Using health surveillance systems data to assess the impact of AIDS and antiretroviral treatment on adult morbidity and mortality in Botswana

Introduction: Botswana's AIDS response included free antiretroviral treatment (ART) since 2002, achieving 80% coverage of persons with CD450% and >30% through 2011, while continuing to increase in older women. Conclusions: Adult mortality in Botswana fell markedly as ART coverage increased. HIV prevalence declines may reflect ART-associated reductions in sexual transmission. Triangulation of surveillance system data offers a reasonable approach to evaluate impact of HIV/AIDS interventions, complementing cohort approaches that monitor individual-level health outcomes

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

Contrasting genetic structures across two hybrid zones of a tropical reef fish, Acanthochromis polyacanthus (Bleeker 1855)

Hybrid zones are natural laboratories offering insights into speciation processes. Narrow hybrid zones are less common in the sea than on land consistent with higher dispersal among marine populations. Acanthochromis polyacanthus is an unusual bony marine fish with philopatric dispersal that exists as allopatric stocks of white, bicoloured and black fish on the Great Barrier Reef (GBR). At two latitudes, different morphs coexist and hybridize at narrow contact zones. Sequence data from mitochondrial Hypervariable Region 1 revealed contrasting patterns of introgression across these zones. At the northern hybrid zone, a single clade of mitochondrial haplotypes was found in all white fish, hybrids and tens of kilometres into pure bicoloured stock. At the southern hybrid zone, there was no introgression of mitochondrial genes into black fish and hybrids shared the bicoloured haplotypes. Based on this asymmetry, we postulate that black fish from the southern GBR have experienced a selective sweep of their mitochondrial genome, which has resulted in almost total reproductive isolation