SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod

BACKGROUND: SARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there are limited data on how disease-modifying therapies (DMTs) alter SARS-CoV-2 mRNA vaccine immunogenicity in patients with autoimmune diseases. METHODS: As part of a prospective cohort study, we investigated the induction, stability and boosting of vaccine-specific antibodies, B cells and T cells in patients with multiple sclerosis (MS) on different DMTs after homologous primary, secondary and booster SARS-CoV-2 mRNA vaccinations. Of 126 patients with MS analysed, 105 received either anti-CD20-based B cell depletion (aCD20-BCD), fingolimod, interferon-β, dimethyl fumarate, glatiramer acetate, teriflunomide or natalizumab, and 21 were untreated MS patients for comparison. RESULTS: In contrast to all other MS patients, and even after booster, most aCD20-BCD- and fingolimod-treated patients showed no to markedly reduced anti-S1 IgG, serum neutralising activity and a lack of receptor binding domain-specific and S2-specific B cells. Patients receiving fingolimod additionally lacked spike-reactive CD4(+) T cell responses. The duration of fingolimod treatment, rather than peripheral blood B and T cell counts prior to vaccination, determined whether a humoral immune response was elicited. CONCLUSIONS: The lack of immunogenicity under long-term fingolimod treatment demonstrates that functional immune responses require not only immune cells themselves, but also access of these cells to the site of inoculation and their unimpeded movement. The absence of humoral and T cell responses suggests that fingolimod-treated patients with MS are at risk for severe SARS-CoV-2 infections despite booster vaccinations, which is highly relevant for clinical decision-making and adapted protective measures, particularly considering additional recently approved sphingosine-1-phosphate receptor antagonists for MS treatment

Childlessness in France

Even though the average age at first childbirth has been increasing and education and employment options for women have improved immensely in recent decades, in France, unlike in other European countries, these developments have not led to a major increase in childlessness. Birth rates remain high and the share of the population who are childless is among the lowest in western Europe. This article discusses the historical roots as well as the societal conditions, institutional regulations, and political decisions that may explain the low levels of childlessness in France. We also discuss differences in rates of childlessness by education and occupation. Using a large representative survey on family life that was conducted parallel to the French census in 2011, we study the fertility histories of men and women born between the 1920s and late 1970s. We find that while the differences in fertility by level of education seem to have declined, having a higher education is still an obstacle to parenthood for women. For men, having a low educational and occupational status is associated with a greater likelihood of being childless. A large part of the differences in rates of childlessness between social groups can be traced back to the men and women who have never lived in a couple relationship; thus, partnership status can be regarded as a decisive parameter of the extent of childlessness

SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic1,2. Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms that determine such variable outcomes remain unresolved. Here we investigated CD4+ T cells that are reactive against the spike glycoprotein of SARS-CoV-2 in the peripheral blood of patients with COVID-19 and SARS-CoV-2-unexposed healthy donors. We detected spike-reactive CD4+ T cells not only in 83% of patients with COVID-19 but also in 35% of healthy donors. Spike-reactive CD4+ T cells in healthy donors were primarily active against C-terminal epitopes in the spike protein, which show a higher homology to spike glycoproteins of human endemic coronaviruses, compared with N-terminal epitopes. Spike-protein-reactive T cell lines generated from SARS-CoV-2-naive healthy donors responded similarly to the C-terminal region of the spike proteins of the human endemic coronaviruses 229E and OC43, as well as that of SARS-CoV-2. This results indicate that spike-protein cross-reactive T cells are present, which were probably generated during previous encounters with endemic coronaviruses. The effect of pre-existing SARS-CoV-2 cross-reactive T cells on clinical outcomes remains to be determined in larger cohorts. However, the presence of spike-protein cross-reactive T cells in a considerable fraction of the general population may affect the dynamics of the current pandemic, and has important implications for the design and analysis of upcoming trials investigating COVID-19 vaccines

Cross-reactive CD4+ T cells enhance SARS-CoV-2 immune responses upon infection and vaccination

The functional relevance of pre-existing cross-immunity to SARS-CoV-2 is a subject of intense debate. Here, we show that human endemic coronavirus (HCoV)-reactive and SARS-CoV-2-cross-reactive CD4+ T cells are ubiquitous but decrease with age. We identified a universal immunodominant coronavirus-specific spike peptide (S816-830) and demonstrate that pre-existing spike- and S816-830-reactive T cells were recruited into immune responses to SARS-CoV-2 infection and their frequency correlated with anti-SARS-CoV-2-S1-IgG antibodies. Spike-cross-reactive T cells were also activated after primary BNT162b2 COVID-19 mRNA vaccination displaying kinetics similar to secondary immune responses. Our results highlight the functional contribution of pre-existing spike-cross-reactive T cells in SARS-CoV-2 infection and vaccination. Cross-reactive immunity may account for the unexpectedly rapid induction of immunity following primary SARS-CoV-2 immunization and the high rate of asymptomatic/mild COVID-19 disease courses

How Many Hours Do You Have to Work to Be Integrated? Full Time and Part Time Employment of Native and Ethnic Minority Women in the Netherlands

Labor market participation is a central factor in the economic integration of migrants in their host country. Labor market integration of ethnic minority women is of special interest, as they may experience a double disadvantage: both as a woman and as a migrant. Since the late nineties this presumed double disadvantage has become more and more the focus of both Dutch integration and Dutch emancipation policy. To test several assumptions underlying Dutch policy this paper focuses on the employment patterns of ethnic minority and native women in the Netherlands. In particular, we analyze to what extent labor market participation of different groups of women and the hours they work are influenced by human capital and household characteristics. Our results show some remarkable differences in employment patterns between native Dutch and ethnic minority women. Controlling for educational level, partnership and the presence of children, native Dutch women are working more often in part time jobs than Mediterranean and Caribbean women. For all women the educational level is an important determinant of employment and the number of hours worked. Whereas the number of children influences both the employment decision and the number of hours worked of native Dutch women, for Mediterranean and Caribbean women there is only an effect of the number of children on the odds of having a full time job

ESWT - tracking organs during focused ultrasound surgery

We report here our results in a multi-sensor setup reproducing the conditions of an automated focused ultrasound surgery environment. The aim is to continuously predict the position of an internal organ (here the liver) under guided and non-guided free breathing, with the accuracy required by surgery. We have performed experiments with 16 healthy human subjects, two of those taking part in full-scale experiments involving a 3 Tesla MRI machine recording a volume containing the liver. For the other 14 subjects we have used the optical tracker as a surrogate target. All subjects where volunteers who agreed to participate in the experiments after being thoroughly informed about it. For the MRI sessions we have analyzed semi-automatically offline the images in order to obtain the ground truth, the true position of the selected feature of the liver. The results we have obtained with continuously updated random forest models are very promising, we have obtained good prediction-target correlation coefficients for the surrogate targets (0.71 ± 0.1) and excellent for the real targets in the MRI experiments (over 0.91), despite being limited to a lower model update frequency, once every 6.16 seconds

Strong-field-induced single and double ionization dynamics from single and double excitations in a two-electron atom

Two-electron dynamics of an excited model atom interacting with moderately strong laser fields is analyzed in the time domain. We solve the time-dependent Schrödinger equation (TDSE) for two electrons confined to the same one-dimensional configuration space, accounting also for the electron-electron interaction. The computational method allows direct access to the time-dependent population of the relevant atomic states during and right after the interaction with a near-infrared (NIR) laser pulse. We compare the ionization dynamics of singly excited states and doubly excited states. We find that doubly-excited initial states exhibit enhanced double ionization yield, with non-trivial dynamics including contributions from direct and sequential processes, while the electrons leave the atom either back-to-back or in the same direction