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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. [ABSTRACT FROM AUTHOR]

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 (P = . 016, R 2 =.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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Study Design and Methods Results Discussion 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).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.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.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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

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., (© 2021 AABB.)