Genomic and Genetic Approaches to Deciphering Acute Respiratory Distress Syndrome Risk and Mortality

Lynn, Heather; Sun, Xiaoguang; Casanova, Nancy G.; Gonzales-Garay, Manuel; Bime, Christian; Garcia, Joe G.N.

doi:10.1089/ars.2018.7701

Cited by 41 publications

(38 citation statements)

References 205 publications

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“…29 Candidate genes associated with ARDS have been identified in bioinformatic analyses, with a strong predominance of inflammatory pathways, including reactive oxygen species, innate immunity-related inflammation and endothelial vascular signalling pathways. 30 Ethnicity may influence cytokine gene polymorphisms and inflammatory profiles following specific challenges, 31 with some ethnic groups more prone to a heightened inflammatory response. Of note, socioeconomic factors might also impact on inflammatory pathways and gene expression.…”

Section: Discussionmentioning

confidence: 99%

Ethnicity and risk of death in patients hospitalised for COVID-19 infection in the UK: an observational cohort study in an urban catchment area

et al. 2020

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BackgroundStudies suggest that certain black and Asian minority ethnic groups experience poorer outcomes from COVID-19, but these studies have not provided insight into potential reasons for this. We hypothesised that outcomes would be poorer for those of South Asian ethnicity hospitalised from a confirmed SARS-CoV-2 infection, once confounding factors, health-seeking behaviours and community demographics were considered, and that this might reflect a more aggressive disease course in these patients.MethodsPatients with confirmed SARS-CoV-2 infection requiring admission to University Hospitals Birmingham NHS Foundation Trust (UHB) in Birmingham, UK between 10 March 2020 and 17 April 2020 were included. Standardised admission ratio (SAR) and standardised mortality ratio (SMR) were calculated using observed COVID-19 admissions/deaths and 2011 census data. Adjusted HR for mortality was estimated using Cox proportional hazard model adjusting and propensity score matching.ResultsAll patients admitted to UHB with COVID-19 during the study period were included (2217 in total). 58% were male, 69.5% were white and the majority (80.2%) had comorbidities. 18.5% were of South Asian ethnicity, and these patients were more likely to be younger and have no comorbidities, but twice the prevalence of diabetes than white patients. SAR and SMR suggested more admissions and deaths in South Asian patients than would be predicted and they were more likely to present with severe disease despite no delay in presentation since symptom onset. South Asian ethnicity was associated with an increased risk of death, both by Cox regression (HR 1.4, 95% CI 1.2 to 1.8), after adjusting for age, sex, deprivation and comorbidities, and by propensity score matching, matching for the same factors but categorising ethnicity into South Asian or not (HR 1.3, 95% CI 1.0 to 1.6).ConclusionsThose of South Asian ethnicity appear at risk of worse COVID-19 outcomes. Further studies need to establish the underlying mechanistic pathways.

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Section: Discussionmentioning

confidence: 99%

Ethnicity and risk of death in patients hospitalised for COVID-19 infection in the UK: an observational cohort study in an urban catchment area

et al. 2020

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“…Using bioinformatic analysis for genetic associations with ARDS, a total of 201 genes were found predominantly involved in pathways modulating inflammation, especially linked to innate immunity, reactive oxygen species, and endothelial vascular signaling (108); it is worth noting that all these pathways are modulated by NOS.…”

Section: Genetic and Translational Factors Involved In Severementioning

confidence: 99%

A dissection of SARS‑CoV2 with clinical implications (Review)

Stancioiu¹,

Papadakis

Kteniadakis

et al. 2020

Int J Mol Med

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We are being confronted with the most consequential pandemic since the Spanish flu of 1918-1920 to the extent that never before have 4 billion people quarantined simultaneously; to address this global challenge we bring to the forefront the options for medical treatment and summarize SARS-coV2 structure and functions, immune responses and known treatments. Based on literature and our own experience we propose new interventions, including the use of amiodarone, simvastatin, pioglitazone and curcumin. In mild infections (sore throat, cough) we advocate prompt local treatment for the naso-pharynx (inhalations; aerosols; nebulizers); for moderate to severe infections we propose a tried-and-true treatment: the combination of arginine and ascorbate, administered orally or intravenously. The material is organized in three sections: i) Clinical aspects of COVID-19; acute respiratory distress syndrome (ARdS); known treatments; ii) Structure and functions of SARS-coV2 and proposed antiviral drugs; iii) The combination of arginine-ascorbate. Contents 1. Clinical aspects of COVID-19 infections; acute respiratory distress syndrome (ARdS); known and potential treatments 2. SARS-coV2 molecules and proposed antiviral drugs 3. The combination of arginine-ascorbate

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“…Thus, personalized medicine approaches are tasked with the capacity to predict the patient phenotype likely to develop progressive disease or that may eventually require lung transplantation. While there has been progress in identifying genetic variants that contribute to complicated sarcoidosis [5,6], and we have previously utilized genomic expression profiling of peripheral mononuclear cells (PBMCs) to subphenotype patients with a variety of inflammatory disorders [7][8][9] including sarcoidosis [10], there remains an important and unmet need for molecular and specific genome-based biomarkers for diagnosis and prediction of disease severity in sarcoidosis.…”

Section: Introductionmentioning

confidence: 99%

Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

et al. 2020

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Rationale Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures. Objective To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). Methods Transcriptomic profiles of immune-related gene from micro-dissected sarcoidosis granulomas within lung and mediastinal lymph node tissues and compared to infectious granulomas from paraffin-embedded blocks. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. Results Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers (STAB1, HBEGF, and NOTCH4), excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, NPR1 and CXCL2. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level. Conclusion These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.

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Genomic and Genetic Approaches to Deciphering Acute Respiratory Distress Syndrome Risk and Mortality

Cited by 41 publications

References 205 publications

Ethnicity and risk of death in patients hospitalised for COVID-19 infection in the UK: an observational cohort study in an urban catchment area

Ethnicity and risk of death in patients hospitalised for COVID-19 infection in the UK: an observational cohort study in an urban catchment area

A dissection of SARS‑CoV2 with clinical implications (Review)

Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

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