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Epigenetic susceptibility to severe respiratory viral infections and its therapeutic implications: a narrative review.

ABSTRACT: The emergence of highly pathogenic strains of influenza virus and coronavirus (CoV) has been responsible for large epidemic and pandemic outbreaks characterised by severe pulmonary illness associated with high morbidity and mortality. One major challenge for critical care is to stratify and minimise the risk of multi-organ failure during the stay in the intensive care unit (ICU). Epigenetic-sensitive mechanisms, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) methylation, histone modifications, and non-coding RNAs may lead to perturbations of the host immune-related transcriptional programmes by regulating chromatin structure and gene expression patterns. Viruses causing severe pulmonary illness can use epigenetic-regulated mechanisms during host-pathogen interaction to interfere with innate and adaptive immunity, adequacy of inflammatory response, and overall outcome of viral infections. For example, Middle East respiratory syndrome-CoV and H5N1 can affect host antigen presentation through DNA methylation and histone modifications. The same mechanisms would presumably occur in patients with coronavirus disease 2019, in which tocilizumab may epigenetically reduce microvascular damage. Targeting epigenetic pathways by immune modulators (e.g. tocilizumab) or repurposed drugs (e.g. statins) may provide novel therapeutic opportunities to control viral-host interaction during critical illness. In this review, we provide an update on epigenetic-sensitive mechanisms and repurposed drugs interfering with epigenetic pathways which may be clinically suitable for risk stratification and beneficial for treatment of patients affected by severe viral respiratory infections.

SUBMITTER: Crimi E

PROVIDER: S-EPMC7438995 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Epigenetic susceptibility to severe respiratory viral infections and its therapeutic implications: a narrative review.

Crimi Ettore E Benincasa Giuditta G Figueroa-Marrero Neisaliz N Galdiero Massimiliano M Napoli Claudio C

British journal of anaesthesia 20200820 6

The emergence of highly pathogenic strains of influenza virus and coronavirus (CoV) has been responsible for large epidemic and pandemic outbreaks characterised by severe pulmonary illness associated with high morbidity and mortality. One major challenge for critical care is to stratify and minimise the risk of multi-organ failure during the stay in the intensive care unit (ICU). Epigenetic-sensitive mechanisms, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) methylation, histon ...[more]

PMID: 32828489

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Project description:BackgroundSevere acute respiratory infections (SARIs) are the leading cause of paediatric death globally, particularly in low- and middle-income countries (LMICs). Given the potential rapid clinical decompensation and high mortality rate from SARIs, interventions that facilitate the early care are critical to improving patient outcomes. Through this systematic review, we aimed to evaluate the impact of emergency care interventions on improving clinical outcomes of paediatric patients with SARIs in LMICs.MethodsWe searched PubMed, Global Health, and Global Index Medicus for peer-reviewed clinical trials or studies with comparator groups published before November 2020. We included all studies which evaluated acute and emergency care interventions on clinical outcomes for children (29 days to 19 years) with SARIs conducted in LMICs. Due to observed heterogeneity of interventions and outcomes, we performed narrative synthesis. We assessed bias using the Risk of Bias 2 and Risk of Bias in Non-Randomized Studies of Interventions tools.ResultsWe screened 20 583, 99 of which met the inclusion criteria. Conditions studied included pneumonia or acute lower respiratory infection (61.6%) and bronchiolitis (29.3%). Studies evaluated medications (80.8%), respiratory support (14.1%), and supportive care (5%). We found the strongest evidence of benefit for decreasing risk of death for respiratory support interventions. Results were inconclusive on the utility of continuous positive airway pressure (CPAP). We found mixed results for interventions for bronchiolitis, but a possible benefit for hypertonic nebulised saline to decrease hospital length of stay. Early use of adjuvant treatments such as Vitamin A, D, and zinc for pneumonia and bronchiolitis did not appear to have convincing evidence of benefit on clinical outcomes.ConclusionsDespite the high global burden of SARI in paediatric populations, few emergency care (EC) interventions have high quality evidence for benefit on clinical outcomes in LMICs. Respiratory support interventions have the strongest evidence for benefit. Further research on the use of CPAP in diverse settings is needed, as is a stronger evidence base for EC interventions for children with SARI, including metrics on the timing of interventions.RegistrationPROSPERO (CRD42020216117).

Dataset Information

Epigenetic susceptibility to severe respiratory viral infections and its therapeutic implications: a narrative review.

Publications

Epigenetic susceptibility to severe respiratory viral infections and its therapeutic implications: a narrative review.

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