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INTRODUCTION: Serological surveillance is useful for assessing SARS-CoV-2 immunity in populations. To effectively study the presence and persistence of antibodies, it is necessary to distinguish between persons with past infection, and persons who only received vaccination. Knowledge of the duration of antibody persistence is essential for correct interpretation of surveillance results. METHODS: Starting in April 2020, waning of SARS-CoV-2 antibodies was studied in a longitudinal cohort study of 495 SARS-CoV-2 antibody-positive Dutch blood donors, not pre-selected by PCR testing or disease severity. Additionally, in May 2021, a sample of donors representative for the Dutch population was tested for antibodies against the SARS-CoV-2 spike (S) protein, using the Wantai Ab ELISA and the Elecsys® Anti-SARS-CoV-2 S assay; and for antibodies against the nucleocapsid protein, which indicate past infection, using the Elecsys® Anti-SARS-CoV-2 assay. RESULTS: The anti-S response in donors that were infected in April or May 2020 remained positive in 100% of donors in the Elecsys® Anti-SARS-CoV-2 S assay one year after infection, after which follow up of waning was no longer possible because of large scale vaccination. The anti-nucleocapsid response results were still positive in approximately 80% of donors two years after infection. In May 2021, 51% of the donors showed anti-S reactivity and 16.8% tested positive for anti-nucleocapsid antibodies. CONCLUSION: Infection with SARS-CoV-2 resulted in spike and nucleocapsid antibody levels still detectable in the majority of donors 1-2 years after infection. In May 2021, 51% of donors were vaccinated and 16.8% had had an infection. Thus, both Elecsys® SARS-CoV-2 antibody assays can be used to reliably assess the vaccination and infection status of individuals.
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Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinação , Humanos , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/diagnóstico , COVID-19/prevenção & controle , COVID-19/virologia , Glicoproteína da Espícula de Coronavírus/imunologia , Estudos Longitudinais , Feminino , Masculino , Pessoa de Meia-Idade , Vacinas contra COVID-19/imunologia , Adulto , Ensaio de Imunoadsorção Enzimática , Países Baixos/epidemiologia , Teste Sorológico para COVID-19/métodos , Doadores de Sangue , IdosoRESUMO
BACKGROUND: Less discriminatory donor selection policies for men who have sex with men (MSM) may impact transfusion safety in terms of higher residual risks for known transfusion-transmitted infections (TTIs), increased vulnerability toward new TTIs that are also transmitted via sex, and HIV infections masked by pre-exposure prophylaxis (PrEP). STUDY DESIGN AND METHODS: TTI trends in Dutch donors were studied over a 13-year period (2011-2023), characterized by successive relaxations of MSM deferral criteria. Structured posttest counseling was performed to determine risk factors in TTI-positive donors. PrEP drug levels were measured in 9977 donations from male donors living in urban areas and in 67 donors with active or resolved syphilis. RESULTS: HIV incidence (from 5.8 to 1.5 per 1,000,000 donor years (DY)) and HBV incidence (from 12.4 to 4.5 per 1,000,000 DY) in Dutch donors decreased with less stringent MSM deferral criteria, while syphilis prevalence (from 26.4 to 44.1 per 100,000 new donors) and syphilis incidence (from 18.3 to 46.3 per 1,000,000 DY) increased over time. The proportion of MSM-related syphilis rose from 2% to 32% in new donors and from 12% to 27% in repeat donors. PrEP was detected in 2 of 9977 (0.02%) donations from male donors living in urban areas, and in 1 of 39 (2.6%) male donors with syphilis. DISCUSSION: To date, phasing out donor deferral for MSM had no significant impact on transfusion safety in the Netherlands. However, rising syphilis rates and (recent) PrEP use in the blood donor population, albeit rare, suggest an influx of donors with higher sexual risk profiles and requires intensified TTI surveillance in donors.
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Parvovirus B19V (B19V) infection during pregnancy can be complicated by potentially life-threatening fetal hydrops, which can be managed by intrauterine transfusion (IUT). This study investigates the long-term temporal patterns in the epidemiology of B19V and evaluates the impact on fetal hydrops, by combining data on B19V infections from the Dutch Sentinel Surveillance system in the period 1990 to 2023, Dutch blood banking data and hospital data on fetal hydrops. Using wavelet analysis, we identified annual epidemic cycles in the Netherlands in the period 1990-2019 and we identified superimposed multiannual cycles in the period 1990-2009. After 2009, no multiannual cycle could be identified, although the incidence fluctuated and correlates with number of IUT performed. As of 2020, weekly reports of B19V infection demonstrated a historically low incidence and B19V-DNA positive blood donors were nearly absent. From May 2020 to May 2023, no IUT for B19V-related hydrops was performed. In the spring of 2023, B19V infections re-emerged, reaching pre-pandemic epidemic levels. Due to the changes in B19V epidemiology over the last 30 years and the near-absence of B19V during the COVID-19 pandemic, the resulting low immunity levels may lead to rebound outbreaks. Alertness to severe complications such as fetal hydrops is warranted.
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COVID-19 , Hidropisia Fetal , Parvovirus B19 Humano , Humanos , Países Baixos/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , Feminino , Gravidez , Hidropisia Fetal/epidemiologia , Hidropisia Fetal/virologia , Incidência , Infecções por Parvoviridae/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2/isolamento & purificação , Pandemias , Eritema Infeccioso/epidemiologia , Transfusão de Sangue Intrauterina , AdultoRESUMO
ABSTRACT: Teclistamab and other B-cell maturation antigen (BCMA)-targeting bispecific antibodies (BsAbs) have substantial activity in patients with heavily pretreated multiple myeloma (MM) but are associated with a high rate of infections. BCMA is also expressed on normal plasma cells and mature B cells, which are essential for the generation of a humoral immune response. The aim of this study was to improve the understanding of the impact of BCMA-targeting BsAbs on humoral immunity. The impact of teclistamab on polyclonal immunoglobulins and B cell counts was evaluated in patients with MM who received once-weekly teclistamab 1.5 mg/kg subcutaneously. Vaccination responses were assessed in a subset of patients. Teclistamabinduced rapid depletion of peripheral blood B cells in patients with MM and eliminated normal plasma cells in ex vivo assays. In addition, teclistamab reduced the levels of polyclonal immunoglobulins (immunoglobulin G [IgG], IgA, IgE, and IgM), without recovery over time while receiving teclistamab therapy. Furthermore, response to vaccines against Streptococcus pneumoniae, Haemophilus influenzae type B, and severe acute respiratory syndrome coronavirus 2 was severely impaired in patients treated with teclistamab compared with vaccination responses observed in patients with newly diagnosed MM or relapsed/refractory MM. Intravenous immunoglobulin (IVIG) use was associated with a significantly lower risk of serious infections among patients treated with teclistamab (cumulative incidence of infections at 6 months: 5.3% with IVIG vs 54.8% with observation only [P < .001]). In conclusion, our data show severe defects in humoral immunity induced by teclistamab, the impact of which can be mitigated by the use of immunoglobulin supplementation. This trial was registered at www.ClinicalTrials.gov as #NCT04557098.
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Anticorpos Biespecíficos , Antineoplásicos , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Imunidade Humoral , Imunoglobulinas Intravenosas/uso terapêutico , Anticorpos Biespecíficos/uso terapêutico , Antígeno de Maturação de Linfócitos B/uso terapêutico , Antineoplásicos/uso terapêutico , Suplementos NutricionaisRESUMO
Introduction: In 2020, the first Dutch West Nile virus (WNV) infected birds were detected through risk-targeted surveillance of songbirds. Retrospective testing of patients with unexplained neurological disease revealed human WNV infections in July and August 2020. Bird ringers are highly exposed to mosquito bites and possibly avian excrements during ringing activities. This study therefore investigates whether bird ringers are at higher risk of exposure to WNV and Usutu virus (USUV). Methods: Dutch bird ringers were asked to provide a single serum sample (May - September 2021) and to fill out a survey. Sera were screened by protein microarray for presence of specific IgG against WNV and USUV non-structural protein 1 (NS1), followed by focus reduction virus neutralization tests (FRNT). Healthcare workers (2009-2010), the national immunity cohort (2016-2017) and blood donors (2021) were used as control groups without this occupational exposure. Results: The majority of the 157 participating bird ringers was male (132/157, 84%) and the median age was 62 years. Thirty-seven participants (37/157, 23.6%) showed WNV and USUV IgG microarray signals above background, compared to 6.4% (6/94) in the community cohort and 2.1% (2/96) in blood donors (p < 0.01). Two seroreactive bird ringers were confirmed WNV or USUV positive by FRNT. The majority of seroreactive bird ringers travelled to EU countries with reported WNV human cases (30/37, 81%) (p = 0.07). No difference was observed between bird ringers with and without previous yellow fever vaccination. Discussion: The higher frequency of WNV and/or USUV IgG reactive bird ringers indicates increased flavivirus exposure compared to the general population, suggesting that individuals with high-exposure professions may be considered to complement existing surveillance systems. However, the complexity of serological interpretation in relation to location-specific exposure (including travel), and antibody cross-reactivity, remain a challenge when performing surveillance of emerging flaviviruses in low-prevalence settings.
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Background: Currently available treatment options for chronic hepatitis B (CHB) are not recommended for HBeAg-negative patients with a low viral load. These patients may however benefit from treatment by achieving a functional cure, defined by HBsAg-loss and undetectable HBV DNA. This study evaluated the long-term effect of combination treatment with peg-interferon-alpha-2a (peg-IFN) and adefovir or tenofovir compared to no treatment in these patients. Methods: HBeAg-negative CHB patients with HBV-DNA levels < 20,000 IU/mL (n = 151) were previously randomised 1:1:1 for peg-IFN 180 µg/week plus either adefovir 10 mg/day or tenofovir 245 mg/day, or no treatment and treated for 48 weeks in an open-label study. In this prospective long-term follow-up study, patients were monitored yearly up to five years after end of treatment (week 308). The primary outcome was sustained HBsAg-loss and secondary outcome the dynamics of HBsAg and HBV-DNA levels over time. Results: Of the 131 followed patients, the HBsAg-status was known for 118 patients after five-year follow-up. HBsAg-loss occurred similarly (P = 0.703) in all arms: 8/43 (18.6%) peg-IFN + adefovir, 4/34 (11.7%) peg-IFN + tenofovir, and 6/41 (14.6%) among the untreated patients. The time to HBsAg-loss did not differ between groups (P = 0.641). Low baseline HBsAg levels and genotype A were independently associated with HBsAg-loss irrespective of allocation. HBsAg and HBV-DNA levels declined similarly during follow-up in all patient groups. Conclusions: This prospective randomised controlled study showed that HBsAg-loss overtime was not influenced by treatment with a combination of nucleotide analogue and Peg-IFN. Low baseline HBsAg levels can predict HBsAg-loss irrespective of treatment allocation.
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BACKGROUND: To better balance the safety of the blood supply and the inclusion of men who have sex with men (MSM), further improvements are needed to the risk management strategy employed in the Netherlands to reduce transfusion-transmissible infections (TTIs). A gender-neutral individual risk assessment could provide a solution by determining donor eligibility based on sexual behaviors known to increase the risk of TTIs. Our objective is to estimate the proportion of blood donors that would be deferred by such an assessment, as well as their discomfort answering such questions. STUDY DESIGN AND METHODS: Two surveys were distributed in May 2020 to assess sexual behavior in blood donors in the last 4, 6, and 12 months, as well as their discomfort reporting such information. A combination of both surveys measured the extent to which discomfort was associated with reporting sexual behavior. A high-risk sexual behavior pattern was defined as having had multiple sexual partners and having engaged in anal sex, without consistent condom use. RESULTS: Of all 2177 participating whole blood donors, 0.8% report engaging in high-risk sexual behaviors over the last 4 months and would therefore be ineligible to donate. When accounting for the additional proportion of donors that reported such questions would stop them from donating, 2.0% and 3.2% of female and male donors, respectively, would be lost. DISCUSSION: Gender-neutral eligibility criteria based on high-risk sexual behaviors may reduce the overall number of eligible donors in the Netherlands, but could make blood donation more accessible to a broader group of donors.
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Infecções por HIV , Minorias Sexuais e de Gênero , Doadores de Sangue , Segurança do Sangue , Seleção do Doador , Feminino , Homossexualidade Masculina , Humanos , Masculino , Países Baixos , Medição de Risco , Comportamento SexualRESUMO
BACKGROUND: Frequent whole blood donors have an increased risk of developing iron deficiency. Iron deficiency can have detrimental health effects when left untreated. Donation intervals are commonly too short to replenish iron stores and extending these reduces donor availability. Oral iron supplementation is known to shorten iron store recovery time but may also induce gastrointestinal complaints. We aim to optimise the effectiveness of iron supplements while minimising the risks of side effects. Therefore, we will evaluate the impact of different iron supplementation protocols in terms of dosage and frequency on ferritin and haemoglobin levels, gastrointestinal side effects, iron deficiency-related symptoms and donor return compared with placebo supplementation. METHODS: Twelve hundred whole blood donors with ferritin levels ≤30 µg/L are included into a double-blind, randomised controlled trial. Participants are randomly allocated to one of six arms, administering capsules containing 0 mg, 30 mg or 60 mg of iron, either on alternate days or daily for 56 days. At baseline and 56, 122 and 182 days of follow-up, ferritin and haemoglobin levels are measured, and compliance, donor return, dietary iron intake, gastrointestinal, iron deficiency-related symptoms and general health are assessed by questionnaire. ETHICS AND DISSEMINATION: This study will provide a comprehensive overview of the effects of different frequencies and dosages of administration of iron supplements on iron status and health effects, thereby considering individual differences in treatment adherence and lifestyle. The outcome will provide scientific evidence to guide the debate if and how oral iron supplements may support the recovery of whole blood donors with low ferritin levels. TRIAL REGISTRATION NUMBER: NL8590; The Dutch trial registry.
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Anemia Ferropriva , Deficiências de Ferro , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/prevenção & controle , Doadores de Sangue , Suplementos Nutricionais , Ferritinas , Hemoglobinas/análise , Humanos , Ferro , Ferro da Dieta , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The Polyomaviridae is a family of ubiquitous dsDNA viruses that establish persistent infection early in life. Screening for human polyomaviruses (HPyVs), which comprise 14 diverse species, relies upon species-specific qPCRs whose validity may be challenged by accelerating genomic exploration of the virosphere. Using this reasoning, we tested 64 published HPyV qPCR assays in silico against the 1781 PyV genome sequences that were divided in targets and nontargets, based on anticipated species specificity of each qPCR. We identified several cases of problematic qPCR performance that were confirmed in vitro and corrected through using degenerate oligos. Furthermore, our study ranked 8 out of 52 tested BKPyV qPCRs as remaining of consistently high quality in the wake of recent PyV discoveries and showed how sensitivity of most other qPCRs could be rescued by annealing temperature adjustment. This study establishes an efficient framework for ensuring confidence in available HPyV qPCRs in the genomic era.
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BACKGROUND: Viruses and bacteria from the nasopharynx are capable of causing community-acquired pneumonia (CAP), which can be difficult to diagnose. We aimed to investigate whether shifts in the composition of these nasopharyngeal microbial communities can be used as diagnostic biomarkers for CAP in adults. METHODS: We collected nasopharyngeal swabs from adult CAP patients and controls without infection in a prospective multicenter case-control study design. We generated bacterial and viral profiles using 16S ribosomal RNA gene sequencing and multiplex polymerase chain reaction (PCR), respectively. Bacterial, viral, and clinical data were subsequently used as inputs for extremely randomized trees classification models aiming to distinguish subjects with CAP from healthy controls. RESULTS: We enrolled 117 cases and 48 control subjects. Cases displayed significant beta diversity differences in nasopharyngeal microbiota (Pâ =â .016, R2 = .01) compared to healthy controls. Our extremely randomized trees classification models accurately discriminated CAP caused by bacteria (area under the curve [AUC] .83), viruses (AUC .95) or mixed origin (AUC .81) from healthy control subjects. We validated this approach using a dataset of nasopharyngeal samples from 140 influenza patients and 38 controls, which yielded highly accurate (AUC .93) separation between cases and controls. CONCLUSIONS: Relative proportions of different bacteria and viruses in the nasopharynx can be leveraged to diagnose CAP and identify etiologic agent(s) in adult patients. Such data can inform the development of a microbiota-based diagnostic panel used to identify CAP patients and causative agents from nasopharyngeal samples, potentially improving diagnostic specificity, efficiency, and antimicrobial stewardship practices.
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Infecções Comunitárias Adquiridas , Microbiota , Infecções Respiratórias , Adulto , Bactérias/genética , Estudos de Casos e Controles , Infecções Comunitárias Adquiridas/diagnóstico , Humanos , Microbiota/genética , Nasofaringe/microbiologia , Estudos Prospectivos , Sistema Respiratório/microbiologiaRESUMO
It is not exactly clear yet which type of immune response prevails to accomplish viral clearance in coronavirus disease 2019 (COVID-19). Studying a patient with chronic lymphocytic leukemia and hypogammaglobulinemia who suffered from COVID-19 provided insight in the immunological responses after treatment with COVID-19 convalescent plasma (CCP). Treatment consisted of oxygen, repeated glucocorticosteroids and multiple dosages of CCP guided by antibody levels. Retrospectively performed humoral and cellular immunity analysis made clear that not every serological test for COVID-19 is appropriate for follow-up of sufficient neutralizing antibodies after CCP. In retrospect, we think that CCP merely bought time for this patient to develop an adequate cellular immune response which led to viral clearance and ultimately clinical recovery.
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INTRODUCTION AND OBJECTIVES: Covalently closed circular (ccc)DNA acts as a viral reservoir in the liver of patients with a chronic hepatitis B (CHB) infection and can only be quantified in liver biopsies. Hepatitis B core-related antigen (HBcrAg) levels in plasma/serum have been proposed to reflect intrahepatic cccDNA-levels and may therefore monitor treatment efficacy. This study aimed to validate the relationship between HBcrAg and other intrahepatic and circulating viral markers in CHB patients with high viral load, before and after combination treatment. MATERIALS AND METHODS: Plasma/serum levels of HBcrAg, HBsAg, HBV-DNA, and HBV pregenomic RNA (HBV-pgRNA), and intrahepatic cccDNA and HBV-DNA levels and fibrosis scores were measured in 89 CHB patients with HBV-DNA levels of >100,000 copies/mL (17,182 IU/mL). Measurements were done before and after a 48-week treatment with pegylated interferon alfa-2a and adefovir in a prospective study (ISRCTN77073364). RESULTS: Baseline HBcrAg-values correlated strongly with intrahepatic cccDNA (ρ 0.77, p < 0.001), intrahepatic HBV-DNA (ρ 0.73, p < 0.001) and plasma/serum HBV-DNA (ρ 0.80, p < 0.001), HBV-pgRNA (ρ 0.80, p < 0.001), and to lesser extend HBsAg (ρ 0.56, p < 0.001). Baseline HBcrAg-levels could not predict functional cure (FC) but HBcrAg-levels declined more strongly in patients who developed FC or HBeAg-loss. Furthermore, most correlations persisted at the end of treatment and follow-up. CONCLUSIONS: HBcrAg reflects cccDNA transcription activity more accurately than HBsAg and may replace HBV-DNA as a marker during future treatment regimens, especially when cccDNA transcription is targeted or nucleot(s)ide analogues are included in the treatment regime.
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DNA Viral/genética , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/tratamento farmacológico , Fígado/patologia , Adulto , Antivirais/uso terapêutico , Biomarcadores/metabolismo , Feminino , Seguimentos , Vírus da Hepatite B/genética , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Fígado/imunologia , Fígado/metabolismo , Masculino , Estudos Prospectivos , Carga ViralRESUMO
INTRODUCTION: Human polyomaviruses (HPyVs) cause disease in immunocompromised patients. BK polyomavirus (BKPyV) for instance persistently infects the kidneys. In kidney transplant recipients, (KTRs) BKPyV can cause allograft nephropathy. JCPyV, MCPyV, TSPyV and HPyV9 reside in the kidneys too, or have been detected in urine. In this study, we investigate exposure to JCPyV, MCPyV, TSPyV and HPyV9 after kidney transplantation by serological means. MATERIALS AND METHODS: Serum samples from 310 KTR collected before and 6 months after transplantation (n = 620), from 279 corresponding kidney donors collected before transplantation, and from blood donor controls collected one year apart (n = 174) were assessed for HPyV species-specific IgG responses using a multiplex immunoassay. KTR HPyV IgG kinetics were compared to those of healthy blood donors by linear mixed modeling, and related to those of their donors by linear regression. RESULTS: In the KTR, increased IgG levels during follow-up were observed for JCPyV (14.8%), MCPyV (7.1%), TSPyV (10.6%), and for HPyV9 (8.1%), while blood donor antibody levels remained stable. Seroconversion was observed for JCPyV (6.5%), MCPyV (2.3%), TSPyV (1.3%), and for HPyV9 (6.5%). The linear mixed model analysis showed that antibody increase was significant for JCPyV (p < 0.001) and HPyV9 (p < 0.001). Post-transplant JCPyV and HPyV9 antibody responses were associated with donor antibody levels against these HPyVs, respectively. CONCLUSIONS: KTR are exposed to JCPyV and HPyV9 after transplantation. Whether the allograft serves as the source, as indicated by the donor serostatus association, deserves further study.
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Vírus BK , Vírus JC , Transplante de Rim , Infecções por Polyomavirus , Polyomavirus , Infecções Tumorais por Vírus , Doadores de Sangue , Estudos de Coortes , Humanos , Transplante de Rim/efeitos adversos , PolyomaviridaeRESUMO
Pigs are suspected to be a major source of zoonotic hepatitis E virus (HEV) infection in industrialized countries, but the transmission route(s) from pigs to humans are ill-defined. Sequence comparison of HEV isolates from pigs with those from blood donors and patients in 372 samples collected in the Netherlands in 1998 and 1999 and between 2008 and 2015 showed that all sequences were genotype 3 except for six patients (with travel history). Subgenotype 3c (gt3c) was the most common subtype. While the proportion of gt3c increased significantly between 1998 and 2008, it remained constant between 2008 and 2015. Among the few circulating HEV subtypes, there was no difference observed between the human and the pig isolates. Hepatitis E viruses in humans are very likely to originate from pigs, but it is unclear why HEV gt3c has become the predominant subtype in the Netherlands.
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Doadores de Sangue , Genótipo , Vírus da Hepatite E/genética , Hepatite E/epidemiologia , Análise de Sequência de DNA , Suínos/virologia , Animais , Hepatite E/virologia , Vírus da Hepatite E/classificação , Humanos , Países Baixos/epidemiologia , Filogenia , RNA Viral/genética , Sus scrofa/virologia , Doenças dos Suínos/virologia , Zoonoses Virais/transmissãoRESUMO
AIMS: Parvovirus B19 (B19V) is often assumed to be a cause of dilated cardiomyopathy (DCM), based on the quantification of B19V DNA in endomyocardial biopsies (EMB). Whether the presence of B19V DNA correlates with active infection is still debated. Application of the enzyme endonuclease to blood samples results in degradation of B19V DNA remnants but leaves viral particles intact, which enables differentiation between active and past infection. In this study, the susceptibility to degradation by endonuclease of B19V DNA in blood was compared between DCM patients and a control group of recent B19V infections. METHODS AND RESULTS: Twenty blood samples from 20 adult patients with DCM, who previously tested positive for B19V DNA in EMB and/or blood, were tested with B19V PCR before and after application of endonuclease to the samples. Six blood samples tested positive for B19V DNA with a mean viral load of 2.3 × 104 IU/mL. In five samples, B19V DNA became undetectable after endonuclease (100% load reduction); in one sample DNA load showed a 23% log load reduction (viral load before endonuclease: 9.1 × 104 IU/mL; after: 6.5 × 103 IU/mL). Presence of cardiac inflammation did not differ between patients with B19V DNAemia (1/4) and patients without B19V DNAemia (6/14) (P value = 1.0). In all 18 control samples of proven recent B19V infections, DNA remained detectable after application of endonuclease, showing only a mean log load reduction of 2.3% (mean viral load before endonuclease: 8.1 × 1011 IU/mL; after: 8.0 × 1011 IU/mL). Load reduction differed significantly between the DCM group and the control group; indicating the presence of intact viral particles in the control group with proven active infection and the presence of DNA remnants in the DCM group (P value = 0.000). CONCLUSION: During recent B19V infection, viral DNA levels in blood were unaffected by endonuclease. In contrast, B19V DNA in blood in patients with DCM became undetectable or strongly reduced after application of endonuclease. Circulating viral DNA in this subset of patients with presumed parvovirus-associated DCM does not consist of intact viral particles. Viral replicative activity cannot be assumed from demonstrating B19V DNA in cardiac tissue or in blood in DCM patients.
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Cardiomiopatia Dilatada , Infecções por Parvoviridae , Parvovirus B19 Humano , Adulto , DNA Viral , Coração , Humanos , Infecções por Parvoviridae/diagnóstico , Parvovirus B19 Humano/genéticaRESUMO
Serodiagnosis of Lyme borreliosis (LB) comes with several drawbacks, among which is limited sensitivity in early disease. This study assesses the sensitivity and specificity of the novel BioPlex 2200 Lyme IgG and Lyme IgM assays. It also assesses potential improvements to the assays through receiver-operating characteristic (ROC) analysis. The BioPlex assays were performed on sera of 158 Dutch patients with physician-confirmed LB (both early localized and disseminated), 800 healthy blood donors from the Netherlands, and 90 cross-reactive controls. The BioPlex (Biopl) assays were compared with two commercial enzyme immunoassays (Euroimmun [Eur]/C6-ELISA) and one immunoblot (recomLine). The highest sensitivity in early LB was achieved with the BioPlex assays, which outperformed the Euroimmun and C6-ELISA (Biopl: 81/88, 92.1%; Eur: 64/88, 72.7%; C6: 72/88, 81.8%). Sensitivity of all assays was comparable in patients with disseminated LB. The BioPlex assays were outperformed in terms of specificity (all healthy blood donors, Biopl: 571/800, 71.4%; Eur: 711/800, 88.9%; C6: 727/800, 90.9%), but further analyses showed promising avenues following cutoff optimization. ROC analysis showed that 2/6 antigens of the combined BioPlex IgG and IgM assays had significantly higher areas under the curve (AUCs) than those of the other analyses. Potential modified versions of the assays based on these antigens largely outperformed the Euroimmun and C6-ELISA in EM patients (Biopl: 81/80, 92.1%) while maintaining a comparable or even higher specificity (Biopl: 714/800, 89.3%). The BioPlex 2200 Lyme IgG and Lyme IgM assays are promising tools for the serodiagnosis of early LB, with the potential to be used as a standalone test. Further research is necessary to validate the findings of this discovery cohort.
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Anticorpos Antibacterianos , Doença de Lyme , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G , Imunoglobulina M , Doença de Lyme/diagnóstico , Países Baixos , Polímeros , Sensibilidade e Especificidade , Testes SorológicosRESUMO
BACKGROUND: In the Netherlands, blood donor screening for hepatitis B virus (HBV) consists of HBsAg screening since the 1970s, HBV DNA minipool testing (MP-NAT) since 2008, and anti-HBc screening since 2011. Anti-HBc reactivity causes deferral only if anti-HBs titers are <200 IU/mL, or when anti-HBc was acquired during follow-up. STUDY DESIGN AND METHODS: Over 5.5 million donations from 582,459 Dutch donors were screened for HBV DNA, HBsAg, anti-HBc, and, if anti-HBc positive, also for anti-HBs. The added value, expressed as the yield of (potentially) infectious and/or recent HBV infections versus unnecessary donor loss, was evaluated for each of the three HBV screening tests. RESULTS: HBV donor screening identified 89 HBV-infected donors with at least two reactive HBV markers (MP-NAT, HBsAg and/or anti-HBc). Single HBV-marker yield was: 5 MP-NAT-only, 0 HBsAg-only, and 20 anti-HBc-only donors. In addition, anti-HBc screening yielded 1,067 potentially infectious donors at risk for occult HBV infection (OBI). In total, 4,126 (0.71%) donors were anti-HBc-reactive at first-time screening, and 1,098 (0.19%) seroconverted during follow-up. Anti-HBc-related donor loss was limited to 2,627 (0.45%) donors using anti-HBs titers and two-strike programs. Donor loss due to MP-NAT and HBsAg screening was extremely low: 0 and 128 donors, respectively. CONCLUSION: HBV donor screening could be limited to MP-NAT and anti-HBc screening. MP-NAT and anti-HBc improved blood safety by intercepting infectious donations from donors with recent infection or OBI, while HBsAg did not. Unnecessary donor loss related to anti-HBc screening is substantial but does not endanger the continuity of the blood supply.
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Doadores de Sangue , Segurança do Sangue , Seleção do Doador , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B/prevenção & controle , Técnicas de Amplificação de Ácido Nucleico , Viremia/sangue , Adulto , DNA Viral/sangue , Hepatite B/sangue , Hepatite B/diagnóstico , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Países Baixos , Procedimentos Desnecessários , Viremia/diagnóstico , Viremia/virologiaRESUMO
OBJECTIVE: Intravenous immunoglobulin (IVIg) consists of pooled donor immunoglobulins (IgG), possibly including anti-Borrelia burgdorferi (Bbsl) antibodies. Apparent IVIg-related Bbsl seroconversion could lead to incorrect diagnosis of Lyme borreliosis. This cohort study was designed to determine how often IVIg treatment leads to apparent Bbsl seroconversion and whether antibodies disappear post-treatment. METHODS: Sera from chronic inflammatory demyelinating polyneuropathy (CIDP) and myositis patients were analyzed, drawn pre-treatment and 6-12 weeks after the start of IVIg. In patients with apparent seroconversion, follow-up samples after treatment withdrawal were analyzed, if available. Patients treated with corticosteroids were included as controls. A two-tier protocol was used for serological testing consisting of the C6 Lyme ELISA (Oxford Immunotec) and confirmation by immunoglobulin M (IgM) and immunoglobulin G (IgG) immunoblot (Mikrogen® ). RESULTS: We included 61 patients: 51 patients were treated with IVIg and 10 with dexamethasone. Of the patients treated with IVIg, 42 had CIDP (82%) and were treated with Nanogam® (Sanquin Plasma Products). Nine patients had myositis (18%) and were treated with Privigen® (CSL Behring). Anti-Bbsl IgG seroprevalence pre-treatment was 3% (2/61). Apparent seroconversion during IVIg treatment occurred in 39% (20/51) of patients, all treated with Nanogam. Post-treatment seroreversion occurred in 92% (12/13) of patients with available follow-up samples; in 78% (7/9) seroreversion was observed within 3 months. CONCLUSIONS: Transient presence of anti-Bbsl IgG antibodies after IVIg is regularly observed. This effect appears to be dependent on the IVIg brand, probably reflecting variation in Bbsl exposure of plasma donors. Lyme borreliosis serological testing during, and weeks to months after, IVIg is therefore of limited utility.
Assuntos
Grupo Borrelia Burgdorferi , Borrelia burgdorferi , Anticorpos Antibacterianos , Estudos de Coortes , Humanos , Imunoglobulina M , Imunoglobulinas Intravenosas , Soroconversão , Estudos SoroepidemiológicosRESUMO
Awareness of infection with SARS-CoV-2 is crucial for the effectiveness of COVID-19 control measures. Here, we investigate awareness of infection and symptoms in relation to antibodies against SARS-CoV-2 in healthy plasma donors. We asked individuals donating plasma across the Netherlands between May 11th and 18th 2020 to report COVID-19-related symptoms, and we tested for antibodies indicative of a past infection with SARS-CoV-2. Among 3,676 with antibodies, and from questionnaire data, 239 (6.5%) are positive for SARS-CoV-2 antibodies. Of those, 48% suspect no COVID-19, despite the majority reporting symptoms; 11% of seropositive individuals report no symptoms and 27% very mild symptoms at any time during the first peak of the epidemic. Anosmia/ageusia and fever are most strongly associated with seropositivity. Almost half of seropositive individuals do not suspect SARS-CoV-2 infection. Improved recognition of COVID-19 symptoms, in particular, anosmia/ageusia and fever, is needed to reduce widespread SARS-CoV-2 transmission.
Assuntos
Doadores de Sangue/estatística & dados numéricos , COVID-19/patologia , Adulto , Anticorpos Antivirais/sangue , COVID-19/virologia , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
Immunoglobulin G (IgG) antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc tail, which is essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anticancer therapeutic antibodies for their increased activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG (approximately 6% of total IgG in humans) are specifically formed against enveloped viruses but generally not against other antigens. This mediates stronger FcγRIIIa responses but also amplifies brewing cytokine storms and immune-mediated pathologies. Critically ill COVID-19 patients, but not those with mild symptoms, had high concentrations of afucosylated IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), amplifying proinflammatory cytokine release and acute phase responses. Thus, antibody glycosylation plays a critical role in immune responses to enveloped viruses, including COVID-19.