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- Manry, Jérémy, et al.
(author)
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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
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Journal article (peer-reviewed)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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| 2. |
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| 3. |
- Bastard, P, et al.
(author)
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Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
- 2022
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In: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 78:7490, s. eabp8966-
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Journal article (peer-reviewed)abstract
- Life-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.
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| 6. |
- Sourikopoulos, Ilias, et al.
(author)
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The H2020-SPACE-SIPHODIAS project: Space-grade optoelectronic interfaces for photonic digital and analogue very-high-throughput satellite payloads
- 2021
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 11852
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Conference paper (peer-reviewed)abstract
- The EU-SIPhoDiAS project deals with the development of critical photonic building blocks needed for high-performance and low size, weight, and power (SWaP) photonics-enabled Very High Throughput Satellites (VHTS). In this presentation, we report on the design and fabrication activities during the first year of the project concerning the targeted family of digital and microwave photonic components. This effort aims to demonstrate components of enhanced reliability at technology readiness level (TRL) 7. Specifically, with respect to microwave photonic links, we report: (i) the design of Ka and Q-bands analogue photodetectors that will be assembled in compact packages, allowing for very high bandwidth per unit area and (ii) on the design of compact V-band GaAs electro-optic modulator arrays, which use a folded-path optical configuration to manage all fiber interfaces packaged opposite direct in-line RF feeds for ease of board layouts and mass/size benefits. With respect to digital links, we report on the development of 100 Gb/s (4 x 25 Gb/s) digital optical transceiver sub-assemblies developed using flip-chip mounting of electronic and opto-parts on a high-reliability borosilicate substrate. The transceiver chipset developed specifically for this project refers to fully-custom 25 Gb/s radiation hard (RH) VCSEL driver and TIA ICs designed in IHP’s 130 nm SiGe BiCMOS Rad-Hard process.
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| 7. |
- Stampoulidis, Leontios, et al.
(author)
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High-speed low-power and board-mountable optical transceivers for scalable & energy efficient advanced on-board digital processors
- 2018
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 11180
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Conference paper (peer-reviewed)abstract
- We present the development and verification testing of a high speed multimode, multicore transceiver technology for intra-satellite optical interconnects. We report the fabrication and functional testing of opto-parts including 25 Gb/s 850 nm VCSEL/PD as well as the verification testing of the VCSELs against radiation and lifetime performance. In addition we report the development and evaluation testing of a multi-core cable assembly that was fabricated and mated with MiniAVIM multi-core connectors to develop hi-rel multi-core optical patchcords for pigtailing the transceiver modules. The fiber optic, electronic and opto-parts were used to assemble the first ever fully packaged and pigtailed, six-core optical transceiver prototype module that operates at 25 Gb/s channel bit rate at an energy consumption of ∠4.5 mW/Gb/s.
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| 8. |
- Stampoulidis, Leontios, et al.
(author)
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The European project Merlin on multi-gigabit, energy-efficient, ruggedized lightwave engines for advanced on-board digital processors
- 2017
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 10563
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Conference paper (peer-reviewed)abstract
- Modern broadband communication networks rely on satellites to complement the terrestrial telecommunication infrastructure. Satellites accommodate global reach and enable world-wide direct broadcasting by facilitating wide access to the backbone network from remote sites or areas where the installation of ground segment infrastructure is not economically viable. At the same time the new broadband applications increase the bandwidth demands in every part of the network - and satellites are no exception. Modern telecom satellites incorporate On-Board Processors (OBP) having analogue-to-digital (ADC) and digital-to-analogue converters (DAC) at their inputs/outputs and making use of digital processing to handle hundreds of signals; as the amount of information exchanged increases, so do the physical size, mass and power consumption of the interconnects required to transfer massive amounts of data through bulk electric wires.
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