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Background/Objectives: Emerging evidence suggests that complement system infection-dependent hyperactivation may worsen COVID-19 outcome. We investigated the role of predicted high impact variants -referred as Qualifying Variants (QVs) -of complement system genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease. Method(s): Exploiting Whole-Exome Sequencing (WES) data and 56 complement system genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (age >= 60 y.o.) and 56,885 European individuals from the gnomAD database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized COVID-19 patients. Result(s): We found an enrichment of QVs in three genes (MASP1, COLEC10 and COLEC11), which belong to the lectin pathway, in the asymptomatic cohort. Moreover, individuals with QVs showed lower serum levels of Masp1 and of prothrombin activity compared to controls while no differences were observed for CH50 and AH50 levels that measure the activity of classical and alternative complement pathways, respectively. Finally, integrative analyses of genome-wide association study and expression quantitative loci traits data showed a correlation between polymorphisms associated with asymptomatic COVID-19 and decreased expression of MASP1, COLEC11 and COLEC10 genes in lung tissue. Conclusion(s): This study suggests that rare genetic variants can protect from severe COVID-19 by mitigating the activation of lectin pathway and prothrombin activity.
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Background: Patients with red blood cell disorders (RBCD), are likely to be at increased risk of complications from SARS-Co-2 (Coid-19), but eidence in this population is scarce due to its low frequency and heterogeneous distribution. Aims: ERN-EuroBloodNet, the European Reference Network in rare hematological disorders, established a European registry to determine the impact of COVID-19 on RBCD patients and identify risk factors predicting seere outcomes. Methods: The ERN-EuroBloodNet registry was established in March 2020 by VHIR based on Redcap software in accordance with the Regulation (EU) 2016/679 on personal data. The local Research Ethics Committee confirmed that the exceptional case of the pandemic justifies the waier of informed consent. Eligible patients had confirmed RBCD and COVID-19. Data collected included demographics, diagnosis, comorbidities, treatments, and COVID-19 symptoms and management. For analysis of COVID-19 seerity, two groups were established 1) Mild: asymptomatic or mild symptoms without clinical pneumonia and 2) Seere: pneumonia requiring oxygen/respiratory support and/or admission to intensie care unit. Continuous ariables were compared using the Wilcoxon rank-sum test or Kruskall Wallis test, while categorical ariables were analyzed using the Chi-square test or Fisher's Exact test. Releant factors influencing disease or seerity were examined by the logistic regression adjusted for age. Results: As of February 25, 2022, 42 medical centers from 10 EU countries had registered 428 patients: 212 Sickle cell disease (SCD), 186 Thalassemia major and intermedia (THAL). The mean age of SCD was lower (22y) than of THAL (39.4y). Splenectomy and comorbidities were higher in THAL (51.4% and 61,3%) than in SCD (16,3% and 46,8%) (p<0.001, p=0.004). Age and BMI correlated with COVID-19 seerity, as described in the general population (p=0.003, p<0.001). Fig 1 shows age distribution and COVID-19 seerity by disease seerity groups. The mean age for seere COVID-19 was lower in patients with seere SCD (SS/SB0 s SC/SB+: 23y s 67.5y) and THAL (major s intermedia: 43.5 s 51.3y) (p<0.001). Potential risk factors such as eleated ferritin, current chelation or history of splenectomy did not confer additional risk for deeloping seere COVID-19 in any patient group. Only diabetes as a comorbidity correlated with seerity grade in SCD (p=0.01) and hypertension in THAL (p=0.009). While seere COVID-19 infection in SCD was associated with both ACS (p<0.001) and kidney failure requiring treatment (p<0.001), this was not predicted by a history of preious ACS or kidney disease in steady state. Oerall, 14,6% RBC patients needed oxygen/respiratory support, 4% were admitted to ICU with an oerall mortality rate of 1%, much lower than reported in other similar cohorts. Hospital Son Espases, Palma de Mallorca, Spain;54 Clinical Pharmacology Serice, Hospital Uniersitari Vall d'Hebron, Barcelona, Spain;55 Vall d'Hebron Institut de Recerca, Barcelona, Spain;56 Diision of Hematology and Oncology, Department of Internal Medicine, American Uniersity of Beirut Medical Center, Beirut, Lebanon;57 UOC Pediatric Hematology Oncology, Uniersity of Padoa, Padoa, Italy;58 Department of Haematology, Oxford Uniersity Hospitals NHS Foundation Trust, Oxford, United Kingdom;59 Translational Research in Child and Adolescent Cancer, Vall d'Hebron Institut de Recerca, Barcelona, Spain Background: Patients with red blood cell disorders (RBCD), are likely to be at increased risk of complications from SARS-Co-2 (Coid-19), but eidence in this population is scarce due to its low frequency and heterogeneous distribution. Aims: ERN-EuroBloodNet, the European Reference Network in rare hematological disorders, established a European registry to determine the impact of COVID-19 on RBCD patients and identify risk factors predicting seere outcomes. Methods: The ERN-EuroBloodNet registry was established in March 2020 by VHIR based on Redcap software in accordance with the Regulation (EU) 2016/679 on personal data. The local Research Ethics Committee confirm d that the exceptional case of the pandemic justifies the waier of informed consent. Eligible patients had confirmed RBCD and COVID-19. Data collected included demographics, diagnosis, comorbidities, treatments, and COVID-19 symptoms and management. For analysis of COVID-19 seerity, two groups were established 1) Mild: asymptomatic or mild symptoms without clinical pneumonia and 2) Seere: pneumonia requiring oxygen/respiratory support and/or admission to intensie care unit. Continuous ariables were compared using the Wilcoxon rank-sum test or Kruskall Wallis test, while categorical ariables were analyzed using the Chi-square test or Fisher's Exact test. Releant factors influencing disease or seerity were examined by the logistic regression adjusted for age. Results: As of February 25, 2022, 42 medical centers from 10 EU countries had registered 428 patients: 212 Sickle cell disease (SCD), 186 Thalassemia major and intermedia (THAL). The mean age of SCD was lower (22y) than of THAL (39.4y). Splenectomy and comorbidities were higher in THAL (51.4% and 61,3%) than in SCD (16,3% and 46,8%) (p<0.001, p=0.004). Age and BMI correlated with COVID-19 seerity, as described in the general population (p=0.003, p<0.001). Fig 1 shows age distribution and COVID-19 seerity by disease seerity groups. The mean age for seere COVID-19 was lower in patients with seere SCD (SS/SB0 s SC/SB+: 23y s 67.5y) and THAL (major s intermedia: 43.5 s 51.3y) (p<0.001). Potential risk factors such as eleated ferritin, current chelation or history of splenectomy did not confer additional risk for deeloping seere COVID-19 in any patient group. Only diabetes as a comorbidity correlated with seerity grade in SCD (p=0.01) and hypertension in THAL (p=0.009). While seere COVID-19 infection in SCD was associated with both ACS (p<0.001) and kidney failure requiring treatment (p<0.001), this was not predicted by a history of preious ACS or kidney disease in steady state. Oerall, 14,6% RBC patients needed oxygen/respiratory support, 4% were admitted to ICU with an oerall mortality rate of 1%, much lower than reported in other similar cohorts. Summary/Conclusion: Results obtained so far show that seere COVID-19 occurs at younger ages in more aggressie forms of SCD and THAL. Current preentie approaches focus on age oer disease seerity. Our data highlights the risk of seere COVID-19 infection in some young patients, particularly those with SS/SB0 SCD, suggesting that immunization should be considered in this pediatric group as well. Results between similar sized cohorts of RBCD patients ary between each other and those presented here, highlighting the importance of collecting all of these small cohorts together to ensure adequate statistical power so that definitie risk factors can be reliably identified and used to guide management of patients with these rare disorders in the light of the ongoing pandemic. (Figure Presented).
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Objectives: Analysis of the results of the 7th National Census (Cs-19) of Peritoneal Dialysis in Italy, conducted in 2020-21 by the Peritoneal Dialysis Project Group of the Italian Society of Nephrology, for the year 2019. Materials and methods: The data was initially collected using specially designed software, which after entering the data of individual patients allows the aggregate extraction of the necessary information. The difficulties due to the COVID pandemic made it necessary to also use the traditional on-line questionnaire used previously. Of the 237 Centers envisaged, 198 responded, of which 177 with complete data for HD also in 2016.
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[Formula presented] PV, NR and MMP contributed equally Introduction Patients with red blood cell disorders (RBCD), chronic life threating multisystemic disorders in their severe forms, are likely to be at increased risk of complications from SARS-Cov-2 (Covid-19), but evidence in this population is scarce due to its low frequency and heterogeneous distribution. ERN-EuroBloodNet, the European Reference Network in rare hematological disorders, established a European registry to determine the impact of COVID-19 on RBCD patients and identify risk factors predicting severe outcomes. Methods The ERN-EuroBloodNet registry was established in March 2020 by Vall d'Hebron Research Institute based on REDcap software in accordance with the Regulation (EU) 2016/679 on personal data. The local Research Ethics Committee confirmed that the exceptional case of the pandemic justifies the waiver of informed consent. The ERN-EuroBloodNet registry on RBCD and COVID-19 is endorsed by the European Hematology Association (EHA). Eligible patients had confirmed RBCD and COVID-19. Data collected included demographics, diagnosis, comorbidities, treatments, and COVID-19 (severity grade, clinical manifestations, acute events, treatments, hospitalization, intensive care unit, death). For analysis of COVID-19 severity, two groups were established 1) Mild: asymptomatic or mild symptoms without clinical pneumonia and 2) Severe: pneumonia requiring oxygen/respiratory support and/or admission to intensive care unit. Continuous variables were compared using the Wilcoxon rank-sum test or Kruskall Wallis test, while categorical variables were analyzed using the Chi-square test or Fisher's Exact test. Relevant factors influencing disease or severity were examined by the logistic regression adjusted for age. Results As of June 2021, 42 medical centers from 10 EU countries had registered 373 patients: 191 Sickle cell disease (SCD), 156 Thalassemia major and intermedia (THAL) and 26 other RBCD. 84% of the SCD patients were reported by Spain, Belgium, Italy and The Netherlands and 92% of the THAL patients by Italy and Greece. The mean age of SCD was lower (22.5y) than of THAL (39.6y) with pediatric population accounting for 50.5% in SCD and 9% in THAL (p <0.001). Splenectomy and comorbidities were higher in THAL (51.3% and 65.8%) than in SCD (16% and 48.1%) (p<0.001, p=0.002). Age and BMI correlated with COVID-19 severity, as described in the general population (p=0.002, p<0.001). Fig 1 shows age distribution and COVID-19 severity by disease severity groups. The mean age for severe COVID-19 was lower in patients with severe SCD (SS/SB0 vs SC/SB+: 23.3y vs 67.5y) and THAL (major vs intermedia: 43.5 vs 51.3y) (p<0.001). Potential risk factors such as elevated ferritin, current chelation or history of splenectomy did not confer additional risk for developing severe COVID-19 in any patient group. Only diabetes as a comorbidity correlated with severity grade in SCD (p=0.011) and hypertension in THAL (p=0.014). While severe COVID-19 infection in SCD was associated with both ACS (p<0.001) and kidney failure requiring treatment (p=0.001), this was not predicted by a history of previous ACS or kidney disease in steady state. Overall, 14.8% RBC patients needed oxygen/respiratory support, 4.4% were admitted to ICU with an overall mortality rate of 0.8% (no deaths were registered in pediatric age), much lower than reported in other similar cohorts. Discussion Results obtained so far show that severe COVID-19 occurs at younger ages in more aggressive forms of SCD and THAL. Current preventive approaches (shielding, vaccinations) focus on age over disease severity. Our data highlights the risk of severe COVID-19 infection in some young patients, particularly those with SS/SB0 SCD, suggesting that immunization should be considered in this pediatric group as well. Results between similar sized cohorts of RBCD patients vary between each other and those presented here, highlighting the importance of collecting all of these small cohorts together to ensure adequate statistical p wer so that definitive risk factors (eg. age, genotype, comorbidities) can be reliably identified and used to guide management of patients with these rare disorders in the light of the ongoing pandemic. [Formula presented] Disclosures: Longo: Bristol Myers Squibb: Honoraria;BlueBird Bio: Honoraria. Bardón-Cancho: Novartis Oncology Spain: Research Funding. Flevari: PROTAGONIST COMPANY: Research Funding;ADDMEDICA: Consultancy, Research Funding;BMS: Research Funding;IMARA COMPANY: Research Funding;NOVARTIS COMPANY: Research Funding. Voskaridou: BMS: Consultancy, Research Funding;IMARA: Research Funding;NOVARTIS: Research Funding;ADDMEDICA: Consultancy, Research Funding;GENESIS: Consultancy, Research Funding;PROTAGONIST: Research Funding. Biemond: GBT: Honoraria, Research Funding, Speakers Bureau;Novartis: Honoraria, Research Funding, Speakers Bureau;Novo Nordisk: Honoraria;Celgene: Honoraria;Sanquin: Research Funding. Nur: Celgene: Speakers Bureau;Roche: Speakers Bureau;Novartis: Research Funding, Speakers Bureau. Beneitez-Pastor: Agios: Honoraria;Alexion: Honoraria;Novartis: Honoraria;Forma Therapeutics: Honoraria. Pepe: Chiesi Farmaceutici S.p.A: Other: no profit support;Bayer S.p.A.: Other: no profit support. de Montalembert: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;Addmedica: Membership on an entity's Board of Directors or advisory committees;BlueBirdBio: Membership on an entity's Board of Directors or advisory committees;Vertex: Membership on an entity's Board of Directors or advisory committees. Glenthøj: Agios: Consultancy;Novo Nordisk: Honoraria;Novartis: Consultancy;Alexion: Research Funding;Bluebird Bio: Consultancy;Bristol Myers Squibb: Consultancy;Saniona: Research Funding;Sanofi: Research Funding. Benghiat: Novartis: Consultancy;BMS: Consultancy. Labarque: Novartis: Consultancy;Bayer: Consultancy;Sobi: Consultancy;NovoNordisk: Consultancy;Octapharma: Consultancy. Diamantidis: Genesis Pharma: Honoraria;Uni-Pharma: Honoraria;Bristol Myers Squibb: Consultancy;IONIS Pharmaceuticals: Research Funding;NOVARTIS, Genesis Pharma SA: Research Funding. Kerkhoffs: Sanofi: Research Funding;Terumo BCT: Research Funding. Iolascon: Celgene: Other: Advisory Board;Bluebird Bio: Other: Advisory Board. Taher: Vifor Pharma: Consultancy, Research Funding;Agios Pharmaceuticals: Consultancy;Ionis Pharmaceuticals: Consultancy, Research Funding;Bristol Myers Squibb: Consultancy, Research Funding;Novartis: Consultancy, Research Funding. Colombatti: Novartis: Membership on an entity's Board of Directors or advisory committees;Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding;Novonordisk: Membership on an entity's Board of Directors or advisory committees;Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees;Addmedica: Membership on an entity's Board of Directors or advisory committees;BlueBirdBio: Research Funding. Mañú Pereira: Novartis: Research Funding;Agios Pharmaceuticals: Research Funding.
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Introduction: Diabetes (DM) increases cardiovascular disease morbidity and mortality and the risk of severe complications/death among patients with COVID-19. We aimed to estimate the trends of DM over time among adults in the US. Hypothesis: We anticipated an increase in DM and persistent disparities by racial/ethnic and socioecnomic subgroups from 1999 to 2018. Methods: Data were from a nationally representative sample of US adults (≥20 years;NHANES 1999-2018). Diagnosed DM was defined as a self-reported previous diagnosis of DM by a physician or any other health professionals (other than during pregnancy). Undiagnosed DM was defined as elevated levels of fasting plasma glucose (FPG≥126 mg/dL) or HbA1c (≥6.5%). Total DM included those who had either diagnosed or undiagnosed diabetes. Prediabetes was defined as no DM but a HbA1c level of 5.7%-6.4% or an FPG level of 100 mg/dL-125 mg/dL. All estimates were agest and ardized to the 2010 US census population for age groups 20-44, 45-64, and 65+ years. All analyses accounted for the complex survey design. Logistic regressions were conducted to calculate a P-value for trend. Results: Our sample included 53,533 US adults. From 1999 to 2018, the age-adjusted prevalence of total DM increased significantly from 9.05% (95% CI, 7.80%-10.2%) to 13.9% (95% CI,12.5%-15.4%) and the prevalence of prediabetes increased from 22.5% (20%-25.2%) to 40.2%(37.4%-43.1%) (P-trends<0.001). The rate of increase in prevalence was higher among MexicanAmericans but lower among non-Hispanic black individuals compared to non-Hispanic whiteindividuals (all P-trends<0.01, P-interaction=0.003). Trends in total DM by education and incomelevels were similar to the overall trend but disparities persisted between low-and high-socioeconomic groups (all P-trends<0.001, P-interaction>0.05) ( Figure 1 ). Conclusions: The prevalence of DM increased significantly from 1999 to 2018 among US adults.There are substantial and persistent disparities between racial/ethnic and socioeconomic subgroups.
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SARS-CoV-2 infection is responsible for the coronavirus disease 2019 (COVID-19). In the complex scenario of COVID-19, it is also possible to find patients with renal damage. The pathogenesis is multifactorial and not unique, and the clinical presentation may include urinary alterations, such as proteinuria and hematuria, accompanied with reduced renal function, or not. Acute kidney injury (AKI) is not uncommon, especially among critically ill patients hospitalized in intensive care unit. AKI is a negative prognostic factor and is associated with high in-hospital mortality. An early diagnosis of AKI and the assessment of any risk factors allow the nephrologist to implement appropriate therapeutic strategies, such as pharmacological or extracorporeal support. Still, mortality in patients with AKI during COVID-19 remains high. COVID-19 AKI is a quickly evolving field of study.
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The Vaccination Calendar for Life is an alliance of scientific and professional societies of public health physicians, paediatricians and general practitioners in Italy which provides a periodical update on the ideal, scientifically driven vaccination calendar throughout lifetime. Since 2012, the Lifetime Immunization Schedule has represented a benchmark for Regional and National Authorities to set up the updated list of vaccines provided actively and free of charge to infants, children, adolescents, adults and the elderly by inclusion in the Triennial National Vaccination Plan (TNVP), and in the Essential Levels of Care (LEA). The impact of the different editions of the Lifetime Immunization Schedule on the TNVP was deep, representing the inspiring source for the present vaccination policy. The 2019 edition called for more attention to pregnant women immunization; risk groups vaccination; uniform high coverage with the MMRV vaccine; extension of Meningococcal B vaccination also at adolescent age; use of quadrivalent conjugate meningococcal vaccine also at 1 year of life; progressive decrease of the age of free-of-charge offer of influenza to ≥ 60 and then to ≥ 50 year-old population; implementation of flu immunization ages 6 months-6 years; HPV vaccination also offered to 25-year old women at the time of the first screening (gender neutral immunization already offered); sequential PCV13-PPV23 pneumococcal vaccination in 65 year-old subjects; increased coverage with rotavirus vaccine in infants and zoster vaccine in the elderly.
Subject(s)
Meningococcal Vaccines , Vaccination , Adolescent , Adult , Aged , Child , Female , Health Policy , Humans , Immunization Schedule , Infant , Italy , Middle Aged , PregnancyABSTRACT
BACKGROUND: The COVID-19 pandemic has caused a severe shortage of personal protective equipment (PPE), especially N95 respirators. Efficient, effective and economically feasible methods for large-scale PPE decontamination are urgently needed. AIMS: (1) to develop protocols for effectively decontaminating PPE using vaporized hydrogen peroxide (VHP); (2) to develop novel approaches that decrease set-up and take-down time while also increasing decontamination capacity; (3) to test decontamination efficiency for N95 respirators heavily contaminated by make-up or moisturizers. METHODS: We converted a decommissioned Biosafety Level 3 laboratory into a facility that could be used to decontaminate N95 respirators. N95 respirators were hung on metal racks, stacked in piles, placed in paper bags or covered with make-up or moisturizer. A VHP® VICTORY™ unit from STERIS was used to inject VHP into the facility. Biological and chemical indicators were used to validate the decontamination process. FINDINGS: N95 respirators individually hung on metal racks were successfully decontaminated using VHP. N95 respirators were also successfully decontaminated when placed in closed paper bags or if stacked in piles of up to six. Stacking reduced the time needed to arrange N95 respirators for decontamination by approximately two-thirds while almost tripling facility capacity. Make-up and moisturizer creams did not interfere with the decontamination process. CONCLUSIONS: Respirator stacking can reduce the hands-on time and increase decontamination capacity. When personalization is needed, respirators can be decontaminated in labelled paper bags. Make up or moisturizers do not appear to interfere with VHP decontamination.
Subject(s)
COVID-19/prevention & control , Decontamination/methods , Equipment Reuse , N95 Respirators/standards , Decontamination/economics , Humans , Hydrogen Peroxide/pharmacology , N95 Respirators/supply & distribution , SARS-CoV-2 , VolatilizationABSTRACT
The Board of the Vaccination Calendar for Life (Bonanni et al., 2014, 2017) [1,2]), a coalition of four major scientific and professional societies of public health physicians, pediatricians and general practitioners in Italy, made an appeal to health authorities in order to sustain vaccination in COVID-19 times. The five pillars to maintain and increase vaccination coverage at all ages are described as follows: 1) Guarantee paediatric vaccination coverage to all newborns and paediatric boosters and adolescent immunizations, not interrupting active calls and scheduled sessions. 2) Re-organise the way paediatric and adolescent vaccinations are offered. 3) Set-up recovery programs for vaccinations not carried out after the start of the COVID-19 emergency. 4) Provide the preparation of tenders for the supply of flu vaccines with suitable quantities to increase coverage in all Regions and Autonomous Provinces with extreme urgency. 5) Prepare plans to increase coverage for influenza, pneumococcal, tetanus diphtheria and shingles. The Board of the Calendar for Life appeals to the National and Local Health Authorities for a strong and coordinated commitment in favor of the widest offer and acceptance of vaccinations, whose vital importance for collective health is now even more evident to all, in order to avoid that delays in the necessary initiatives should add damage from other epidemics to those suffered by our population due to the COVID-19 pandemic.
Subject(s)
Immunization Programs/organization & administration , Pandemics , Vaccination Coverage , Adolescent , Adult , Aged , COVID-19 , Child , Humans , Infant, Newborn , Italy/epidemiology , Pandemics/prevention & controlABSTRACT
BACKGROUND: Coronavirus disease 2019 has stretched the ability of many institutions to supply needed personal protective equipment, especially N95 respirators. N95 decontamination and re-use programmes provide one potential solution to this problem. Unfortunately, a comprehensive evaluation of the effects of decontamination on the fit of various N95 models using a quantitative fit test (QNFT) approach is lacking. AIMS: To investigate the effects of up to eight rounds of vaporized hydrogen peroxide (VHP) decontamination on the fit of N95 respirators currently in use in a hospital setting, and to examine if N95 respirators worn by one user can adapt to the face shape of a second user with no compromise to fit following VHP decontamination. METHODS: The PortaCount Pro+ Respirator Fit Tester Model 8038 was used to quantitatively define functional integrity, measured by fit, of N95 respirators following decontamination with VHP. FINDINGS: There was an observable downward trend in the functional integrity of Halyard Fluidshield 46727 N95 respirators throughout eight cycles of decontamination with VHP. Functional integrity of 3M 1870 N95 respirators was reduced significantly after the respirator was worn, decontaminated with VHP, and then quantitatively fit tested on a second user. Furthermore, inconsistencies between qualitative fit test and QNFT results were uncovered that may have strong implications on the fit testing method used by institutions. CONCLUSIONS: The data revealed variability in the functional integrity of different N95 models after VHP decontamination, and exposed potential limitations of N95 decontamination and re-use programmes.