Evolution of antibodies against SARS-CoV-2 over seven months: experience of the Nationwide Seroprevalence ENE-COVID Study in Spain [preprint]

Objectives To analyse temporal trends in SARS-CoV-2 anti-nucleocapsid IgG throughout the four rounds of the nationwide seroepidemiologic study ENE-COVID (April-November 2020), and to compare the fourth-round results of two immunoassays detecting antibodies against nucleocapsid and to S protein receptor-binding domain (RBD). Methods A chemiluminescent microparticle immunoassay (CMIA) was offered to all participants in the first three rounds (Abbott; anti-nucleocapsid IgG). In the fourth round we offered this test and a chemiluminescence immunoassay (CLIA) (Beckman; anti-RBD IgG) to i) a randomly selected sub-cohort, ii) participants who were IgG-positive in any of the three first rounds; and iii) participants who were IgG-positive in the fourth round by point-of-care immunochromatography. Results Immunoassays involving 10,153 participants (82.2% of people invited to donate samples) were performed in the fourth round. A total of 2595 participants (35.1% of participants with immunoassay results in the four rounds) were positive for anti-nucleocapsid IgG in at least one round. Anti-nucleocapsid IgG became undetectable in 43.3% of participants with positive first-round results. Pneumonia was more frequent in participants with anti-nucleocapsid IgG in all four rounds (11.2%) than those in which IgG became undetectable (2.4%). In fourth round, anti-nucleocapsid and anti-RBD IgG were detected in 5.5% and 5.4% participants of the randomly selected sub-cohort, and in 26.6% and 25.9% participants with at least one previous positive result, respectively. Agreement between techniques was 90.3% (kappa: 0.72). Conclusions The response of IgG to SARS-CoV-2 is heterogeneous and conditioned by infection severity. A substantial proportion of the SARS-CoV-2 infected population may have negative serologic results in the post-infection months.N

Normalization of blood clotting characteristics using prothrombin complex concentrate, fibrinogen and FXIII in an albumin based fluid : experimental studies in thromboelastometry

Colloid fluids supplemented with adequate combinations of coagulation factor concentrates with the capability to restore coagulation could be a desirable future treatment component in massive transfusion. Starting from a coagulation factor and blood cell-free albumin solution we added Prothrombin Complex Concentrate, Fibrinogen Concentrate and Factor XIII in different combinations and concentrations to analyze their properties to restore thromboelastometry parameters without the use of plasma. Further analysis under the presence of platelets was performed for comparability to whole blood conditions. Albumin solutions enriched with Fibrinogen Concentrate, Factor XIII and Prothrombin Complex Concentrate at optimized concentrations show restoring coagulation potential. Prothrombin Complex Concentrate showed sufficient thrombin formation for inducing fibrinogen polymerization. The combination of Prothrombin Complex Concentrate and Fibrinogen Concentrate led to the formation of a stable in vitro fibrin clot. Fibrinogen and Factor XIII showed excellent capacity to improve fibrin clot firmness expressed as Amplitude at 10 min and Maximal Clot Firmness. Fibrinogen alone, or in combination with Factor XIII, was able to restore normal Amplitude at 10 min and Maximal Clot Firmness values. In the presence of platelets, the thromboelastometry surrogate parameter for thrombin generation (Clotting Time) improves and normalizes when compared to whole blood. Combinations of coagulation factor concentrates suspended in albumin solutions can restore thromboelastometry parameters in the absence of plasma. This kind of artificial colloid fluids with coagulation-restoring characteristics might offer new treatment alternatives for massive transfusion. Study registered at the institutional ethic committee "Institut de Recerca, Hospital Santa Creu i Sant Pau, with protocol number IIBSP-CFC-2013-165

ENE-COVID nationwide serosurvey served to characterize asymptomatic infections and to develop a symptom-based risk score to predict COVID-19

Objectives: To characterize asymptomatic SARS-CoV-2 infections and develop a symptom-based risk score useful in primary healthcare. Study design and setting: Sixty-one thousand ninty-two community-dwelling participants in a nationwide population-based serosurvey completed a questionnaire on COVID-19 symptoms and received an immunoassay for SARS-CoV-2 IgG antibodies between April 27 and June 22, 2020. Standardized prevalence ratios for asymptomatic infection were estimated across participant characteristics. We constructed a symptom-based risk score and evaluated its ability to predict SARS-CoV-2 infection. Results: Of all, 28.7% of infections were asymptomatic (95% CI 26.1-31.4%). Standardized asymptomatic prevalence ratios were 1.19 (1.02-1.40) for men vs. women, 1.82 (1.33-2.50) and 1.45 (0.96-2.18) for individuals <20 and ≥80 years vs. those aged 40-59, 1.27 (1.03-1.55) for smokers vs. nonsmokers, and 1.91 (1.59-2.29) for individuals without vs. with case contact. In symptomatic population, a symptom-based score (weights: severe tiredness = 1; absence of sore throat = 1; fever = 2; anosmia/ageusia = 5) reached standardized seroprevalence ratio of 8.71 (7.37-10.3), discrimination index of 0.79 (0.77-0.81), and sensitivity and specificity of 71.4% (68.1-74.4%) and 74.2% (73.1-75.2%) for a score ≥3. Conclusion: The presence of anosmia/ageusia, fever with severe tiredness, or fever without sore throat should serve to suspect COVID-19 in areas with active viral circulation. The proportion of asymptomatics in children and adolescents challenges infection control.The ENE-COVID study was supported by the Spanish Ministry of Health, the Institute of Health Carlos III, and the Spanish National Health System. The funders were in- volved in the study logistics, but they had no role in study design or in the collection, analysis, interpretation of data, or the decision to submit the article for publicationS

Infection fatality risk for SARS-CoV-2 in community dwelling population of Spain: nationwide seroepidemiological study.

To estimate the infection fatality risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on deaths with confirmed coronavirus disease 2019 (covid-19) and excess deaths from all causes. Nationwide seroepidemiological study. First wave of covid-19 pandemic in Spain. Community dwelling individuals of all ages. The main outcome measure was overall, and age and sex specific, infection fatality risk for SARS-CoV-2 (the number of covid-19 deaths and excess deaths divided by the estimated number of SARS-CoV-2 infections) in the community dwelling Spanish population. Deaths with laboratory confirmed covid-19 were obtained from the National Epidemiological Surveillance Network (RENAVE) and excess all cause deaths from the Monitoring Mortality System (MoMo), up to 15 July 2020. SARS-CoV-2 infections in Spain were derived from the estimated seroprevalence by a chemiluminescent microparticle immunoassay for IgG antibodies in 61 098 participants in the ENE-COVID nationwide seroepidemiological survey between 27 April and 22 June 2020. The overall infection fatality risk was 0.8% (19 228 of 2.3 million infected individuals, 95% confidence interval 0.8% to 0.9%) for confirmed covid-19 deaths and 1.1% (24 778 of 2.3 million infected individuals, 1.0% to 1.2%) for excess deaths. The infection fatality risk was 1.1% (95% confidence interval 1.0% to 1.2%) to 1.4% (1.3% to 1.5%) in men and 0.6% (0.5% to 0.6%) to 0.8% (0.7% to 0.8%) in women. The infection fatality risk increased sharply after age 50, ranging from 11.6% (8.1% to 16.5%) to 16.4% (11.4% to 23.2%) in men aged 80 or more and from 4.6% (3.4% to 6.3%) to 6.5% (4.7% to 8.8%) in women aged 80 or more. The increase in SARS-CoV-2 infection fatality risk after age 50 appeared to be more noticeable in men than in women. Based on the results of this study, fatality from covid-19 was greater than that reported for other common respiratory diseases, such as seasonal influenza.The ENE-COVID was funded by the Spanish Ministry of Health, the Institute of Health Carlos III, and the Spanish National Health System. The funders were involved in the study logistics but had no role in study design or in the collection, analysis, interpretation of data, or the decision to submit the article for publicationS

Mutational Landscape of Bladder Cancer in Mexican Patients: <i>KMT2D</i> Mutations and chr11q15.5 Amplifications Are Associated with Muscle Invasion

Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute—Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and exome sequenced. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade

Integrate and learn. Building a farm-to-table blockchain

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