Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

NGDEEP Epoch 1: The Faint End of the Luminosity Function at z ∼ 9–12 from Ultradeep JWST Imaging

We present a robust sample of very high redshift galaxy candidates from the first epoch of JWST/NIRCam imaging from the Next Generation Deep Extragalactic Exploratory Public (NGDEEP) survey. The NGDEEP NIRCam imaging, spanning 9.7 arcmin ^2 in the Hubble Ultra Deep Field Parallel Field 2, reaches m = 30.4 (5 σ , point-source, 2″ diameter apertures corrected to total) in F277W, making it the deepest public JWST GO imaging data set to date. We describe our detailed data reduction process of the six-filter broadband JWST/NIRCam imaging, incorporating custom corrections for systematic effects to produce high-quality calibrated images. Using robust photometric redshift selection criteria, we identify a sample of 38 z ≳ 9 galaxy candidates. These objects span a redshift range of z = 8.5–15.8 and apparent magnitudes of m _F277W = 27–30.5 AB mag, reaching ∼1.5 mag deeper than previous public JWST imaging surveys. We calculate the rest-frame ultraviolet luminosity function at z ∼ 9 and 11 and present a new measurement of the luminosity function faint-end slope at z ∼ 11. We find a faint-end slope of α = −2.5 ± 0.4 and −2.2 ± 0.2 at z ∼ 9 and 11, respectively. This is consistent with no significant evolution in the faint-end slope and number density from z = 9 to 11. Comparing our results with theoretical predictions, we find that some models produce better agreement at the faint end than the bright end. These results will help to constrain how stellar feedback impacts star formation at these early epochs

HETDEX Public Source Catalog 1: 220 K Sources Including Over 50 K Lyα Emitters from an Untargeted Wide-area Spectroscopic Survey* * Based on observations obtained with the Hobby-Eberly Telescope, which is a joint project of the University of Texas at Austin, the Pennsylvania State University, Ludwig-Maximilians-Universität München, and Georg-August-Universität Göttingen. The HET is named in honor of its principal benefactors, William P. Hobby and Robert E. Eberly.

We present the first publicly released catalog of sources obtained from the Hobby-Eberly Telescope Dark Energy Experiment (HETDEX). HETDEX is an integral field spectroscopic survey designed to measure the Hubble expansion parameter and angular diameter distance at 1.88 < z < 3.52 by using the spatial distribution of more than a million Lyα-emitting galaxies over a total target area of 540 deg2. The catalog comes from contiguous fiber spectra coverage of 25 deg2 of sky from 2017 January through 2020 June, where object detection is performed through two complementary detection methods: one designed to search for line emission and the other a search for continuum emission. The HETDEX public release catalog is dominated by emission-line galaxies and includes 51,863 Lyα-emitting galaxy (LAE) identifications and 123,891 [O ii]-emitting galaxies at z < 0.5. Also included in the catalog are 37,916 stars, 5274 low-redshift (z < 0.5) galaxies without emission lines, and 4976 active galactic nuclei. The catalog provides sky coordinates, redshifts, line identifications, classification information, line fluxes, [O ii] and Lyα line luminosities where applicable, and spectra for all identified sources processed by the HETDEX detection pipeline. Extensive testing demonstrates that HETDEX redshifts agree to within Δz < 0.02, 96.1% of the time to those in external spectroscopic catalogs. We measure the photometric counterpart fraction in deep ancillary Hyper Suprime-Cam imaging and find that only 55.5% of the LAE sample has an r-band continuum counterpart down to a limiting magnitude of r ∼ 26.2 mag (AB) indicating that an LAE search of similar sensitivity to HETDEX with photometric preselection would miss nearly half of the HETDEX LAE catalog sample. Data access and details about the catalog can be found online at http://hetdex.org/. A copy of the catalogs presented in this work (Version 3.2) is available to download at Zenodo doi:10.5281/zenodo.7448504

A CEERS Discovery of an Accreting Supermassive Black Hole 570 Myr after the Big Bang: Identifying a Progenitor of Massive z > 6 Quasars

We report the discovery of an accreting supermassive black hole at z = 8.679. This galaxy, denoted here as CEERS_1019, was previously discovered as a Ly α -break galaxy by Hubble with a Ly α redshift from Keck. As part of the Cosmic Evolution Early Release Science (CEERS) survey, we have observed this source with JWST/NIRSpec, MIRI, NIRCam, and NIRCam/WFSS and uncovered a plethora of emission lines. The H β line is best fit by a narrow plus a broad component, where the latter is measured at 2.5 σ with an FWHM ∼1200 km s ^−1 . We conclude this originates in the broadline region of an active galactic nucleus (AGN). This is supported by the presence of weak high-ionization lines (N V, N IV], and C III]), as well as a spatial point-source component. The implied mass of the black hole (BH) is log ( M _BH / M _⊙ ) = 6.95 ± 0.37, and we estimate that it is accreting at 1.2 ± 0.5 times the Eddington limit. The 1–8 μ m photometric spectral energy distribution shows a continuum dominated by starlight and constrains the host galaxy to be massive (log M/M _⊙ ∼9.5) and highly star-forming (star formation rate, or SFR ∼ 30 M _⊙ yr ^−1 ; log sSFR ∼ − 7.9 yr ^−1 ). The line ratios show that the gas is metal-poor ( Z / Z _⊙ ∼ 0.1), dense ( n _e ∼ 10 ^3 cm ^−3 ), and highly ionized (log U ∼ − 2.1). We use this present highest-redshift AGN discovery to place constraints on BH seeding models and find that a combination of either super-Eddington accretion from stellar seeds or Eddington accretion from very massive BH seeds is required to form this object

A CEERS Discovery of an Accreting Supermassive Black Hole 570 Myr after the Big Bang: Identifying a Progenitor of Massive z > 6 Quasars

We report the discovery of an accreting supermassive black hole at z = 8.679. This galaxy, denoted here as CEERS_1019, was previously discovered as a Lyα-break galaxy by Hubble with a Lyα redshift from Keck. As part of the Cosmic Evolution Early Release Science (CEERS) survey, we have observed this source with JWST/NIRSpec, MIRI, NIRCam, and NIRCam/WFSS and uncovered a plethora of emission lines. The Hβ line is best fit by a narrow plus a broad component, where the latter is measured at 2.5σ with an FWHM ∼1200 km s−1. We conclude this originates in the broadline region of an active galactic nucleus (AGN). This is supported by the presence of weak high-ionization lines (N V, N IV], and C III]), as well as a spatial point-source component. The implied mass of the black hole (BH) is log (M BH/M ⊙) = 6.95 ± 0.37, and we estimate that it is accreting at 1.2 ± 0.5 times the Eddington limit. The 1–8 μm photometric spectral energy distribution shows a continuum dominated by starlight and constrains the host galaxy to be massive (log M/M⊙ ∼9.5) and highly star-forming (star formation rate, or SFR ∼ 30 M⊙ yr−1; log sSFR ∼ − 7.9 yr−1). The line ratios show that the gas is metal-poor (Z/Z ⊙ ∼ 0.1), dense (n e ∼ 103 cm−3), and highly ionized (log U ∼ − 2.1). We use this present highest-redshift AGN discovery to place constraints on BH seeding models and find that a combination of either super-Eddington accretion from stellar seeds or Eddington accretion from very massive BH seeds is required to form this object

COSMOS-Web: An Overview of the JWST Cosmic Origins Survey

We present the survey design, implementation, and outlook for COSMOS-Web, a 255 hour treasury program conducted by the James Webb Space Telescope in its first cycle of observations. COSMOS-Web is a contiguous 0.54 deg$^2$ NIRCam imaging survey in four filters (F115W, F150W, F277W, and F444W) that will reach 5$\sigma$ point source depths ranging $\sim$27.5-28.2 magnitudes. In parallel, we will obtain 0.19 deg$^2$ of MIRI imaging in one filter (F770W). COSMOS-Web will build on the rich heritage of multiwavelength observations and data products available in the COSMOS field. The design of COSMOS-Web is motivated by three primary science goals: (1) to discover thousands of galaxies in the Epoch of Reionization ($64$ and place constraints on the formation of the Universe's most massive galaxies ($M_\star>10^{10}$ M$_\odot$), and (3) directly measure the evolution of the stellar mass to halo mass relation using weak gravitational lensing out to $z\sim2.5$ and measure its variance with galaxies' star formation histories and morphologies. In addition, we anticipate COSMOS-Web's legacy value to reach far beyond these scientific goals, touching many other areas of astrophysics, such as the identification of the first direct collapse black hole candidates, ultracool sub-dwarf stars in the Galactic halo, and possibly the identification of $z>10$ pair-instability supernovae. In this paper we provide an overview of the survey's key measurements, specifications, goals, and prospects for new discovery

Dusty Starbursts Masquerading as Ultra-high Redshift Galaxies in JWST CEERS Observations

Lyman-break galaxy (LBG) candidates at z ≳ 10 are rapidly being identified in James Webb Space Telescope (JWST)/NIRCam observations. Due to the (redshifted) break produced by neutral hydrogen absorption of rest-frame UV photons, these sources are expected to drop out in the bluer filters while being well detected in redder filters. However, here we show that dust-enshrouded star-forming galaxies at lower redshifts (z ≲ 7) may also mimic the near-infrared (near-IR) colors of z > 10 LBGs, representing potential contaminants in LBG candidate samples. First, we analyze CEERS-DSFG-1, a NIRCam dropout undetected in the F115W and F150W filters but detected at longer wavelengths. Combining the JWST data with (sub)millimeter constraints, including deep NOEMA interferometric observations, we show that this source is a dusty star-forming galaxy (DSFG) at z ≈ 5.1. We also present a tentative 2.6σ SCUBA-2 detection at 850 μm around a recently identified z ≈ 16 LBG candidate in the same field and show that, if the emission is real and associated with this candidate, the available photometry is consistent with a z ∼ 5 dusty galaxy with strong nebular emission lines despite its blue near-IR colors. Further observations on this candidate are imperative to mitigate the low confidence of this tentative submillimeter emission and its positional uncertainty. Our analysis shows that robust (sub)millimeter detections of NIRCam dropout galaxies likely imply z ∼ 4–6 redshift solutions, where the observed near-IR break would be the result of a strong rest-frame optical Balmer break combined with high dust attenuation and strong nebular line emission, rather than the rest-frame UV Lyman break. This provides evidence that DSFGs may contaminate searches for ultra-high redshift LBG candidates from JWST observations

A Long Time Ago in a Galaxy Far, Far Away: A Candidate z ∼ 12 Galaxy in Early JWST CEERS Imaging

We report the discovery of a candidate galaxy with a photo-z of z ∼ 12 in the first epoch of the James Webb Space Telescope (JWST) Cosmic Evolution Early Release Science Survey. Following conservative selection criteria, we identify a source with a robust z phot = 11.8−0.2+0.3 (1σ uncertainty) with m F200W = 27.3 and ≳7σ detections in five filters. The source is not detected at λ 1.9 mag (2σ lower limit) with a blue continuum slope, resulting in 99.6% of the photo-z probability distribution function favoring z > 11. All data-quality images show no artifacts at the candidate’s position, and independent analyses consistently find a strong preference for z > 11. Its colors are inconsistent with Galactic stars, and it is resolved (r h = 340 ± 14 pc). Maisie’s Galaxy has log M */M ⊙ ∼ 8.5 and is highly star-forming (log sSFR ∼ −8.2 yr−1), with a blue rest-UV color (β ∼ −2.5) indicating little dust, though not extremely low metallicity. While the presence of this source is in tension with most predictions, it agrees with empirical extrapolations assuming UV luminosity functions that smoothly decline with increasing redshift. Should follow-up spectroscopy validate this redshift, our universe was already aglow with galaxies less than 400 Myr after the Big Bang

Dusty starbursts masquerading as ultra-high redshift galaxies in JWST CEERS observations

Lyman Break Galaxy (LBG) candidates at z ≳ 10 are rapidly being identified in JWST/NIRCam observations. Due to the (redshifted) break produced by neutral hydrogen absorption of rest-frame UV photons, these sources are expected to drop out in the bluer filters while being well-detected in redder filters. However, here we show that dust-enshrouded star-forming galaxies at lower redshifts (z ≲ 7) may also mimic the near-infrared colors of z > 10 LBGs, representing potential contaminants in LBG candidate samples. First, we analyze CEERS-DSFG-1, a NIRCam dropout undetected in the F115W and F150W filters but detected at longer wavelengths. Combining the JWST data with (sub)millimeter constraints, including deep NOEMA interferometric observations, we show that this source is a dusty star-forming galaxy (DSFG) at z ≈ 5.1. We also present a tentative 2.6σ SCUBA-2 detection at 850 µm around a recently identified z ≈ 16 LBG candidate in the same field and show that, if the emission is real and associated with this candidate, the available photometry is consistent with a z ∼ 5 dusty galaxy with strong nebular emission lines despite its blue near-IR colors. Further observations on this candidate are imperative to mitigate the low confidence of this tentative emission and its positional uncertainty. Our analysis shows that robust (sub)millimeter detections of NIRCam dropout galaxies likely imply z ∼ 4 − 6 redshift solutions, where the observed near-IR break would be the result of a strong rest-frame optical Balmer break combined with high dust attenuation and 2 The CEERS collaboration strong nebular line emission, rather than the rest-frame UV Lyman break. This provides evidence that DSFGs may contaminate searches for ultra high-redshift LBG candidates from JWST observations

Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial

Background: Additional safe and efficacious vaccines are needed to control the COVID-19 pandemic. We aimed to analyse the efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate. Methods: HERALD is a randomised, observer-blinded, placebo-controlled, phase 2b/3 clinical trial conducted in 47 centres in ten countries in Europe and Latin America. By use of an interactive web response system and stratification by country and age group (18–60 years and ≥61 years), adults with no history of virologically confirmed COVID-19 were randomly assigned (1:1) to receive intramuscularly either two 0·6 mL doses of CVnCoV containing 12 μg of mRNA or two 0·6 mL doses of 0·9% NaCl (placebo) on days 1 and 29. The primary efficacy endpoint was the occurrence of a first episode of virologically confirmed symptomatic COVID-19 of any severity and caused by any strain from 15 days after the second dose. For the primary endpoint, the trial was considered successful if the lower limit of the CI was greater than 30%. Key secondary endpoints were the occurrence of a first episode of virologically confirmed moderate-to-severe COVID-19, severe COVID-19, and COVID-19 of any severity by age group. Primary safety outcomes were solicited local and systemic adverse events within 7 days after each dose and unsolicited adverse events within 28 days after each dose in phase 2b participants, and serious adverse events and adverse events of special interest up to 1 year after the second dose in phase 2b and phase 3 participants. Here, we report data up to June 18, 2021. The study is registered at ClinicalTrials.gov, NCT04652102, and EudraCT, 2020–003998–22, and is ongoing. Findings: Between Dec 11, 2020, and April 12, 2021, 39 680 participants were enrolled and randomly assigned to receive either CVnCoV (n=19 846) or placebo (n=19 834), of whom 19 783 received at least one dose of CVnCoV and 19 746 received at least one dose of placebo. After a mean observation period of 48·2 days (SE 0·2), 83 cases of COVID-19 occurred in the CVnCoV group (n=12 851) in 1735·29 person-years and 145 cases occurred in the placebo group (n=12 211) in 1569·87 person-years, resulting in an overall vaccine efficacy against symptomatic COVID-19 of 48·2% (95·826% CI 31·0–61·4; p=0·016). Vaccine efficacy against moderate-to-severe COVID-19 was 70·7% (95% CI 42·5–86·1; CVnCoV 12 cases in 1735·29 person-years, placebo 37 cases in 1569·87 person-years). In participants aged 18–60 years, vaccine efficacy against symptomatic disease was 52·5% (95% CI 36·2–64·8; CVnCoV 71 cases in 1591·47 person-years, placebo, 136 cases in 1449·23 person-years). Too few cases occurred in participants aged 61 years or older (CVnCoV 12, placebo nine) to allow meaningful assessment of vaccine efficacy. Solicited adverse events, which were mostly systemic, were more common in CVnCoV recipients (1933 [96·5%] of 2003) than in placebo recipients (1344 [67·9%] of 1978), with 542 (27·1%) CVnCoV recipients and 61 (3·1%) placebo recipients reporting grade 3 solicited adverse events. The most frequently reported local reaction after any dose in the CVnCoV group was injection-site pain (1678 [83·6%] of 2007), with 22 grade 3 reactions, and the most frequently reported systematic reactions were fatigue (1603 [80·0%] of 2003) and headache (1541 [76·9%] of 2003). 82 (0·4%) of 19 783 CVnCoV recipients reported 100 serious adverse events and 66 (0·3%) of 19 746 placebo recipients reported 76 serious adverse events. Eight serious adverse events in five CVnCoV recipients and two serious adverse events in two placebo recipients were considered vaccination-related. None of the fatal serious adverse events reported (eight in the CVnCoV group and six in the placebo group) were considered to be related to study vaccination. Adverse events of special interest were reported for 38 (0·2%) participants in the CVnCoV group and 31 (0·2%) participants in the placebo group. These events were considered to be related to the trial vaccine for 14 (<0·1%) participants in the CVnCoV group and for five (<0·1%) participants in the placebo group. Interpretation: CVnCoV was efficacious in the prevention of COVID-19 of any severity and had an acceptable safety profile. Taking into account the changing environment, including the emergence of SARS-CoV-2 variants, and timelines for further development, the decision has been made to cease activities on the CVnCoV candidate and to focus efforts on the development of next-generation vaccine candidates. Funding: German Federal Ministry of Education and Research and CureVac