Sara Clohisey
A5066792179- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- interferon and immune responses
- Intensive Care Unit Cognitive Disorders
- COVID-19 and Mental Health
- Immune cells in cancer
- Influenza Virus Research Studies
- Respiratory Support and Mechanisms
- RNA and protein synthesis mechanisms
- Respiratory viral infections research
- COVID-19 and healthcare impacts
- Immune Response and Inflammation
- Sepsis Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA modifications and cancer
- Inflammasome and immune disorders
- Genetic Associations and Epidemiology
- Animal Virus Infections Studies
- Neonatal Respiratory Health Research
- Frailty in Older Adults
- RNA Research and Splicing
- Diabetes and associated disorders
- Viral gastroenteritis research and epidemiology
- Bioinformatics and Genomic Networks
University of Edinburgh
2014-2024
Roslin Institute
2016-2024
Imperial College London
2022-2024
Centre for Inflammation Research
2022-2024
The Queen's Medical Research Institute
2022-2024
Johns Hopkins Hospital
2024
University of Oxford
2021-2023
NIHR Newcastle Biomedical Research Centre
2023
Oxford Health NHS Foundation Trust
2021-2023
UK Health Security Agency
2023
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with may identify mechanistic targets for therapeutic development3. Here we report results of GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study 2,244 critically ill patients COVID-19 from 208 UK intensive care units. We have identified replicated following new significant associations: on...
Abstract Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care 1 or hospitalization 2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics Mortality in Care) study enables comparison genomes from individuals who are critically ill those population controls to find underlying disease mechanisms. Here we use whole-genome sequencing 7,491 compared 48,400 discover and replicate 23...
Inherited genetic factors can influence the severity of COVID-19, but molecular explanation underpinning a association is often unclear. Intracellular antiviral defenses inhibit replication viruses and reduce disease severity. To better understand relevant to we used interferon-stimulated gene (ISG) expression screening reveal that 2′-5′-oligoadenylate synthetase 1 (OAS1), through ribonuclease L, potently inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show common...
Studies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed characterise people disease, assess the level care received, measure in-hospital mortality, examine effect use.We analysed International Severe Acute Respiratory emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK)...
Abstract The subset of patients who develop critical illness in Covid-19 have extensive inflammation affecting the lungs 1 and are strikingly different from other patients: immunosuppressive therapy benefits critically-ill patients, but may harm some non-critical cases. 2 Since susceptibility to life-threatening infections immune-mediated diseases both strongly heritable traits, we reasoned that host genetic variation identify mechanistic targets for therapeutic development Covid-19. 3...
We have produced Csf1r-deficient rats by homologous recombination in embryonic stem cells. Consistent with the role of Csf1r macrophage differentiation, there was a loss peripheral blood monocytes, microglia brain, epidermal Langerhans cells, splenic marginal zone macrophages, bone-associated macrophages and osteoclasts, peritoneal macrophages. Macrophages red pulp, liver, lung, gut were less affected. The pleiotropic impacts on development multiple organ systems distinct from those reported...
Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). This study investigated adults hospitalized with COVID-19 and hypothesized that risk factors for AKI would include comorbidities non-White race.
Abstract Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, often neglected. In present study, we have shown that ARDS patients were hypoxemic monocytopenic within first 48 h ventilation. Monocytopenia was also observed in mouse models hypoxic lung injury, which hypoxemia drove suppression type I interferon signaling bone marrow....
Macrophage colony-stimulating factor (CSF1) is an essential growth and differentiation for cells of the macrophage lineage. To explore role CSF1 in steady-state control monocyte production tissue repair, we previously developed a bioactive protein with longer half-life circulation by fusing pig Fc region IgG1a. CSF1-Fc administration to pigs expanded progenitor pools marrow selectively increased numbers their expression maturation marker CD163. There was rapid increase size liver, extensive...
Immunopathology occurs in the lung and spleen fatal coronavirus disease (COVID-19), involving monocytes/macrophages plasma cells. Antiinflammatory therapy reduces mortality, but additional therapeutic targets are required. We aimed to gain mechanistic insight into COVID-19 immunopathology by targeted proteomic analysis of pulmonary splenic tissues. Lung parenchymal tissue was obtained from 13 postmortem examinations patients with COVID-19. Control cancer resection samples (lung) deceased...
Synonymous recoding of RNA virus genomes is a promising approach for generating attenuated viruses to use as vaccines. Problematically, typically hinders growth, but this may be rectified using CpG dinucleotide enrichment. CpGs are recognised by cellular zinc-finger antiviral protein (ZAP), and so in principle, removing ZAP sensing from propagation system will reverse attenuation CpG-enriched virus, enabling high titre yield vaccine virus. We tested strain influenza A (IAV) engineered...
RNA viruses are a major human health threat. The life cycles of many highly pathogenic like influenza A virus (IAV) and Lassa depends on host mRNA, because viral polymerases cleave 5′-m7G-capped transcripts to prime mRNA synthesis ("cap-snatching"). We hypothesized that start codons within cap-snatched could generate chimeric human-viral mRNAs with coding potential. report the existence this mechanism gene origination, which we named "start-snatching." Depending reading frame,...
The response of the human acute myeloid leukemia cell line THP-1 to phorbol esters has been widely-studied test candidate therapies and as a model cycle arrest monocyte-macrophage differentiation. Here we have employed Cap Analysis Gene Expression (CAGE) analyse dense time course transcriptional regulation in cells treated with myristate acetate (PMA) over 96 hours. PMA treatment greatly reduced numbers entering S phase also blocked exiting G2/M. PMA-treated became adherent expression mature...
Abstract Background Predicting bed occupancy for hospitalised patients with COVID-19 requires understanding of length stay (LoS) in particular types. LoS can vary depending on the patient’s “bed pathway” - sequence transfers individual between types during a hospital stay. In this study, we characterise these pathways, and their impact predicted occupancy. Methods We obtained data from University College Hospital (UCH) ISARIC4C Clinical Information Network (CO-CIN) who required care general...
Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although was higher bacterial coinfection, this neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area...
An intense, nonresolving airway inflammatory response leads to destructive lung disease in cystic fibrosis (CF). Dysregulation of macrophage immune function may be a key facet governing the progression CF disease, but underlying mechanisms are not fully understood. We used 5′ end centered transcriptome sequencing profile P. aeruginosa LPS-activated human macrophages, showing that and non-CF macrophages deploy substantially distinct transcriptional programs at baseline following activation....
Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 COVID-19 cases 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 present 2.4% young (<60 years) no reported clinical (n = 378), compared 0.24% (odds ratio [OR] 12.3, p 1.27 × 10