140 research outputs found
New developments in the genetics, pathogenesis, and therapy of IgA nephropathy
Recent years have brought notable progress in the field of IgA nephropathy. Here, we highlight important new directions and latest developments, including successful discovery of several genetic susceptibility loci, formulation of the multihit pathogenesis model, introduction of the Oxford pathology scoring system, and formalization of the Kidney Disease Improving Global Outcomes (KDIGO) consensus treatment guidelines. We focus on the latest genetic findings that confirm a strong contribution of inherited factors and explain some of the geoethnic disparities in disease susceptibility. Most IgA nephropathy susceptibility loci discovered to date encode genes involved in the maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The concerted pattern of interpopulation allelic differentiation across all genetic loci parallels the disease prevalence and correlates with variation in local pathogens, suggesting that multilocus adaptation might have shaped the present-day landscape of IgA nephropathy. Importantly, the 'Intestinal Immune Network for IgA Production' emerged as one of the new targets for potential therapeutic intervention. We place these findings in the context of the multihit pathogenesis model and existing knowledge of IgA immunobiology. Lastly, we provide our perspective on the existing treatment options, discuss areas of clinical uncertainty, and outline ongoing clinical trials and translational studies.Kidney International advance online publication, 16 September 2015; doi:10.1038/ki.2015.252
Epidemiologic characteristics of amniotic band sequence with limb malformations without body wall defect: data from the Polish Registry of Congenital Malformations
Abstract Amniotic Band Sequence (ABS) is a rare disruptive condition, with a variable spectrum of congenital defects caused by fibrous bands emerging as a result of amniotic rupture in the first trimester of gestation. Several factors, such as young parental age, primigravidity, febrile maternal illness, and drug use in the first trimester, were postulated to have substantial influence on ABS prevalence rate. We aimed our study to determine the prevalence of ABS with limb defects, but no body wall affectation, in a Polish population. We also examined the influence of different parental, gestational and environmental factors on the ABS prevalence value, and assessed the rate of gestational complications associated with this disorder. Among 1 706 639 births surveilled between 1998 and 2005, 36 liveborn infants with ABS-L were reported to the Polish Registry of Congenital Malformations, giving a global prevalence for a Polish population of 1 per 47 619 livebirths. We found that young maternal age, young paternal age, and primigravidity significantly increase the risk of ABS-L, when their effect was analyzed independently. However, because of a close relationship of these variables, we analyzed their mutually adjusted effect using conditional logistic regression models, and found that young maternal age proved the strongest risk factor for ABS-L (p = 0.0508). The condition was also more prevalent in infants with low birthweight (OR = 5.71; p < 0.0001). Since gestational complications are often relevant to maternal age and birth order, we introduced an adjustment for these variables, and found that respiratory tract infections and vaginal bleeding/spotting convey approximately fourfold increased risk of ABS-L (OR = 3.72/p = 0.0058 and OR = 3.70/p = 0.0014 respectively)
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A Panel of Serum Biomarkers Differentiates IgA Nephropathy from Other Renal Diseases
Background and Objectives:
There is increasing evidence that galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1-containing immune complexes are important for the pathogenesis of IgA nephropathy (IgAN). In the present study, we assessed a novel noninvasive multi-biomarker approach in the diagnostic test for IgAN.
Materials and Methods:
We compared serum levels of IgA, IgG, Gd-IgA1, Gd-IgA1-specific IgG and Gd-IgA1-specific IgA in 135 IgAN patients, 79 patients with non-IgAN chronic kidney disease (CKD) controls and 106 healthy controls. Serum was collected at the time of kidney biopsy from all IgAN and CKD patients.
Results:
Each serum marker was significantly elevated in IgAN patients compared to CKD (P<0.001) and healthy controls (P<0.001). While 41% of IgAN patients had elevated serum Gd-IgA1 levels, 91% of these patients exhibited Gd-IgA1-specific IgG levels above the 90th percentile for healthy controls (sensitivity 89%, specificity 92%). Although up to 25% of CKD controls, particularly those with immune-mediated glomerular diseases including lupus nephritis, also had elevated serum levels of Gd-IgA1-specific IgG, most IgAN patients had elevated levels of Gd-IgA1-specific antibody of both isotypes. Serum levels of Gd-IgA1-specific IgG were associated with renal histological grading. Furthermore, there was a trend toward higher serum levels of Gd-IgA1-specific IgG in IgAN patients with at least moderate proteinuria (â„1.0 g/g), compared to patients with less proteinuria.
Conclusions
Serum levels of Gd-IgA1-specific antibodies are elevated in most IgAN patients, and their assessment, together with serum levels of Gd-IgA1, improves the specificity of the assays. Our observations suggest that a panel of serum biomarkers may be helpful in differentiating IgAN from other glomerular diseases
Cystatin C is associated with adverse COVID-19 outcomes in diverse populations
COVID-19 has highly variable clinical courses. The search for prognostic host factors for COVID-19 outcome is a priority. We performed logistic regression for ICU admission against a polygenic score (PGS) for Cystatin C (CyC) production in patients with COVID-19. We analyzed the predictive value of longitudinal plasma CyC levels in an independent cohort of patients hospitalized with COVID-19. In four cohorts spanning European and African ancestry populations, we identified a significant association between CyC-production PGS and odds of critical illness (n cases=2,319), with the strongest association captured in the UKB cohort (OR 2.13, 95% CI 1.58-2.87, p=7.12e-7). Plasma proteomics from an independent cohort of hospitalized COVID-19 patients ( n cases = 131) demonstrated that CyC production was associated with COVID-specific mortality (p=0.0007). Our findings suggest that CyC may be useful for stratification of patients and it has functional role in the host response to COVID-19.Peer reviewe
Predicting Progression of IgA Nephropathy: New Clinical Progression Risk Score
IgA nephropathy (IgAN) is a common cause of end-stage renal disease (ESRD) in Asia. In this study, based on a large cohort of Chinese patients with IgAN, we aim to identify independent predictive factors associated with disease progression to ESRD. We collected retrospective clinical data and renal outcomes on 619 biopsy-diagnosed IgAN patients with a mean follow-up time of 41.3 months. In total, 67 individuals reached the study endpoint defined by occurrence of ESRD necessitating renal replacement therapy. In the fully adjusted Cox proportional hazards model, there were four baseline variables with a significant independent effect on the risk of ESRD. These included: eGFR [HRâ=â0.96(0.95â0.97)], serum albumin [HRâ=â0.47(0.32â0.68)], hemoglobin [HRâ=â0.79(0.72â0.88)], and SBP [HRâ=â1.02(1.00â1.03)]. Based on these observations, we developed a 4-variable equation of a clinical risk score for disease progression. Our risk score explained nearly 22% of the total variance in the primary outcome. Survival ROC curves revealed that the risk score provided improved prediction of ESRD at 24th, 60th and 120th month of follow-up compared to the three previously proposed risk scores. In summary, our data indicate that IgAN patients with higher systolic blood pressure, lower eGFR, hemoglobin, and albumin levels at baseline are at a greatest risk of progression to ESRD. The new progression risk score calculated based on these four baseline variables offers a simple clinical tool for risk stratification
Genome-Wide Study Updates in the International Genetics and Translational Research in Transplantation Network (iGeneTRAiN)
The prevalence of end-stage renal disease (ESRD) and the number of kidney transplants performed continues to rise every year, straining the procurement of deceased and living kidney allografts and health systems. Genome-wide genotyping and sequencing of diseased populations have uncovered genetic contributors in substantial proportions of ESRD patients. A number of these discoveries are beginning to be utilized in risk stratification and clinical management of patients. Specifically, genetics can provide insight into the primary cause of chronic kidney disease (CKD), the risk of progression to ESRD, and post-transplant outcomes, including various forms of allograft rejection. The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN), is a multi-site consortium that encompasses >45 genetic studies with genome-wide genotyping from over 51,000 transplant samples, including genome-wide data from >30 kidney transplant cohorts (n = 28,015). iGeneTRAiN is statistically powered to capture both rare and common genetic contributions to ESRD and post-transplant outcomes. The primary cause of ESRD is often difficult to ascertain, especially where formal biopsy diagnosis is not performed, and is unavailable in âŒ2% to >20% of kidney transplant recipients in iGeneTRAiN studies. We overview our current copy number variant (CNV) screening approaches from genome-wide genotyping datasets in iGeneTRAiN, in attempts to discover and validate genetic contributors to CKD and ESRD. Greater aggregation and analyses of well phenotyped patients with genome-wide datasets will undoubtedly yield insights into the underlying pathophysiological mechanisms of CKD, leading the way to improved diagnostic precision in nephrology
The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis
Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (ï»żrs230540, OR = 1.25, P = 3.4 Ă 10â12) and IRF4 (ï»żrs9405192, OR = 1.29, P = ï»ż1.4 Ă 10â14), fine-map the PLA2R1 locus (ï»żrs17831251, OR = 2.25, P = 4.7 Ă 10â103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 Ă 10â49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 Ă 10â93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 Ă 10â23 and OR = 3.39, P = 5.2 Ă 10â82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20â37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk
Genetic Drivers of Kidney Defects in the DiGeorge Syndrome
Background The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. Methods We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. Results We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5Ă10(-14)). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. Conclusions We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.)
Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study
Introduction:
The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients.
Methods:
Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment.
Results:
A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001).
Conclusion:
This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies
Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality
AG has received support by NordForsk Nordic Trial Alliance (NTA) grant, by Academy of
Finland Fellow grant N. 323116 and the Academy of Finland for PREDICT consortium N.
340541.
The Richards research group is supported by the Canadian Institutes of Health Research
(CIHR) (365825 and 409511), the Lady Davis Institute of the Jewish General Hospital, the
Canadian Foundation for Innovation (CFI), the NIH Foundation, Cancer Research UK,
Genome Québec, the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in
Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS). TN is supported
by a research fellowship of the Japan Society for the Promotion of Science for Young
Scientists. GBL is supported by a CIHR scholarship and a joint FRQS and Québec Ministry of
Health and Social Services scholarship. JBR is supported by an FRQS Clinical Research
Scholarship. Support from Calcul Québec and Compute Canada is acknowledged. TwinsUK is
funded by the Welcome Trust, the Medical Research Council, the European Union, the
National Institute for Health Research-funded BioResource and the Clinical Research Facility
and Biomedical Research Centre based at Guyâs and St. Thomasâ NHS Foundation Trust in
partnership with Kingâs College London. The Biobanque QuĂ©bec COVID19 is funded by FRQS,
Genome Québec and the Public Health Agency of Canada, the McGill Interdisciplinary
Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé. These funding
agencies had no role in the design, implementation or interpretation of this study.
The COVID19-Host(a)ge study received infrastructure support from the DFG Cluster of
Excellence 2167 âPrecision Medicine in Chronic Inflammation (PMI)â (DFG Grant: âEXC2167â).
The COVID19-Host(a)ge study was supported by the German Federal Ministry of Education
and Research (BMBF) within the framework of the Computational Life Sciences funding
concept (CompLS grant 031L0165). Genotyping in COVID19-Host(a)ge was supported by a
philantropic donation from Stein Erik Hagen.
The COVID GWAs, Premed COVID-19 study (COVID19-Host(a)ge_3) was supported by
"Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia"and also by
the Instituto de Salud Carlos III (CIBERehd and CIBERER). Funding comes from
COVID-19-GWAS, COVID-PREMED initiatives. Both of them are supported by "Consejeria de
Salud y Familias" of the Andalusian Government. DMM is currently funded by the the
Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018).
The Columbia University Biobank was supported by Columbia University and the National
Center for Advancing Translational Sciences, NIH, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official
views of the NIH or Columbia University.
The SPGRX study was supported by the ConsejerĂa de EconomĂa, Conocimiento, Empresas y
Universidad #CV20-10150.
The GEN-COVID study was funded by: the MIUR grant âDipartimenti di Eccellenza 2018-2020â
to the Department of Medical Biotechnologies University of Siena, Italy; the âIntesa San Paolo
2020 charity fundâ dedicated to the project NB/2020/0119; and philanthropic donations to the
Department of Medical Biotechnologies, University of Siena for the COVID-19 host genetics
research project (D.L n.18 of March 17, 2020). Part of this research project is also funded by
Tuscany Region âBando Ricerca COVID-19 Toscanaâ grant to the Azienda Ospedaliero
Universitaria Senese (CUP I49C20000280002). Authors are grateful to: the CINECA
consortium for providing computational resources; the Network for Italian Genomes (NIG)
(http://www.nig.cineca.it) for its support; the COVID-19 Host Genetics Initiative
(https://www.covid19hg.org/); the Genetic Biobank of Siena, member of BBMRI-IT, Telethon
Network of Genetic Biobanks (project no. GTB18001), EuroBioBank, and RD-Connect, for
managing specimens.
Genetics against coronavirus (GENIUS), Humanitas University (COVID19-Host(a)ge_4) was
supported by Ricerca Corrente (Italian Ministry of Health), intramural funding (Fondazione
Humanitas per la Ricerca). The generous contribution of Banca Intesa San Paolo and of the
Dolce&Gabbana Fashion Firm is gratefully acknowledged.
Data acquisition and sample processing was supported by COVID-19 Biobank, Fondazione
IRCCS CĂ Granda Milano; LV group was supported by MyFirst Grant AIRC n.16888, Ricerca
Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS
Caâ Granda Ospedale Maggiore Policlinico, the European Union (EU) Programme Horizon
2020 (under grant agreement No. 777377) for the project LITMUS- âLiver Investigation:
Testing Marker Utility in Steatohepatitisâ, Programme âPhotonicsâ under grant agreement
â101016726â for the project âREVEAL: Neuronal microscopy for cell behavioural examination
and manipulationâ, Fondazione Patrimonio Caâ Granda âLiver Bibleâ PR-0361. DP was
supported by Ricerca corrente Fondazione IRCCS Caâ Granda Ospedale Maggiore Policlinico,
CV PREVITAL âStrategie di prevenzione primaria nella popolazione Italianaâ Ministero della
Salute, and Associazione Italiana per la Prevenzione dellâEpatite Virale (COPEV).
Genetic modifiers for COVID-19 related illness (BeLCovid_1) was supported by the "Fonds
Erasme". The Host genetics and immune response in SARS-Cov-2 infection (BelCovid_2)
study was supported by grants from Fondation LĂ©on Fredericq and from Fonds de la
Recherche Scientifique (FNRS).
The INMUNGEN-CoV2 study was funded by the Consejo Superior de Investigaciones
CientĂficas.
KUL is supported by the German Research Foundation (LU 1944/3-1) SweCovid is funded by the SciLifeLab/KAW national COVID-19 research program project
grant to Michael Hultström (KAW 2020.0182) and the Swedish Research Council to Robert
Frithiof (2014-02569 and 2014-07606). HZ is supported by Jeansson Stiftelser, Magnus
Bergvalls Stiftelse.
The COMRI cohort is funded by Technical University of Munich, Munich, Germany.
Genotyping for the COMRI cohort was performed and funded by the Genotyping Laboratory of
Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki,
Helsinki, Finland.
These funding agencies had no role in the design, implementation or interpretation of this
study.Background: There is considerable variability in COVID-19 outcomes amongst younger
adultsâand some of this variation may be due to genetic predisposition. We characterized the
clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent
effect, using individual-level data in a large international multi-centre consortium.
Method: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by
the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive
patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this
genetic marker with mortality, COVID-19-related complications and laboratory values. We next
examined if the magnitude of these associations varied by age and were independent from
known clinical COVID-19 risk factors.
Findings: We found that rs10490770 risk allele carriers experienced an increased risk of
all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2â1·6) and COVID-19
related mortality (HR 1·5, 95%CI 1·3â1·8). Risk allele carriers had increased odds of several
COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6),
venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI
1·2-2·0). Risk allele carriers †60 years had higher odds of death or severe respiratory failure
(OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction
p-value=0·04). Amongst individuals †60 years who died or experienced severe respiratory
COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers,
compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes.
Prediction of death or severe respiratory failure among those †60 years improved when
including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770
risk allele was similar to, or better than, most established clinical risk factors.
Interpretation: The major common COVID-19 risk locus on chromosome 3 is associated with
increased risks of morbidity and mortalityâand these are more pronounced amongst individuals
†60 years. The effect on COVID-19 severity was similar to, or larger than most established risk
factors, suggesting potential implications for clinical risk management.Academy of
Finland Fellow grant N. 323116Academy of Finland for PREDICT consortium N.
340541.Canadian Institutes of Health Research
(CIHR) (365825 and 409511)Lady Davis Institute of the Jewish General HospitalCanadian Foundation for Innovation (CFI)NIH FoundationCancer Research UKGenome QuébecPublic Health Agency of CanadaMcGill Interdisciplinary Initiative in
Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS)Japan Society for the Promotion of Science for Young
ScientistsCIHR scholarship and a joint FRQS and Québec Ministry of
Health and Social Services scholarshipFRQS Clinical Research
ScholarshipCalcul QuébecCompute CanadaWelcome TrustMedical Research CouncEuropean UnionNational Institute for Health Research-funded BioResourceClinical Research Facility
and Biomedical Research Centre based at Guyâs and St. Thomasâ NHS Foundation TrustKingâs College LondonGenome QuĂ©becPublic Health Agency of CanadaMcGill Interdisciplinary
Initiative in Infection and ImmunityFonds de Recherche QuĂ©bec SantĂ©(DFG Grant: âEXC2167â)(CompLS grant 031L0165)Stein Erik Hagen"Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia"Instituto de Salud Carlos III (CIBERehd and CIBERER)COVID-19-GWASCOVID-PREMED initiatives"Consejeria de
Salud y Familias" of the Andalusian GovernmentAndalusian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018)Columbia UniversityNational
Center for Advancing Translational SciencesNIH Grant Number UL1TR001873ConsejerĂa de EconomĂa, Conocimiento, Empresas y
Universidad #CV20-10150MIUR grant âDipartimenti di Eccellenza 2018-2020ââIntesa San Paolo
2020 charity fundâ dedicated to the project NB/2020/0119Tuscany Region âBando Ricerca COVID-19 ToscanaâCINECA
consortiumNetwork for Italian Genomes (NIG)COVID-19 Host Genetics InitiativeGenetic Biobank of SienaEuroBioBankRD-ConnectRicerca Corrente (Italian Ministry of Health)Fondazione
Humanitas per la RicercaBanca Intesa San PaoloDolce&Gabbana Fashion FirmCOVID-19 BiobankFondazione
IRCCS CĂ Granda MilanoMyFirst Grant AIRC n.16888Ricerca
Finalizzata Ministero della Salute RF-2016-02364358Ricerca corrente Fondazione IRCCS
Caâ Granda Ospedale Maggiore PoliclinicoEuropean Union (EU) Programme Horizon
2020 (under grant agreement No. 777377)âPhotonicsâ â101016726âFondazione Patrimonio Caâ Granda âLiver Bibleâ PR-0361CV PREVITAL âStrategie di prevenzione primaria nella popolazione Italianaâ Ministero della
Salute, and Associazione Italiana per la Prevenzione dellâEpatite Virale (COPEV)"Fonds
Erasme"Fondation LĂ©on FredericqFonds de la
Recherche Scientifique (FNRS)Consejo Superior de Investigaciones
CientĂficasGerman Research Foundation (LU 1944/3-1)SciLifeLab/KAW national COVID-19 research program project (KAW 2020.0182)Swedish Research Council (2014-02569 and 2014-07606)Jeansson Stiftelser, Magnus
Bergvalls StiftelseTechnical University of Munich, Munich, GermanyGenotyping Laboratory of
Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki,
Helsinki, Finlan
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