Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Observation of H2O in a strongly lensed Herschel-ATLAS source at z=2.3

The Herschel survey, H-ATLAS, with its large areal coverage, has recently discovered a number of bright, strongly lensed high-z submillimeter galaxies. The strong magnification makes it possible to study molecular species other than CO, which are otherwise difficult to observe in high-z galaxies. Among the lensed galaxies already identified by H-ATLAS, the source J090302.9-014127B (SDP.17b) at z = 2.305 is remarkable because of its excitation conditions and a tentative detection of the H2O 202-111 emission line (Lupu et al. 2010, ApJ, submitted). We report observations of this line in SDP.17b using the IRAM interferometer equipped with its new 277–371 GHz receivers. The H2O line is detected at a redshift of z = 2.3049 ± 0.0006, with a flux of 7.8 ± 0.5 Jy km s-1 and a FWHM of 250 ± 60   km   s-1. The new flux is 2.4 times weaker than the previous tentative detection, although both remain marginally consistent within 1.6σ. The intrinsic line luminosity and ratio of H2O(202 − 111)/CO(8 − 7) are comparable with those of the nearby starburst/enshrouded-AGN Mrk 231, and the ratio I(H2O)/LFIR is even higher, suggesting that SDP.17b could also host a luminous AGN. The detection of a strong H2O 202 − 111 line in SDP.17b implies an efficient excitation mechanism of the water levels that must occur in very dense and warm interstellar gas probably similar to Mrk 231

The Detection of a Population of Submillimeter-Bright, Strongly Lensed Galaxies

Original article can be found at : http://www.sciencemag.org/magazine Copyright AAAS. "This is the author's version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science 330 (6005) pp.800 - 804, doi:http://dx.doi.org/10.1126/science.1193420 "Gravitational lensing is a powerful astrophysical and cosmological probe and is particularly valuable at submillimeter wavelengths for the study of the statistical and individual properties of dusty star-forming galaxies. However, the identification of gravitational lenses is often time-intensive, involving the sifting of large volumes of imaging or spectroscopic data to find few candidates. We used early data from the Herschel Astrophysical Terahertz Large Area Survey to demonstrate that wide-area submillimeter surveys can simply and easily detect strong gravitational lensing events, with close to 100% efficiency.Peer reviewe