•Knowledge of the extent of COVID-19 epidemic and the level of herd immunity is urgently needed•We develop a Multiplex bead-based IgG detection tool for pathogenic human coronaviruses.•The novel ...assay is highly sensitive and specific.•Our novel assay is more sensitive than a commercial EIA.•We show that an immunoassay using a single antigen can lead to false positive results.
Knowledge of the COVID-19 epidemic extent and the level of herd immunity is urgently needed to help manage this pandemic.
We used a panel of 167 samples (77 pre-epidemic and 90 COVID-19 seroconverters) and SARS-CoV1, SARS-CoV2 and MERS-CoV Spike and/or Nucleopcapsid (NC) proteins to develop a high throughput multiplex screening assay to detect IgG antibodies in human plasma. Assay performances were determined by ROC curves analysis. A subset of the COVID-19+ samples (n = 36) were also tested by a commercial NC-based ELISA test and the results compared with those of the novel assay.
On samples collected ≥14 days after symptoms onset, the accuracy of the assay is 100 % (95 % CI: 100−100) for the Spike antigen and 99.9 % (95 % CI:99.7−100) for NC. By logistic regression, we estimated that 50 % of the patients have seroconverted at 5.7 ± 1.6; 5.7 ± 1.8 and 7.9 ± 1.0 days after symptoms onset against Spike, NC or both antigens, respectively and all have seroconverted two weeks after symptoms onset. IgG titration in a subset of samples showed that early phase samples present lower IgG titers than those from later phase. IgG to SARS-CoV2 NC cross-reacted at 100 % with SARS-CoV1 NC. Twenty-nine of the 36 (80.5 %) samples tested were positive by the commercial ELISA while 31/36 (86.1 %) were positive by the novel assay.
Our assay is highly sensitive and specific for the detection of IgG antibodies to SARS-CoV2 proteins, suitable for high throughput epidemiological surveys. The novel assay is more sensitive than a commercial ELISA.
We read with deep interest the report by Tepasse et al .1 concerning two cases of persisting viraemia in coronavirus disease 2019 (COVID‐19) with fatal outcome. Whilst severe acute respiratory ...syndrome coronavirus‐2 (SARS‐CoV‐2) infection in the early stages of infection has been well described, less is known about the development of antibodies to SARS‐CoV‐2, clearance of RNA shedding and clinical outcome of COVID‐19. In addition, the impact of immunosuppressive treatments on disease severity is not yet established, but several reports suggest a more prolonged disease in patients under rituximab, a B‐cell depleting drug.2-4 Here we report a case of persisting COVID‐19, following combined treatment with rituximab and bendamustine for lymphoma, which immediately recovered after convalescent plasma transfusion. We think that this case raises promising perspectives for immunocompromised patients with persisting COVID‐19.
Introduction: Human adenovirus (HAdV)-derived vectors have been used in numerous pre-clinical and clinical trials during the last 40 years. Current research in HAdV-based vaccines focuses on ...improving transgene immunogenicity and safety. Because pre-existing humoral immunity against HAdV types correlate with reduced vaccine efficacy and safety, many groups are exploring the development of HAdV types vectors with lower seroprevalence. However, global seroepidemiological data are incomplete. Areas covered: The goal of this review is to centralize 65 years of research on (primarily) HAdV epidemiology. After briefly addressing adenovirus biology, we chronical HAdV seroprevalence studies and highlight major milestones. Finally, we analyze data from about 50 studies with respect to HAdVs types that are currently used in the clinic, or are in the developmental pipeline. Expert opinion: Vaccination is among the most efficient tools to prevent infectious disease. HAdV-based vaccines have undeniable potential, but optimization is needed and antivector immunity remains a challenge if the same vectors are to be administrated to different populations. Here, we identify gaps in our knowledge and the need for updated worldwide epidemiological data.
Abstract
We assessed the expression of CD169, a type I interferon-inducible receptor, on monocytes (monocyte CD169 mCD169) in 53 adult patients admitted to the hospital during the coronavirus disease ...2019 (COVID-19) outbreak for a suspicion of severe acute respiratory syndrome coronavirus 2 infection. Monocyte CD169 was strongly overexpressed in 30 of 32 (93.7%) confirmed COVID-19 cases, compared with 3 of 21 (14.3%) patients in whom the diagnosis of COVID-19 was finally ruled out. Monocyte CD169 was associated with the plasma interferon-alpha level and thrombocytopenia. Monocyte CD169 testing may be helpful for the rapid triage of suspected COVID-19 patients during an outbreak.
Blood collected and dried on a paper card - dried blood spot (DBS) - knows a growing interest as a sampling method that can be performed outside care facilities by capillary puncture, and transported ...in a simple and safe manner by mail. The benefits of this method for blood collection and transport has recently led the World Health Organization to recommend DBS for HIV and hepatitis B and C diagnosis. The clinical utility of DBS sampling to improve diagnostics and care of HIV and hepatitis B and C infection in hard to reach populations, key populations and people living in low-income settings was highlighted. Literature about usefulness of DBS specimens in the therapeutic cascade of care - screening, confirmation, quantification of nucleic acids, and resistance genotyping -, was reviewed. DBS samples are suitable for testing antibodies, antigens, or nucleic acids using most laboratory methods. Good sensibility and specificity have been reported for infant HIV diagnosis and diagnosis of hepatitis B and C. The performance of HIV RNA testing on DBS to identified virological failure on antiretroviral therapy is also high but not optimal because of the dilution of dried blood in the elution buffer, reducing the analytical sensitivity, and because of the contamination by intracellular HIV DNA. Standardized protocols are needed for inter-laboratory comparisons, and manufacturers should pursue regulatory approval for
diagnostics using DBS specimens. Despite these limitations, DBS sampling is a clinically relevant tool to improve access to infectious disease diagnosis worldwide.
Initiating breastfeeding within the first hour of life confers an important benefit in terms of child mortality and severe morbidity. Intestinal permeability to ingested macromolecules and ...immunoglobulins is limited to the first days of human life. These exchanges cease in the very early post‐partum period but may increase beyond the neonatal period in response to local inflammation or introduction of a weaning food. From animal‐ and limited human‐based observations, compelling evidence points out to breastmilk cells also trafficking from mother to infant mucosal tissues and participating to the maternal microchimerism. The precise nature of breastmilk cells that are involved is presently not known but likely includes progenitor/stem cells—representing up to 6% of breastmilk cells—with possible contribution of mature immune cells. Stem cell microchimerism may induce tolerance to non‐inherited maternal antigens (NIMAs), breastfeeding generating regulatory T cells (Treg) that suppress antimaternal immunity. Therefore, in complement to pregnancy‐induced microchimerism, breastfeeding‐induced microchimerism may be pivotal in infant immune development, intestinal tissue repair/growth and protection against infectious diseases. As a continuum of the gestational period, the neonatal gut may be considered as a temporary, but important developmental extension of the role played by the placenta during intrauterine life; breastmilk playing the role of maternal blood by delivering maternal soluble factors (macromolecules, Ig, cytokines) and immunologically active milk cells. A better understanding of breastfeeding‐induced maternal microchimerism would provide further evidence in support of public health messages that reinforce the importance of early initiation of breastfeeding.
The detection and quantification of hepatitis B (HBV) DNA and hepatitis C (HCV) RNA in whole blood collected on dried blood spots (DBS) may facilitate access to diagnosis and treatment of HBV and HCV ...infection in resource-poor settings. We evaluated the diagnostic performance of DBS compared to venous blood samples for detection and quantification of HBV-DNA and HCV-RNA in two systematic reviews and meta-analyses on the diagnostic accuracy of HBV DNA and HCV RNA from DBS compared to venous blood samples.
We searched MEDLINE, Embase, Global Health, Web of Science, LILAC and Cochrane library for studies that assessed diagnostic accuracy with DBS. Heterogeneity was assessed and where appropriate pooled estimates of sensitivity and specificity were generated using bivariate analyses with maximum likelihood estimates and 95% confidence intervals. We also conducted a narrative review on the impact of varying storage conditions or different cut-offs for detection from studies that undertook this in a subset of samples. The QUADAS-2 tool was used to assess risk of bias.
In the quantitative synthesis for diagnostic accuracy of HBV-DNA using DBS, 521 citations were identified, and 12 studies met the inclusion criteria. Overall quality of studies was rated as low. The pooled estimate of sensitivity and specificity for HBV-DNA was 95% (95% CI: 83-99) and 99% (95% CI: 53-100), respectively. In the two studies that reported on cut-offs and limit of detection (LoD) - one reported a sensitivity of 98% for a cut-off of ≥2000 IU/ml and another reported a LoD of 914 IU/ml using a commercial assay. Varying storage conditions for individual samples did not result in a significant variation of results. In the synthesis for diagnostic accuracy of HCV-RNA using DBS, 15 studies met the inclusion criteria, and this included six additional studies to a previously published review. The pooled sensitivity and specificity was 98% (95% CI:95-99) and 98% (95% CI:95-99.0), respectively. Varying storage conditions resulted in a decrease in accuracy for quantification but not for reported positivity.
These findings show a high level of diagnostic performance for the use of DBS for HBV-DNA and HCV-RNA detection. However, this was based on a limited number and quality of studies. There is a need for development of standardized protocols by manufacturers on the use of DBS with their assays, as well as for larger studies on use of DBS conducted in different settings and with varying storage conditions.
Total HIV DNA is a standard marker to monitor the HIV reservoir in people living with HIV. We investigated HIV DNA quantification accuracy by a real-time PCR kit (qPCR) and digital PCR (dPCR) method ...within the same set of primers and probes. Among 48 aviremic patients followed for up to 7 years with qPCR, the mean coefficient of variation of total HIV DNA between two successive measurements was 77% (± 0.42log
HIVDNA copies/10
PBMC). The total HIV DNA quantified by the two PCR methods has a high correlation (0.99 and 0.83, for 8E5 and PLHIV samples, respectively), but we observed better repeatability and reproducibility of the dPCR compared to the qPCR (CV of 11.9% vs. 24.7% for qPCR, p-value = 0.024). Furthermore, we highlighted a decay of the number of HIV copies in the 8E5 cell line qPCR standard over time (from 0.73 to 0.43 copies per cell), contributing to variations of HIV DNA results in patients whose HIV reservoir should be theoretically stabilized. Our study highlighted that absolute quantification of total HIV DNA by dPCR allows more accurate monitoring of the HIV reservoir than qPCR in patients under prolonged antiretroviral therapy.
Dried blood spots (DBS) are a convenient tool to enable diagnostic testing for viral diseases due to transport, handling and logistical advantages over conventional venous blood sampling. A better ...understanding of the performance of serological testing for hepatitis C (HCV) and hepatitis B virus (HBV) from DBS is important to enable more widespread use of this sampling approach in resource limited settings, and to inform the 2017 World Health Organization (WHO) guidance on testing for HBV/HCV.
We conducted two systematic reviews and meta-analyses on the diagnostic accuracy of HCV antibody (HCV-Ab) and HBV surface antigen (HBsAg) from DBS samples compared to venous blood samples. MEDLINE, EMBASE, Global Health and Cochrane library were searched for studies that assessed diagnostic accuracy with DBS and agreement between DBS and venous sampling. Heterogeneity of results was assessed and where possible a pooled analysis of sensitivity and specificity was performed using a bivariate analysis with maximum likelihood estimate and 95% confidence intervals (95%CI). We conducted a narrative review on the impact of varying storage conditions or limits of detection in subsets of samples. The QUADAS-2 tool was used to assess risk of bias.
For the diagnostic accuracy of HBsAg from DBS compared to venous blood, 19 studies were included in a quantitative meta-analysis, and 23 in a narrative review. Pooled sensitivity and specificity were 98% (95%CI:95%-99%) and 100% (95%CI:99-100%), respectively. For the diagnostic accuracy of HCV-Ab from DBS, 19 studies were included in a pooled quantitative meta-analysis, and 23 studies were included in a narrative review. Pooled estimates of sensitivity and specificity were 98% (CI95%:95-99) and 99% (CI95%:98-100), respectively. Overall quality of studies and heterogeneity were rated as moderate in both systematic reviews.
HCV-Ab and HBsAg testing using DBS compared to venous blood sampling was associated with excellent diagnostic accuracy. However, generalizability is limited as no uniform protocol was applied and most studies did not use fresh samples. Future studies on diagnostic accuracy should include an assessment of impact of environmental conditions common in low resource field settings. Manufacturers also need to formally validate their assays for DBS for use with their commercial assays.
Environmental factors such as chemicals, stress and pathogens are now widely believed to play important roles in the onset of some brain diseases, as they are associated with neuronal impairment and ...acute or chronic inflammation. Alzheimer's disease (AD) is characterized by progressive synaptic dysfunction and neurodegeneration that ultimately lead to dementia. Neuroinflammation also plays a prominent role in AD and possible links to viruses have been proposed. In particular, the human immunodeficiency virus (HIV) can pass the blood-brain barrier and cause neuronal dysfunction leading to cognitive dysfunctions called HIV-associated neurocognitive disorders (HAND). Similarities between HAND and HIV exist as numerous factors involved in AD such as members of the amyloid and Tau pathways, as well as stress-related pathways or blood brain barrier (BBB) regulators, seem to be modulated by HIV brain infection, leading to the accumulation of amyloid plaques or neurofibrillary tangles (NFT) in some patients. Here, we summarize findings regarding how HIV and some of its proteins such as Tat and gp120 modulate signaling and cellular pathways also impaired in AD, suggesting similarities and convergences of these two pathologies.
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