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1

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A second update on mapping the human genetic architecture of COVID-19

The COVID-19 Host Genetics Initiative ; Kanai, Masahiro ; Andrews, Shea J. ; [weitere]

Springer Science and Business Media LLC ; 2023

In: Nature Vol. 621, No. 7977 ( 2023-09-07), p. E7-E26

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In: Nature, Springer Science and Business Media LLC, Vol. 621, No. 7977 ( 2023-09-07), p. E7-E26

Materialart: Online-Ressource

ISSN: 0028-0836 , 1476-4687

URL: Article

DOI: 10.1038/s41586-023-06355-3

RVK:

TA 1000

RVK:

UA 1000

RVK:

WA 15000

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2023

ZDB Id: 120714-3

ZDB Id: 1413423-8

SSG: 11

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2

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Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Pisani, Luigi ; Algera, Anna Geke ; Neto, Ary Serpa ; [weitere]

Elsevier BV ; 2022

In: The Lancet Global Health Vol. 10, No. 2 ( 2022-02), p. e227-e235

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In: The Lancet Global Health, Elsevier BV, Vol. 10, No. 2 ( 2022-02), p. e227-e235

Materialart: Online-Ressource

ISSN: 2214-109X

URL: Article

DOI: 10.1016/S2214-109X(21)00485-X

Sprache: Englisch

Verlag: Elsevier BV

Publikationsdatum: 2022

ZDB Id: 2723488-5

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3

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GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Pairo-Castineira, Erola ; Rawlik, Konrad ; Bretherick, Andrew D. ; [weitere]

Springer Science and Business Media LLC ; 2023

In: Nature Vol. 617, No. 7962 ( 2023-05-25), p. 764-768

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In: Nature, Springer Science and Business Media LLC, Vol. 617, No. 7962 ( 2023-05-25), p. 764-768

Kurzfassung: Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown 1 to be highly efficient for discovery of genetic associations 2 . Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group 3 . Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling ( JAK1 ), monocyte–macrophage activation and endothelial permeability ( PDE4A ), immunometabolism ( SLC2A5 and AK5 ), and host factors required for viral entry and replication ( TMPRSS2 and RAB2A ).

Materialart: Online-Ressource

ISSN: 0028-0836 , 1476-4687

URL: Article

DOI: 10.1038/s41586-023-06034-3

RVK:

TA 1000

RVK:

UA 1000

RVK:

WA 15000

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2023

ZDB Id: 120714-3

ZDB Id: 1413423-8

SSG: 11

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4

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Author Correction: GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Pairo-Castineira, Erola ; Rawlik, Konrad ; Bretherick, Andrew D. ; [weitere]

Springer Science and Business Media LLC ; 2023

In: Nature Vol. 619, No. 7971 ( 2023-07-27), p. E61-E61

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In: Nature, Springer Science and Business Media LLC, Vol. 619, No. 7971 ( 2023-07-27), p. E61-E61

Materialart: Online-Ressource

ISSN: 0028-0836 , 1476-4687

URL: Article

DOI: 10.1038/s41586-023-06383-z

RVK:

TA 1000

RVK:

UA 1000

RVK:

WA 15000

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2023

ZDB Id: 120714-3

ZDB Id: 1413423-8

SSG: 11

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5

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Mapping the human genetic architecture of COVID-19

COVID-19 Host Genetics Initiative ; Niemi, Mari E. K. ; Karjalainen, Juha ; [weitere]

Springer Science and Business Media LLC ; 2021

In: Nature Vol. 600, No. 7889 ( 2021-12-16), p. 472-477

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In: Nature, Springer Science and Business Media LLC, Vol. 600, No. 7889 ( 2021-12-16), p. 472-477

Kurzfassung: 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-19 1,2 , 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 diseases 3–7 . 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.

Materialart: Online-Ressource

ISSN: 0028-0836 , 1476-4687

URL: Article

DOI: 10.1038/s41586-021-03767-x

RVK:

TA 1000

RVK:

UA 1000

RVK:

WA 15000

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2021

ZDB Id: 120714-3

ZDB Id: 1413423-8

SSG: 11

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6

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Death in hospital following ICU discharge: insights from the LUNG SAFE study

Madotto, Fabiana ; McNicholas, Bairbre ; Rezoagli, Emanuele ; [weitere]

Springer Science and Business Media LLC ; 2021

In: Critical Care Vol. 25, No. 1 ( 2021-12)

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In: Critical Care, Springer Science and Business Media LLC, Vol. 25, No. 1 ( 2021-12)

Kurzfassung: To determine the frequency of, and factors associated with, death in hospital following ICU discharge to the ward. Methods The Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE study was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted across 459 ICUs from 50 countries globally. This study aimed to understand the frequency and factors associated with death in hospital in patients who survived their ICU stay. We examined outcomes in the subpopulation discharged with no limitations of life sustaining treatments (‘treatment limitations’), and the subpopulations with treatment limitations. Results 2186 (94%) patients with no treatment limitations discharged from ICU survived, while 142 (6%) died in hospital. 118 (61%) of patients with treatment limitations survived while 77 (39%) patients died in hospital. Patients without treatment limitations that died in hospital after ICU discharge were older, more likely to have COPD, immunocompromise or chronic renal failure, less likely to have trauma as a risk factor for ARDS. Patients that died post ICU discharge were less likely to receive neuromuscular blockade, or to receive any adjunctive measure, and had a higher pre- ICU discharge non-pulmonary SOFA score. A similar pattern was seen in patients with treatment limitations that died in hospital following ICU discharge. Conclusions A significant proportion of patients die in hospital following discharge from ICU, with higher mortality in patients with limitations of life-sustaining treatments in place. Non-survivors had higher systemic illness severity scores at ICU discharge than survivors. Trial Registration : ClinicalTrials.gov NCT02010073 .

Materialart: Online-Ressource

ISSN: 1364-8535

URL: Article

DOI: 10.1186/s13054-021-03465-0

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2021

ZDB Id: 2051256-9

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7

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Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the LUNG SAFE study

Amado-Rodríguez, Laura ; Rodríguez-Garcia, Raquel ; Bellani, Giacomo ; [weitere]

Springer Science and Business Media LLC ; 2022

In: Journal of Intensive Care Vol. 10, No. 1 ( 2022-12-25)

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In: Journal of Intensive Care, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2022-12-25)

Kurzfassung: Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality. Methods Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied. Relationships between ventilatory parameters and outcomes (ICU discharge/hospital mortality) were assessed using latent mixture analysis and a marginal structural model. Results From 4499 patients, 391 meeting CPE criteria (median age 70 [interquartile range 59–78], 40% female) were included. ICU and hospital mortality were 34% and 40%, respectively. ICU survivors were younger (67 [57–77] vs 74 [64–80] years, p 〈 0.001) and had lower driving (12 [8–16] vs 15 [11–17] cmH 2 O, p 〈 0.001), plateau (20 [15–23] vs 22 [19–26] cmH 2 O, p 〈 0.001) and peak (21 [17–27] vs 26 [20–32] cmH 2 O, p 〈 0.001) pressures. Latent mixture analysis of patients receiving invasive mechanical ventilation on ICU day 1 revealed a subgroup ventilated with high pressures with lower probability of being discharged alive from the ICU (hazard ratio [HR] 0.79 [95% confidence interval 0.60–1.05] , p = 0.103) and increased hospital mortality (HR 1.65 [1.16–2.36], p = 0.005). In a marginal structural model, driving pressures in the first week (HR 1.12 [1.06–1.18], p 〈 0.001) and tidal volume after day 7 (HR 0.69 [0.52–0.93], p = 0.015) were related to survival. Conclusions Higher airway pressures in invasively ventilated patients with CPE are related to mortality. These patients may be exposed to an increased risk of ventilator-induced lung injury. Trial registration Clinicaltrials.gov NCT02010073

Materialart: Online-Ressource

ISSN: 2052-0492

URL: Article

DOI: 10.1186/s40560-022-00648-x

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2022

ZDB Id: 2739853-5

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8

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Geo-economic variations in epidemiology, patterns of care, and outcomes in patients with acute respiratory distress syndrome: insights from the LUNG SAFE prospective cohort study

Laffey, John G ; Madotto, Fabiana ; Bellani, Giacomo ; [weitere]

Elsevier BV ; 2017

In: The Lancet Respiratory Medicine Vol. 5, No. 8 ( 2017-08), p. 627-638

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In: The Lancet Respiratory Medicine, Elsevier BV, Vol. 5, No. 8 ( 2017-08), p. 627-638

Materialart: Online-Ressource

ISSN: 2213-2600

URL: Article

DOI: 10.1016/S2213-2600(17)30213-8

Sprache: Englisch

Verlag: Elsevier BV

Publikationsdatum: 2017

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9

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Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis

Maddali, Manoj V ; Churpek, Matthew ; Pham, Tai ; [weitere]

Elsevier BV ; 2022

In: The Lancet Respiratory Medicine Vol. 10, No. 4 ( 2022-04), p. 367-377

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In: The Lancet Respiratory Medicine, Elsevier BV, Vol. 10, No. 4 ( 2022-04), p. 367-377

Materialart: Online-Ressource

ISSN: 2213-2600

URL: Article

DOI: 10.1016/S2213-2600(21)00461-6

Sprache: Englisch

Verlag: Elsevier BV

Publikationsdatum: 2022

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