Host Genetic Factors and Vaccine-Induced Immunity to Hepatitis B Virus Infection

BACKGROUND: Vaccination against hepatitis B virus infection (HBV) is safe and effective; however, vaccine-induced antibody level wanes over time. Peak vaccine-induced anti-HBs level is directly related to antibody decay, as well as risk of infection and persistent carriage despite vaccination. We investigated the role of host genetic factors in long-term immunity against HBV infection based on peak anti-HBs level and seroconversion to anti-HBc. METHODS: We analyzed 715 SNP across 133 candidate genes in 662 infant vaccinees from The Gambia, assessing peak vaccine-induced anti-HBs level and core antibody (anti-HBc) status, whilst adjusting for covariates. A replication study comprised 43 SNPs in a further 393 individuals. RESULTS: In our initial screen we found variation in IFNG, MAPK8, and IL10RA to affect peak anti-HBs level (GMTratio of 1.5 and P < or = 0.001) and lesser associations in other genes. Odds of core-conversion was associated with variation in CD163. A coding change in ITGAL (R719V) with likely functional relevance showed evidence of association with increased peak anti-HBs level in both screens (1st screen: s595_22 GMTratio 1.71, P = 0.013; 2nd screen: s595_22 GMTratio 2.15, P = 0.011). CONCLUSION: This is to our knowledge the largest study to date assessing genetic determinants of HBV vaccine-induced immunity. We report on associations with anti-HBs level, which is directly related to durability of antibody level and predictive of vaccine efficacy long-term. A coding change in ITGAL, which plays a central role in immune cell interaction, was shown to exert beneficial effects on induction of peak antibody level in response to HBV vaccination. Variation in this gene does not appear to have been studied in relation to immune responses to viral or vaccine challenges previously. Our findings suggest that genetic variation in loci other than the HLA region affect immunity induced by HBV vaccination

From skin to microscope, case report of a rare manifestation of tophaceous gout: Miliary gout

International audienceJoint symptoms associated with gout, mostly characterized by joint flare-ups, are well known. Tophi represent the main cutaneous manifestation of gout, most often associated with a chronic and inadequately controlled disease. On rare occasions, atypical skin manifestations may occur. We present the case of a miliary form of gout in a 36-year-old man known to have hyperuricemia. Microscopic direct analysis of the skin material revealed the presence of monosodium urate (MSU) crystals. Rash disappeared with corticosteroid therapy in parallel with joint symptoms recovery. Knowledge of this unusual gout-related skin disease is essential to diagnosing uncommon presentations of gout, which sometimes occur before joint symptoms. This case highlights the importance of sampling any skin lesion suspected of being tophus, for MSU crystal identification, and provides a definitive diagnosis

Hybrid sulfurothioate-based electrolyte improving aesthetics, performance, and stability of transparent NIR-dye-sensitized solar cells

International audienceEnhancing performance, stability, and aesthetics is crucial for the development of transparent photovoltaics (TPV). In TPV, aesthetics are equally or even more important than performance because social acceptance requires maintaining aesthetics to a high level. In this work, we report a colorless hybrid electrolyte consisting of a thioate/iodide mixture. When integrated into wavelength-selective near-infrared-dye-sensitized solar cells (NIR-DSSCs), this electrolyte improves the power conversion efficiency (PCE) to up to 2.9% with a scattering layer and 2.1% in a transparent cell under AM1.5G conditions. It also reaches as high as 96% PCE retention over 1,800 h and confers an outstanding aesthetic level, up to 80% average visible transmittance (AVT), a color rendering index (CRI) of 96, and color purity as low as 14%, thus equaling the aesthetics of a double-glazed glass window

Revealing Donor–Acceptor Interaction on the Printed Active Layer Morphology and the Formation Kinetics for Nonfullerene Organic Solar Cells at Ambient Conditions

Slot-die coating is a powerful method for upscaling the production of organic solar cells (OSCs) with low energy consumption print processes at ambient conditions. Herein, chlorobenzene (CB) and chloroform (CF) are compared as host solvents for printing films of the neat novel fused-ring unit based wide-bandgap donor polymer (PDTBT2T-FTBDT), the small molecule nonfullerene acceptor based on a fused ring with a benzothiadiazole core (BTP-4F) as well as the respective PDTBT2T-FTBDT:BTP-4F blend films at room temperature in air. Using CF printing of the PDTBT2T-FTBDT:BTP-4F active layer, OSCs with a high power conversion efficiency of up to 13.2% are reached in ambient conditions. In comparison to CB printed blend films, the active layer printed out of CF has a superior morphology, a smoother film surface and a more pronounced face-on orientation of the crystallites, which altogether result in an enhanced exciton dissociation, a superior charge transport, and suppressed nonradiative charge carrier recombination. Based on in situ studies of the slot-die coating process of PDTBT2T-FTBDT, BTP-4F, and PDTBT2T-FTBDT:BTP-4F films, the details of the film formation kinetics are clarified, which cause the superior behavior for CF compared to CB printing due to balancing the aggregation and crystallization of donor and acceptor

Sustainable Thermosetting Polyurethane Resins as interlayers and primary Encapsulants in emerging photovoltaics

International audienceNowadays, polyurethane-based materials are massively exploited in a plethora of applications, from adhesives to foams, from building insulations to athletic tracks. Recently, the specifical use of aliphatic thermosetting polyurethanes (aPUs) has enormously increased in the industrial context for their versatile synthesis and tunable physicochemical properties. In the context of photovoltaics, and more specifically, the emerging field of Perovskite Solar Cells (PSCs), we proposed the use of thermosetting polyurethanes as low-cost but effective encapsulants on rigid devices. [1]The advantage of thermosetting PUs over other polymeric encapsulants lies in their tunable flexibility. Indeed, a properly designed combination of precursors leads to a PU that could be coupled with PET in flexible PSCs, allowing PU-protected devices to outperform the non-encapsulated cells in both conventional and high-humidity (RH > 70%) environments. Another possibility with thermosetting PU is their application as both encapsulant and interlayer in tandem devices; more in detail, we exploited a specifically designed formulation (i.e., having a refractive index comparable to the one of glass and a transmittance higher than 90%) to glue together a NIR-Dye Sensitized Solar Cell and a UV-absorbing PSC. The final tandem device reached a total efficiency close to 10% with an Average Visible Transmittance (AVT) as high as 35%, leading to a Light Utilization Efficiency close to 3.5%. All the proposed formulations have been engineered to improve their sustainability by replacing fossil fuel precursors with bio-based or waste-derived ones [2], thus leading to high-performing but sustainable encapsulants and interlayers for emerging photovoltaics

Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

International audienceObjectives: There is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.Methods: Individuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate-severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.Results: Of 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05-1.10), female gender (OR=0.45, 95% CI: 0.25-0.80), body mass index (OR=1.07, 95% CI: 1.02-1.12), hypertension (OR=1.86, 95% CI: 1.01-3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09-3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47-29.62) and rituximab (OR=4.21, 95% CI: 1.61-10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87-2.42) (n=175 each group).Conclusions: In the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD

Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

International audienceObjectives: There is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.Methods: Individuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate-severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.Results: Of 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05-1.10), female gender (OR=0.45, 95% CI: 0.25-0.80), body mass index (OR=1.07, 95% CI: 1.02-1.12), hypertension (OR=1.86, 95% CI: 1.01-3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09-3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47-29.62) and rituximab (OR=4.21, 95% CI: 1.61-10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87-2.42) (n=175 each group).Conclusions: In the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD

COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study

International audienceBackground: Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases.Methods: In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609.Findings: Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66-6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46-0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55-3·19, p=0·53).Interpretation: Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases