Study from GELTAMO/GETH-TC Spanish Groups

Simple Summary Follicular lymphoma (FL) is the most prevalent subtype of indolent lymphoma, accounting for 70% of all cases. The estimated risk of histological transformation (tFL), such as diffuse large B cell lymphoma (DLBCL), varies from 2-3% per year to 7-8% at 10 years in different series. Treatment after transformation is not clearly established. Allogeneic hematopoietic stem cell transplantation (alloSCT) could be an option for these patients, but it has not been widely explored. We analyze the efficacy and toxicity of alloSCT in 43 patients from 14 Spanish centers. We observed long-term survival in around one third of the patients, especially those who developed chronic graft versus host disease, indicating that alloSCT continues to be a potentially curative option for patients with tFL, mainly due to the graft versus lymphoma effect. Background: Transformation of follicular lymphoma into an aggressive lymphoma (tFL) worsens the prognosis and the standard treatment is not completely defined. Allogeneic hematopoietic stem cell transplantation (alloSCT) could be a potentially curative option for these patients, but it has not been widely explored. Methods: We designed a retrospective multicenter study to analyze the efficacy and toxicity of alloSCT in tFL patients and potential prognostic factors of survival. Results: A total of 43 patients diagnosed with tFL who underwent alloSCT in 14 Spanish centers between January 2000 and January 2019 were included. Median age was 44 (31-67) years. After a median follow-up of 58 months, estimated 5-year overall survival (OS) and progression-free survival (PFS) were both 35%. Estimated 100-day and 1-year non-relapse mortality (NRM) were 20% and 34%, respectively. The type of conditioning regimen (3-year OS of 52% vs. 20%, respectively, for reduced-intensity vs. myeloablative conditioning) and development of chronic graft versus host disease (cGVHD) (3-year OS of 75% vs. 40%) were the only factors significantly associated with OS. The only variable with an independent association with OS was cGVHD (HR, 3.4; 95% CI, 1.2-9.6). Conclusions: Our results indicate that alloSCT continues to be a potentially curative option for patients with tFL

Host-dependent editing of SARS-CoV-2 in COVID-19 patients

A common trait among RNA viruses is their high capability to acquire genetic variability due to viral and host mechanisms. Next-generation sequencing (NGS) analysis enables the deep study of the viral quasispecies in samples from infected individuals. In this study, the viral quasispecies complexity and single nucleotide polymorphisms of the SARS-CoV-2 spike gene of coronavirus disease 2019 (COVID-19) patients with mild or severe disease were investigated using next-generation sequencing (Illumina platform). SARS-CoV-2 spike variability was higher in patients with long-lasting infection. Most substitutions found were present at frequencies lower than 1%, and had an A → G or T → C pattern, consistent with variants caused by adenosine deaminase acting on RNA-1 (ADAR1). ADAR1 affected a small fraction of replicating genomes, but produced multiple, mainly non-synonymous mutations. ADAR1 editing during replication rather than the RNA-dependent RNA polymerase (nsp12) was the predominant mechanism generating SARS-CoV-2 genetic variability. However, the mutations produced are not fixed in the infected human population, suggesting that ADAR1 may have an antiviral role, whereas nsp12-induced mutations occurring in patients with high viremia and persistent infection are the main source of new SARS-CoV-2 variants

Unraveling the effects of the COVID-19 pandemic on the hospital burden of respiratory syncytial virus

The research leading to these results received funding from Fundació La Marató TV3 under Grant Agreement No 202134‐30‐31.Peer ReviewedObjectius de Desenvolupament Sostenible::3 - Salut i BenestarPostprint (published version

The burden of non-SARS-CoV2 viral lower respiratory tract infections in hospitalized children in Barcelona (Spain): A long-term, clinical, epidemiologic and economic study

Cost of illness; Hospitalization; VirusesCost de la malaltia; Hospitalització; VirusCoste de la enfermedad; Hospitalización; VirusBackground Viral lower respiratory tract infections (LRTI) are the leading cause of hospitalization in children. In Catalonia (Spain), information is scarce about the burden of viral LRTIs in paediatric hospitalizations. The aim of this study is to describe epidemiological, clinical, virological and economic features of paediatric hospitalizations due to viral LRTI. Methods From October 2012 to December 2020, children aged <16 years admitted to a tertiary paediatric hospital in Catalonia (Spain) with confirmed viral LRTI were included in the study. Virus seasonality, prevalence, age and sex distribution, clinical characteristics, hospital costs and bed occupancy rates were determined. Results A total of 3,325 children were included (57.17% male, 9.44% with comorbidities) accounting for 4056 hospitalizations (32.47% ≤ 12 months): 53.87% with wheezing/asthma, 37.85% with bronchiolitis and 8.28% with pneumonia. The most common virus was respiratory syncytial virus (RSV) (52.59%). Influenza A was associated with pneumonia (odds ratio [OR] 7.75) and caused longer hospitalizations (7 ± 31.58 days), while RSV was associated with bronchiolitis (OR 6.62) and was the most frequent reason for admission to the paediatric intensive care unit (PICU) (11.23%) and for respiratory support (78.76%). Male sex, age ≤12 months, chronic conditions and bronchiolitis significantly increased the odds of PICU admission. From October to May, viral LRTIs accounted for 12.36% of overall hospital bed days. The total hospitalization cost during the study period was €16,603,415. Conclusions Viral LRTIs are an important cause of morbidity, hospitalization and PICU admission in children. The clinical burden is associated with significant bed occupancy and health-care costs, especially during seasonal periods.This work was partially supported by the Spanish National R + D + I Plan 2008–2011 and by the Carlos III Health Institute, the Subdirectorate-General of Networks and Cooperative Research Centers, the Spanish Ministry of Economy and Competitiveness, the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), and by the Health Research Fund, the Spanish Ministry of Economy and Competitiveness (grants FIS PI14/01838 and FIS PI18/00685), and the European Regional Development Fund (ERDF). Editorial assistance for revision of the English language and edition of the manuscript was provided by Vanessa Marfil, medical writer from MSC (Spain) and funded by Sanofi