Asgard archaea shed light on the evolutionary origins of the eukaryotic ubiquitin-ESCRT machinery.

The ESCRT machinery, comprising of multiple proteins and subcomplexes, is crucial for membrane remodelling in eukaryotic cells, in processes that include ubiquitin-mediated multivesicular body formation, membrane repair, cytokinetic abscission, and virus exit from host cells. This ESCRT system appears to have simpler, ancient origins, since many archaeal species possess homologues of ESCRT-III and Vps4, the components that execute the final membrane scission reaction, where they have been shown to play roles in cytokinesis, extracellular vesicle formation and viral egress. Remarkably, metagenome assemblies of Asgard archaea, the closest known living relatives of eukaryotes, were recently shown to encode homologues of the entire cascade involved in ubiquitin-mediated membrane remodelling, including ubiquitin itself, components of the ESCRT-I and ESCRT-II subcomplexes, and ESCRT-III and Vps4. Here, we explore the phylogeny, structure, and biochemistry of Asgard homologues of the ESCRT machinery and the associated ubiquitylation system. We provide evidence for the ESCRT-I and ESCRT-II subcomplexes being involved in ubiquitin-directed recruitment of ESCRT-III, as it is in eukaryotes. Taken together, our analyses suggest a pre-eukaryotic origin for the ubiquitin-coupled ESCRT system and a likely path of ESCRT evolution via a series of gene duplication and diversification events.

Cardiovascular risk factors and clinical outcomes of patients hospitalized with COVID-19 pneumonia in Somalia.

Background: Coronavirus disease-2019 (COVID-19) is a potentially life-threatening illness with no established treatment. Cardiovascular risk factors (CRFs) exacerbate COVID-19 morbidity and mortality. Objective: To determine the prevalence of CRF and clinical outcomes of patients hospitalized with COVID-19 in a tertiary hospital in Somalia. Methods: We reviewed the medical records of patients aged 18 years or older with a real-time polymerase chain reaction (RT-PCR)-confirmed COVID-19 hospitalized at the De Martino Hospital in Mogadishu, Somalia, between March and July 2020. Results: We enrolled 230 participants; 159 (69.1%) males, median age was 56 (41-66) years. In-hospital mortality was 19.6% (n = 45); 77.8% in the intensive care unit (ICU) compared with 22.2%, in the general wards (p < 0.001). Age ⩾ 40 years [odds ratio (OR): 3.6, 95% confidence interval (CI): 1.2-10.6, p = 0.020], chronic heart disease (OR: 9.3, 95% CI: 2.2-38.9, p = 0.002), and diabetes mellitus (OR: 3.2, 95% CI: 1.6-6.2, p < 0.001) were associated with increased odds of mortality. Forty-three (18.7%) participants required ICU admission. Age ⩾ 40 years (OR: 7.5, 95% CI: 1.7-32.1, p = 0.007), diabetes mellitus (OR: 3.2, 95% CI: 1.6-6.3, p < 0.001), and hypertension (OR: 2.5, 95% CI: 1.2-5.2, p = 0.014) were associated with ICU admission. For every additional CRF, the odds of admission into the ICU increased threefold (OR: 2.7, 95% CI: 1.2-5.2, p < 0.001), while the odds of dying increased twofold (OR: 2.1, 95% CI: 1.3-3.2, p < 0.001). Conclusions: We report a very high prevalence of CRF among patients hospitalized with COVID-19 in Somalia. Mortality rates were unacceptably high, particularly among those with advanced age, underlying chronic heart disease, and diabetes.