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The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Bioindicators are organisms able to provide indirectly or directly information on the impact of pollutants in the environment. The content of heavy metals or other toxic compounds in these living organisms is of great interest to assess the level of contaminants. Leaves of the most common deciduous trees (Acer pseudoplatanus L., Betula pendula Roth, Carpinus betulus L., Cercis siliquastrum L., Ginkgo biloba L., Liquidambar styraciflua, Quercus robur L. and Tilia cordata Miller) and two invasive tree species Ailanthus altissima P. Mill. and Robinia pseudoacacia L., in the City of Bolzano (southern Alps in Northern Italy), were therefore studied to assess their suitability as bioindicators for the trace elements Cd, Cu, Mn, Pb, and Zn, mainly considered as traffic related elements. Leaves and soil samples were investigated, both from high-density traffic roads and control sites of minor traffic impact, such as parks. Our data reveal that Betula pendula has a considerable Zn accumulation potential compared to the other investigated tree species. The maximum value measured for Zn in a Betula specimen is 200 mg kg-1 dry weight. With regard to the soils, considering the geoaccumulation index, most of the analyzed soils belong to the first class, i. e. uncontaminated (Igeo ≤ 0) for all analyzed elements. Moreover, in several samples collected in high traffic areas, Cu and Zn show values within 1 < Igeo ≤ 2 (moderately contaminated). This allows to hypothesize a traffic-related origin for these elements. For this reason, B. pendula can be considered a potential heavy metal accumulator and therefore a good bioindicator for these urban pollutants. Since B. pendula is widely distributed in urban areas in Central and Northern Europe, it can be considered a species suitable for a systematic and comparative monitoring network.
Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium. Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs.