The emergence of SARS-CoV-2 variant 20I/501Y.V1 (VOC-202012/1 or GR/501Y.V1) is concerning given its increased transmissibility. We reanalysed 11,916 PCR-positive tests (41% of all positive tests) ...performed on 7-8 January 2021 in France. The prevalence of 20I/501Y.V1 was 3.3% among positive tests nationwide and 6.9% in the Paris region. Analysing the recent rise in the prevalence of 20I/501Y.V1, we estimate that, in the French context, 20I/501Y.V1 is 52-69% more transmissible than the previously circulating lineages, depending on modelling assumptions.
Abstract
Background
We investigated whether dolutegravir (DTG) monotherapy could be used to maintain virological suppression in people living with human immunodeficiency virus (HIV) on a successful ...dolutegravir-based triple therapy.
Methods
MONCAY (MONotherapy of TiviCAY) was a 48-week, multicentric, randomized, open-label, 12% noninferiority margin trial. Patients with CD4 nadir >100/μL, plasma HIV-1 RNA <50 copies/mL for ≥12 months, and stable regimen with DTG/abacavir (ABC)/lamivudine (3TC) were 1:1 randomized to continue their regimen or to DTG monotherapy. The primary endpoint was the proportion of patients with HIV RNA <50 copies/mL at week 24 in intention-to-treat snapshot analysis. Virologic failure (VF) was defined as 2 consecutive HIV RNA >50 copies/mL within 2 weeks apart.
Results
Seventy-eight patients were assigned to DTG monotherapy and 80 to continue DTG/ABC/3TC. By week 24, 2 patients in the DTG group experienced VF without resistance to the integrase strand transfer inhibitor (INSTI) class; 1 patient discontinued DTG/ABC/3TC due to an adverse event. The success rate at week 24 was 73/78 (93.6%) in the DTG arm and 77/80 (96.3%) in the DTG/ABC/3TC arm (difference, 2.7%; 95% confidence interval CI, –5.0 to 10.8). During subsequent follow-up, 5 additional VFs occurred in the DTG arm (2 of which harbored emerging resistance mutation to INSTI). The cumulative incidence of VF at week 48 was 9.7% (95% CI, 2.8 to 16.6) in the DTG arm compared with 0% in the DTG/ABC/3TC arm (P = .005 by the log-rank test). The Data Safety Monitoring Board recommended to reintensify the DTG arm with standardized triple therapy.
Conclusions
Because the risk of VF with resistance increases over time, we recommend avoiding DTG monotherapy as a maintenance strategy among people living with chronic HIV infection.
Clinical Trials Registration
NCT02596334 and EudraCT 2015-002853-36.
In a randomized, noninferiority trial, dolutegravir monotherapy was not a valid option to maintain virological suppression over week 24 in people living with chronic human immunodeficiency virus infection on a successful dolutegravir/abacavir/lamivudine regimen and favored emergence of integrase strand transfer inhibitor resistance.
Host defence mechanisms to counter virus infection include the activation of the broncho-alveolar haemostasis. Fibrin degradation products secondary to extravascular fibrin breakdown could contribute ...to the marked increase in D-Dimers during COVID-19. We sought to examine the prognostic value on lung injury of D-Dimers in non-critically ill COVID-19 patients without thrombotic events.
This study retrospectively analysed hospitalized COVID-19 patients classified according to a D-Dimers threshold following the COVID-19 associated haemostatic abnormalities (CAHA) classification at baseline and at peak (Stage 1: D-Dimers less than three-fold above normal; Stage 2: D-Dimers three- to six-fold above normal; Stage 3: D-Dimers six-fold above normal). The primary endpoint was the occurrence of critical lung injuries on chest computed tomography. The secondary outcome was the composite of in-hospital death or transfer to the intensive care unit (ICU).
Among the 123 patients included, critical lung injuries were evidenced in 8 (11.9%) patients in Stage 1, 6 (20%) in Stage 2 and 15 (57.7%) in Stage 3 (
= 0.001). D-Dimers staging at peak was an independent predictor of critical lung injuries regardless of the inflammatory burden assessed by CRP levels (OR 2.70, 95% CI (1.50-4.86);
< 0.001) and was significantly associated with increased in-hospital death or ICU transfer (14.9 % in Stage 1, 50.0% in Stage 2 and 57.7% in Stage 3 (
< 0.001)). D-Dimers staging at peak was an independent predictor of in-hospital death or ICU transfer (OR 2.50, CI 95% (1.27-4.93);
= 0.008).
In the absence of overt thrombotic events, D-Dimers quantification is a relevant marker of critical lung injuries and dismal patient outcome.
Two-photon scanning microscopy (TPSM) is a powerful tool for imaging deep inside living tissues with sub-cellular resolution. The temporal resolution of TPSM is however strongly limited by the ...galvanometric mirrors used to steer the laser beam. Fast physiological events can therefore only be followed by scanning repeatedly a single line within the field of view. Because acousto-optic deflectors (AODs) are non-mechanical devices, they allow access at any point within the field of view on a microsecond time scale and are therefore excellent candidates to improve the temporal resolution of TPSM. However, the use of AOD-based scanners with femtosecond pulses raises several technical difficulties. In this paper, we describe an all-digital TPSM setup based on two crossed AODs. It includes in particular an acousto-optic modulator (AOM) placed at 45° with respect to the AODs to pre-compensate for the large spatial distortions of femtosecond pulses occurring in the AODs, in order to optimize the spatial resolution and the fluorescence excitation. Our setup allows recording from freely selectable point-of-interest at high speed (1
kHz). By maximizing the time spent on points of interest, random-access TPSM (RA-TPSM) constitutes a promising method for multiunit recordings with millisecond resolution in biological tissues.
Introduction
COVID-19 long-haulers, also decribed as having “long-COVID” or post-acute COVID-19 syndrome, represent 10% of COVID-19 patients and remain understudied.
Methods
In this prospective ...study, we recruited 30 consecutive patients seeking medical help for persistent symptoms (> 30 days) attributed to COVID-19. All reported a viral illness compatible with COVID-19. The patients underwent a multi-modal evaluation, including clinical, psychologic, virologic and specific immunologic assays and were followed longitudinally. A group of 17 convalescent COVID-19 individuals without persistent symptoms were included as a comparison group.
Results
The median age was 40 interquartile range: 35–54 years and 18 (60%) were female. At a median time of 152 102–164 days after symptom onset, fever, cough and dyspnea were less frequently reported compared with the initial presentation, but paresthesia and burning pain emerged in 18 (60%) and 13 (43%) patients, respectively. The clinical examination was unremarkable in all patients, although the median fatigue and pain visual analog scales were 7 5–8 and 5 2–6, respectively. Extensive biologic studies were unremarkable, and multiplex cytokines and ultra-sensitive interferon-α2 measurements were similar between long-haulers and convalescent COVID-19 individuals without persistent symptoms. Using SARS-CoV-2 serology and IFN-γ ELISPOT, we found evidence of a previous SARS-CoV-2 infection in 50% (15/30) of patients, with evidence of a lack of immune response, or a waning immune response, in two patients. Finally, psychiatric evaluation showed that 11 (36.7%), 13 (43.3%) and 9 (30%) patients had a positive screening for anxiety, depression and post-traumatic stress disorder, respectively.
Conclusions
Half of patients seeking medical help for post-acute COVID-19 syndrome lack SARS-CoV-2 immunity. The presence of SARS-CoV-2 immunity, or not, had no consequence on the clinical or biologic characteristics of post-acute COVID-19 syndrome patients, all of whom reported severe fatigue, altered quality of life and psychologic distress.
Background
The diagnosis of atypical inflammatory demyelinating lesions can be difficult. Brain biopsy is often required to exclude neoplasms. Moreover, the relationship between these lesions and ...multiple sclerosis and NMOSD is not clear.
Objectives
Our objectives were to describe radiological and pathological characteristics of patients with acute inflammatory demyelinating lesions.
Methods
We retrospectively identified patients with brain biopsy performed for diagnostic uncertainty revealing a demyelinating lesion. A complete clinical, biological, radiological and pathological analysis was performed.
Results
Twenty patients (15 with a single lesion) were included. MRI disclosed a wide range of lesions including infiltrative lesions (40%), ring-like lesion (15%) Baló-like lesion (15%) and acute haemorrhagic leukoencephalitis (20%). In spite of a marked heterogeneity, some findings were common: a peripheral B1000 hyperintense rim (70%), a slight oedema with mild mass effect (75%) and an open-rim peripheral enhancement (75%). Histopathology revealed that all cases featured macrophages distributed throughout, extensive demyelination, axonal preservation and absence of haemorrhagic changes. In the majority of cases, macrophages were the predominant inflammatory infiltrate and astrocytes were reactive and dystrophic. Aquaporin-4 staining was systematically preserved. After a mean follow-up of 5 years (1–12), 16/20 patients had a diagnosis of monophasic acute atypical inflammatory demyelinating lesion. One patient was diagnosed with MS and 3 with AQP4 negative NMOSD.
Discussion
Although imaging findings in patients with atypical inflammatory demyelinating lesions are heterogeneous, some common features such as peripheral DWI hyperintense rim with open-rim enhancement and absence of oedema argue in favour of a demyelinating lesion and should preclude a brain biopsy. In this context, AQP4 staining is systematically preserved and argues against an AQP4-positive NMOSD. Moreover, long-term follow-up is characterized by low recurrence rate.
Among the distinctive features of coronavirus disease 2019 (COVID-19), numerous reports have stressed the importance of vascular damage associated with coagulopathy onset 1. Histological analysis of ...pulmonary vessels in patients with COVID-19 revealed severe endothelial injury associated with intracellular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and disrupted endothelial cell membranes together with widespread thrombosis and occlusion of alveolar capillaries. Microparticles (MPs) shed by apoptotic/stimulated cells of various cellular lineages, including platelets, leukocytes, macrophages or endothelial cells, are reliable markers of vascular damage 2 released upon pro-inflammatory conditions and behave as active participants in the early steps of clot formation 3. Circulating MPs promote procoagulant responses due to the exposure of tissue factor, the physiological activator of the coagulation cascade, and of negatively charged phospholipids, such as phosphatidylserine, required for the assembly of the tenase and prothrombinase coagulation complexes ultimately leading to thrombin generation, through which they can precisely be quantified 4. MPs carry angiotensin-converting enzyme (ACE)1 and upregulate ACE1 expression in neighbouring endothelial cells 5. By contrast, exosomes were recently reported to convey ACE2, the cell-entry receptor for SARS-CoV-2 4, in the vasculature 6. ACE2 converts angiotensin II (Ang II) into angiotensin 1–7 (Ang 1–7), which by virtue of its actions on the Mas receptor, limits the noxious effects of Ang II. Pioneering data have demonstrated that the renin–angiotensin system has a crucial role in severe acute injury and that ACE2 has a protective role in acute lung injury mediated by SARS-CoV 7. According to this paradigm, the loss of ACE2 function following binding by SARS-CoV-2 may contribute to unopposed Ang II accumulation that further exacerbates tissue injury and promotes inflammation, MPs release and thrombosis. During SARS-CoV-2 infection, we hypothesised that various factors including inflammatory burden, Ang II, altered shear stress and hypoxic vasoconstriction, could enhance MPs shedding by various cell lineages including the alveolar vascular endothelium and contribute to clot formation.
Procoagulant microparticles are associated with the extent of lung injuries in #COVID19 and pulmonary thrombosis
https://bit.ly/3eX2LPc
Over-exploitation and fragmentation are serious problems for tropical forests. Most sustainable forest management practices avoid clear-cuts and apply selective logging systems focused on a few ...commercial species. We applied a simulation model to estimate the impact of such selective logging scenarios on the genetic diversity and demography of four tropical tree species from French Guiana. The simulations used data on genetic and demographic composition, growth, phenology and pollen and seed dispersal obtained for
Dicorynia guianensis,
Sextonia rubra,
Symphonia globulifera and
Vouacapoua americana at the experimental site in Paracou. Whereas
Symphonia globulifera serves as a model for a species with low logging pressure, the other three species represent the most exploited tree species in French Guiana. In simulations with moderate logging, typical for French Guiana, with large cutting diameter (>60
cm diameter) and long cutting cycles (65 years), the two species
V. americana and
Sextonia rubra were not able to recover their initial stock at the end of the rotation period, with a large decrease in the number of individuals and in basal area. Under a more intensive logging system (cutting diameter >45
cm diameter, cutting cycles of 30 years) that is common practice in the Brazilian Amazon, only
Symphonia globulifera showed no negative impact. Generally, the differences between the genetic parameters in the control scenarios without logging and the logging scenarios were surprisingly small. The main reasons for this were the overlapping of generations and the effective dispersal ability of gene vectors in all species, which guarantee relative homogeneity of the genetic structure in different age classes. Nevertheless, decreasing the population size by logging reduced the number of genotypes and caused higher genetic distances between the original population and the population at the end of the logging cycles. Sensitivity analysis showed that genetic changes in the logging scenarios were principally determined by the growth, densities and cutting diameter of each species, and only to a very small extent by the reproductive system including factors such as pollen and seed dispersal and flowering phenology.
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