Héma-Québec

Mitochondrial DNA (mtDNA) is a highly potent inflammatory trigger and is reportedly found outside the cells in blood in various pathologies. Platelets are abundant in blood where they promote hemostasis. Although lacking a nucleus, platelets contain functional mitochondria. On activation, platelets produce extracellular vesicles known as microparticles. We hypothesized that activated platelets could also release their mitochondria. We show that activated platelets release respiratory-competent mitochondria, both within membrane-encapsulated microparticles and as free organelles. Extracellular mitochondria are found in platelet concentrates used for transfusion and are present at higher levels in those that induced acute reactions (febrile nonhemolytic reactions, skin manifestations, and cardiovascular events) in transfused patients. We establish that the mitochondrion is an endogenous substrate of secreted phospholipase A2 IIA (sPLA2-IIA), a phospholipase otherwise specific for bacteria, likely reflecting the ancestral proteobacteria origin of mitochondria. The hydrolysis of the mitochondrial membrane by sPLA2-IIA yields inflammatory mediators (ie, lysophospholipids, fatty acids, and mtDNA) that promote leukocyte activation. Two-photon microscopy in live transfused animals revealed that extracellular mitochondria interact with neutrophils in vivo, triggering neutrophil adhesion to the endothelial wall. Our findings identify extracellular mitochondria, produced by platelets, at the midpoint of a potent mechanism leading to inflammatory responses.

In humans, up to 40% of peripheral B cells express CD27 and have hypermutated variable regions in their Ig genes. The CD27+ B cells are considered to be derived from germinal center following specific antigenic stimulation. Actually, somatic hypermutation in Ig genes and CD27 expression are hallmarks of memory B cells. However, the blood IgM+ IgD+ CD27+ B cells were recently associated to splenic marginal zone B cells and proposed to be a subset distinct from germinal center-derived memory B cells showing premutated Igs. The results presented herein further weaken this bona fide association because B cells expressing surface IgG, but not CD27, were found in human blood. Representing 1-4% of all peripheral B cells and approximately 25% of the IgG+ blood B cells, this population expressed mutated IgG genes showing antigenic selection characteristics but with lower mutation frequencies than that of CD27+ IgG+ B cells. However, their morphology and phenotype were similar to that of CD27+ IgG+ cells. Interestingly, the proportion of IgG2 over IgG3 transcripts was opposite in CD27- IgG+ and CD27+ IgG+ cells, suggesting distinct functions or origins. Overall, these findings extend the memory B cell reservoir beyond the CD27+ compartment and could provide further insights into B cell disorders of unknown etiology.

The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset ( NCT04348656 ). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm-relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94-1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02-1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57-0.95 and OR = 0.66, 95% CI 0.50-0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

OBJECTIVE: The present research assessed the simultaneous effects of four attitude variables (cognitive attitudes, affective attitudes, anticipated negative affective reactions, and anticipated positive affective reactions) in the context of the theory of planned behavior (TPB) on blood-donation intentions and behavior. METHODS: Experienced blood donors (N = 1108) completed questionnaires measuring attitude variables plus components of the TPB and a measure of attitudinal ambivalence in relation to giving blood again in the next six months. Records were used to assess whether participants subsequently donated blood again in the six months after completing the questionnaire. The main outcome measures were objectively assessed blood donation and intentions to make an additional donation of blood. RESULTS: Confirmatory factor analysis supported a distinction between cognitive attitudes about giving blood, affective attitudes about giving blood, anticipated negative affective reactions about not giving blood, and anticipated positive affective reactions about giving blood. Multiple regression analyses indicated that perceived behavioral control, anticipated negative affective reactions, cognitive attitude, anticipated positive affective reactions and subjective norms were significant simultaneous predictors of intentions to donate blood. Logistic regression analyses indicated that intentions, perceived behavioral control, and anticipated positive affective reactions were significant, simultaneous predictors of blood donation. Attitudinal ambivalence significantly moderated the effects of cognitive attitudes on intentions, and the effects of anticipated negative affective reactions on both intentions and donation behavior. CONCLUSION: The findings point to the value of considering different types of attitudes, and anticipated negative affective reaction in particular, for predicting health behaviors.

SARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoproteins of SARS-CoV-2 mediate viral entry and are the main targets for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic, and public health interventions. Here, we perform a cross-sectional study on 106 SARS-CoV-2-infected individuals to evaluate humoral responses against SARS-CoV-2 Spike. Most infected individuals elicit anti-Spike antibodies within 2 weeks of the onset of symptoms. The levels of receptor binding domain (RBD)-specific immunoglobulin G (IgG) persist over time, and the levels of anti-RBD IgM decrease after symptom resolution. Although most individuals develop neutralizing antibodies within 2 weeks of infection, the level of neutralizing activity is significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.

Defects in insulin production and signaling are suspected to share a key role in diabetes and Alzheimer disease (AD), two age-related pathologies. In this study, we investigated the interrelation between AD and diabetes using a high-fat diet (HFD) in a mouse model of genetically induced AD-like neuropathology (3xTg-AD). We first observed that cerebral expression of human AD transgenes led to peripheral glucose intolerance, associated with pancreatic human Aβ accumulation. High-fat diet enhanced glucose intolerance, brain soluble Aβ, and memory impairment in 3xTg-AD mice. Strikingly, a single insulin injection reversed the deleterious effects of HFD on memory and soluble Aβ levels, partly through changes in Aβ production and/or clearance. Our results are consistent with the development of a vicious cycle between AD and diabetes, potentiating both peripheral metabolic disorders and AD neuropathology. The capacity of insulin to rapidly break the deleterious effects of this cycle on soluble Aβ concentrations and memory has important therapeutic implications.

While waiting for an efficient vaccine to protect against SARS-CoV-2 infection, alternative approaches to treat or prevent acute COVID-19 are urgently needed. Transfusion of convalescent plasma to treat COVID-19 patients is currently being explored; neutralizing activity in convalescent plasma is thought to play a central role in the efficacy of this treatment. Here, we observed that plasma neutralization activity decreased a few weeks after the onset of the symptoms. If neutralizing activity is required for the efficacy of convalescent plasma transfer, our results suggest that convalescent plasma should be recovered rapidly after the donor recovers from active infection.

IMPORTANCE: The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive. OBJECTIVE: To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONS: The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURES: The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS: Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11 secondary outcomes. Serious adverse events were reported in 3.0% (32/1075) of participants in the convalescent plasma group and in 1.3% (12/905) of participants in the no convalescent plasma group. CONCLUSIONS AND RELEVANCE: Among critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support-free days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.

Objective: To review and qualitatively synthesize the evidence related to the economic burden of COVID-19, including healthcare resource utilization and costs. Methods: A systematic review of studies that assessed the economic burden [eg, direct costs, productivity, macroeconomic impact due to non-pharmaceutical interventions (NPIs) and equity] of COVID-19 was conducted by searches in EMBASE, MEDLINE, MEDLINE-IN-PROCESS, and The Cochrane Library, as well as manual searches of unpublished research for the period between January 2020 to February 2021. Single reviewer data extraction was confirmed independently by a second reviewer. Results: The screening process resulted in a total of 27 studies: 25 individual publications, and 2 systematic literature reviews, of narrower scopes, that fulfilled the inclusion criteria. The patients diagnosed with more severe COVID-19 were associated with higher costs. The main drivers for higher costs were consistent across countries and included ICU admission, in-hospital resource use such as mechanical ventilation, which lead to increase costs of $2082.65 ± 345.04 to $2990.76 ± 545.98. The most frequently reported indirect costs were due to productivity losses. On average, older COVID-19 patients incurred higher costs when compared to younger age groups. An estimation of a 20% COVID-19 infection rate based on a Monte Carlo simulation in the United States led to a total direct medical cost of $163.4 billion over the course of the pandemic. Conclusion: The COVID-19 pandemic has generated a considerable economic burden on patients and the general population. Preventative measures such as NPIs only have partial success in lowering the economic costs of the pandemic. Implementing additional preventative measures such as large-scale vaccination is vital in reducing direct and indirect medical costs, decreased productivity, and GDP losses.

With the recent approval of highly effective coronavirus disease 2019 (COVID-19) vaccines, functional and lasting immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently under investigation as antibody levels in plasma were shown to decline during convalescence. Since the absence of antibodies does not equate to absence of immune memory, we evaluate the presence of SARS-CoV-2-specific memory B cells in convalescent individuals. Here, we report a longitudinal assessment of humoral immune responses on 32 donors up to 8 months post-symptom onset. Our observations indicate that anti-Spike and anti-receptor binding domain (RBD) immunoglobulin M (IgM) in plasma decay rapidly, whereas the reduction of IgG is less prominent. Neutralizing activity also declines rapidly when compared to Fc-effector functions. Concomitantly, the frequencies of RBD-specific IgM+ B cells wane significantly when compared to RBD-specific IgG+ B cells, which remain stable. Our results add to the current understanding of immune memory following SARS-CoV-2 infection, which is critical for secondary infection prevention and vaccine efficacy.

Intravenous immunoglobulin (IVIg) is currently evaluated in clinical trials for the treatment of various disorders of the central nervous system. To assess its capacity to reach central therapeutic targets, the brain bioavailability of IVIg must be determined. We thus quantified the passage of IVIg through the blood-brain barrier (BBB) of C57Bl/6 mice using complementary quantitative and qualitative methodologies. As determined by enzyme-linked immunosorbent assay, a small proportion of systemically injected IVIg was detected in the brain of mice (0.009±0.001% of injected dose in the cortex) whereas immunostaining revealed localization mainly within microvessels and less frequently in neurons. Pharmacokinetic analyses evidenced a low elimination rate constant (0.0053 per hour) in the cortex, consistent with accumulation within cerebral tissue. In situ cerebral perfusion experiments revealed that a fraction of IVIg crossed the BBB without causing leakage. A dose-dependent decrease of brain uptake was consistent with a saturable blood-to-brain transport mechanism. Finally, brain uptake of IVIg after a subchronic treatment was similar in the 3xTg-AD mouse model of Alzheimer disease compared with nontransgenic controls. In summary, our results provide evidence of BBB passage and bioavailability of IVIg into the brain in the absence of BBB leakage and in sufficient concentration to interact with the therapeutic targets.

BACKGROUND: The maintenance of a safe level of blood supply is provided by a small number of volunteers, and their retention is difficult. The aim of this study was to identify factors predicting repeated blood donation among experienced and new donors. STUDY DESIGN AND METHODS: A random sample of 2,231 donors (2,070 experienced and 161 new) completed a questionnaire assessing psychosocial factors as defined by the most prominent social cognitive theories. Six months later, an objective measure of frequency of registrations to give blood was obtained from the database of the local official agency for blood donation. RESULTS: Logistic regression analysis indicated that for experienced donors, the predictors were intention, perceived control, anticipated regret, moral norm, age, and frequency of blood donation in the past. For new donors, intention and age were the only determinants of behavior. Important differences in the determinants of intention were also noted between experienced and new donors. CONCLUSION: In summary, the results of this study support the idea that distinct promotion strategies should be adopted to increase repeated blood donation among experienced versus new donors.

BACKGROUND: Within an ongoing HIV/STD prevention project aimed at female sex workers (FSW) in Cotonou, Benin, we evaluated time trends in HIV and STD prevalences from 1993 to 1999. DESIGN: Three serial cross-sectional surveys were conducted in 1993 (n = 374), 1995-1996 (n = 365), and 1998-1999 (n = 591). A questionnaire was administered to the FSW and they were screened for HIV, syphilis, Neisseria gonorrhoeae, and Chlamydia trachomatis. RESULTS: The mean percentage of condom use with clients in the week preceding the interview increased from 62.2% in 1993 to 80.7% in 1998-1999 (P = 0.0001). The prevalence of all infections decreased significantly (all P < 0.02; chi-square for trend) over time: HIV from 53.3% in 1993 to 40.6% in 1998-1999; syphilis from 8.9 to 1.5%; gonorrhoea from 43.2 to 20.5%; and chlamydia from 9.4 to 5.1%. However, the mean age of FSW decreased from 31.0 to 28.4 years between 1993 and 1998-1999. Moreover, the country of origin of these women changed dramatically over time: the proportion of Ghanaian women decreased from 66.3% in 1993 to 21.6% in 1998-1999 when the predominant group became Nigerian (38.0%). When controlling for age and country of origin, HIV prevalence was stable over time (P = 0.71), whereas the downward trend remained significant for syphilis and gonorrhoea (both P < 0.001), and was present but not significant for chlamydia (P = 0.13). CONCLUSION: These data suggest that the time trends in HIV and STD prevalences are partly due to the changing sex work milieu, but that the intervention also had an impact. Prevention programmes aimed at FSW should be highly prioritized.

BACKGROUND AND OBJECTIVES: The aim of this study was to identify factors explaining the intention to donate blood. MATERIALS AND METHODS: A random sample of 4000 respondents drawn from the general population received a questionnaire by mail. This questionnaire assessed variables as defined by the most prominent social cognitive theories. RESULTS: Overall, the respondents expressed a neutral mean level of intention to give blood in the next 6 months (2.84 on a five-point scale); 56.2% had never given blood in the past. The variables explaining 74% of the variance of intention were: perceived behavioural control (beta = 0.39; P < 0.001); factors facilitating taking action (beta = 0.25; P < 0.001); anticipated regret (beta = 0.16; P < 0.001); moral norm (beta = 0.11; P < 0.001); attitude (beta = 0.08; P < 0.01); level of education (beta = -0.03; P < 0.05); and past experience in giving blood (beta = 0.09; P < 0.001). Nonetheless, the predictive power of perceived behavioural control and moral norm was higher among the ever donors (both at P < 0.01) compared to the never donors, whereas the reverse was observed for attitude (P < 0.05). CONCLUSIONS: People's intentions are mainly determined by perceived barriers and obstacles regarding blood donations. This suggests that promotional strategies should focus on the elimination of barriers to action as well as the development of a higher perception of control. Also, messages should be adapted to the targeted population, based on their previous blood donation behaviour (i.e. never donors vs. ever donors).

// Silvia Selleri 1,2,* , Panojot Bifsha 1,2,* , Sara Civini 3 , Consiglia Pacelli 4 , Mame Massar Dieng 1,5 , William Lemieux 1,2 , Ping Jin 3 , Ren&eacute;e Bazin 6 , Natacha Patey 7 , Francesco M. Marincola 3,8 , Florina Moldovan 1,9 , Charlotte Zaouter 1 , Louis-Eric Trudeau 4 , Basma Benabdhalla 1 , Isabelle Louis 1,10 , Christian Beaus&eacute;jour 1,4 , David Stroncek 3 , Fran&ccedil;oise Le Deist 1,2,10 and Elie Haddad 1,2,10 1 CHU Sainte-Justine Research Center, Montreal, QC, Canada 2 Department of Microbiology, Infectiology and Immunology, University of Montreal, Montreal, QC, Canada 3 Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, MD, USA 4 Department of Pharmacology, University of Montreal, Montreal, QC, Canada 5 Department of Biology, New York University, Abu Dhabi, United Arab Emirates 6 Department of Research and Development, H&eacute;ma-Qu&eacute;bec, Qu&eacute;bec, QC, Canada 7 Department of Pathology, University of Montreal, Montreal, QC, Canada 8 Sidra Medical and Research Center, Doha, Qatar 9 Faculty of Dentistry, University of Montreal, Montreal, QC, Canada 10 Department of Pediatrics, University of Montreal, Montreal, QC, Canada * These authors have contributed equally to this work Correspondence to: Elie Haddad, email: // Keywords : mesenchymal stromal cells, dendritic cell differentiation, M2-macrophages, lactate, metabolism, Immunology and Microbiology Section, Immune response, Immunity Received : August 10, 2015 Accepted : March 26, 2016 Published : April 06, 2016 Abstract Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize na&iuml;ve allogeneic CD4 + T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to-DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation.

The Additional sex combs like 1 (Asxl1) gene is 1 of 3 mammalian homologs of the Additional sex combs (Asx) gene of Drosophila. Asx is unusual because it is required to maintain both activation and silencing of Hox genes in flies and mice. Asxl proteins are characterized by an amino terminal homology domain, by interaction domains for nuclear receptors, and by a C-terminal plant homeodomain protein-protein interaction domain. A recent study of patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) revealed a high incidence of truncation mutations that would delete the PHD domain of ASXL1. Here, we show that Asxl1 is expressed in all hematopoietic cell fractions analyzed. Asxl1 knockout mice exhibit defects in frequency of differentiation of lymphoid and myeloid progenitors, but not in multipotent progenitors. We do not detect effects on hematopoietic stem cells, or in peripheral blood. Notably, we do not detect severe myelodysplastic phenotypes or leukemia in this loss-of-function model. We conclude that Asxl1 is needed for normal hematopoiesis. The mild phenotypes observed may be because other Asxl genes have redundant function with Asxl1, or alternatively, MDS or oncogenic phenotypes may result from gain-of-function Asxl mutations caused by genomic amplification, gene fusion, or truncation of Asxl1.

OBJECTIVE: Evidence indicates that receiving a questionnaire about a behavior increases the likelihood that the person will perform that behavior--a phenomenon termed the mere measurement effect. This research tested the role of (a) the type of questions, and (b) questionnaire completion in optimizing the impact of mere measurement interventions designed to retain novice blood donors. DESIGN: Novice blood donors (N = 4391) were randomly allocated to four conditions that varied the content of a questionnaire about blood donation (behavioral intention-only, behavioral intention plus regret, implementation intention-only, implementation intention plus regret) or to a no-questionnaire control condition. MAIN OUTCOME MEASURES: Objective measures of registration at blood drives were obtained at 6 and 12 months postbaseline. RESULTS: Participants in the implementation intention-only condition donated more frequently at 6 months compared to participants in each of the other conditions. At 12 months both implementation intention conditions outperformed the other conditions. Implementation intentions increased the frequency of donations over 1 year by 12%. Measuring anticipated regret did not augment the impact of interventions whereas questionnaire completion had an important impact on donation behavior. CONCLUSION: Questions about implementation intentions but not behavioral intentions promote retention of novice blood donors.

Perreault and colleagues examined antibody titers in sequential samples from serum donors recovering from COVID-19 and demonstrated that antibody titers fall over 3-4 months. These results have important implications for convalescent serum collection and seroprevalence studies.

Characterization of the humoral response to SARS-CoV-2, the etiological agent of COVID-19, is essential to help control the infection. The neutralization activity of plasma from patients with COVID-19 decreases rapidly during the first weeks after recovery. However, the specific role of each immunoglobulin isotype in the overall neutralizing capacity is still not well understood. In this study, we select plasma from a cohort of convalescent patients with COVID-19 and selectively deplete immunoglobulin A, M, or G before testing the remaining neutralizing capacity of the depleted plasma. We find that depletion of immunoglobulin M is associated with the most substantial loss of virus neutralization, followed by immunoglobulin G. This observation may help design efficient antibody-based COVID-19 therapies and may also explain the increased susceptibility to SARS-CoV-2 of autoimmune patients receiving therapies that impair the production of immunoglobulin M (IgM).

The majority of contrast agents used in magnetic resonance imaging (MRI) is based on the rare-earth element gadolinium. Gadolinium-based nanoparticles could find promising applications in pre-clinical diagnostic procedures of certain types of cancer, such as glioblastoma multiforme. This is one of the most malignant, lethal and poorly accessible forms of cancer. Recent advances in colloidal nanocrystal synthesis have led to the development of ultra-small crystals of gadolinium oxide (US-Gd(2)O(3), 2-3 nm diameter). As of today, this is the smallest and the densest of all Gd-containing nanoparticles. Cancer cells labeled with a sufficient quantity of this compound appear bright in T(1)-weighted MRI images. Here we demonstrate that US-Gd(2)O(3) can be used to label GL-261 glioblastoma multiforme cells, followed by localization and visualization in vivo using MRI. Very high amounts of Gd are efficiently internalized and retained in cells, as confirmed with TEM and ICP-MS. Labeled cells were visualized in vivo at 1.5 T using the chicken embryo model. This is one more step toward the development of "positively contrasted" cell tracking procedures with MRI.