Impacts of chronic wasting disease on a low density mule deer (Odocoileus hemionus) population in the San Andres Mountains, Chihuahuan Desert, New Mexico

Chronic wasting disease (CWD), a contagious neurodegenerative disease of cervids, is becoming increasingly prevalent in the arid Southwest including the Chihuahuan Desert ecoregion. Population effects of CWD are uncertain, particularly in arid environments, as previous work has been on relatively high density deer populations in semi-arid or temperate environments. In 2002, CWD was detected in a low density mule deer (Odocoileus hemionus) population in the arid San Andres Mountains, a Chihuahuan Desert range in southern New Mexico. We determined prevalence and distribution of CWD, and mortality and movements of deer, to assess the potential impact on low density deer populations in arid environments. Repeated seasonal primarily ante-mortem sampling found stable prevalence of 0.000–0.091, 2003–2008. Annual CWD mortality rate was <0.02, including deer that were culled. Monitoring of adult radio-collared deer showed no dispersal movements away from home ranges, with maximum movements of ≤20 km; similarly, no juveniles dispersed from maternal ranges. Distribution of infected deer was strongly related to presence of other infected deer. Annual survival rates of mule deer and population rate-of-increase suggested little effect of CWD on population-level mortality given observed prevalence. Transmission and reservoirs of CWD in the SAM were likely limited by low deer densities, patchy distribution, and environmental characteristics (i.e., low clay content of soils) unfavorable to prion persistence, characteristics that are typical of most mule deer populations in the Chihuahuan Desert ecoregion.La enfermedad crónica degenerativa (por sus siglas en inglés: CWD), una enfermedad neurodegenerativa contagiosa de los cérvidos, se está haciendo cada vez más frecuente en el suroeste árido americano incluyendo la ecoregión del desierto de Chihuahua. Los efectos de la CWD sobre poblaciones de cérvidos silvestres son inciertos, particularmente en ambientes áridos, ya que el trabajo previo ha estado en poblaciones de ciervos de densidad relativamente alta en ambientes semi-áridos o templados. En 2002, la CWD fue detectada en una población de venado bura (Odocoileus hemionus) de baja densidad en las áridas montañas de San Andrés, una región del Desierto Chihuahuense en el sur de Nuevo México. Se determinó la prevalencia y distribución de CWD, y la mortalidad y los movimientos de los venados, para evaluar su impacto potencial en poblaciones de baja densidad en ambientes áridos. En el muestreo ante-mortem previo repetido estacionalmente se encontró prevalencia estable de 0,000–0,091, 2003–2008. La tasa anual de mortalidad por CWD fue <0,02, incluyendo venados que fueron sacrificados. El monitoreo de venados con radio-collares adultos no mostró movimientos de dispersión fuera de los rangos de origen, con movimientos máximos de ≤20 km; de manera similar, no hay juveniles dispersos de los rangos maternos. La distribución de los venados infectados estaba fuertemente relacionada con la presencia de otros venados infectados. Las tasas anuales de supervivencia del venado mula y la tasa de aumento de la población sugirieron un efecto pequeño de la CWD en la mortalidad a nivel de la población dada la prevalencia observada. La transmisión y los depósitos de CWD en el SAM (Montañas San Andrés) fueron probablemente limitados por la baja densidad de los venados, su distribución irregular y las características ambientales (es decir, bajo contenido de arcilla de los suelos) desfavorables a la persistencia de priones, características típicas de la mayoría de las poblaciones de venados bura en la ecorregión del Desierto Chihuahuense

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

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Factors influencing survival of desert mule deer in the greater San Andres Mountains, New Mexico

Mule deer numbers have declined precipitously in the San Andres Mountains of southcentral New Mexico. To assess reasons for population declines, we monitored condition, survival, and causes of mortality for a range of 37 to 64 radio-collared, \u3e1.5-year-old female mule deer annually, and a range of 14 to 31 radio-collared, \u3e1.5-year-old male mule deer annually from 2003 to 2009, and modeled environmental factors affecting survival. We found annual survival rates of 0.74 to 0.86 for females and 0.74 to 0.92 for males, rates that were similar among years within sexes. Causes of mortality for 50 radio-collared females and 22 radio-collared males included predation (13 females, 2 males), accidents (4 females, 1 male), malnutrition (13 females, 7 males), disease (6 females, 2 males), unknown-not-predation (3 females, 6 males), unknown (11 females, 3 males), and harvest (0 females, 1 male). Condition of females varied among years and was poor in most years (i.e., lactating females had1.0] \u3e 0.937). Potential rates of increase of mule deer in the greater San Andres Mountains were limited by production and survival of fawns, rather than adult mortality