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| 2. |
- Bastard, P, et al.
(författare)
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Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
- 2022
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 78:7490, s. eabp8966-
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Gaziano, Liam, et al.
(författare)
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Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19
- 2021
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Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 27:4
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale Mendelian randomization and colocalization analyses using gene expression and soluble protein data for 1,263 actionable druggable genes, which encode protein targets for approved drugs or drugs in clinical development, identify IFNAR2 and ACE2 as the most promising therapeutic targets for early management of COVID-19. Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 x 10(-6); IFNAR2, P = 9.8 x 10(-11) and IL-10RB, P = 2.3 x 10(-14)) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19.
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| 4. |
- Manry, Jérémy, et al.
(författare)
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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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Ingår i: 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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Tidskriftsartikel (refereegranskat)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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| 5. |
- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Aybas, Deniz, et al.
(författare)
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Search for Axionlike Dark Matter Using Solid-State Nuclear Magnetic Resonance
- 2021
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Ingår i: Physical Review Letters. - : American Physical Society (APS). - 0031-9007 .- 1079-7114. ; 126:14
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of an experimental search for ultralight axionlike dark matter in the mass range 162-166 neV. The detection scheme of our Cosmic Axion Spin Precession Experiment is based on a precision measurement of Pb-207 solid-state nuclear magnetic resonance in a polarized ferroelectric crystal. Axionlike dark matter can exert an oscillating torque on Pb-20(7) nuclear spins via the electric dipole moment coupling g(d) or via the gradient coupling g(aNN). We calibrate the detector and characterize the excitation spectrum and relaxation parameters of the nuclear spin ensemble with pulsed magnetic resonance measurements in a 4.4 T magnetic field. We sweep the magnetic field near this value and search for axionlike dark matter with Compton frequency within a 1 MHz band centered at 39.65 MHz. Our measurements place the upper bounds vertical bar g(d)vertical bar < 9.5 x 10(-4) GeV-2 and vertical bar g(aNN)vertical bar( )< 2.8 x 10(-1) GeV-1 (95% confidence level) in this frequency range. The constraint on g d corresponds to an upper bound of 1.0 x 10(-21) e cm on the amplitude of oscillations of the neutron electric dipole moment and 4.3 x 10(-6) on the amplitude of oscillations of CP-violating theta parameter of quantum chromodynamics. Our results demonstrate the feasibility of using solid-state nuclear magnetic resonance to search for axionlike dark matter in the neV mass range.
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| 7. |
- Breitburg, Denise, et al.
(författare)
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Declining oxygen in the global ocean and coastal waters
- 2018
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 359:6371
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Forskningsöversikt (refereegranskat)abstract
- Oxygen is fundamental to life. Not only is it essential for the survival of individual animals, but it regulates global cycles of major nutrients and carbon. The oxygen content of the open ocean and coastal waters has been declining for at least the past half-century, largely because of human activities that have increased global temperatures and nutrients discharged to coastal waters. These changes have accelerated consumption of oxygen by microbial respiration, reduced solubility of oxygen in water, and reduced the rate of oxygen resupply from the atmosphere to the ocean interior, with a wide range of biological and ecological consequences. Further research is needed to understand and predict long-term, global-and regional-scale oxygen changes and their effects on marine and estuarine fisheries and ecosystems.
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| 8. |
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| 9. |
- Centers, Gary P., et al.
(författare)
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Stochastic fluctuations of bosonic dark matter
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Numerous theories extending beyond the standard model of particle physics predict the existence of bosons that could constitute dark matter. In the standard halo model of galactic dark matter, the velocity distribution of the bosonic dark matter field defines a characteristic coherence time τc. Until recently, laboratory experiments searching for bosonic dark matter fields have been in the regime where the measurement time T significantly exceeds τc, so null results have been interpreted by assuming a bosonic field amplitude Φ0 fixed by the average local dark matter density. Here we show that experiments operating in the T ≪ τc regime do not sample the full distribution of bosonic dark matter field amplitudes and therefore it is incorrect to assume a fixed value of Φ0 when inferring constraints. Instead, in order to interpret laboratory measurements (even in the event of a discovery), it is necessary to account for the stochastic nature of such a virialized ultralight field. The constraints inferred from several previous null experiments searching for ultralight bosonic dark matter were overestimated by factors ranging from 3 to 10 depending on experimental details, model assumptions, and choice of inference framework.
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