Divergent adaptive immune responses define two types of long COVID

BackgroundThe role of adaptive immune responses in long COVID remains poorly understood, with contrasting hypotheses suggesting either an insufficient antiviral response or an excessive immune response associated with inflammatory damage. To address this issue, we set to characterize humoral and CD4+ T cell responses in long COVID patients prior to SARS-CoV-2 vaccination.MethodsLong COVID patients who were seropositive (LC+, n=28) or seronegative (LC-, n=23) by spike ELISA assay were recruited based on (i) an initial SARS-CoV-2 infection documented by PCR or the conjunction of three major signs of COVID-19 and (ii) the persistence or resurgence of at least 3 symptoms for over 3 months. They were compared to COVID patients with resolved symptoms (RE, n=29) and uninfected control individuals (HD, n=29).ResultsThe spectrum of persistent symptoms proved similar in both long COVID groups, with a trend for a higher number of symptoms in the seronegative group (median=6 vs 4.5; P=0.01). The use a highly sensitive S-flow assay enabled the detection of low levels of SARS-CoV-2 spike-specific IgG in 22.7% of ELISA-seronegative long COVID (LC-) patients. In contrast, spike-specific IgG levels were uniformly high in the LC+ and RE groups. Multiplexed antibody analyses to 30 different viral antigens showed that LC- patients had defective antibody responses to all SARS-CoV-2 proteins tested but had in most cases preserved responses to other viruses. A sensitive primary T cell line assay revealed low but detectable SARS-CoV-2-specific CD4 responses in 39.1% of LC- patients, while response frequencies were high in the LC+ and RE groups. Correlation analyses showed overall strong associations between humoral and cellular responses, with exceptions in the LC- group.ConclusionsThese findings provide evidence for two major types of antiviral immune responses in long COVID. Seropositive patients showed coordinated cellular and humoral responses at least as high as those of recovered patients. In contrast, ELISA-seronegative long COVID patients showed overall low antiviral responses, with detectable specific CD4+ T cells and/or antibodies in close to half of patients (52.2%). These divergent findings in patients sharing a comparable spectrum of persistent symptoms raise the possibility of multiple etiologies in long COVID

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Valeur clinique de l'épreuve de rinne d'après les résultats fournis par le diapason La (Travail du service de Monsieur le Professeur Moure)

Thèse : Médecine : Université de Bordeaux : 1907N° d'ordre :

Cartes d'une petite ville du Tamilnadu en 1970 (Maps of a little town in Tamilnadu)

Abstract. - This paper is a short comment of maps of a little town of Tamilnadu in 1970 : Tindivan (Republic of India).Résumé. - Présentation de cartes établies en 1970 d'une petite ville du Tamilnadu (République indienne) : Tindivan. Etude des activités économiques et des structures sociales.Pierre A.M., Charleux Jean-Louis, Pietri René. Cartes d'une petite ville du Tamilnadu en 1970 (Maps of a little town in Tamilnadu). In: Bulletin de l'Association de géographes français, 65e année, 1988-2 ( avril). pp. 113-123

Tindivanam, une ville moyenne de l'Inde du Sud : centre de services et entrepôt pour les métropoles

Pierre Anne-Marie, Pietri René, Charleux Jean-Louis. Tindivanam, une ville moyenne de l'Inde du Sud : centre de services et entrepôt pour les métropoles. In: Tiers-Monde, tome 12, n°46, 1971. pp. 387-392

JAK2 allele burden is correlated with a risk of venous but not arterial thrombosis

International audienceBackground: Thrombosis is the main complication in myeloproliferative neoplasms (MPN). A JAK2V617F mu-tation has been shown to be a risk factor for thrombosis. The implication of other risk factors alongside a mu-tation allele burden needs to be clarified (Trifa et al., 2018; Borowczyk et al., 2015). Objective: Our aim was to investigate the role of the JAK2 mutation allele burden in the risk of cardiovascular events (CVE) and/or venous thrombosis (VTE) in a cohort of patients with confirmed MPN, as well as in patients without confirmed MPN. Methods: We restrospectively included all consecutive patients who were positive for JAK2V617F seen by our unit between December 2008 and September 2016. Inclusion criteria were a positive test for the JAK2V617F mutation, with at least 1% allele burden, with or without confirmed MPN. Results: We included 239 patients of median age 71 years [60-81], followed-up for a median of 82.8 months [41.08-146.88]. For JAK2V617F positive patients having an allele burden superior to 50% the cumulative incidence of VTE was significantly higher than for those with an allele burden inferior to 50% (HR 3.11 95% CI [1.10-8.76] p = 0.031). The cumulative incidence of VTE was also higher in patients with obesity (HR 4.58 95% CI [1.33-15.8] p = 0.016). There was no significant association between a JAK2V617F allele burden and arterial thrombosis (manifesting as CVE). Previous VTE was also associated with a higher cumulative incidence of recurrence during follow-up HR 3.22 95% CI [1.17-8.81] p = 0.0231. Conclusion: We show that a JAK2V617F allele burden is associated with risk of VTE but not with CVE

The Cellular Prion Protein—ROCK Connection: Contribution to Neuronal Homeostasis and Neurodegenerative Diseases

International audienceAmyloid-based neurodegenerative diseases such as prion, Alzheimer's, and Parkinson's diseases have distinct etiologies and clinical manifestations, but they share common pathological events. These diseases are caused by abnormally folded proteins (pathogenic prions PrP Sc in prion diseases, β-amyloids/Aβ and Tau in Alzheimer's disease, α-synuclein in Parkinson's disease) that display β-sheet-enriched structures, propagate and accumulate in the nervous central system, and trigger neuronal death. In prion diseases, PrP Sc -induced corruption of the physiological functions exerted by normal cellular prion proteins (PrP C ) present at the cell surface of neurons is at the root of neuronal death. For a decade, PrP C emerges as a common cell surface receptor for other amyloids such as Aβ and α-synuclein, which relays, at least in part, their toxicity. In lipid-rafts of the plasma membrane, PrP C exerts a signaling function and controls a set of effectors involved in neuronal homeostasis, among which are the RhoA-associated coiled-coil containing kinases (ROCKs). Here we review (i) how PrP C controls ROCKs, (ii) how PrP C -ROCK coupling contributes to neuronal homeostasis, and (iii) how the deregulation of the PrP C -ROCK connection in amyloid-based neurodegenerative diseases triggers a loss of neuronal polarity, affects neurotransmitter-associated functions, contributes to the endoplasmic reticulum stress cascade, renders diseased neurons highly sensitive to neuroinflammation, and amplifies the production of neurotoxic amyloids