Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Capture, Movement, Trade, and Consumption of Mammals in Madagascar.

Wild meat trade constitutes a threat to many animal species. Understanding the commodity chain of wild animals (hunting, transportation, trade, consumption) can help target conservation initiatives. Wild meat commodity chain research has focused on the formal trade and less on informal enterprises, although informal enterprises contribute to a large portion of the wild meat trade in sub-Saharan Africa. We aimed to provide a more comprehensive understanding of the formal and informal components of these commodity chains by focusing on the mammalian wild meat trade in Madagascar. Our objectives were to: (1) identify hunting strategies used to capture different wild mammals; (2) analyze patterns of movement of wild meat from the capture location to the final consumer; (3) examine wild meat prices, volumes, and venues of sale; and (4) estimate the volume of wild meat consumption. Data were collected in May-August 2013 using semi-structured interviews with consumers (n = 1343 households, 21 towns), meat-sellers (n = 520 restaurants, open-air markets stalls, and supermarkets, 9 towns), and drivers of inter-city transit vehicles (n = 61, 5 towns). We found that: (1) a wide range of hunting methods were used, though prevalence of use differed by animal group; (2) wild meat was transported distances of up to 166 km to consumers, though some animal groups were hunted locally (<10 km) in rural areas; (3) most wild meat was procured from free sources (hunting, gifts), though urban respondents who consumed bats and wild pigs were more likely to purchase those meats; and (4) wild meat was consumed at lower rates than domestic meat, though urban respondents consumed wild meat twice as much per year compared to rural respondents. Apart from the hunting stage, the consumption and trade of wild meat in Madagascar is also likely more formalized than previously thought

Distances that meat was transported prior to consumption.

<p>Data taken from meat consumption interviews. Distances that meat was transported to, or that urban and rural consumers traveled, to (A) procure wild meat as a gift, from hunting, or purchase; and (B) domestic and wild meat purchased from restaurants, markets, hunters, and middlemen. The whiskers extend to data points within 1.5 times the interquartile range; black circles indicate outliers. Towns are replicates. ND: No Data; UW: Urban seller of wild meat; UD: Urban seller of domestic meat; RW: Rural seller of wild meat; RD: Rural seller of domestic meat.</p

Table of study sites included in research project.

<p>Table of study sites included in research project.</p

Comparison of hunting methods used to capture wild mammals for sale and for personal consumption (percentages).

<p>Individuals are replicates; data taken from meat consumption interviews. Hands = catching with hands by one or multiple people. Trap/Net = includes nets, cable traps, bait with traps. Spit Tube = a blow tube or a device to shoot darts. Stick = includes hitting animal with stick or spearing animal with stick. Individuals are replicates. Other = includes all other hunting methods (e.g. slingshots, fire, using a cross bow).</p

Hunting methods used pre-2009 and between 2009–2013 for (A) urban- and (B) rural hunters (percentages).

<p>Data taken from meat consumption interviews. Only animal groups with ≥5 respondents in each time class are presented. Individuals are replicates. Hands = catching with hands by one or multiple people. Trap/Net = includes nets, cable traps, bait with traps. Spit Tube = a blow tube or a device to shoot darts. Stick = includes hitting animal with stick or spearing animal with stick. Individuals are replicates. Other = includes other hunting methods (e.g. fire, using a cross bow).</p

Urban towns in central and northern Madagascar where interviews were conducted.

<p>The shaded rectangle shows the location of rural towns (in the vicinity of the Ankarana National Park) where interviews were conducted but exact locations are not shown to protect respondent anonymity. Figure originally published in Reuter et al. 2015 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0150305#pone.0150305.ref027" target="_blank">27</a>].</p

Time of year when respondents hunt for different types of wild mammals (individuals are replicates).

<p>Sample sizes are listed for each animal group. Data taken from meat consumption interviews. Quarter 1: January-March; Quarter 2: April-June; Quarter 3: July-September; Quarter 4: October-December.</p